Treatment-Resistant Unipolar Depression Treatment Switching Strategies

Switching Strategies
When patients do not respond to treatment with one antidepressant, a common clinical strategy is to switch antidepressants. Although a change to an antidepressant of the same class may be efficacious, especially if the second agent offers a milder side-effect burden, most clinicians believe a switch from one antidepressant class to another would yield a greater chance of benefit (Fredman et al. 2000; Nierenberg and Amsterdam 1990). Results from the clinical studies of switching strategies for patients with treatment-resistant unipolar depression are compiled in Table 45-4.

How should antidepressants be switched? When patients do not respond to treatment with an antidepressant alone, switching from a TCA to an SSRI or vice versa does not typically require washout but rather a taper of the first antidepressant and initiation of the second one. When time is an issue, clinicians can start the new drug while tapering the first, although the period of overlap increases the possibility of drug interaction side effects. Before switching to an MAOI, clinicians should wait at least 1 week after discontinuing either TCAs (with the exception of protriptyline, which requires 3 weeks of washout) or atypical antidepressants and at least 2 weeks after discontinuing SSRIs (with the exception of fluoxetine, which requires at least 5 weeks of washout). Clinicians switching from an MAOI to an SSRI, a TCA, or an atypical antidepressant should wait at least 2 weeks before starting the second antidepressant. When clinicians switch to an antidepressant of the same class, no washout is necessary, except for the change from phenelzine to tranylcypromine.

How long should the new agent be continued after a response? A reasonable approach is to maintain the patient on the antidepressant for at least 9 months following response and then gradually discontinue the drug. However, if the patient has a history of highly recurrent or chronic depression, consideration should be given to an indefinite duration of maintenance treatment.

What reports suggest efficacy of switching to specific agents? Switching from SSRIs to TCAs Even though the switch to TCAs has also been shown to be effective (response rate = 47%) among SSRI nonresponders in a large randomized and controlled crossover study (Kocsis et al. 1995), the popularity of this strategy has declined because of the improved safety profile of the newer agents.

Switching from TCAs to SSRIs Although systematically ascertained controlled data are limited, the switch to an SSRI from a TCA may prove effective. In an open-label study of 132 patients who had not responded to TCAs or had not tolerated side effects, investigators observed a rate of response to fluoxetine between 51.4% and 62.1%, depending on the definition of response (Beasley et al. 1990). A large crossover study has also shown that 63% of imipramine nonresponders responded to sertraline (Kocsis et al. 1995). Thus, patients who have not responded to TCAs may show a favorable response to an SSRI.