Dose and Duration
When antidepressants are employed by clinicians inexperienced in treating depression, they are often given in inadequate doses for inadequate durations. All available antidepressants require approximately 3 to 8 weeks to achieve maximal benefit. Although some patients may respond in the first weeks, particularly with improvement in sleep and anxiety, trials of less than 4 weeks at therapeutic doses are generally inadequate. The available data, however, would suggest that if the patient does not respond at all to a given dose for 4 weeks, then he or she is unlikely to respond at that dose even if the trial is considerably longer. Thus, the dose should be increased as tolerated by the patient or a switch to a different antidepressant should be considered.
What constitutes a therapeutic dose of a given antidepressant is sometimes debatable. It is clear, for example, that 20 mg/d of some SSRIs such as fluoxetine, paroxetine, or citalopram is probably therapeutic for most patients. However, that does not indicate that higher doses might not be more efficacious. If 20 mg/d does not produce at least a partial response at 4 weeks, then a higher dosage seems to be indicated. For other classes of antidepressants, some clinicians have suggested that two thirds of the maximum dose was a reasonable target for a therapeutic trial. Therefore, 200 mg imipramine, 60 mg phenelzine, and 300 mg bupropion might be the minimum doses for at least 4 weeks before a higher dose or a different medication would be considered. Nonetheless, not every patient will respond even to an adequate trial of an antidepressant. The overall efficacy of a first trial of an antidepressant is probably in the range of 50% to 700/0. The remaining patients usually can be described as either partial responders (decreased but still significant symptoms of depression) or nonresponders (no significant improvement in symptoms). Many strategies have been tried for patients in these groups, including switching to new antidepressants, adding an augmentation agent (e.g., lithium, L-triiodothyronine), combining more than one antidepressant, or other non medication treatments (e.g., electroconvulsive therapy). Unfortunately, there are little empirical data to guide the clinician; our general preference is to try an augmentation or combination strategy with the patient's first agent if there is a partial response and to switch to a new antidepressant of a different class if there is no significant response.
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