Alexandria S. Coles

Bipolar disorder is a disabling psychiatric disorder that presents in approximately 1.5% to 2.5% of the population.

 It is characterized by mood instability (hypomania/mania), depression, or mixed manic and depressive episodes. Fluctuations in mood are frequently accompanied by changes in energy levels and sleep patterns.

Substance use disorders (SUDs) are common among individuals with BD. Findings from a large meta-analysis indicate that the lifetime prevalence of alcohol and cannabis use disorders in BD is 42% and 20%, respectively.

 The lifetime prevalence of tobacco smoking in BD is as high as 60% to 80% compared with approximately 15% in the general US population.

 Co-occurring substance use is associated with earlier illness onset, suicidality, rapid cycling and mixed features, and more severe symptoms.

 Furthermore, there can be serious societal and economic consequences, including higher rates of violence, crime, homelessness, and health care costs. A better understanding of this comorbidity is important for diagnosing and treating these dual diagnosis patients.

John is a 22-year-old white single male with a history of bipolar I disorder. He was a student at a local community college until a month ago when he dropped out abruptly. Since age 16, he has been taking valproate sodium (1000 mg daily) and sertraline (100 mg daily), but he is only partially responsive to these medications (frequent mood instability, currently experiencing depressed mood). Over the past year, he admits to regularly drinking beer (3-4 times per week, 2-3 standard drinks per session). Although he rarely drinks to intoxication, his parents and friends consider him increasingly unreliable. He has also been smoking cannabis and crack cocaine in the past 6 weeks and says that he has “never felt better.” He thinks that he has no real drug problems and regards drinking as his way of coping.

Possible explanations for co-occurring BD and SUDs

A bidirectional relationship exists between BD and SUDs. Compared with individuals without psychiatric disorders, those with bipolar illness may be more vulnerable to initiating substance use; moreover, chronic substance users may be at greater risk of mood disorders than non-substance users.

 Although the exact mechanism underlying these co-occurring disorders remains largely unclear, several different explanations have been offered.

First, there appear to be genetic associations between BD and SUDs. A recent study estimated that 47% to 57% of the genetic variance in bipolar illness predisposition is linked to alcohol use disorder, which supports the idea that the two disorders may be genetically correlated.

Second, BD and SUDs share common neurobiological pathways, and behavioral sensitization (eg, “kindling”) may be a common mechanism. Repeated exposure to alcohol and drugs sensitizes neurons and is associated with increasingly rewarding effects. Interestingly, the course of BD follows a similar pattern (ie, episode sensitization). Therefore, individuals with a tendency to sensitization may be at greater risk of developing both bipolar illness and SUDs. This has led to the proposal that co-occurring BD and SUDs may respond better to anticonvulsant mood-stabilizers rather than lithium.

Third, certain traits associated with BD may elevate the risk for patients to engage in substance use.9 These include impulsivity, poor coping strategies for stress, and excessive pleasure-seeking associated with the manic or hypomanic phases of the illness. These findings are compatible with the hypothesis of addiction vulnerability in patients with psychiatric disorders.

An alternative explanation for co-occurring BD and SUDs is the self-medication hypothesis, which proposes that patients use substances to help alleviate BD symptoms. Empirical evidence regarding this hypothesis is mixed. Notably, mood symptom improvement is generally observed once abstinence is initiated, which is inconsistent with the self-medication hypothesis of SUDs in bipolar illness.

Assessing and diagnosing co-occurring BD and SUDs

Assessment and diagnosis of patients with co-occurring BD and SUDs can be challenging for a number of reasons. First, bipolar illness itself is a heterogeneous disorder with different subtypes and presentations. In fact, it is not uncommon for it to be misdiagnosed as unipolar depression.

Second, symptoms of alcohol and drug intoxication and withdrawal may resemble BD symptoms, making it often difficult to distinguish between the two. For instance, acute administration of central nervous system stimulants such as cocaine and amphetamines can lead to euphoria and increased energy, which overlap with symptoms of mania and hypomania.

