Comorbid Bipolar Disorder and Substance Abuse: A Challenge to Diagnose and Treat

drinking alone
drinking alone
Bipolar disorder is often comorbid with substance use disorders, with alcohol being the top substance. Clinicians should take a thorough history to uncover substance use disorder because it will guide the management of both disorders.

Comorbid bipolar disorder and substance use disorder are frequently the rule rather than the exception.1 Bipolar disorder has among the highest rates of comorbidities, including anxiety disorders, obsessive compulsive disorder, impulse control disorders, eating disorders, cardiovascular and respiratory disorders, and sleep apnea.1 Not only are comorbid bipolar disorder and substance use disorder difficult to manage, but they also increase a patient’s likelihood for chronic infectious diseases, injury, and suicide.1

Who Is Most Likely to Have Comorbid Bipolar Disorder and Substance Use Disorder?

More men than women have substance use disorder, most often alcohol abuse.2 The same applies to men with bipolar disorder, who are more likely to have substance use disorder.2 Of the patients with bipolar disorder, those with mania are 14 times more likely to have a drug abuse disorder and 6 times more likely to have alcoholism.1 People with substance use disorder have higher rates of mania and hypomania (3.7%-13.4%) than the general population.1

In a meta-analysis of 22 large multicenter studies and 56 individual studies of comorbid bipolar disorder and substance use disorder, Hunt and colleagues found that both bipolar disorder I and bipolar disorder II had the same prevalence of substance use disorder.2 They characterized the prevalence of bipolar disorder comorbidities, and alcohol use by far was the largest subgroup, at 42%, followed by cannabis (20%), illicit drugs (17%), and cocaine and amphetamine (11%).2

For patients with a lifetime substance use disorder, the mean age of onset of bipolar disorder was 20.7 years vs 24.0 years for those without substance use disorder.2 Patients who had bipolar disorder and comorbid substance use disorder had an earlier age of onset for both disorders and tended to have more hospitalizations than nonusing patients.2 Researchers theorize that early onset of substance use disorder may be both a cause and a consequence of being predisposed to bipolar disorder.2

Diagnosing Comorbid Bipolar Disorder and Substance Use Disorder

Because bipolar disorder and substance use disorder share symptoms, such as impulsivity, Isabelle Bauer, PhD, from the University of Texas Health Science Center at Houston, and colleagues thought that by measuring patients’ degree of impulsiveness, they could better predict treatment response.3 Patients with bipolar disorder (N=103; mean age, 36.8 years; 40 men) with and without lifetime substance use disorder were given the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders Axis I (SCID I), the Barratt Impulsivity Scale, and portions of the Cambridge Neuropsychological Test Automated Battery (CANTAB).3 To the researchers’ surprise, bipolar disorder chronicity or substance use disorder did not predict impulsivity.3

“In bipolar disorder, high impulsivity tendencies are associated with poor clinical outcomes such as poor treatment adherence, relapse, rehospitalization, and reduced chances of going back to a normal life even after remission,” explained Dr Bauer. “It is unclear whether impulsivity is a symptom of bipolar disorder, or rather, the result of brain damage associated with repeated mood episodes and/or substance use.”

One of the hallmarks of personalized management of bipolar disorder is to identify and treat the disorder early and help predict its course.4 A combination of family history of bipolar disorder and completed suicide, childhood anxiety or mood lability, and poor response to antidepressants may unravel an early diagnosis. When genetic markers and neuroimaging, particularly an increase in gray matter density in the right inferior front gyrus, are considered, they could identify people who are likely to get bipolar disorder.4

“The personalized approach for early diagnosis can be helpful, as it may differentiate people who are likely to develop mood disorder as opposed to those who have substance abuse ‘alone,’ ” explained Martin Alda, MD, FRCPC, psychiatry professor at Dalhousie University and the director of the Mood Disorders Program for the Nova Scotia Health Authority in Halifax, Nova Scotia, Canada.

