Bipolar affective disorder and substance abuse.
Brady, Kathleen T. and Lydiard, R. Bruce
Journal of Clinical Psychopharmacology, Vol 12(1, Suppl), Feb, 1992. pp. 17-22.

Abstract:
Addresses the issue of comorbidity of bipolar affective disorder (BPAD) with substance abuse disorders (SBADs). Data are presented concerning prevalence in the community and treatment-seeking samples, the genetics of these disorders, diagnostic and treatment difficulties, and suggestions for future directions for research. The prevalence of BPAD in the US is slightly more than 1%, and the percent of persons with BPADs in the SBAD treatment-seeking population exceeds this number. Patients with SBAD also have a history of excessive drinking, and excessive drinkers are more likely to require psychiatric hospitalization. There is much difficulty in diagnosing BPAD with SBAD because the effects of drugs can mimic nearly any psychiatric disorder.

Comorbidity of mental and addictive disorders.
Manley, Audrey
Journal of Health Care for the Poor and Underserved, Vol 3(1), Sum 1992. pp. 60-72.

Abstract:
Argues that deinstitutionalization and national patterns of illicit drug use have contributed to comorbidity of mental and addictive disorders in the US. A study by the National Institute of Mental Health (D. A. Regier et al; see PA, Vol 73:1361) found that among those with a history of drug abuse, 53.1% also had a mental disorder (4 times the risk in the general population); 47.3% had an alcohol abuse disorder (7 times the risk in the general population). Of all individuals with a lifetime diagnosis of schizophrenia (1.5% of the US population), 47.3% met criteria for some form of substance abuse. Rates of substance abuse among individuals with bipolar disorder are several times higher than in those with unipolar depression. From a service systems perspective, mental disorders must be addressed as a central part of drug abuse prevention efforts.

Substance abuse and bipolar affective disorder.
Sonne, Susan C., et.al.
Journal of Nervous and Mental Disease, Vol 182(6), Jun, 1994. pp. 349-352.

Abstract:
Explored the onset, course, and features of bipolar affective disorder (BPAD) complicated by substance abuse (SA). 44 patients with a diagnosis of BPAD (30 with current or past SA and 14 without SA) were interviewed using various measures including the Structured Clinical Interview for DSM-III—R and the Hamilton Rating Scale for Depression. Current substance users averaged twice as many hospitalizations for mood problems. The age of onset of mood problems for substance users was significantly earlier than that of the nonusers. Substance users were 4 times as likely to have other comorbid axis I disorders and twice as likely to have dysphoric mania at time of interview.

The relationship between substance abuse and bipolar disorder.
Brady, Kathleen T. and Sonne, Susan C.
The Journal of Clinical Psychiatry, Vol 56(Suppl 3), 1995. pp. 19-24.

Abstract:
Discusses issues related to the comorbidity of bipolar disorder and substance use disorders, including its prevalence in community and treatment-seeking samples, its impact on the course and presentation of illness, the associated diagnostic and treatment difficulties, and the pharmacologic approaches to its treatment. A review of research data indicates that bipolar disorder is very likely to co-occur with alcohol or drug abuse, and that bipolar patients who also abuse drugs or alcohol have an earlier onset and worse course of illness compared with those who do not. They are more likely to experience irritable and dysphoric mood states, increased treatment resistance, and a greater need for hospitalization. Caution about diagnosing bipolar disorder in the presence of substance abuse is advised because of overlapping symptomatology. A rationale for the pharmacologic approach to treatment is explored.

The effect of alcohol and substance abuse on the course of bipolar affective disorder.
Feinman, Jessica A. and Dunner, David L.
Journal of Affective Disorders, 37(1), Mar, 1996. pp. 43-49.

Abstract:
Examined the effect of substance abuse on demographic and clinical features and on the course of bipolar affective illness with 188 bipolar patients. Results show differences in demographics, clinical features and course of illness between patient groups. More men had a history of substance abuse. Complicated bipolar Ss had earlier age of onset, and this was linked to substance abuse. Higher rates of suicide were also found in complicated bipolar Ss, but this was attributed to the large number of women in this group. Substance abuse was determined to worsen the course of bipolar disorder. Results also indicate differences between Ss whose bipolar disorder began prior to and those whose disorder began after the onset of substance abuse.

Manic-depressive manic–depressive illness and substance abuse.
Swann, Alan C.
Psychiatric Annals, Vol 27(7), Jul, 1997. Bipolar Illness Update. pp. 507-511.

Abstract:
Discusses the mechanisms by which bipolar affective disorder (BAD) and substance abuse (SA) disorders, including alcoholism, can co-exist, strategies for exploring their relationships, course and phenomenology of illness, and treatment outcome. There appear to be 2 groups of patients with BAD and SA. In 1 group, SA is linked with severe BAD, characterized by strongly positive family history, early onset, and frequent episodes. A 2nd group is characterized by relatively mild BAD, perhaps requiring neurochemical of environmental stress of SA to trigger the onset of BAD. In both cases, there may be a predisposition to SA due to increased sensitivity to rewarding effects of abused drugs, and cross-conditioning between drug effects and affective episodes may occur, complicating treatment.

Substance abuse and bipolar comorbidity.
Sonne, Susan C. and Brady, Kathleen T.
Psychiatric Clinics of North America, Vol 22(3), Sep, 1999. pp. 609-627.

Abstract:
Bipolar disorder and substance abuse commonly co-occur. In fact, as many as 50% of individuals with bipolar disorder have been found to have a lifetime history of substance abuse or dependence. This article discusses the very important comorbidity of bipolar disorder as it is complicated by substance abuse, focusing on the prevalence, course, diagnostic considerations and treatment.

The co-occurrence of bipolar and substance use disorders.
Strakowski, Stephen M. and DelBello, Melissa P.
Clinical Psychology Review, Vol 20(2), Mar, 2000. pp. 191-206.

Abstract:
Substance use disorders are exceptionally common in bipolar patients. Although the frequency of this co-occurrence is well-documented, the reasons for this association are not clear. In this review, the authors examine 4 potential hypotheses for why substance use and bipolar disorders co-occur: (a) substance abuse occurs as a symptom of bipolar disorder; (b) substance abuse is an attempt by bipolar patients to self-medicate symptoms; (c) substance abuse causes bipolar disorder; and (d) substance use and bipolar disorders share a common risk factor. None of these 4 hypotheses have unequivocal support for explaining all cases of bipolar and substance use disorder co-occurrence, and it is probable that all 4 mechanisms play some role in the excess of substance abuse observed in bipolar patients. Additional studies are warranted to clarify the complex relationships between these 2 conditions as better understanding of this co-occurrence could lead to better treatment for patients afflicted with both disorders.

Psychosocial functioning of people with substance abuse and bipolar disorders.
Pollack, Linda E., et.al.
Substance Abuse, Vol 21(3), Sep, 2000. pp. 193-203.

Abstract:
Assessed whether a secondary diagnosis of a substance use disorder in hospitalized people with bipolar disorder was associated with poorer outcomes on self-reported measures of mood (Profile of mood States), subjective distress (Behavior and Symptom Identification Scale), and coping resources (Coping Resources Inventory), and with specific patient characteristics. 62 patients (all patients aged 18–65 yrs) with bipolar disorder and a secondary diagnosis of a substance use disorder and 60 patients with only a bipolar disorder diagnosis participated. Patients with bipolar disorder and a secondary diagnosis of a substance use disorder perceived significantly more impairment on all 3 measures than did patients without the secondary diagnosis. Moreover, the background characteristics of a history of violence, past or current involvement with the criminal justice system, and not having an antipsychotic medication prescribed during hospitalization had the strongest association with having a secondary diagnosis of a substance use disorder among the characteristics examined. These findings suggest the existence of a subgroup of patients with substance abuse and bipolar disorders who have substantial psychosocial impairment and probably require more intense treatment.

The impact of substance abuse on the course of bipolar disorder.
Strakowski, Stephen M., et.al.
Biological Psychiatry, Vol 48(6), Sep, 2000. Special Issue: A special issue on bipolar disorder. pp.

Abstract:
Substance abuse occurs at high rates in bipolar disorder. Alcohol use disorders have been associated with both earlier and later age of onset of bipolar disorder (BD), in part based on the temporal associations of the two conditions. Both drug and alcohol use disorders are associated with impaired outcome of bipolar illness. This influence may involve both direct effects of alcohol or drugs on the initiation of affective symptoms and indirect effects on treatment compliance. The authors examined the temporal associations of substance abuse and affective symptoms in 50 patients (mean age 25 yrs) with new onset BD. Associations between affective symptoms and alcohol and cannabis use disorder symptoms were evaluated using regression and time-series correlative methods in the new-onset bipolar patients. Results indicate that the duration of alcohol abuse during follow-up was associated with the time patients experienced depression. The duration of cannabis abuse was associated with the duration of mania. Several subgroups could be identified with different temporal relationships among these disorders. Although the relationships among substance use and BDs are complex, systematic study of the courses of the disorders might clarify how these conditions interact longitudinally.

Parsing the association between bipolar, conduct, and substance use disorders: A familial risk analysis.
Biederman, Joseph, et.al.
Biological Psychiatry, Vol 48(11), Dec, 2000. pp. 1037-1044.

Abstract:
Examined the association between bipolar disorder (BPD), conduct disorder (CD) and substance use disorders (SUDs) using familial risk analysis. The 1st sample comprised 29 youths with BPD and their 99 first-degree relatives. The 2nd sample comprised 16 consecutively referred BPD children and their 46 first degree relatives. 4 proband groups of relatives were compared: (1) CD and BPD; (2) BPD without CD; (3) CD without BPD; (4) control Ss with BPD or CD. Results indicate that BPD in probands is a risk factor for both drug and alcohol addiction in relatives, independent of CD in probands, which was a risk factor for alcohol dependence in relatives independent of BP in probands, but not for drug dependence. The effects of BPD and CD in probands combined additively to predict the risk for SUDs in relatives.

Bipolar disorder with comorbid substance abuse: Diagnosis, prognosis, and treatment.
Goldberg, Joseph F.
Journal of Psychiatric Practice, Vol 7(2), Mar, 2001. pp. 109-122.

Abstract:
Alcohol and drug abuse occur frequently in individuals with bipolar disorder, but clinicians may often feel ill-prepared to identify such multi-diagnosis syndromes, to contextualize drug abuse alongside affective symptoms, and to formulate appropriate treatment strategies. Plausible explanations for high comorbidity rates between bipolar illness and substance use disorders are complex and likely embrace numerous factors that extend beyond simple, older theories about drug use as sheer ‘self-medication.’ Evidence from epidemiologic, family-genetic, pharmacologic, psychosocial, and clinical psychopathology studies suggest that a majority of bipolar patients are at risk for developing lifetime drug or alcohol-related problems, which may in turn contribute to more varied and complex clinical presentations, accelerated relapses, worsening of depressive features, poorer lithium response, functional disability, and elevated suicide risk. In this article, the author reviews essential concepts about the phenomenology and treatment outcome of bipolar illness with substance use comorbidities and offers a systematic approach to the diagnosis and management of patients with such dual diagnoses.

Bipolar disorder and substance abuse: Considerations of etiology, comorbidity, evaluation, and treatment.
Clodfelter, Reynolds C. Jr., et.al.
Psychiatric Annals, Vol 31(5), May, 2001. pp. 294-299.

Abstract:
Bipolar disorder and substance use disorders each present difficult treatment issues. When these disorders co-occur, vexing diagnostic situations arise and treatment issues become more complex. Understanding and treating bipolar disorder when it co-occurs with substance abuse is one of the more difficult clinical situations for the clinician. A thorough history, often involving collateral sources and including a family history, the chronology of symptoms, and data more easily objectified, is paramount. Common sense, good judgement, and as much information as possible are critical to the accurate diagnosis and judicious treatment of these patients.

Drug abuse and bipolar disorder: Comorbidity or misdiagnosis?
Brown, E. Sherwood, et.al.
Journal of Affective Disorders, Vol 65(2), Jul, 2001. pp. 105-115.

