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

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Bipolar disorder is a disabling psychiatric disorder that presents in approximately 1.5% to 2.5% of the population.¹ 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.² The lifetime prevalence of tobacco smoking in BD is as high as 60% to 80% compared with approximately 15% in the general US population.^3,4 Co-occurring substance use is associated with earlier illness onset, suicidality, rapid cycling and mixed features, and more severe symptoms.^5-7 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.

CASE VIGNETTE

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.⁶ 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.⁸

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.⁶

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.¹⁰

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.¹¹

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.¹² Valproate has also been found to be effective at improving affective symptoms, decreasing substance craving, and reducing alcohol and drug use.^13,14 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.¹⁵

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.^15,17 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.¹⁸

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.¹⁹ 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.²⁰

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.

Conclusions

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.²¹ 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.

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

Disclosures:

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.

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