Alternatively, misuse of alcohol and benzodiazepines can mimic depressive symptoms. Symptoms of withdrawal (eg, depression, dysphoria, sleep difficulties) also parallel BD symptoms in the depressed or mixed phases. Moreover, there is some evidence that BD comorbid with SUDs more commonly presents clinically with rapid cycling (eg, > 3 cycles per year between mania and depression) and mixed (dysphoric) manic features, which further complicates the diagnostic process.

Integrated treatment for co-occurring BD and SUDs

Diagnosis is the first challenge in the care of patients with co-occurring bipolar illness and SUDs; finding effective treatment is arguably just as challenging. Although there is no one single optimal treatment strategy, the management of these co-occurring disorders should integrate both pharmacological and psychosocial interventions.

A number of different pharmacotherapies have been efficacious in treating co-occurring BD and SUDs. In early studies, lithium was found to improve BD symptoms and reduce levels of substance use.

 Valproate has also been found to be effective at improving affective symptoms, decreasing substance craving, and reducing alcohol and drug use.

 Compared with valproate, lithium is associated with lower suicide risk during treatment, but it may be less effective in treating bipolar illness associated with SUDs.

A number of studies have examined quetiapine in treating patients with co-occurring disorders. While quetiapine may reduce depressive symptoms, it did not reduce alcohol use.16 Findings indicate that lamotrigine and topiramate are not particularly useful in treating comorbid bipolar illness and SUDs.

 Thus, while the use of anticonvulsant mood stabilizers and second generation antipsychotics for co-occurring bipolar disorder and SUDs is an attractive concept and may have some clinical utility, further research to substantiate these observations is warranted.

In addition to mood-stabilizing agents, adjunctive addiction pharmacotherapies should also be considered in treating dual diagnosis patients. Naltrexone has been shown to significantly reduce both manic and depressive symptom severity and decrease alcohol use in patients with bipolar disorder and alcohol dependence.

Psychotherapy should also be included in the treatment plan to support pharmacotherapies. Psychosocial interventions are important for addressing issues such as diagnosis acceptance, treatment compliance, and relapse prevention. Integrated group therapy, for instance, has been shown to be effective at reducing drug problem severity, encouraging abstinence, and decreasing the risk of mood episodes.

 This type of group therapy typically consists of five to eight patients for approximately 20 weekly sessions, and focuses on themes common to both BD and SUDs, such as identifying and dealing with triggers.

Cognitive behavioral therapy (CBT), which involves identifying and changing biased thoughts and beliefs, also shows promise in the treatment of co-occurring BD and SUDs. Patients who received CBT treatment had reduced symptom severity, decreased substance use, and longer abstinence periods.

Psychoeducation is effective at improving mood symptoms and reducing relapse in patients with bipolar illness. Because it enables patients to develop a more objective understanding of the disorder and learn strategies to manage mood symptoms, it should also be suitable for individuals with co-occurring disorders. Finally, motivational interviewing (MI) should be used to engage patients with co-occurring BD and SUDs into initial treatment.

Co-occurring bipolar illness and SUDs are associated with adverse clinical, social, and economic consequences. They are not only difficult to diagnose, but are linked to increased symptom severity, poorer treatment outcomes, and greater suicide risk. Treatment should integrate pharmacotherapy (mood stabilizers and adjunctive addiction medication) and psychotherapy (integrated group therapy, CBT, psychoeducation, MI).

Neuromodulation methods such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have shown promise in treating mood disorders and SUDs.

 While many challenges remain in the accurate and timely assessment and treatment of patients with co-occurring BD and SUDs, considerable progress has been made towards improving the care of these complex patients.

More research into this important area, particularly on clinical differences in bipolar illness with and without SUDs, and on matching treatments to SUD comorbidity (eg, pharmacological, behavioral), is needed if we are to make further improvements in treatment outcomes and quality of life for patients.