Abstract:
Bipolar disorder is a common, severe and cyclic psychiatric illness. A strong association between alcohol dependence and bipolar disorder has been reported in numerous studies. The abuse of other drugs including cocaine, amphetamines, opiates, cannabis, and prescription medications in bipolar patients is also an important public health concern and has been less extensively investigated. This review examines the abuse of drugs other than alcohol or nicotine in people with bipolar disorder. The high rates of milder affective symptoms but not mania observed in patients in drug abuse treatment settings suggests the symptoms may in many cases be associated with the drug use. However, such patients presenting in psychiatric settings might be suffering from cyclothymic and related attenuated bipolar disorders (type II). Substance abuse may be associated with medication non-compliance, more mixed or dysphoric mania and possibly an earlier onset of affective symptoms and more hospitalizations. The pharmacotherapy of patients with bipolar disorder and drug abuse is examined, including evidence on the use of mood stabilizers, neuroleptics and the newer atypical antipsychotics in this population.

Substance abuse in bipolar disorder.
Cassidy, Frederick, et.al.
Bipolar Disorders, Vol 3(4), Aug, 2001. pp. 181-188.

Abstract:
Substance abuse histories were obtained in 392 patients (aged <30 to >60 yrs) hospitalized for manic or mixed episodes of bipolar disorder and rates of current and lifetime abuse calculated. Analyses comparing sex, subtype (manic vs mixed) and clinical history variables were conducted. Rates of lifetime substance abuse were high for both alcohol (48.5%) and drugs (43.9%). Nearly 60% of the cohort had a history of some lifetime substance abuse. Males had higher rates of abuse than females, but no differences in substance abuse were observed between Ss in manic and mixed bipolar states. Rates of active substance abuse were lower in older age cohorts. Ss with a comorbid diagnosis of lifetime substance abuse had more psychiatric hospitalizations. The authors conclude that substance abuse is a major comorbidity in bipolar patients. Although rates decrease in older age groups, substance abuse is still present at clinically important rates in the elderly. Bipolar patients with comorbid substance abuse may have a more severe course. These data underscore the significance of recognition and treatment of substance abuse in bipolar disorder patients.

Comorbid Substance Abuse: Affects Treatment for Bipolar Disorder.
Lawson, William B., et.al.
Psychiatric Annals, Vol 34(1), Jan, 2004. pp. 41-45.

Abstract:
Bipolar disorder is a chronic, relapsing, psychiatric disorder that is difficult to manage even without comorbidities. The addition of substance abuse clearly affects the diagnosis and treatment of this disorder. This article has examined how substance abuse is an key component of the clinical pathology of this disorder due to its effects on diagnosis, course of illness, and likelihood of medical comorbidities. Promising therapies are beginning to emerge, however, the problems that make this population difficulty to treat also make them unpopular for research protocols. There is a clear-cut societal need for more evidence-based treatment options for this population.

The Bipolar Patient with Comorbid Substance Use Disorder: Recognition and Management.
Albanese, Mark J., et.al.
CNS Drugs, Vol 18(9), 2004. pp. 585-596.

Abstract:
Bipolar patients with comorbid substance abuse or dependence (‘dual diagnosis’ patients) represent a major public health problem. Substance abuse generally predicts poor outcome and higher morbidity/mortality in bipolar disorder. For the purposes of this review, open and controlled studies of dual diagnosis assessment and treatment were located through electronic searches of several databases. Pertinent case reports were also evaluated. The results of the search were evaluated in light of the authors’ own research on dual diagnosis patients. Literature searching revealed few controlled studies to guide pharmacotherapy of bipolar patients with comorbid substance abuse or dependence. However, preliminary evidence suggests that the best outcomes are usually achieved with antiepileptic mood stabilisers and/or atypical antipsychotics, combined with appropriate psychosocial interventions. The latter may include classical 12-step groups, integrated group therapy or individual psychotherapy. While it is often difficult to determine the precise pathway to comorbid bipolar disorder/substance abuse, it is clear that both disorders must be vigorously treated. This requires a carefully integrated biopsychosocial approach, involving appropriate mood stabilisers and psychosocial interventions. Many more controlled studies of these combined treatment approaches are needed.

Impulsivity: A link between bipolar disorder and substance abuse.
Swann, Alan C., et.al.
Bipolar Disorders, Vol 6(3), Jun, 2004. pp. 204-212.

Abstract:
Background: Substance abuse is present in most patients with bipolar disorder and associated with poor treatment outcome and increased risk of suicide. Increased impulsivity may be a link between bipolar disorder and substance abuse. Methods: First, we compared impulsivity as a stable trait (Barratt Impulsiveness Scale, BIS) and as state-dependent behavioral laboratory performance (Immediate Memory-Delayed Memory task, derived from the Continuous Performance Task) in interepisode bipolar and non-bipolar subjects with and without substance abuse. Secondly, we compared impulsivity in interepisode and manic bipolar subjects with and without substance abuse. Results: The BIS scores were increased in interepisode bipolar disorder and in subjects with histories of substance abuse, and were increased further in interepisode bipolar subjects with substance abuse. Performance impulsivity was increased in subjects with substance abuse, regardless of whether they had bipolar disorder. Among subjects with bipolar disorder, after correction for age, BIS scores were increased in those with substance abuse…

Are some forms of substance abuse related to the bipolar spectrum? Hypothetical considerations and therapeutic implications.
Camacho, Alvaro.
Primary Psychiatry, Vol 11(9), Sep, 2004. pp. 42-46.

Abstract:
The use of addictive substances is prevalent among individuals with bipolar disorder (the so-called ‘dual diagnosis’ phenomenon). New studies have led to the proposal that the two groups of disorders exist on a continuum. The Akiskal-Pinto bipolar spectrum schema describes this continuum as bipolar type III 1/2. This review explores the possibility that some forms of substance abuse, especially stimulant abuse, can belong to the bipolar spectrum. These forms of substance abuse respond to anticonvulsant medications used as mood stabilizers. The review is divided into the following sections: neurobiology of addictive disorders, epidemiology of bipolar illness and comorbid substance abuse (particularly stimulant abuse), and clinical correlation with proposed treatment options. The proposed spectrum, with emphasis on stimulant use and bipolar disorder, provides an alternative understanding to a phenomenon that otherwise remains a diagnostic dilemma and therapeutic quagmire. Anticonvulsant medications appear to be a viable joint option for a proportion of patients with this condition.

Priority Actions to Improve the Care of Persons with Co-occurring Substance Abuse and Other Mental Disorders: A Call to Action.
O’Brien, Charles P., et.al.
Biological Psychiatry, Vol 56(10), Nov, 2004. pp. 703-713.

Abstract:
The Depression and Bipolar Support Alliance (DBSA) is the nation’s largest, illness-specific organization run by and for people living with depression or bipolar disorder. In November 2003, the DBSA convened a conference to address the unmet needs of substance use disorders in persons with depression or bipolar disorder. The prevalence and severity of substance use disorders that are comorbid with other mental illnesses was acknowledged; however, the DBSA conference focused on comorbid mood and substance use disorders. Unless otherwise specified, the term ‘substance use disorders’ is used in this statement to include the full spectrum of abuse and dependence on alcohol, nicotine, and illegal and prescription drugs. Participants included 43 experts in psychiatry, psychology, addiction treatment, health care policy, primary care, adolescent health, epidemiology, and advocacy. Presentations and deliberations from the conference and articles published in this special issue of Biological Psychiatry (Vol 56) are reflected herein. Participants listened to presentations, debated workgroup reports, and provided input to interim versions of this statement. All authors approved the final version. The objectives of this statement are to assess available data, describe unmet needs, and outline priority clinical actions and research directions that are needed to improve treatment, access to care, and professional training. Recommendations for priority actions are evidence-based, when possible; however, there is a remarkable lack of empirical data in this area. When data are available, they are often gleaned from heterogeneous populations that include patients with psychiatric diagnoses other than mood disorders. Thus, by necessity, the remaining priority action recommendations are based on the opinions and clinical experiences of the experts who participated in this conference. This statement reflects input from all participants.

Treating patients with bipolar disorder and substance dependence: Lessons learned.
Weiss, Roger D.
Journal of Substance Abuse Treatment, Vol 27(4), Dec, 2004. pp. 307-312.

Abstract:
Although bipolar disorder is the Axis I psychiatric disorder associated with the highest rate of co-occurring substance use disorders, little research has focused on treatments specifically designed for these patients. The author and his colleagues have developed and studied Integrated Group Therapy (IGT) for this population. This paper describes common themes that have emerged in carrying out IGT for patients with bipolar disorder and substance dependence. These include the strong emphasis on depression, as opposed to mania; the predominance of hopelessness; specific patterns of medication noncompliance; and the implications of patients’ labeling their substance use as self-medication. Therapeutic aspects involved in addressing these themes are discussed.

Gender differences in criminality: Bipolar disorder with co-occurring substance abuse.
Friedman, Susan Hatters., et.al.
Journal of the American Academy of Psychiatry and the Law, Vol 33(2), 2005. pp. 188-195.

Abstract:
Outpatient interviews to collect criminal history data were conducted with 55 women and 77 men who had the dual diagnosis of rapid-cycling bipolar disorder with co-morbid substance abuse disorders (DD-RCBD), to ascertain gender-related similarities and differences. Fifty-three percent of women and 79 percent of men reported that they had been charged with a crime, and nearly half of those charged had been incarcerated. Men with DD-RCBD were more likely to have committed a felony and had a trend of committing more misdemeanors. Although women with DD-RCBD were less likely to have a criminal history than their male counterparts, they were far more likely to have a criminal history than were women in the general population. Implications from this pilot study include the need for earlier identification of bipolar disorder and for the increased availability of psychiatric and substance abuse services within correctional facilities.

Prevalence and distinct correlates of anxiety, substance, and combined comorbidity in a multi-site public sector sample with bipolar disorder.
Bauer, Mark S., et.al.
Journal of Affective Disorders, Vol 85(3), Apr, 2005. pp. 301-315.

Abstract:
Background: Recent data indicate high prevalence of both anxiety and substance comorbidity in bipolar disorder. However, few studies have utilized public sector samples, and only one has attempted to separate contributions of each type of comorbidity. Methods: 328 inpatient veterans with bipolar disorder across 11 sites were assessed using selected Structured Clinical Interview for DSM-IV modules and self-reports. Results: Comorbidity was common (current: 57.3%; lifetime: 78.4%), with multiple current comorbidities in 29.8%. Substance comorbidity rate was comparable to rates typically reported in non-veteran inpatient samples (33.8% current, 72.3% lifetime). Selected anxiety comorbidity rates exceeded those in other inpatient samples and appeared more chronic than episodic/recurrent (38.3% current, 43.3% lifetime). 49% of PTSD was due to non-combat stressors. Major correlates of current substance comorbidity alone were younger age, worse marital status, and higher current employability. Correlates of current anxiety comorbidity alone were early age of onset, greater number of prior-year depressive episodes, higher rates of disability pension receipt, and lower self-reported mental and physical function. Combined comorbidity resembled anxiety comorbidity. Limitations: This is a cross-sectional analysis of acutely hospitalized veterans. Conclusions: Distinct patterns of substance and anxiety comorbidity are striking, and may be subserved by distinct neurobiologic mechanisms. The prevalence, chronicity and functional impact of anxiety disorders indicate the need for improved recognition and treatment of this other dual diagnosis group is warranted. Clinical and research interventions should recognize these divergent comorbidity patterns and provide individualized treatment built ‘from the patient out.’

Bipolarità e abuso di sostanze: Due disturbi in frequente comorbilità.
Translated Title: Bipolar and substance abuse disorders: Two frequently comorbid conditions.
Paniccia, Manuela., et.al.
Psichiatria e Psicoterapia, Vol 24(2), Jun, 2005. pp. 142-155.

Abstract:
Comorbidity between substance abuse disorder and bipolar disorder is frequent. Both disorders share some neurobiological correlates and have some common pathogenetic mechanisms. The question whether substance abuse precedes, induces or follows bipolar disorder is still unresolved, but it is a more frequent occurrence that bipolar onset precedes substance abuse. The type of abused substance appears to modulate the clinical expression of bipolar disorder, but the underlying disorder as well as its phase may also influence the choice of the abused substance. Comorbidity constitutes a negative prognostic factor for clinical course, inasmuch it is associated with decreased compliance and increased treatment resistance. Lithium and clozapine appear the most effective treatments in Comorbidity cases, but another atypical antipsychotic, quetiapine, is also promising. Early recognition and treatment of bipolar disorder may reduce Comorbidity with substance abuse disorder, thereby improving the clinical course and outcome of the former.

