Antidepressants for bipolar depression: Tips to stay out of trouble
When it makes sense to use them and for how long.
- A euthymic mood state in the previous 2 months represented a uniphasic pattern and an isolated depressive episode.
- A preceding hypomanic/manic mood state indicated a biphasic pattern.
Approximately 60% of bipolar patients show a biphasic pattern, although the episode sequence is usually depression-hypomania/mania rather than hypomania/mania-depression. These authors included patients whose breakthrough depressive episodes were treated with an antidepressant or a putative mood stabilizer but not an atypical antipsychotic.
In patients treated with an antidepressant, the response-to-switch ratio was 10:1 for those previously euthymic, compared with a less beneficial 0.75:1 in previously hypomanic/manic patients. This small study suggests that a patient’s cycle pattern may help you decide whether to use an antidepressant for bipolar depression.
How to use antidepressants. As described, some depressed bipolar patients are better candidates for antidepressant therapy than others (Table 3).
Table 3
Antidepressants for bipolar depression? Consider ‘ideal patient’ traits
| Severe depression refractory to optimal doses of ≥1 mood stabilizers |
| Uniphasic cycle pattern |
| Not rapid cycling |
| No history of switching or mood destabilization |
| No comorbid substance abuse |
Use antidepressants cautiously and conservatively in a minority of bipolar patients (approximately 20% to 40%) and usually for short periods (discussed below). SSRIs or bupropion are first-line agents because:
- they appear to be relatively less likely to cause switching than other antidepressant classes
- controlled trials have examined these antidepressants in bipolar depression.
Depressed patients with very mild, nonrapid-cycling, bipolar II disorder and no more than three previous hypomanic episodes might be candidates for antidepressant monotherapy. In other bipolar patients, always use at least one mood stabilizer if you decide to use an antidepressant.
TREATMENT DURATION
No randomized, controlled trial has examined what duration of antidepressant treatment may be optimum for bipolar depression, but consensus guidelines recommend:
- approximately 3 to 7 months, depending on depression severity
- approximately one-half that duration (2 to 4 months) for rapid-cycling bipolar disorder.20
Because of the switching risk, one could also argue for a shorter treatment duration in patients with a biphasic cycle pattern—especially with an episode sequence of depression to hypomania/mania to euthymia.
Ideally, patients would stay on antidepressants no longer than the natural course of their depression (usually 2 to 6 months in bipolar depression), although it could be shorter in rapid cyclers. Approximately 15% to 20% of patients may have a robust initial response to antidepressants and need to be maintained on these medications, especially after several tapers and relapses have failed.
Related resources
- Bipolar Clinic and Research Program. Massachusetts General Hospital. Includes tools for clinicians and the clinical site for the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). www.manicdepressive.org.
- Goodwin FK, Jamison KR. Manic-depressive illness. New York: Oxford University Press, 1990.
Drug brand names
- Bupropion • Wellbutrin
- Imipramine • Tofranil
- Lamotrigine • Lamictal
- Lithium • Lithobid, others
- Olanzapine/fluoxetine • Symbyax
- Paroxetine • Paxil
- Quetiapine • Seroquel
- Venlafaxine • Effexor
Disclosures
Dr. Altman is a speaker for Forest Pharmaceuticals, Janssen Pharmaceutica, AstraZeneca Pharmaceuticals, and Abbott Laboratories.
