Antidepressant Monotherapy for Bipolar Disorder

Editor, Primary Psychiatry and Psychiatry Weekly, Professor of Psychiatry, New York University School of Medicine

The two major concerns about the use of antidepressant monotherapy to treat a bipolar disorder (BD) episode are 1) sending the patient from the depressed phase into a manic phase, and 2) accelerating the frequency of mood shifts. A clearer understanding is needed of the best approach to manage patients with this diagnosis.

On October 20th, the FDA approved quetiapine to treat BD. Quetiapine, initially approved for the treatment of schizophrenia, got an indication in January of 2004 for the treatment of acute mania, either as monotherapy or as an adjunct to lithium or valproate. The latest approval makes quetiapine the first drug to treat both the depressive and manic phases of BD, but does not extend the treatment of unipolar depression, nor does it address the use of quetiapine as a maintenance treatment.

The approval is based on the findings of an 8-week study of quetiapine versus placebo in 1,045 patients. Those taking quetiapine showed greater improvement in BD symptoms, overall quality of life, and satisfaction related to functioning. Two doses of quetiapine 300 milligrams and 600 mg per day were studied, but the higher dose showed no added benefits.

All of the atypical psychotic agents, with the exception of clozapine, are indicated for the treatment of schizophrenia and BD (See Table). They differ, however, in what phase of BD (e.g., manic, depressed, mixed) they have proven to be effective, and in whether they are intended for acute or maintenance therapy, or both.

The only other drug to win regulatory approval as a treatment for the depressive phase of BD is the combination of fluoxetine and olanzapine—approved in December 2003 after it was shown in short-term studies to treat the depressed phase of BD without triggering mania. Both aripiprazole and ziprasidone are being examined for effectiveness in patients with bipolar I depression and may soon have their BD indications expanded to cover depression.

It is yet to be determined if quetiapine as monotherapy for acute treatment of BD will result in a simplified regimen for a typical patient. Very few BD patients, in fact, are treated with just one drug. It would be clinically helpful if studies were undertaken to examine the effects of quetiapine in combination with antidepressants as an intervention for treatment-resistant BD.

Another recent study delineated existing patterns of psychopharmacological treatment for BD. Of the 500 participants, standard mood stabilizers (lithium, valproate, or carbamazepine) were the most commonly prescribed class of drugs participants were taking at intake, at 71.9%. The second most common class of agents was antidepressants at 40.6%, followed by novel anticonvulsants at 31.8%, second-generation neuroleptics at 27.2%, and benzodiazepines at 25%. Only 11% of patients were treated with standard mood stabilizer monotherapy.

Disclosure: Dr. Sussman has received honoraria from AstraZeneca, Bristol-Myers Squibb, and GlaxoSmithKline.

References:

www.clinicaltrials.gov, accessed 10/22/06

www.centerwatch.com/patient, accessed 10/22/06

Nassir Ghaemi SN, Hsu DJ, Thase ME, Wisniewski SR, Nierenberg AA, Miyahara S, Sachs G. Pharmacological Treatment Patterns at Study Entry for the First 500 STEP-BD Participants. Psychiatr Serv 2006: 57:660-665