Bipolar Disorder and Substance Abuse.
Brown, E. Sherwood.
Psychiatric Clinics of North America, Vol 28(2), Jun, 2005. pp. 415-425.

Abstract:
Substance use disorders are common in patients with bipolar disorder. This article reviews recent data on the prevalence, impact, risk factors, and etiology of substance use disorder in patients with bipolar disorder and discusses treatment using pharmacotherapeutic and psychotherapeutic approaches. The limitations of the current knowledge and directions for future research are highlighted.

Bipolar disorder.
Brown, E. Sherwood, (Ed).
Psychiatric Clinics of North America, Vol 28(2), Jun, 2005. pp. xiii-xiv.

Abstract:
Bipolar disorder is a common and disabling illness. Research on the cause and treatment of bipolar disorder has become one of the more active areas within psychiatry. A number of outstanding scholars have contributed articles to this issue. The emphasis is on clinical aspects of bipolar disorder, although some recent basic science findings are also discussed. In one of the articles, the authors review recent findings on the ever-changing field of bipolar disorder genetics. Another article discusses some of these important and clinically relevant findings. The remainder of the issue is devoted to clinical research, particularly treatment, although pertinent preclinical findings are frequently highlighted. The treatment armamentarium for bipolar disorder seems to grow each year. Several articles on the treatment of adults and children with bipolar disorder are included in this issue. Some of the many co-occurring conditions associated with bipolar disorder are also discussed. Perhaps the most common comorbidity of bipolar disorder is substance abuse. The editor has contributed an article on recent research in this area

Komorbidität von alkohol- und substanzmittel-assoziierten Störungen mit bipolaren Erkrankungen.
Translated Title: Comorbidity of alcohol- and substance use disorders with bipolar affective disorders: What is chicken, what is egg?
Preuss, U. W.. Klinik
Die Psychiatrie: Grundlagen & Perspektiven, Vol 3(2), 2006. pp. 78-85.

Abstract:
Although numerous studies reported a range of higher frequency of alcohol and substance use disorders (ASUD) in patients with bipolar affective disorder (BAS), there is much less evidence for more BAS in ASUD subjects. However, the broad variance of results on increased rate of comorbid BAS and ASUD in previous studies might be influenced by the use of bipolar spectrum diagnostic criteria, the assessment instruments employed and sample characteristics (inpatient vs. outpatient, epidemiological). This comorbidity is noted to result in higher rates of hospital admissions, more severe courses of disease, worse prognosis and more suicidal behaviour in BAS subjects. However, the findings on an accrual of rapid cycling and mixed states episodes in these patients are controversial. For future studies to improve diagnostic validity for the diagnosis of comorbid ASUD and BAS, it is crucial to employ standardized assessment instruments for both disorders and to use longitudinal approaches to separate primary from secondary disorders and acute effects of alcohol and substances from longer lasting affective symptoms. Both issues have significant influence on treatment strategies and prognosis of patients.

A Comprehensive Current Overview of Bipolar Affective Disorder: Almost but Not Quite.
Haas, Leonard J. and Kiraly, Bernadette
PsycCRITIQUES, Vol 51(49), 2006.

Abstract:
Reviews the book, Surviving Manic Depression: A Manual on Bipolar Disorder for Patients, Families, and Providers by E. Fuller Torrey and Michael B. Knable (see record 2006-02215-000). Bipolar affective disorder, or manic-depressive illness as it is frequently known, is a costly, disabling, challenging disorder. It may also be significantly underdiagnosed, especially in its earlier stages and particularly in its Type II variant (depression predominant, with at least one episode of hypomania). Thus the volume Surviving Manic Depression: A Manual on Bipolar Disorder for Patients, Families, and Providers by such a well-known psychiatric figure as E. Fuller Torrey and his coauthor Michael B. Knable is a welcome resource. On the positive side of the ledger, the book provides an excellent review of the history of this disorder and useful discussion of differential diagnosis. The authors succinctly and clearly delineate issues regarding childhood bipolar disorder, particularly how one might differentiate between attention-deficit/hyperactivity disorder, childhood schizophrenia, conduct disorder, and bipolar disorder first manifesting in childhood. Important and helpful sections on substance abuse note the devastating complexities that this problem adds to the treatment of bipolar disorder. Despite these strengths, and despite a comprehensive review of etiological theories, the review of possible causes of bipolar disorder is rather inconclusive and is likely to be particularly frustrating to nonprofessionals. On balance, this book is helpful, even if flawed; it is clearly written and at least touches on all the important aspects of this disorder. We eagerly await a revised and updated edition.

Underdiagnosis of bipolar disorder in men with substance use disorder.
Albanese, Mark J., et.al.
Journal of Psychiatric Practice, Vol 12(2), Mar, 2006. pp. 124-127.

Abstract:
Objective: Recent reports indicate that bipolar disorder is frequently underdiagnosed in the clinical population, leading to overuse of antidepressants and underuse of mood stabilizers. This study assessed rates of diagnosis of bipolar disorder in a substance abuse population. Method: The study involved a retrospective chart review of data from 295 patients admitted to an inpatient substance abuse program for men. Data were then analyzed from the 85 patients in the sample who were diagnosed as meeting DSM-IV criteria for bipolar disorder on intake into the program. Charts were reviewed for relevant clinical and demographic data. The primary outcome measure was the rate of previous misdiagnosis. Results: Of the 85 patients diagnosed with bipolar disorder upon intake, 42 (49%) had not been previously diagnosed with bipolar disorder; of these 42, 6 (14%) patients had not been assessed previously, while 36 (86%) had been assessed previously and had received many other psychiatric diagnoses, including major depression (77%), attention-deficit/hyperactivity disorder (20%), and panic disorder (3%). Among the comorbid substance use disorders in these patients, alcohol dependence was the most common (62%), followed by cocaine (38%), opioid (26%), polysubstance (12%), and sedative-hypnotic (2%) dependence. Other comorbid Axis I disorders included posttraumatic stress disorder (14%), attention-deficit/hyperactivity disorder (10%), panic disorder (2%), and generalized anxiety disorder (2%). Conclusion: This study found that bipolar disorder had not been previously diagnosed in approximately 50% of a sample of Caucasian males in a substance abuse population who were diagnosed with bipolar disorder upon admission to an inpatient substance abuse program.

Toward a unitary perspective on the bipolar spectrum and substance abuse: Opiate addiction as a paradigm.
Maremmani, Icro., et.al.
Journal of Affective Disorders, Vol 93(1-3), Jul, 2006. pp. 1-12.

Abstract:
Bipolar spectrum disorders and addiction often co-occur and constitute reciprocal risk factors that the authors believe are best considered under a unitary perspective. In particular, we submit that patients whose disorders fall under the bipolar spectrum–and its hyperthymic and cyclothymic temperamental substrates–are at increased risk for substance use, possibly moving towards addiction through exposure to intrinsically dependence-producing substances. In our experience, the contribution of bipolar spectrum disorders to the addictive process is often clinically missed, because attenuated and subclinical expressions of such mood disorders as bipolar II and cyclothymia are not adequately appreciated by our current formal diagnostic system (e.g. DSM-IV, as well as research and clinical practice based on it). The use of agonist treatment in dual diagnosis heroin addicts has allowed us to gather valuable knowledge about the intrinsic, and historically and clinically documented mood-regulating effects of opiates. From the therapeutic point of view, the challenge of double diagnosis requires double competence from clinicians. The combination of opiate agonists and mood stabilizers often produces results difficult to obtain with the use of the two types of drugs separately. We therefore submit that the present conceptualization of the link between bipolar spectrum and addictive disorders has not only heuristic and scientific values, but also an important message for the clinician.

Aggression and substance abuse in bipolar disorder.
Grunebaum, Michael F., et.al.
Bipolar Disorders, Vol 8(5 pt 1), Oct, 2006. pp. 496-502.

Abstract:
Objectives: The goal of this retrospective study was to examine factors differentiating persons with bipolar disorder who did or did not have comorbid lifetime substance use disorders (SUD) at an index assessment. We also explored the chronology of onset of mood and SUD. Methods: We studied 146 subjects with DSM-defined bipolar disorder. Subgroups with and without lifetime SUD were compared on demographic and clinical measures. Results: Substance abuse disorders in this bipolar sample were associated with male sex, impulsive-aggressive traits, comorbid conduct and Cluster B personality disorders, number of suicide attempts and earlier age at onset of a first mood episode. In a multivariable logistic regression analysis, male sex and aggression and possibly earlier age at mood disorder onset were associated with SUD. In those with or without SUD, the first mood episode tended to be depressive and to precede the onset of SUD. Conclusions: In persons with bipolar disorder, an earlier age of onset and aggressive traits appear to be factors associated with later development of comorbid SUD.

Bıpolar bozukluğa eşlık eden Eksen I ve Eksen II tanilari.
Translated Title: Axis I and Axis II disorders accompanying bipolar disorder.
Ünal, Ahmet., et.al.
Türkiye’de Psikiyatri, Vol 9(1), 2007. pp. 18-25.

Abstract:
Objective: Bipolar disorder have frequent comorbid axis-I and axis II disorder. This leads to change the phenomenology of bipolar disorder and consequently affects the symptom severity, prognosis and response to treatment. In the present study, it was aimed to determine the rates of comorbid axis-I and II disorders in bipolar disorder and to evaluate socio demographic and clinical features. Method: The study comprised the patients with bipolar disorder according to DSM-IV. At first, 50 patients with bipolar disorder were psychiatrically examined and then, they were evaluated by using Structured Clinical Interview for DSM-IV (SCID-I) and Structured Clinical Interview for DSM-III-R Personality Disorder (SCID-II). Results: Bipolar disorder exhibited a proportion of 46% axis-I and 48% axis-II comorbid disorders. The proportion of multiple comorbidity was 22% of 50 patients. The most frequent comorbid axis-I disorders were obsessive-compulsive disorder. On the other hand, the most prevalent comorbid axis-II disorders were borderline personality disorder. In the comorbid axis-I and II disorder groups, the age of onset was earlier and in these groups the duration of illness was longer. In the group with comorbid axis-II disorders, the proportion of rapid cycling bipolar disorder was higher. In case of comorbidity, the episodes were more severe. Conclusion: Other psychiatric disorders frequently accompany bipolar disorder. The patients with multiple axis-I disorders should be followed regarding the development of affective disorders, especially bipolar disorder. Anxiety disorders with early onset, substance abuse and eating disorders may be prodromal symptoms of bipolar disorder especially in patients who come from families with the history of bipolar disorder. The comorbidity is an important condition which should be focused on because of its high prevalence and confusing effect on both investigations and clinical practice.

Bipolar spectrum and drug addiction.
Altamura, A. Carlo.
Journal of Affective Disorders, Vol 99(1-3), Apr, 2007. pp. 285.

Abstract:
Comments on the article by Maremmani et al (see record 2006-07896-001). The article hypothesized that drug addiction can be regarded as part of the ‘bipolar spectrum’. The current author totally agrees with this assumption and to endorse it the current author would like to cite a publication of many years ago (Altamura, 1975) that unexpectedly was not considered among the references in the original paper.

Manic symptoms and impulsivity during bipolar depressive episodes.
Swann, Alan C., et.al.
Bipolar Disorders, Vol 9(3), May, 2007. pp. 206-212.

Abstract:
Objectives: In contrast to the extensive literature on the frequent occurrence of depressive symptoms in manic patients, there is little information about manic symptoms in bipolar depressions. Impulsivity is a prominent component of the manic syndrome, so manic features during depressive syndromes may be associated with impulsivity and its consequences, including increased risk of substance abuse and suicidal behavior. Therefore, we investigated the prevalence of manic symptoms and their relationships to impulsivity and clinical characteristics in patients with bipolar depressive episodes. Methods: In 56 bipolar I or II depressed subjects, we investigated the presence of manic symptoms, using Mania Rating Scale (MRS) scores from the Schedule for Affective Disorders and Schizophrenia (SADS), and examined its association with other psychiatric symptoms (depression, anxiety, and psychosis), age of onset, history of alcohol and/or other substance abuse and of suicidal behavior, and measures of impulsivity. Results: MRS ranged from 0 to 29 (25th-75th percentile, range 4-13), and correlated significantly with anxiety and psychosis, but not with depression, suggesting the superimposition of a separate psychopathological mechanism. Impulsivity and history of substance abuse, head trauma, or suicide attempt increased with increasing MRS. Receiver-operating curve analysis showed that MRS could divide patients into two groups based on history of alcohol abuse and suicide attempt, with an inflection point corresponding to an MRS score of 6. Discussion: Even modest manic symptoms during bipolar depressive episodes were associated with greater impulsivity, and with histories of alcohol abuse and suicide attempts. Manic symptoms during depressive episodes suggest the presence of a potentially dangerous combination of depression and impulsivity.

