Involvement in the criminal justice system and medical comorbidities, particularly HCV, also complicate diagnosis and treatment of BD patients with SUDs. For more information about these topics, see Box1 and Box2.
Table 1
Why is substance abuse so prevalent among bipolar patients?
| Proposed hypothesis | Selected limitations of this hypothesis |
|---|---|
| Self-medication: substance abuse occurs as an attempt to regulate mood | High rates of substance use during euthymia; high prevalence of alcohol/depressant use during depressive phase, stimulant use during manic phase |
| Common neurobiologic or genetic risk factors | Specific evidence from linkage/association studies currently is lacking |
| Substance use occurs as a symptom of bipolar disorder | High percentage of patients with bipolar disorder do not have SUDs; there is a poor correlation of onset, course of bipolar, and SUD symptoms |
| Substance use unmasks bipolar disorder or a bipolar diathesis | Emergence of mania before SUD is common and predictive of more severe course of bipolar disorder |
| High comorbidity rates are an artifact of misdiagnosis based on overlapping symptoms and poor diagnostic boundaries | Very high prevalence of SUDs also is observed in longitudinal studies of patients initially hospitalized for mania |
| SUDs: substance use disorders | |
| Source: References 14,15 | |
Integrated clinical management
Assessment. Although not intended to be comprehensive, suggestions for routine assessment of patients with suspected SUDs and/or BD are listed in Table 2. Because clinicians may encounter dual diagnosis patients in general psychiatric clinics or specialty (addiction or mood disorder) clinics, it is useful to obtain a thorough substance use history in all patients with known or suspected BD as well as a thorough history of hypomania/mania and depression in all patients with addictive disorders. BD diagnoses by self-report or chart history in patients with SUDs should be considered cautiously because BD often is overdiagnosed in persons engaged in active substance abuse or experiencing withdrawal.21 If past or present mood symptoms and substance use have co-occurred, further focused assessment of mood symptoms before alcohol and drug use or during extended periods of abstinence are necessary to make the diagnosis of bipolar disorder with confidence. Family history of SUDs and/or BD are neither necessary nor sufficient for either diagnosis; however, collateral information from family or significant others could help make the diagnosis and may identify aids and obstacles to treatment planning and engagement.
When a patient’s clinical history strongly supports the diagnoses of BD and co-occurring SUDs, more detailed inquiry is warranted. Determining the patient’s age at onset of each disorder may have prognostic value because onset of mania before SUDs developed, especially in adolescence, may predict a more severe course of both illnesses.22 A complete alcohol use history should include routine questioning about past withdrawal. Previous withdrawal seizures in an actively drinking BD patient may tip the balance toward adding an anticonvulsant for mood stabilization. A thorough SUD history should elicit information about polysubstance abuse or dependence and include screening for injection drug use and other risk factors for HCV and human immunodeficiency virus (HIV), such as hypersexuality during manic or hypomanic episodes. Document the date of the last screening for HCV/ HIV in BD patients at high risk of infection. The U.S. Centers for Disease Control and Prevention recommends that all patients at high risk for HIV consider voluntary screening at least annually.23
Assess your patient’s historical and ongoing alcohol and other drug abuse at the initial visit, and continue to monitor substance use at all subsequent visits, especially in patients with HCV. When feasible, order urine drug screening and laboratory testing for alcohol use biomarkers such as carbohydrate-deficient transferrin and gamma-glutamyltransferase to supplement self-report data, especially in patients with poor insight or low motivation. Assess suicidal ideation and any changes in suicide risk factors at every visit.
Treatment. No biologic therapies have been FDA-approved for treating patients with co-occurring BD and SUDs. Comorbid SUDs in BD patients—as well as rapid cycling and mixed mood episodes, both of which are more common in patients with comorbid SUDs—predict poor response to lithium.17 However, the evidence base for optimal pharmacotherapy remains extremely limited. Published double-blind, placebo-controlled RCTs in persons with BD and co-morbid SUDs are limited to only 1 trial each of lithium, carbamazepine, quetiapine, and naltrexone, and 2 comparisons of lithium plus divalproex vs lithium alone (Table 3).24-29
Salloum et al24 reported that bipolar I disorder patients with alcohol dependence who received divalproex plus lithium as maintenance treatment had fewer heavy drinking days and fewer drinks per heavy drinking day than those receiving lithium plus placebo. However, the addition of divalproex did not improve manic or depressive symptoms, and depression remission rates remained relatively low in both groups. A recent 6-month study comparing lithium vs lithium plus divalproex in patients with SUDs and rapid-cycling BD found no additional benefit of divalproex over lithium monotherapy in retention, mood, or substance use outcomes.28 However, modest evidence that anticonvulsants such as valproic acid and carbamazepine may help treat acute alcohol withdrawal2 could support their preferential use as mood stabilizers over lithium in actively drinking BD patients.