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ANTIDEPRESSANT AUGMENTATION

Augmentation refers to the addition of a second agent which does not possess primary antidepressant properties to an existing antidepressant. Augmentation can be employed either when patients have failed to respond to an acute trial of antidepressant medication, or when an adequate antidepressant response is achieved with the acute phase of therapy, but the effect is then lost over the ensuing months. Most practitioners will be concerned with augmenting an antidepressant trial which has failed. Here, several agents have proven effective. The most commonly used agents include T-3 (tri-iodothyromine); lithium, and, to a lesser extent, L-tryptophan and buspirone. Because T-3 and lithium are more commonly used than the other two agents, recommendations for their use alone follow.

First, evidence suggests that T-3 augmentation therapy works in approximately 60 percent of patients when added to an existing antidepressant. Typically, 25 to 50 mcg, taken in the morning is recommended; some individuals may achieve doses as low as 5 mcg a day, however. Treatment should continue for two to three weeks before the augmentation effect can be properly evaluated. For patients who achieve a response with T-3 augmentation, most practitioners recommend that patients remain on augmentation therapy concomitantly for the duration of the antidepressant regimen. In general, T-3 therapy is well tolerated, and mild headache and/or tachycardia, which some patients experience, tend to quickly dissipate.

The main disadvantage of T-3 is the possible development of high thyroid hormone levels; at recommended augmentation doses, this is extremely unlikely.

Second, similar in effect to T-3 augmentation therapy, lithium is effective in approximately 60 percent of patients when added to an existing antidepressant. Empirically, doses of between 600 to 900 mg a day are currently recommended. This may be taken once-a-day or in divided dose, depending on patient preference and side effects. Short-term side effects on introduction of lithium augmentation include gastrointestinal upset and tremor.

Longer-term use of lithium can also impair thyroid function and cause weight gain. Anecdotal evidence suggests that lithium will not produce a therapeutic response unless blood levels go above 0.5 mmol/L. Others, however, argue that neither blood levels nor dosage are related to treatment response, and clinical judgment at present is the best guide.

As is true for T-3 therapy, lithium augmentation should be continued for a minimum of two to three weeks before judging the response. Patients who do respond may remain on lithium augmentation for the duration of the antidepressant course as well. Although lithium has antidepressant properties on its own, in unipolar as well as bipolar depression, its effectiveness alone is probably less than its effectiveness as an augmentation agent.

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Reviewed: 02/2006