The spectrum of substance abuse in bipolar disorder: Reasons for use, sensation seeking and substance sensitivity.
Bizzarri, Jacopo V., et.al.
Bipolar Disorders, Vol 9(3), May, 2007. pp. 213-220.

Abstract:
Objectives: To examine the spectrum of alcohol and substance abuse, including reasons for use, in patients with bipolar I disorder, compared with patients with substance use disorder and healthy controls, with a specific focus on the relationship between substance use, substance sensitivity, other comorbid psychiatric symptoms and traits related to sensation seeking. Methods: This study included 104 patients with bipolar I disorder (BPD I), of whom 57 (54.8%) met DSM-IV criteria for lifetime alcohol or substance use disorder (BPD + SUD), 35 patients with substance use disorder (SUD) and no psychiatric disorder and 50 healthy controls. Assessments included the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) and the Structured Clinical Interview for the Spectrum of Substance Use (SCI-SUBS). Results: Patients with BPD + SUD and SUD had significantly higher scores on the SCI-SUBS domains of self-medication, substance sensitivity and sensation seeking compared with patients with BPD and healthy controls. Reasons for substance use did not differ between patients with BPD + SUD and patients with SUD. Those most frequently cited were: improving mood; relieving tension; alleviating boredom; achieving/maintaining euphoria; and increasing energy. Conclusions: Recourse to substances is associated with increased mood and anxiety symptoms, substance sensitivity, and sensation seeking among patients with BPD + SUD and SUD. Substance sensitivity and sensation seeking traits should be investigated in all patients with BPD as possible factors associated with a development of SUD, in order to warn patients of the specific risks related to improper use of medications and substances.

Is bipolar disorder overdiagnosed among patients with substance abuse?
Stewart, Christopher., et.al.
Bipolar Disorders, Vol 9(6), Sep, 2007. pp. 646-648.

Abstract:
Background: Bipolar illness is frequently misdiagnosed. Several studies have focused on the underdiagnosis of this condition and the frequent long delay in its recognition. However, the illness is difficult to diagnose and many of its symptoms are shared by other conditions. In order to determine the accuracy of the diagnosis of bipolar illness among subjects with substance abuse, we carried out a study in patients with a previous diagnosis of bipolar disorder (BD) and known history of substance abuse or dependence, who were currently engaged in treatment for substance abuse. Methods: Individuals participating in a community-based substance treatment program and who had a previous diagnosis of BD were invited to undergo a structured clinical interview for diagnosis performed by a psychiatrist. In addition to the interview, previous hospital records were reviewed whenever possible. Diagnosis was made following strict DSM-IV criteria. Results: Only 9 of 21 (42.9%) subjects met diagnostic criteria for BD. Seven were BD type II and two were BD I. Conclusions: Bipolar disorder is frequently misdiagnosed following strict DSM-IV criteria. Among subjects with substance abuse, it may be overdiagnosed by psychiatrists.

The prevalence and significance of substance use disorders in bipolar type I and II disorder.
Cerullo, Michael A., et.al.
Substance Abuse Treatment, Prevention, and Policy, Vol 2, Oct 1, 2007. ArtID: 29

Abstract:
The aim of this paper is to provide a systematic review of the literature examining the epidemiology, outcome, and treatment of patients with bipolar disorder and co-occurring substance use disorders (SUDs). Articles for this review were initially selected via a comprehensive Medline search and further studies were obtained from the references in these articles. Given the lack of research in this field, all relevant studies except case reports were included. Prior epidemiological research has consistently shown that substance use disorders (SUDs) are extremely common in bipolar I and II disorders. The lifetime prevalence of SUDs is at least 40% in bipolar I patients. Alcohol and cannabis are the substances most often abused, followed by cocaine and then opioids. Research has consistently shown that co-occurring SUDs are correlated with negative effects on illness outcome including more frequent and prolonged affective episodes, decreased compliance with treatment, a lower quality of life, and increased suicidal behavior. Recent research on the causal relationship between the two disorders suggests that a subgroup of bipolar patients may develop a relatively milder form of affective illness that is expressed only after extended exposure to alcohol abuse. There has been very little treatment research specifically targeting this population. Three open label medication trials provide limited evidence that quetiapine, aripiprazole, and lamotrigine may be effective in treating affective and substance use symptoms in bipolar patients with cocaine dependence and that aripiprazole may also be helpful in patients with alcohol use disorders. The two placebo controlled trials to date suggest that valproate given as an adjunct to lithium in bipolar patients with co-occurring alcohol dependence improves both mood and alcohol use symptoms and that lithium treatment in bipolar adolescents improves mood and SUD symptoms. Given the high rate of SUD co-occurrence, more research investigating treatments in this population is needed. Specifically, double blind placebo controlled trials are needed to establish the effectiveness of medications found to be efficacious in open label treatments. New research also needs to be conducted on medications found to treat either bipolar disorder or a SUD in isolation. In addition, it may be advisable to consider including patients with prior SUDs in clinical trials for new medications in bipolar disorder.

Current issues in bipolar disorder: A critical review.
Oswald, Pierre., et.al.
European Neuropsychopharmacology, Vol 17(11), Nov, 2007. pp. 687-695.

Abstract:
Although awareness on bipolar disorder has increased during the last decade, this condition remains characterized by a disabling burden, in terms of morbidity and functional impairment. This paper aims to review some critical issues in the current knowledge on bipolar disorder. Although large European epidemiological studies are lacking, Bipolar disorder is characterized by a set of severe features, including an early age of onset, a chronic outcome and an important suicidal risk. A majority of bipolar patients also experience a comorbid Axis I condition, including substance abuse, anxiety disorder and attention-deficit hyperactivity disorder. This situation presents a therapeutic challenge, since antidepressants or methylphenidate may be associated with the risk of inducing mania. Recently, a large number of studies have provided evidence for the efficacy of new compounds in the treatment of both mania and bipolar depression, but also in long-term relapse prevention. Recent research has also allowed for the redefinition of the concept of mood stabilizer and for improving existing guidelines on the clinical management of bipolar disorder.

Cannabis and psychiatric disorders: It is not only addiction.
Leweke, F. Markus., et.al.
Addiction Biology, Vol 13(2), Jun, 2008. pp. 264-275.

Abstract:
Since the discovery of the endocannabinoid system, a growing body of psychiatric research has emerged focusing on the role of this system in major psychiatric disorders like schizophrenia (SCZ), bipolar disorder (BD), major depression and anxiety disorder. Continuing in the line of earlier epidemiological studies, recent replication studies indicate that frequent cannabis use doubles the risk for psychotic symptoms and SCZ. Further points of clinical research interest are alterations of endocannabinoids and their relation to symptoms as well as postmortem analyses of cannabinoid CB₁ receptor densities in SCZ. A possible neurobiological mechanism for the deleterious influence of cannabis use in SCZ has been suggested, involving the disruption of endogenous cannabinoid signaling and functioning. Even though the number of studies is still limited for affective and anxiety disorders, previous results suggest these diseases to be exciting objectives of cannabinoid-associated research. Therefore, it became apparent that cannabis use is not only frequent in patients suffering from BD, but that it also induces manic symptoms in this group. In addition, prior antipsychotic treatment decreased the numerical density of CB₁ immunoreactive glial cells in bipolar patients. Although the data on the influence of cannabis use on the development of major depression is controversial, cannabinoid compounds could display a new class of medication, as suggested by the antidepressive effects of the fatty acid amino hydrolase inhibitor URB597 in animal models. With numerous open questions and controversial results, further research is required to specify and extend the findings in this area, which provides a promising target for novel pharmacotherapeutic interventions.

Sequencing of substance use and affective morbidity in 166 first-episode bipolar I disorder patients.
Baethge, Christopher., et.al.
Bipolar Disorders, Vol 10(6), Sep, 2008. pp. 738-741.

Abstract:
Objectives: Since bipolar disorder (BPD) patients have high rates of comorbid substance abuse, and the temporal relationships involved are unclear, we evaluated the sequencing of specific substance use and affective morbidity. Methods: Prospective follow-up (4.7 years) of 166 first-episode DSM-IV type I BPD patients with reliable, standardized assessments provided data for longitudinal analysis of temporal distribution of alcohol and cannabis use versus manic or depressive episodes or symptoms, using generalized estimating equation regression modeling. Results: By quarters, cannabis use selectively and strongly preceded and coincided with mania/hypomania, and alcohol use preceded or coincided with depression, whereas substance use was unassociated with mood states in preceding quarters. Conclusions: These preliminary findings suggest potentially predictive temporal associations, in which the abuse of cannabis or alcohol anticipated or corresponded with, but did not follow, affective morbidity, including selective association of cannabis with mania and alcohol with depression.

Overdiagnosis of bipolar disorder among substance use disorder inpatients with mood instability.
Goldberg, Joseph F., et.al.
The Journal of Clinical Psychiatry, Vol 69(11), Nov, 2008. pp. 1751-1757.

Abstract:
Background: Among substance use disorder (SUD) patients, mood instability and high-risk behaviors may suggest the presence of bipolar disorder. However, active substance abuse impedes efforts to diagnose bipolar illness validly in patients with mood complaints. Method: The authors retrospectively reviewed records for 85 adults admitted sequentially over a 1-year period (August 1, 2005, to July 31, 2006) to a private inpatient dual-diagnosis unit for substance abuse/dependence and mood disorders. A senior research psychiatrist conducted diagnostic interviews based on DSM-IV criteria to ascertain current and lifetime manic or hypomanic episodes during abstinent periods. Results: Only 33% of subjects with suspected bipolar diagnoses (28/85) met DSM-IV criteria for bipolar I or II disorder. DSM-IV bipolar patients were significantly older (p = .029) and more likely to have made past suicide attempts (p = .027), abused fewer substances (p = .027), and were less likely to abuse cocaine (p < .001) than those failing to meet DSM-IV criteria. Inability to affirm bipolar diagnoses most often resulted from insufficient DSM-IV ‘B’ symptoms associated with mania or hypomania (55% or 45/82), inability to identify abstinent periods for assessing mood symptoms (36%, 29/81), and inadequate durations of manic/hypomanic symptoms for DSM-IV syndromic criteria (12%, 10/84). Patients not meeting DSM-IV criteria were most often presumed to have bipolar disorder solely on the basis of the presence of mood instability, although this feature held little predictive value for DSM-IV bipolar diagnoses. Conclusions: Many patients with active SUDs who are diagnosed in the community with bipolar disorder may not actually meet DSM-IV criteria for bipolar I or II disorder. Caution must be exercised when attempting to diagnose such patients, particularly when mood instability or cocaine use is present.

Substance use disorders as risk factors for psychiatric hospitalization in bipolar disorder.
Hoblyn, Jennifer C., et.al.
Psychiatric Services, Vol 60(1), Jan, 2009. pp. 50-55.

