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October 2010

Exercise in Schizophrenia
Regular exercise can positively affect mental and physical health in people with schizophrenia.

Recognizing and Mitigating Delirium
Preventing delirium in hospitalized older patients saves lives and decreases dementia.

Lorcaserin: A New Drug for Weight Loss?
Lorcaserin has a better safety and adverse event profile but no greater efficacy than currently available weight loss agents.

In Brief
Bupropion during Pregnancy May Increase Risk of ADHD in Offspring; Bipolar Disorder Screening Recommended for Patients with Fibromyalgia

Treating Bipolar II Depression
Only quetiapine (Seroquel) is established as a first-line treatment for bipolar II depression; lithium, selective serotonin reuptake inhibitors (SSRIs), lamotrigine (Lamictal), and pramipexole (Mirapex and others) are second-line options.

Treating Bipolar II Depression

October 2010

Bipolar II disorder is common, recurrent, and disabling. Patients meet criteria for bipolar II disorder when they have had at least one major depressive episode and at least one episode of hypomania. A full-blown manic episode rules out this diagnosis.

Many clinicians have incorrectly assumed that bipolar II is a milder form of bipolar I disorder. However, epidemiologic data testify that it is at least as disabling as bipolar I disorder and often features multiple and more protracted episodes of depression. Compared with bipolar I patients, bipolar II patients experience a more chronic course of illness, spend more days depressed over their lifetime, and are less likely to return to premorbid functioning between episodes. It also carries a high risk of suicide. Epidemiologic, clinical, genetic, and neuroimaging studies emphasize that bipolar I and bipolar II disorders are distinct.

How best to treat acute depression in a patient with bipolar II disorder? Swartz and Thase conducted a literature review of randomized trials.1

The only two compounds rigorously tested for the treatment of bipolar II depression to date are quetiapine (Seroquel) and lamotrigine (Lamictal). The strongest evidence supports the efficacy of quetiapine, which shows a moderate effect size compared with placebo. The reviewers caution, however, that all the evidence about this antipsychotic comes from trials sponsored by its manufacturer.

Lamotrigine also has been subjected to rigorous testing for bipolar depression. Many studies included subjects with both bipolar I and bipolar II depression. In a review of treatments for bipolar disorder, Sachs et al note two positive studies of lamotrigine for acute bipolar depression but four negative or failed trials.2 Thus, data concerning lamotrigine in bipolar II depression can be considered suggestive but far from definitive. Sachs et al cite evidence that a positive response of some patients to lamotrigine might reflect genetic polymorphisms that influence brain dopamine transmission.

Available data about the efficacy of lithium, antidepressants, and pramipexole (Mirapex and others) for the treatment of bipolar II depression are inconclusive. Swartz and Thase point out the importance of clarifying the differential effects of antidepressants as monotherapy versus adjunctive therapy in this population. They find data on pramipexole and lithium promising but call for more rigorous testing. They classify lithium, selective serotonin reuptake inhibitor (SSRI) antidepressant monotherapy, and adjunctive pramipexole as second-line options for the management of bipolar II depression. Data on modafinil (Provigil), valproate (Depakote and others), and omega-3 fatty acids in the management of bipolar II depression are considered inadequate and insufficient, allowing no definitive conclusions.

Sachs et al note small studies supporting the idea of subsets of bipolar II patients who benefit from standard antidepressant medication, even as monotherapy. They also observe that the US Food and Drug Administration has approved the combination of olanzapine and fluoxetine (Symbyax) for bipolar I (but not bipolar II) depression.

The public expects physicians to practice evidence-based medicine. At this stage of knowledge, only quetiapine appears established as a first-line treatment for bipolar II depression. Lithium, SSRIs, lamotrigine, and pramipexole can be considered second-line alternatives. Antidepressants can be thought of as adjuncts or, cautiously, as monotherapy. Some other compounds merit additional research and occasional case-by-case consideration as off-label treatments.

1Swartz HA, Thase ME: Pharmacotherapy for the treatment of acute bipolar II depression: Current evidence. J Clin Psychiatry, in press.

2Sachs GS, Dupuy JM, Wittmann CW: The pharmacologic treatment of bipolar disorder. J Clin Psychiatry, in press.