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Treating Comorbid Bipolar Disorder and Substance Use Disorder

Pharmacotherapy for concomitant bipolar disorder and substance use disorder is delicate at best, because an inappropriate medication could put patients in jeopardy of severe aggressive behavior or suicide.2 One of the more common agent pairings is valproate and quetiapine to treat bipolar disorder and alcoholism.2 Given the frequency with which bipolar disorder and substance use disorder occur, there remains a dearth of solid evidence to guide clinicians.2

Treatment is especially challenging for youth who also may abuse nonmedical opioid prescription drugs.5 The cross-sectional Rhode Island Young Adult Prescription Drug Study (RAPiDS) examined nonmedical prescription opioid (NMPO) use in 200 young adults aged 18 to 29 years who admitted to nonmedical prescription opioid use in the last 30 days.

Of the study participants, 85.5% had ever used benzodiazepines, and 62.5% admitted to regular use.5 Nearly a third of these patients (29.6%) had been diagnosed with bipolar disorder. Most troubling was that accidental overdose rates were higher in young adults who were prescribed the benzodiazepine they used most frequently vs those who were not (41.9% vs 24.4%; P =.06).5 From 2004 to 2011, benzodiazepine and opioid overdose deaths increased from 11.0 to 34.2 per 100,000.5

“These findings are alarming, as concurrent opioid and benzodiazepine use is a significant risk factor for overdose,” said co-author Brandon D.L. Marshall, PhD, associate professor of epidemiology at the Brown University School of Public Health in Providence, Rhode Island. “Clinicians who treat young adults for opioid use disorder should also consider interventions to address benzodiazepine addiction, including treatment of withdrawal symptoms and psychotherapy.”

Given the challenge of managing patients with comorbid bipolar disorder and substance use disorder, a multifaceted approach with pharmacotherapy and psychosocial interventions may be warranted. As such, Dr Gold and colleagues conducted a qualitative review of 8 studies of psychosocial therapy for comorbid bipolar disorder and substance use disorder.6 Despite the heterogeneous mix of studies (6 were for alcohol and illicit drugs and 2 were for smoking), the researchers identified integrated group therapy as the most consistent intervention for the comorbidities.6 Integrated group therapy, which involves weekly sessions that identify abuse triggers, relationships, and coping without substances, had the best efficacy for treating both the substance abuse and the mood disorder of the comorbidities.6

“In the absence of formal guidelines, it may be important for clinicians to consider how an integrated treatment focused on addressing both mood and substance use symptoms (as opposed to just the mood or substance use symptoms alone) can yield particular benefits for a given bipolar, substance-using patient,” said lead author Alexandra K. Gold, a clinical psychology doctoral student at Boston University in Massachusetts.


Bipolar disorder is often comorbid with substance use disorders, with alcohol being the top substance. Clinicians should take a thorough history to uncover substance use disorder, because it will guide the management of both disorders.


  1. Salloum IM, Brown ES. Management of comorbid bipolar disorder and substance use disorders. Am J Drug Alcohol Abuse. 2017;43(4):366-376.
  2. Hunt GE, Malhi GS, Cleary M, Lai HM, Sitharthan T. Prevalence of comorbid bipolar and substance use disorders in clinical settings, 1990-2015: systematic review and meta-analysis. J Affect Disord. 2016;206:331-349.
  3. Bauer IE, Meyer TD, Sanches M, Zunta-Soares G, Soares JC. Does a history of substance abuse and illness chronicity predict increased impulsivity in bipolar disorder?J Affect Disord. 2015;179:142-147.
  4. Alda M, Manchia M. Personalized management of bipolar disorder. Neurosci Lett. 2018;669:3-9.
  5. Bouvier BA, Waye KM, Elston B, Hadland SE, Green TC, Marshall BDL. Prevalence and correlates of benzodiazepine use and misuse among young adults who use prescription opioids non-medically. Drug Alcohol Depend. 2018;183:73-77.
  6. Gold AK, Otto MW, Deckersbach T, Sylvia LG, Nierenberg AA, Kinrys G. Substance use comorbidity in bipolar disorder: a qualitative review of treatment strategies and outcomes. Am J Addict. 2018;27(3):188-2016.