Abstract:
Objective: This study developed risk profiles of psychiatric hospitalization for veterans diagnosed as having bipolar disorder. Methods: This study included 2,963 veterans diagnosed as having bipolar disorder (types I, II, or not otherwise specified) during the 2004 fiscal year. Data were derived from the Veterans Affairs administrative database. Risk profiles for psychiatric hospitalization were generated with an iterative application of the receiver operating characteristic. Results: In this sample 20% of the patients with bipolar disorder were hospitalized psychiatrically during the one-year study period. Patients diagnosed as having both an alcohol use disorder and polysubstance dependence and who also were separated from their spouse or partner had a 100% risk of psychiatric hospitalization; risk of psychiatric hospitalization decreased to 52% if the patients were not separated from their partner. Patients who were not diagnosed as having alcohol use disorders or polysubstance dependence and who were not separated from their partners exhibited the lowest risk of psychiatric hospitalization (12%). Among patients with a psychiatric hospitalization, 41% had longer lengths of stay (>14 days), with the strongest predictor of a longer length of stay being an age older than 77 years, which conferred a 77% risk. Conclusions: Alcohol use and polysubstance dependence can significantly affect the course of bipolar disorder, as evidenced by their associations with psychiatric hospitalizations. Increased focus on substance abuse among older adults with bipolar disorder may decrease length of psychiatric hospitalization. Our findings suggest that implementing substance treatment programs early in the course of bipolar disorder could reduce health service use.

Letter to the editor regarding: ‘Is bipolar disorder overdiagnosed among patients with substance abuse?’
Kelly, Tammas.
Bipolar Disorders, Vol 11(1), Feb, 2009. pp. 107-108.

Abstract:
Comments on an article by Christopher Stewart and Rif S. El-Mallakh (see record 2007-13479-012). The authors have failed to prove their case that bipolar disorder (BD) may be overdiagnosed in subjects with substance abuse. There are five major concerns regarding the paper. First, relying on a single interview with a patient as the sole source of information does not rule out BD. Second, structured interviews are of questionable reliability in diagnosing bipolar II disorder. Third, ‘overruling’ a previous psychiatrist’s diagnosis should not be done without caution and also should not be done without examination of all prior medical records. Fourth, the authors made the diagnosis of substance-induced mood disorder in 100% of patients not diagnosed with bipolar I or II disorder. Historically, it can be very difficult to tell when a mood state starts to destabilize in relationship to a substance relapse even in those with good insight. Fifth, and most important, is the omission of bipolar disorder not otherwise specified (BD NOS), which invalidates the study.

Response to Dr. Kelly: Letter to the editor regarding: ‘Is bipolar disorder over-diagnosed among patients with substance abuse?’
El-Mallakh, Rif S., et.al.
Bipolar Disorders, Vol 11(1), Feb, 2009. pp. 109.

Abstract:
Reply by the current author to the comments made by Tammas Kelly (see record 2009-00516-014) on the original article (see record 2007-13479-012). We examined a population of patients that was highly and chronically symptomatic, and whose symptoms were compatible with several psychiatric conditions. We utilized the Structured Clinical Interview for Diagnosis (SCID) DSM-IV criteria, which are the current research gold standard for diagnosis. We found the research diagnosis discrepant with the clinical diagnosis nearly half of the time. There are limitations with utilization of the SCID, as pointed out by Dr. Kelly, but there are also daunting limitations with clinical diagnosis. There are many pressures facing clinicians that can influence their decision making. For example, Medicaid does not reimburse for substance-related diagnoses, but does reimburse for a bipolar diagnosis, thus creating a subtle force for clinicians to minimize their patients’ drug-related symptomatology.

Bipolar disorder and addiction.
Kuehn, Bridget M.
JAMA: Journal of the American Medical Association, Vol 303(20), May 26, 2010. pp. 2022.

Abstract:
Substance abuse by patients with bipolar disorder does not appear to slow their recovery, but it may indicate that patients have a more rapid cycling form of the disease, according to a study funded by the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Institute on Alcohol Abuse and Alcoholism. A team of scientists studied 3750 patients with bipolar 1 or 2 disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a multicenter prospective observational trial conducted from 1999 to 2005. The researchers hypothesized that patients with a current or past comorbid substance use disorder would experience a longer period between a major depressive episode and recovery than would those without such comorbidity. Although they did not find an association with past or current substance abuse with a longer time to recovery, they did find that patients with past or current substance abuse were more likely to experience rapid cycling from depression to manic, hypomanic, or mixed states. Based on the findings, the authors emphasize the importance of treating bipolar patients even if they have an active substance abuse disorder.

Substance abuse and switch from depression to mania in bipolar disorder.
Goldberg, Joseph F.
The American Journal of Psychiatry, Vol 167(7), Jul, 2010. pp. 868-869.

Abstract:
Comments on an article by Michael J. Ostacher et al. (see record 2010-04564-010). Michael J. Ostacher et al. identified an association between current or past substance abuse or dependence in bipolar disorder patients and a greater likelihood for affective polarity switch from depression to mania, hypomania, or mixed state relative to when comorbid substance use disorders were absent. Consistent with this finding, previous naturalistic data from a study that I co-authored demonstrated that a history of comorbid alcohol or substance use disorders conferred an approximate 7-fold increased risk in bipolar disorder patients for developing antidepressant-induced mania, regardless of cotherapy with antimanic agents. Insofar as Dr. Ostacher et al. identify bipolar disorder patients with comorbid substance use disorders as especially vulnerable to mood instability, yet no less likely to recover from a depressive episode as those without substance use disorder comorbidity, the potential safety versus efficacy of adjunctive antidepressants in this particular subset of individuals with bipolar depression warrants further examination.

Bipolar disorder and violent crime: Time at risk reanalysis.
Fazel, Seena., et.al.
Archives of General Psychiatry, Vol 67(12), Dec, 2010. pp. 1325-1326.

Abstract:
[Correction Notice: An erratum for this article was reported in Vol 68(2) of Archives of General Psychiatry (see record 2011-06663-002). Error in Title and Related Letter. The letter ‘[Bipolar Disorder and Violent Crime: Time at Risk Reanalysis]— Reply’ by Gibbons et al, published in the December 2010 issue of the Archives (2010;67(12):1326-1327), was not in reply to the letter ‘Bipolar Disorder and Violent Crime: Time at Risk Reanalysis’ by Fazel et al. It was in response to a letter published in the September 2010 issue of the Archives ‘Antiepileptic Drugs and Suicide Attempts in Patients With Bipolar Disorder’ by Mentari et al. The Gibbons et al letter was corrected online.] Comments on Bipolar disorder and violent crime: New evidence from population-based longitudinal studies and systematic review (see record 2010-19602-009) by Fazel et al. It has come to our attention that the design that we used in the 2 longitudinal studies on violent crime in bipolar disorder underestimated the relative risks of violent crime associated with patients with bipolar disorder, although the absolute risks of violent offending and substance abuse in bipolar disorder remain unchanged. Our design measured rates of violent crime in controls from age 15 years and in cases from after diagnosis. This meant that the time at risk was not similar between cases and controls. We discussed various other potential biases in our article, including the reliance on hospital data to ascertain the cases (which will likely overestimate relative risks) and conviction information to measure violence as an outcome (which will underestimate absolute risks), but would like to address this limitation in the present letter.

Treatment delay and excessive substance use in bipolar disorder.
Lagerberg, Trine Vik., et.al.
Journal of Nervous and Mental Disease, Vol 198(9), Sep, 2010. pp. 628-633.

Abstract:
The aim of the present study was to investigate the relationship between treatment delay and excessive substance use. A total of 151 bipolar disorder (BD) I and II patients were consecutively recruited from in- and outpatient psychiatric units, and categorized as primary or secondary BD (without or with antecedent excessive substance use). Predictors of treatment delay among all patients, and predictors of subsequent excessive substance use among primary BD patients, were investigated with logistic regression analyses. The median treatment delay was 2.0 years (IQR 14.0). The risk of long treatment delays was increased in patients with BD II disorder, no lifetime psychosis, a higher age at first contact with specialized psychiatric services, primary BD, and excessive substance use. In primary BD, the risk for developing excessive substance use was increased in males, in patients with shorter education and longer treatment delays. Patients with antecedent excessive substance use had reduced risk of long treatment delays. The risk of developing excessive substance use after BD onset increased with longer treatment delays.

Impulse control disorder comorbidity among patients with bipolar I disorder.
Karakus, Gonca., et.al.
Comprehensive Psychiatry, Vol 52(4), Jul-Aug, 2011. pp. 378-385.

Abstract:
Objective: Impulsivity is associated with mood instability, behavioral problems, and action without planning in patients with bipolar disorder. Increased impulsivity levels are reported at all types of mood episodes. This association suggests a high comorbidity between impulse control disorders (ICDs) and bipolar disorder. The aim of this study is to compare the prevalence of ICDs and associated clinical and sociodemographic variables in euthymic bipolar I patients. Method: A total of 124 consecutive bipolar I patients who were recruited from regular attendees from the outpatient clinic of our Bipolar Disorder Unit were included in the study. All patients were symptomatically in remission. Diagnosis of bipolar disorder was confirmed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Impulse control disorders were investigated using the modified version of the Minnesota Impulsive Disorders Interview. Impulsivity was measured with the Barratt Impulsiveness Scale Version 11. Furthermore, all patients completed the Zuckerman Sensation-Seeking Scale Form V. Results: The prevalence rate of all comorbid ICDs in our sample was 27.4% (n = 34). The most common ICD subtype was pathologic skin picking, followed by compulsive buying, intermittent explosive disorder, and trichotillomania. There were no instances of pyromania or compulsive sexual behavior. There was no statistically significant difference between the sociodemographic characteristics of bipolar patients with and without ICDs with regard to age, sex, education level, or marital status. Comorbidity of alcohol/substance abuse and number of suicide attempts were higher in the ICD (+) group than the ICD (−) group. Length of time between mood episodes was higher in the ICD(−) group than the ICD(+) group. There was a statistically significant difference between the total number of mood episodes between the 2 groups, but the number of depressive episodes was higher in the ICD (+) patients as compared with the ICD (−) patients. There was no statistically significant difference between the age of first episode, seasonality, presence of psychotic features, and chronicity of illness. A statistically significant difference was observed between the ICD(+) and ICD(−) groups in terms of total impulsivity, attention, nonplanning, and motor impulsivity scores as determined by the Barratt Impulsiveness Scale Version 11. Conclusion: The present study revealed that there is a high comorbidity rate between bipolar disorder and ICDs based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, criteria. Alcohol/substance use disorders, a high number of previous suicide attempts, and depressive episodes should alert the physician to the presence of comorbid ICDs among bipolar patients that could affect the course and treatment of the disorder.

The lived experience of adults with bipolar disorder and comorbid substance use disorder.
Ward, Terry Dionne.
Issues in Mental Health Nursing, Vol 32(1), Jan, 2011. pp. 20-27.

Abstract:
There is a high incidence of comorbid substance use in the bipolar population. Co-occurring substance use in this population increases negative outcomes and changes the illness presentation. Currently there is a lack of insight into the lived experience of adults with bipolar disorder and comorbid substance abuse. This descriptive phenomenological study describes and enhances the understanding of what it is like to live with bipolar disorder and comorbid substance used disorder. The data were collected using face-to-face in-depth interviews. Six distinctive themes were developed and validated by the descriptions of the experiences of the participants. The six themes that emerged from analysis of formulated meanings were: (1) Life is Hard; (2) Feeling the Effects; (3) Trying to Escape; (4) Spiritual Support; (5) Being Pushed Beyond the Limits; and (6) A Negative Connotation. All the themes came from the interconnection of bipolar disorder and substance use disorder. This study has implications for nursing practice, research, and education. If nursing and health care professionals understand the problem as these patients’ perceive it, management of mood swings and relapses from periods of sobriety along with selection of treatment modalities will be improved.

Classification of bipolar disorder in psychiatric hospital. A prospective cohort study.
Øiesvold, Terje., et.al.
BMC Psychiatry, Vol 12, Feb 29, 2012. ArtID: 13

Abstract:
Background: This study has explored the classification of bipolar disorder in psychiatric hospital. A review of the literature reveals that there is a need for studies using stringent methodological approaches. Methods: 480 first-time admitted patients to psychiatric hospital were found eligible and 271 of these gave written informed consent. The study sample was comprised of 250 patients (52%) with hospital diagnoses. For the study, expert diagnoses were given on the basis of a structured diagnostic interview (M.I.N.I.PLUS) and retrospective review of patient records. Results: Agreement between the expert’s and the clinicians’ diagnoses was estimated using Cohen’s kappa statistics. 76% of the primary diagnoses given by the expert were in the affective spectrum. Agreement concerning these disorders was moderate (kappa ranging from 0.41 to 0.47). Of 58 patients with bipolar disorder, only 17 received this diagnosis in the clinic. Almost all patients with a current manic episode were classified as currently manic by the clinicians. Forty percent diagnosed as bipolar by the expert, received a diagnosis of unipolar depression by the clinician. Fifteen patients (26%) were not given a diagnosis of affective disorder at all. Conclusions: Our results indicate a considerable misclassification of bipolar disorder in psychiatric hospital, mainly in patients currently depressed. The importance of correctly diagnosing bipolar disorder should be emphasized both for clinical, administrative and research purposes. The findings questions the validity of psychiatric case registers. There are potential benefits in structuring the diagnostic process better in the clinic.