This work is supported in part by NIDA grant R21-DA-043949 to Dr George.

Ms Ma is an undergraduate student in psychology at the University of Toronto; Ms Coles is research coordination in the Biobehavioral Addictions and Mental Health Laboratory, Addictions Division, Centre for Addiction and Mental Health; Dr George is Professor, Department of Psychiatry, University of Toronto and Chief, Addictions Division, Centre for Addiction and Mental Health.

 Vieta EBM, Schulze TG, Carvalho AF, et al. Bipolar disorders. 

 Hunt GE, Malhi GS, Cleary M, et al. Prevalence of comorbid bipolar and substance use disorders in clinical settings, 1990-2015: systematic review and meta-analysis. 

 Mackowick KM, Lynch M., Weinberger AH, George TP. Treatment of tobacco dependence in people with mental health and addictive disorders. 

 George TP. Nicotine and tobacco. Schafer A, Ed. 

, 26th ed. New York: Elsevier; 2018; Chapter 32.

 Dalton EJ, Cate-Carter T D, Mundo E, et al. Suicide risk in bipolar patients: the role of co-morbid substance use disorders. 

 Brady.T, Sonne SC. The relationship between substance abuse and bipolar disorder. I. 1995;56(Supp 3):19-24.

 Salloum IM, Cornelius JR, Mezzich JE, Kirisci L. Impact of concurrent alcohol misuse on symptom presentation of acute mania at initial evaluation. 

 Carmiol N, Peralta JM, Almasy L, et al. Shared genetic factors influence risk for bipolar disorder and alcohol use disorders. 

 Salloum IM, Brown ES. Management of comorbid bipolar disorder and substance use disorders. 

 Chambers R, Krystal JH, Self DA. A Neurobiological basis for substance abuse comorbidity in schizophrenia. 

 Morozova M, Rabin RA, George TP. Co-morbid tobacco use disorder and depression: a re-evaluation of smoking cessation therapy in depressed smokers. 

 Geller B, Cooper TB, Sun K, et al. Double-blind and placebo-controlled study of lithium for adolescent bipolar disorders with secondary substance dependency. 

 Salloum IM, Cornelius JR, Daley DC, et al. Efficacy of valproate maintenance in patients with bipolar disorder and alcoholism. 

 Brady KT, Sonne SC, Anton R, Ballenger JC. Valproate in the treatment of acute bipolar affective episodes complicated by substance abuse: a pilot study. 

 Brown ES, Sunderajan P, Hu LT, et al. A randomized, double-blind, placebo-controlled, trial of lamotrigine therapy in bipolar disorder, depressed or mixed phase and cocaine dependence. 

 Brown ES, Garza M, Carmody TJ. A randomized, double-blind, placebo-controlled add-on trial of quetiapine in outpatients with bipolar disorder and alcohol use disorders. 

 Sylvia LG, Gold AK, Stange JP, et al. A randomized, placebo-controlled proof-of-concept trial of adjunctive topiramate for alcohol use disorders in bipolar disorder. 

 Brown ES, Beard L, Dobbs L, Rush AJ. Naltrexone in patients with bipolar disorder and alcohol dependence. 

 Weiss RD, Griffin ML, Jaffee WB, et al. A “community-friendly” version of integrated group therapy for patients with bipolar disorder and substance dependence: a randomized controlled trial. 

 Gregory Jr, VL. Cognitive-behavioral therapy for comorbid bipolar and substance use disorders: a systematic review of controlled trials. 

 Coles AS, Kozak K, George TP. A review of brain stimulation for treatment of substance use disorders. 

Articles

Symptoms of alcohol and drug intoxication and withdrawal may resemble symptoms of bipolar disorder, making it difficult to diagnose and treat.

Alexandria S. Coles

Articles

Understanding and Treating Co-Occurring Bipolar Disorder and Substance Use Disorders