Combined Antidepressant Treatments
How should antidepressants be combined and for how long? The term combination strategy in resistant depression typically refers to the addition to an antidepressant of a compound with well-established efficacy as a single agent in the treatment of depression. A typical example of this is the SSRI-TCA combination. When patients do not respond to treatment with a TCA alone, SSRIs in standard doses can be added to a reduced dose of the TCA, but TCA blood levels should be monitored. On the other hand, when patients do not respond to treatment with an SSRI alone, clinicians may initially add TCAs in low dosages from 10 to 25 mg/day without changing the SSRI dose and can raise the TCA dose while monitoring TCA blood levels. Relatively more user-friendly combination strategies involve the simultaneous use of SSRIs with atypical antidepressants such as bupropion, mirtazapine, and nefazodone. Despite the evident risks, MAOIs have been combined with TCAs; the safest approach is to initiate both drugs simultaneously and to gradually raise their doses to standard antidepressant levels. As mentioned before, neither SSRIs (including venlafaxine) nor clomipramine should be combined with MAOIs.
No guidelines exist as to the duration of an adequate trial of a combination strategy. Patients who respond have shown improvement as early as within 24-48 hours and as late as after several weeks. Unfortunately, no longitudinal or double-blind discontinuation studies of responders to combination strategies are available. A reasonable strategy is to test whether the added antidepressant remains necessary for maintaining a response by a trial of discontinuation 16 weeks or more after a response. If the patient experiences a relapse during discontinuation, the discontinued agent can be reinstated.
Revision date: June 22, 2011
Last revised: by Janet A. Staessen, MD, PhD