Greater executive and visual memory dysfunction in comorbid bipolar disorder and substance use disorder.
Marshall, David F.. et.al.
Psychiatry Research, Vol 200(2-3), Dec 30, 2012. pp. 252-257.

Abstract:
Measures of cognitive dysfunction in Bipolar Disorder (BD) have identified state and trait dependent metrics. An influence of substance abuse (SUD) on BD has been suggested. This study investigates potential differential, additive, or interactive cognitive dysfunction in bipolar patients with or without a history of SUD. Two hundred fifty-six individuals with BD, 98 without SUD and 158 with SUD, and 97 Healthy Controls (HC) completed diagnostic interviews, neuropsychological testing, and symptom severity scales. The BD groups exhibited poorer performance than the HC group on most cognitive factors. The BD with SUD exhibited significantly poorer performance than BD without SUD in visual memory and conceptual reasoning/set-shifting. In addition, a significant interaction effect between substance use and depressive symptoms was found for auditory memory and emotion processing. BD patients with a history of SUD demonstrated worse visual memory and conceptual reasoning skills above and beyond the dysfunction observed in these domains among individuals with BD without SUD, suggesting greater impact on integrative, gestalt-driven processing domains. Future research might address longitudinal outcome as a function of BD, SUD, and combined BD/SUD to evaluate neural systems involved in risk for, and effects of, these illnesses.

Comorbid substance use as a predictor of bipolar classification in men and women: Findings from the collaborative psychiatric epidemiological surveys.
Stevens, Maria Blancarte.
Dissertation Abstracts International: Section B: The Sciences and Engineering, Vol 73(7-B)(E), 2013.

Abstract:
The purpose of the current study was to investigate the relationship between substance use and bipolar disorder, specifically whether comorbid substance use could predict the diagnostic classification of bipolar disorder (bipolar Ior II). The investigation was based on a secondary analysis of archival data from the Collaborative Psychiatric Epidemiological Surveys (CPES). The researcher hypothesized that the psychobiological effects of substance abuse could account for the high prevalence of bipolar disorder and comorbid substance abuse. This was thought to be particularly true for drug abuse which can produce symptoms that mimic bipolar disorder. Gender was included in order to identify any significant differences among males and females. Results indicated that bipolar I was associated with an increased risk of comorbid substance abuse, particularly drug abuse. There was a significant association between bipolar I and comorbid drug abuse in the female sample compared with bipolar II. A statistically significant association between comorbid drug and alcohol abuse combined and bipolar I provided further evidence supporting the positive relationship between bipolar I and comorbid substance abuse. Logistic regressions were run on comorbidity of substance abuse and bipolar disorder diagnoses. Participants who had a bipolar I diagnosis were found to be almost four times more likely to have comorbid drug abuse than were those with bipolar II. Females with bipolar disorder were found to be four times less likely to carry a comorbid diagnosis of drug abuse than were their male counterparts. The logistic regression on comorbid alcohol abuse and bipolar disorder was not significant. The researcher’s finding relative to substance use comorbidity among individuals with bipolar I is consistent with previous research. The current study extends previous research with results that indicate that the specific association between bipolar I and drug abuse is more powerful in women, with comorbid substance abuse being more prevalent in men than women across both bipolar disorder categories. Recommendations for future research include a more comprehensive look at the onset and course of each of the respective disorders in relation to gender in order to better understand the relationship between these variables.

Bipolar spectrum disorder: Origins and state of the art.
Tamayo, Jorge M., et.al.
Current Psychiatry Reviews, Vol 9(1), Feb, 2013. pp. 3-20.

Abstract:
The threshold chosen by categorical mental health classifications like DSM-IV-TR or ICD-10 for the diagnosis of bipolar disorders(BP) is too high, elevating the risk of misdiagnosing cases that closely resemble BP under several clinical variables like ‘major depressive disorder’. Acknowledging and providing the necessary weight to the BP subthreshold forms may improve the clinical practice and reduce the number of patients with misdiagnosis, creating opportunities for better treatment. Increasing evidence support the bipolar spectrum disorder (BPS) concept and factors such us earlier onset age of the first major depressive episode (MDE), brief duration of MDEs, rapid onset of MDEs, more than five previous MDEs, family history of BP, treatment-resistant depression, suicidal behavior, postpartum depression, atypical features, psychotic traits, irritability, overactivity, comorbidity with anxiety disorders, substance abuse, borderline personality disorder, migraine, and irritable temperament are well validated differentiators between unipolar and bipolar depressive disorders. Identifying those factors could increase the lifetime prevalence of BPS to at least 4.8%. New studies on the diagnosis and management of BP should focus on the development of diagnostics dimensional models with categorical benchmarks to recognize BP sub-threshold forms, on the selection of biomarkers for early identification of patients with BPS, especially those with BP family history, and on the promotion of joint efforts between academia, industry, government, and community to search new interventions in BPS management.

Screening for bipolar disorder among outpatients with substance use disorders.
Nallet, A., et.al.
European Psychiatry, Vol 28(3), Mar, 2013. pp. 147-153.

Abstract:
Background: Comorbidity of bipolar disorder and alcohol or substance abuse/dependence is frequent and has marked negative consequences on the course of the illness and treatment compliance. The objective of this study was to compare the validity of two short instruments aimed at screening bipolar disorders among patients treated for substance use disorders. Methods: The Mood Disorder Questionnaire (MDQ) and the Hypomania Checklist-32 (HCL-32) were tested with reference to the mood section of the Structured Clinical Interview for DSM-IV axis I disorders (SCID) in 152 patients, recruited in two outpatient clinics providing specialized treatment for alcohol and opiate dependence. Results: According to the SCID, 33 patients (21.7%) had a diagnosis within the bipolar spectrum (two bipolar I, 21 bipolar II and 10 bipolar not otherwise specified). The HCL-32 was more sensitive (90.9% vs. 66.7%) and the MDQ more specific (38.7% vs. 77.3%) for the whole sample. The MDQ displayed higher sensitivity and specificity in patients treated for alcohol than for opiate dependence, whereas the HCL-32 was highly sensitive but poorly specific in both samples. Both instruments had a positive predictive value under 50%. Conclusions: Caution is needed when using the MDQ and HCL-32 in patients treated for substance use disorders.

Is impulsivity a common trait in bipolar and unipolar disorders?
Henna, Elaine., et.al.
Bipolar Disorders, Vol 15(2), Mar, 2013. pp. 223-227.

Abstract:
Objectives: Impulsivity is increased in bipolar and unipolar disorders during episodes and is associated with substance abuse disorders and suicide risk. Impulsivity between episodes predisposes to relapses and poor therapeutic compliance. However, there is little information about impulsivity during euthymia in mood disorders. We sought to investigate trait impulsivity in euthymic bipolar and unipolar disorder patients, comparing them to healthy individuals and unaffected relatives of bipolar disorder patients. Methods: Impulsivity was evaluated by the Barratt Impulsiveness Scale (BIS-11A) in 54 bipolar disorder patients, 25 unipolar disorder patients, 136 healthy volunteers, and 14 unaffected relatives. The BIS-11A mean scores for all four groups were compared through the Games–Howell test for all possible pairwise combinations. Additionally, we compared impulsivity in bipolar and unipolar disorder patients with and without a history of suicide attempt and substance abuse disorder. Results: Bipolar and unipolar disorder patients scored significantly higher than the healthy controls and unaffected relatives on all measures of the BIS-11A except for attentional impulsivity. On the attentional impulsivity measures there were no differences among the unaffected relatives and the bipolar and unipolar disorder groups, but all three of these groups scored higher than the healthy participant group. There was no difference in impulsivity between bipolar and unipolar disorder subjects with and without suicide attempt. However, impulsivity was higher among bipolar and unipolar disorder subjects with past substance use disorder compared to patients without such a history. Conclusions: Questionnaire-measured impulsivity appears to be relatively independent of mood state in bipolar and unipolar disorder patients; it remains elevated in euthymia and is higher in individuals with past substance abuse. Elevated attentional and lower non-planning impulsivity in unaffected relatives of bipolar disorder patients distinguished them from healthy participants, suggesting that increased attentional impulsivity may predispose to development of affective disorders, while reduced attentional impulsivity may be protective.

Impulsivity in bipolar disorder: Relationships with neurocognitive dysfunction and substance use history.
Powers, Robyn L., et.al.
Bipolar Disorders, Vol 15(8), Dec, 2013. pp. 876-884.

Abstract:
Objectives: Impulsivity is a core feature in bipolar disorder. Although mood symptoms exacerbate impulsivity, self‐reports of impulsivity are elevated, even during euthymia. Neurocognitive processes linked to impulsivity (e.g., attention, inhibition) are also impaired in patients with bipolar disorder, and a high frequency of comorbidities associated with impulsivity, such as substance use disorders, further highlights the clinical relevance of this dimension of the illness. Our objective was to assess the relationship between impulsivity and cognition in bipolar disorder. Methods: We evaluated impulsivity in 98 patients with bipolar disorder and its relationship with symptoms, cognition, and substance use history. We assessed self‐reports of trait impulsivity [Barrett Impulsiveness Scale (BIS)] and impulsive behaviors on the Iowa Gambling Task (IGT). A comprehensive clinical and neurocognitive battery was also completed. Patients were compared with 95 healthy controls. Results: Patients with bipolar disorder had higher scores versus healthy controls on all BIS scales. Performance on the IGT was significantly impaired and patients showed a tendency toward more erratic choices. Depressive symptoms were positively correlated with trait impulsivity and with an increased tendency to attend more readily to losses versus gains on the IGT. We found no significant associations between impulsivity and neurocognition in the full bipolar sample; however, when sub‐grouped based on substance abuse history, significant relationships were revealed only in subjects without a substance abuse history. Conclusions: Our data support prior reports of increased trait impulsivity and impairment on behavioral tasks of impulsiveness in bipolar disorder and suggest a differential relationship between these illness features that is dependent upon history of substance abuse.

Impulsivity and risk taking in bipolar disorder and schizophrenia.
Reddy, L. Felice., et.al.
Neuropsychopharmacology, Vol 39(2), Jan, 2014. pp. 456-463.

Abstract:
Impulsive risk taking contributes to deleterious outcomes among clinical populations. Indeed, pathological impulsivity and risk taking are common in patients with serious mental illness, and have severe clinical repercussions including novelty seeking, response disinhibition, aggression, and substance abuse. Thus, the current study seeks to examine self-reported impulsivity (Barratt Impulsivity Scale) and performance-based behavioral risk taking (Balloon Analogue Risk Task) in bipolar disorder and schizophrenia. Participants included 68 individuals with bipolar disorder, 38 with schizophrenia, and 36 healthy controls. Self-reported impulsivity was elevated in the bipolar group compared with schizophrenia patients and healthy controls, who did not differ from each other. On the risk-taking task, schizophrenia patients were significantly more risk averse than the bipolar patients and controls. Aside from the diagnostic group differences, there was a significant effect of antipsychotic (AP) medication within the bipolar group: bipolar patients taking AP medications were more risk averse than those not taking AP medications. This difference in risk taking because of AP medications was not explained by history of psychosis. Similarly, the differences in risk taking between schizophrenia and bipolar disorder were not fully explained by AP effects. Implications for clinical practice and future research are discussed.

12‐month longitudinal cognitive functioning in patients recently diagnosed with bipolar disorder.
Torres, Ivan J., et.al.
Bipolar Disorders, Vol 16(2), Mar, 2014. pp. 159-171.

