0
1

The impact (in terms of duration of episodes and quality of life) of depressive episodes in bipolar patients is substantially worse than the impact of manic episodes (32, 33). Unfortunately, far less research attention has been paid to the treatment of bipolar depression (34, 35). This section reviews three studies published since the 2002 publication of the second edition practice guideline.

In an 8-week placebo-controlled, double-blind study, olanzapine monotherapy and the combination of olanzapine and fluoxetine were examined in the acute treatment of bipolar I depression (36). Although both olanzapine and the combination of olanzapine and fluoxetine were superior to placebo in efficacy, the response in the combination group was much greater, and only the combination of olanzapine and fluoxetine received an indication from the Food and Drug Administration for the acute treatment of bipolar depression. The first separation from placebo occurred at week 1 and continued throughout the trial. The mean dosage in the combination group was 7.4 mg/day of olanzapine and 39.3 mg/day of fluoxetine. By the end of the study, 8 of 10 core symptoms of depression had improved relative to placebo. Side effects included somnolence, weight gain, increased appetite, dry mouth, asthenia, and diarrhea. Neither olanzapine monotherapy nor the combination of olanzapine and fluoxetine caused switching into mania or hypomania.

A large randomized, double-blind, placebo-controlled trial supported the efficacy of quetiapine monotherapy for the treatment of bipolar I or II depression (37). Quetiapine initiated at 50 mg/day and titrated to either 300 mg/day or 600 mg/day within 1 week was found to be effective compared with placebo at both doses, with no significant difference in efficacy between the two dosage groups. Onset of action occurred by 1 week and continued throughout the trial. Statistical significance was achieved at endpoint in 9 of 10 core features of depression. Side effects included dry mouth, sedation, somnolence, dizziness, and constipation and were substantially greater in the 600 mg/day group compared with the 300 mg/day group. Incidence of treatment-emergent mania did not differ from that of placebo.

A single-blind, randomized, nonplacebo-controlled comparison of venlafaxine and paroxetine was conducted with patients with bipolar disorder who were currently presenting with a major depressive episode and who were currently taking a mood stabilizer (38). Both medications yielded significant improvements in depressive symptomatology with no significant differences in safety measures. Among the patients treated with paroxetine, 3% switched to hypomania or mania, compared with 13% in the venlafaxine group.

Two small, controlled studies of the adjunctive use of the dopamine agonist pramipexole in the treatment of bipolar depression suggest efficacy (39, 40). Both studies were 6-week placebo-controlled studies of pramipexole (mean peak dosage = 1.7 mg/day) added to the therapeutic levels of traditional mood stabilizers. Results were strongly positive in both studies, with few adverse events.

In conclusion, medications having the strongest evidence for efficacy for acute treatment of depression in patients with bipolar I disorder are the olanzapine-fluoxetine combination, quetiapine, and lamotrigine. There is suggestive evidence that the adjunctive use of pramipexole may be helpful. Evidence for the efficacy of an antidepressant with adjunctive mood stabilizer is modest. Prescription of antidepressants in the absence of a mood stabilizer is not recommended for bipolar I patients.

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Related Content
Articles
Books
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 3.  >
The American Psychiatric Publishing Textbook of Psychiatry, 5th Edition > Chapter 11.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 23.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 24.  >
The American Psychiatric Publishing Textbook of Psychiatry, 5th Edition > Chapter 26.  >
Psychiatric News
Read more at Psychiatric News >>
PubMed Articles
 
  • Print
  • PDF
  • E-mail
  • Chapter Alerts
  • Get Citation