Abstract:
Objectives: Although cognitive deficits are observed in the early stages of bipolar disorder, the longitudinal course of neuropsychological functioning during this period is unknown. Such knowledge could provide etiologic clues into the cognitive deficits associated with the illness, and could inform early treatment interventions. The purpose of the present study was to evaluate cognitive change in bipolar disorder in the first year after the initial manic episode. Methods: From an initial pool of 65 newly diagnosed patients with bipolar disorder (within three months of the end of the first manic or mixed episode) and 36 demographically similar healthy participants, 42 patients [mean age 22.9 years, standard deviation (SD) = 4.0] and 23 healthy participants [mean age 22.9 years (SD = 4.9)] completed baseline, six-month, and one-year neuropsychological assessments of multiple domains including processing speed, attention, verbal and nonverbal memory, working memory, and executive function. Patients also received clinical assessments, including mood ratings. Results: Although patients showed consistently poorer cognitive performance than healthy individuals in most cognitive domains, patients showed a linear improvement over time in processing speed (p = 0.008) and executive function (p = 0.004) relative to the comparison group. Among patients, those without a history of alcohol/substance abuse or who were taken off an antipsychotic treatment during the study showed better improvement. Conclusions: The early course of cognitive functioning in bipolar disorder is likely influenced by multiple factors. Nevertheless, patients with bipolar disorder showed select cognitive improvements in the first year after resolution of their initial manic episode. Several clinical variables were associated with better recovery, including absence of substance abuse and discontinuation of antipsychotic treatment during the study. These and other factors require further investigation to better understand their contributions to longitudinal cognitive functioning in early bipolar disorder.

Impulsivity in bipolar and substance use disorders.
Ozten, Mustafa., et.al.
Comprehensive Psychiatry, Vol 59, May, 2015. pp. 28-32.

Abstract:
Background: Bipolar disorder (BD) is commonly associated with increased impulsivity, particularly during manic and depressed episodes; also impulsivity remains elevated during euthymic phases. Impulsivity is also a factor in the initiation and maintenance of substance use disorders (SUD). Impulsivity can predispose to substance abuse or can result from it. Impulsivity appears to be relatively independent of mood state and is higher in individuals with past substance use. Thus, we wanted to compare the impulsivity of BD and SUD closely associated with impulsivity and identify potential differences. Methods: Impulsivity was evaluated by the Barratt Impulsiveness Scale (BIS-11A), in 35 bipolar interepisode disorder male patients without comorbid substance use disorder and 40 substance use disorder male patients. The BIS-11A mean scores for the two groups were compared through one-way between-groups ANOVA. Results: There was no difference between the BD and substance use disorder groups on total and subscale attentional, motor impulsivity measures. However, for the male patients there was difference on the nonplanning subscale. The male BD patient group scored higher than the male substance use disorder patient group regarding nonplanning impulsivity. Conclusions: Our results replicate the findings that interepisode BD and substance use disorder patients both have increased total impulsivity; furthermore, the findings also indicate that trait impulsivity is not completely the same in subscales. Both groups were similar on attention and motor impulsivity subscales; however, on the nonplanning subscale, BD patients were more impulsive than the substance use disorder patients.

Functioning in bipolar disorder with substance abuse/dependence in a community sample of young adults.
de Azevedo Cardoso, Taiane., et.al.
Journal of Affective Disorders, Vol 187, Nov 15, 2015. pp. 179-182.

Abstract:
Aim: To assess the functional impairment of young adults with bipolar disorder with substance abuse/dependence comorbidity. Method: Cross-sectional study within a community sample. Bipolar Disorder was assessed by qualified psychologists using The Mini International Neuropsychiatric Interview—PLUS (MINI-PLUS). Substance abuse and dependence was assessed using the ‘Alcohol, Smoking and Substance Involvement Screening Test’ (ASSIST). Functional impairment was assessed using the Functional Assessment Short Test (FAST). Results: The sample included 1259 young adults. The prevalence of Bipolar Disorder (BD) without Substance Abuse/Dependence (SAD) comorbidity was 5.9% (n = 74), and the prevalence of bipolar disorder with substance abuse/dependence comorbidity was 1.4% (n = 17). Both groups showed higher impairment in overall functioning, interpersonal relationship, and leisure time as compared to controls. In addition, BD + SAD showed higher impairment in the cognitive functioning domain of FAST. Limitation: A battery of neuropsychological tests was not performed. Conclusion: Functional impairment is associated with BD, independently of substance abuse or dependence. In addition, BD + SAD present a more severe impairment in the cognitive domain of FAST as compared to controls.

The neurocognitive functioning in bipolar disorder: A systematic review of data.
Tsitsipa, Eirini., et.al.
Annals of General Psychiatry, Vol 14, Dec, 2015. ArtID: 42

Abstract:
Background: During the last decades, there have been many different opinions concerning the neurocognitive function in Bipolar disorder (BD). The aim of the current study was to perform a systematic review of the literature and to synthesize the data in a comprehensive picture of the neurocognitive dysfunction in BD. Methods: Papers were located with searches in PubMed/MEDLINE, through June 1st 2015. The review followed a modified version of the recommendations of the Preferred Items for Reporting of Systematic Reviews and Meta-Analyses statement. Results: The initial search returned 110,403 papers. After the deletion of duplicates, 11,771 papers remained for further evaluation. Eventually, 250 were included in the analysis. Conclusion: The current review supports the presence of a neurocognitive deficit in BD, in almost all neurocognitive domains. This deficit is qualitative similar to that observed in schizophrenia but it is less severe. There are no differences between BD subtypes. Its origin is unclear. It seems it is an enduring component and represents a core primary characteristic of the illness, rather than being secondary to the mood state or medication. This core deficit is confounded (either increased or attenuated) by the disease phase, specific personal characteristics of the patients (age, gender, education, etc.), current symptomatology and its treatment (especially psychotic features) and long-term course and long-term exposure to medication, psychiatric and somatic comorbidity and alcohol and/or substance abuse.

Bipolar disorders and substance use disorders.
Duffy, Anne., et.al.
Youth substance abuse and co-occurring disorders. Kaminer, Yifrah, (Ed); pp. 157-167; Arlington, VA, US: American Psychiatric Publishing, Inc.; 2016. xvii, 368 pp.

Abstract:
A wealth of evidence supports an association between substance misuse and risk of mood disorders (Levin and Hennessy 2004). The most commonly misused substances in both the general population and patients with mood disorders including bipolar disorder are cannabis and alcohol. Cannabis is considered a gateway drug that leads to an increased risk of polysubstance dependence. Furthermore, exposure to cannabis during adolescence has been strongly and specifically associated with the subsequent risk of developing schizophrenia and psychotic mania, as well as reducing the age at onset (De Hert et al. 2011). These associations may be related to the accelerated neurobiological development that is taking place during adolescence (Paus et al. 2008). However, most adolescents who are exposed to or regularly use alcohol and/or cannabis do not develop psychosis or psychotic mood disorders. It appears that exposure to substances in adolescence requires the interaction of other causal factors to result in psychiatric illness. In patients with established bipolar disorder, there is some evidence of a temporal sequence of substance use related to the polarity of the episodes and the course of illness (Baethge et al. 2005, 2008). Nonetheless, the relationship between mood disorders and substance use is complex. There are likely different causal pathways leading to substance use in subgroups of vulnerable high-risk individuals and different factors maintaining substance use in subgroups of patients with established illness. The overarching observation is that substance use is associated with worsened outcomes in vulnerable youths and patients across all measurable domains, including clinical, functional, and quality-of-life domains (Khalsa et al. 2008; Nery et al. 2014; Strakowski et al. 2000; Treuer and Tohen 2010). Although substance use is neither necessary nor sufficient to explain the development of psychotic and bipolar disorders, it is definitely a major risk factor and complicating influence and therefore should be an intensive target of preventive and early intervention efforts (Arseneault et al. 2004).

Clinical and cognitive factors affecting psychosocial functioning in remitted patients with bipolar disorder.
Konstantakopoulos, G., et.al.
Psychiatriki, Vol 27(3), Jul-Sep, 2016. pp. 182-191.

Abstract:
Impaired interpersonal, social, and occupational functioning is very often observed in patients with bipolar disorder, not only at the acute stages of the illness but in remission as well. This finding raises the question of multiple factors that might affect psychosocial functioning in bipolar patients, such as residual subsyndromal symptoms and neuropsychological deficits. Social cognition impairment, especially impaired Theory of Mind (ToM), might also play an important role in bipolar patients’ every-day functioning, similarly to what was found in patients with schizophrenia. The present study aimed to investigate the potential effect of clinical and cognitive factors on the psychosocial functioning of patients with bipolar disorder during remission, assessing ToM along with a broad range of basic cognitive functions. Forty-nine patients with bipolar disorder type I in remission and 53 healthy participants were assessed in general intelligence, working memory, attention, speed processing, verbal learning and memory, and executive functions using a comprehensive battery of neuropsychological tests. The Faux Pas Recognition Test was used to assess ToM. The two groups were matched for gender, age and education level. The Hamilton Rating Scale for Depression (HDRS), the Young Mania Rating Scale (YMRS), and the Brief Psychiatric Rating Scale (BPRS) were also administered to the patients. Every-day functioning was assessed with the Global Assessment of Functioning (GAF). In order to examine the contribution of many factors in psychosocial functioning, we used hierarchical multiple regression analysis. Bipolar patients presented significant impairment compared to healthy participants in all the basic cognitive functions tested with the exception of verbal memory. Moreover, patients had significant poorer performance than healthy controls in overall and cognitive ToM but not in affective ToM as measured by Faux Pas. Psychosocial functioning in patient group was significantly correlated to symptom severity-especially depressive (p < 0.001) and psychotic symptoms (p = 0.001), history of psychotic episodes (p = 0.031) and ToM, overall (p = 0.001) as well as its cognitive (p = 0.023) and affective (p = 0.004) components. Only the contribution of ToM in psychosocial functioning remained significant in the final multiple regression model. The findings of the current study indicate that residual symptoms and cognitive dysfunctions, especially deficits in social cognition, negatively affect psychosocial functioning of remitted patients with bipolar disorder. Moreover, our results suggest that ToM may play a central role in these patients’ functioning. ToM is a mediator of the relationship between other clinical or cognitive variables and functioning, while it has also significant effect on social skills independently of other factors. Therefore, specific therapeutic interventions targeting social cognitive dysfunction might improve functional outcome in bipolar disorder. Putative contribution of other clinical characteristics (comorbid personality disorders, substance abuse, anxiety) and psychosocial factors (stigma, self-stigma, lack of social network) in bipolar patients’ functioning should be examined in future studies.

Bipolar disorder and substance use disorders. Madrid study on the prevalence of dual disorders/pathology.
Arias, Francisco., et.al.
Adicciones, Vol 29(3), 2017. pp. 186-194.

Abstract (English):
Given its prevalence and impact on public health, the comorbidity of bipolar and substance use disorders is one of the most relevant of dual diagnoses. The objective was to evaluate the characteristics of patients from community mental health and substance abuse centres in Madrid. The sample consisted of 837 outpatients from mental health and substance abuse centres. We used the Mini International Neuropsychiatric Interview (MINI) and Personality Disorder Questionnaire (PDQ4+) to evaluate axis I and II disorders. Of these patients, 174 had a lifetime bipolar disorder, 83 had bipolar disorder type I and 91 had type II. Most patients had dual pathology. Of the 208 participants from the mental health centres, 21 had bipolar disorder and 13 (61.9%) were considered dually-diagnosed patients, while 33.2% of non-bipolar patients had a dual diagnoses (p = 0.03). Of the 629 participants from the substance abuse centres, 153 patients (24.3%) had a bipolar diagnosis. Bipolar dual patients had higher rates of alcohol and cocaine dependence than non-bipolar patients. Moreover, age at onset of alcohol use was earlier in bipolar dually-diagnosed patients than in other alcoholics. Bipolar dually-diagnosed patients had higher personality and anxiety disorder comorbidities and greater suicide risk. Thus, alcohol and cocaine are the drugs most associated with bipolar disorder. Given the nature of the study, the type of relationship between these disorders cannot be determined.

Structural and metabolic differentiation between bipolar disorder with psychosis and substance-induced psychosis: An integrated MRI/PET study.
Altamura, A. C., et.al.
European Psychiatry, Vol 41, Mar, 2017. pp. 85-94.

Abstract:
Background: Bipolar disorder (BD) may be characterized by the presence of psychotic symptoms and comorbid substance abuse. In this context, structural and metabolic dysfunctions have been reported in both BD with psychosis and addiction, separately. In this study, we aimed at identifying neural substrates differentiating psychotic BD, with or without substance abuse, versus substance-induced psychosis (SIP) by coupling, for the first time, magnetic resonance imaging (MRI) and positron emission tomography (PET). Methods: Twenty-seven BD type I psychotic patients with (n =10) or without (n =17) substance abuse, 16 SIP patients and 54 healthy controls were enrolled in this study. 3T MRI and 18-FDG-PET scanning were acquired. Results: Gray matter (GM) volume and cerebral metabolism reductions in temporal cortices were observed in all patients compared to healthy controls. Moreover, a distinct pattern of fronto-limbic alterations were found in patients with substance abuse. Specifically, BD patients with substance abuse showed volume reductions in ventrolateral prefrontal cortex, anterior cingulate, insula and thalamus, whereas SIP patients in dorsolateral prefrontal cortex and posterior cingulate. Common alterations in cerebellum, parahippocampus and posterior cingulate were found in both BD with substance abuse and SIP. Finally, a unique pattern of GM volumes reduction, with concomitant increased of striatal metabolism, were observed in SIP patients. Conclusions: These findings contribute to shed light on the identification of common and distinct neural markers associated with bipolar psychosis and substance abuse. Future longitudinal studies should explore the effect of single substances of abuse in patients at the first-episode of BD and substance-induced psychosis.

Novel psychoactive substance consumption is more represented in bipolar disorder than in psychotic disorders: A multicenter‐observational study.
Acciavatti, Tiziano., et.al.
Human Psychopharmacology: Clinical and Experimental, Vol 32(3), May, 2017. pp. 1-6.

Abstract:
Objective: Comorbidities between psychiatric diseases and use of traditional substances of abuse are common. Nevertheless, there are few data regarding the use of novel psychoactive substances (NPS) among psychiatric patients. Aim of this multicentre survey is to investigate the consumption of a number of psychoactive substances in a young psychiatric sample. Methods: Between December 2013 and September 2015, a questionnaire was administered in 10 Italian psychiatric care facilities to a sample of 671 patients, aged 18–26 (mean age 22.24; SD 2.87). Results: About 8.2% of the sample declared to have used NPS at least once, and 2.2% had consumed NPS in the previous 3 months. The three psychiatric diagnoses most frequently associated with NPS use were bipolar disorder (23.1%), personality disorders (11.8%), and schizophrenia and related disorders (11.6%). In univariate regression analysis, bipolar disorder was positively associated with NPS consumption, an association that did not reach statistical significance in the multivariate analysis. Conclusions: The use of NPS in a young psychiatric population appears to be frequent, and probably still underestimated. Bipolar disorder shows an association with NPS use. Careful and constant monitoring and an accurate evaluation of possible clinical effects related to NPS use are necessary.

Substance abuse in patients with bipolar disorder: A systematic review and meta-analysis.
Messer, Thomas., et.al.
Psychiatry Research, Vol 253, Jul, 2017. pp. 338-350.

Abstract:
By considering the debilitating outcome of co-occurring of bipolar disorder (BD) and substance abuse, determination of risk factors of substance use disorders (SUD: abuse or dependence of drugs and/or alcohol) is essential to identify the susceptible patients. The purpose of this study was to clarify the major determinant factors of SUD among adults with BD by reviewing the relevant literature. We systematically searched electronic databases including PubMed (MEDLINE), EMBASE, OVID, Cochrane and Scopus for human studies addressing the co-existence of bipolar disorder and SUD. All potential published papers up to September 2016 have been reviewed. The statistical analysis was performed using Comprehensive Meta-analysis version 2. Male gender (Odds ratio: 2.191 (95% CI: 1.121–4.281), P 0.022), number of manic episodes (P: 0.001) and previous history of suicidality (Odds ratio: 1.758 (95% CI: 1.156–2.674), P: 0.008) were associated to SUD in patients with BD. SUD was not related to age, subtype of BD, hospitalization and co-existence of anxiety disorders or psychotic symptoms. SUD affects many aspects of BD regarding clinical course, psychopathology and prognosis. Our study demonstrates that male gender, history of higher number of manic episodes and suicidality are associated to higher susceptibility to SUD. Thus, assignment of more intensive therapeutic interventions should be considered in patients with increased risk of drug abuse to prevent development of SUD.

Management of comorbid bipolar disorder and substance use disorders.
The American Journal of Drug and Alcohol Abuse, Vol 43(4), Jul, 2017. pp. 366-376.

Abstract:
Background: The comorbidity of substance use disorders (SUDs) in bipolar disorder is among the highest in psychiatric disorders. Evidence-based controlled psychosocial or pharmacological interventions trials, which may guide treatment decisions, have not been systematically reviewed. Objective: To present a narrative review of the public health and clinical significance of this condition, including diagnostic and treatment implications, and to evaluate controlled trials conducted to date. Methods: Controlled trials reports in the English language were identified from multiple electronic databases and hand-searching bibliographies. We searched for treatment studies of bipolar disorder and comorbid SUDs (alcohol, cocaine, stimulants, opioid, tobacco, cannabis). Search period included all reports through September of 2016. We selected only randomized psychosocial studies or double-blind, placebo-controlled pharmacotherapy trials. We also reviewed reports of the public health and clinical significance and principle of managements of this condition. Results: We identified 16 treatment studies: 3 psychotherapy, and 13 pharmacotherapy trials. The following medications were evaluated: lithium carbonate, valproate, lamotrigine, topiramate, naltrexone, acamprosate, disulfiram, quetiapine, and citicoline. SUDs have substantial impact on the recognition and management of bipolar disorder. Integrated psychosocial interventions are helpful in decreasing substance abuse. Valproate and naltrexone may decrease alcohol use and citicoline may decrease cocaine use and enhance cognition. Conclusions: There is a very limited number of pharmacotherapy and an even smaller number of psychosocial interventions. Our review highlights the need for more research in this area and for larger, multisite studies with generalizable samples to provide more definite guidance for clinical practice.

A review of the neurobiological underpinning of comorbid substance use and mood disorders.
Gómez-Coronado, Nieves., et.al.
Journal of Affective Disorders, Vol 241, Dec 1, 2018. pp. 388-401.

Abstract:
Background: There is evidence that substance use disorders and other mental disorders may have shared biological mechanisms. However, the neurobiological basis of this comorbidity remains only partially explained. This review describes the historical evolution of the dual disorders concept and approach, and reviews the existing literature on neurobiological findings specifically regarding comorbid substance use and mood disorders. Methods: Searches were conducted using PubMed and Scopus in December 2017. A Boolean search was performed using combinations of ‘dual diagnosis’ or ‘dual disorder’ or ‘depression’ or ‘bipolar’ or ‘affective disorder’ or ‘mood disorder’ and ‘substance use’ or ‘substance abuse’ and ‘neurobiology’ or ‘functional neuroimaging’ or ‘genetics’ or ‘neurotransmitters’ or ‘neuroendocrinology’ in the title or abstract, or as keywords, using no language restriction. Results: 32 studies met the inclusion criteria. We found robust evidence for involvement of the neurotransmitters dopamine, GABA and glutamate and their receptors, as well as by the central corticotrophin-releasing hormone, hypothalamic–pituitary–adrenal axis activation, oxidative stress and inflammation. Recent studies focusing on neuroimaging and genetics have not shown consistent results. Limitations: Only two search tools were used; most identified studies excluded the population of interest (comorbid mood and substance abuse disorders). Conclusions: The neurobiological relevance for the occurrence of comorbid mood and substance abuse disorders has not been fully elucidated. Considering the high levels of individuals who experience comorbidity in these areas as well as the negative associated outcomes, this is clearly an area that requires further in-depth investigation. Furthermore, findings from this area can help to inform drug abuse prevention and intervention efforts, and especially how they relate to populations with psychiatric symptoms.

Family members’ experiences: People with comorbid bipolar and substance use disorder.
September, Uwarren., et.al.
International Journal of Mental Health and Addiction, Vol 17(5), Oct, 2019. pp. 1162-1179.

Abstract:
People with comorbid bipolar and substance use disorders are complex, whose families experienced challenges contributing significantly to their burden of care. The aim of the study was to explore these lived experiences of family members caring for relatives, as well as the situations or contexts in which they experience these. A qualitative phenomenological research approach with explorative, descriptive research designs was adopted. In-depth phenomenological interviews were done with six purposive selected participants. Phenomenological data analyses focusing on the textural (lived experience) and structural (the context in which it was experienced) were followed after data collection. The lived experiences of participants included feelings of helplessness and emotional and physical exhaustion, as well as the causes of these feelings. The situations contributing to these feelings included non-compliance with prescribed medicine for bipolar disorder combined with drug abuse as well as a threat to the safety of the patient and others, stigmatisation, embarrassment and shame.

Post-traumatic stress burden in a sample of hospitalized patients with Bipolar Disorder: Which impact on clinical correlates and suicidal risk?Carmassi, Claudia., et.al.
Journal of Affective Disorders, Vol 262, Feb 1, 2020. pp. 267-272.

Abstract:
Background: Increasing evidence suggests Bipolar Disorder (BD) to be frequently associated to a history of traumatic experiences and Post-traumatic Stress Disorder (PTSD), with consequent greater symptoms severity, number of hospitalizations and worsening in quality of life. The aim of the present study was to investigate the lifetime exposure to traumatic events and PTSD rates in-patients with BD and to analyze the relationships between PTSD symptoms, clinical characteristics and severity of the mood disorder. Methods: A consecutive sample of 212 in-patients with a DSM-5 diagnosis of BD was enrolled at the psychiatric unit of a major University hospital in Italy and assessed by the SCID-5 and MOOD Spectrum-Self Report lifetime version (MOODS-SR). Socio-demographic characteristics, clinical features, substance or alcohol abuse, history of suicide related behaviors were also collected. Results: Lifetime trauma exposure emerged in 72.3% subjects, with a DSM-5 PTSD diagnosis reported by 35.6%. Patients with PTSD showed more frequently a (hypo)manic episode at onset, alcohol or substance abuse, psychotic features, suicide behaviors, higher scores in almost all the MOODS-SR domains, compared to those without PTSD. Limitations: Cross sectional study. Lack of data about the time since trauma exposure or PTSD onset. Conclusions: Our findings show a history of multiple traumatic experiences in hospitalized patients with BD besides high rates of PTSD, with the co-occurrence of these conditions appearing to be related to a more severe BD. Detailed investigation of post-traumatic stress symptoms is recommended for the relevant implications on the choice of a tailored treatment and the prognosis assessment.

Mood symptoms and impairment due to substance use: A network perspective on comorbidity.
Moriarity, Daniel P., et.al.
Journal of Affective Disorders, Vol 278, Jan 1, 2021. pp. 423-432.

Abstract:
Background: Mood disorders and problematic substance use co-occur and confer reciprocal risk for each other. Few studies use analytic approaches appropriate for testing whether specific features of one disorder confer risk for the other. Methods: 445 participants (59.8% female, Mean age = 20.3 years) completed measures of depression and hypo/mania symptoms and substance use-related impairment; 330 had complete data at follow-up. Of these, 28% reported a history of depression, 4% of bipolar spectrum disorder, 11% of substance use disorder, and 55% reported substance-related impairment. Symptoms and domains of substance-related impairment were modeled in cross-sectional and cross-lagged panel network models. Results: Impulsive and interpersonal impairment were most highly comorbid with mood symptoms. Suicidal ideation, sadness, decreased need for sleep, and guilt were the symptoms most highly comorbid with impairment. Interpersonal impairment due to substance use was the strongest cross-construct predictor of mood symptoms and suicidal ideation was most predictive of impairment. Social, intrapersonal, and physical impairment due to substance use were most predicted by previous mood symptoms and decreased need for sleep, guilt, and euphoria were most strongly predicted by past impairment. Limitations: Measures do not assess all mood symptoms, participants with low reward sensitivity were excluded, only self-report measures were used, and some variables were single-items. Conclusions: Components of these syndromes that confer cross-construct risk might not be the same components that are predicted by the other construct. The bidirectional relationship between mood symptoms and problematic substance use might be better conceptualized at the element, rather than diagnostic, level.