Relapse During SSRI Treatment for Depression


Medscape Psychiatry & Mental Health eJournal. 1996;1(5) 

In This Article


All 114 respondents who completed questionnaires reported having prescribed SSRIs in the preceding 2 years. The group reported a median efficacy rate of 73% in using SSRIs for major depression during this time. When asked about the extent to which they observed any salient re-emergence of symptoms after a marked improvement, almost all (89%) had observed some degree of relapse despite continuing antidepressant treatment. Most clinicians (41%) estimated the incidence of recurrent depression as being between 11% to 25% of cases in a 1-year period.

Most respondents (28%) judged relapse of depression to occur usually between 3 and 6 months in patients taking SSRIs, after an initial marked improvement. Relapse while continuing an SSRI was thought to be relatively rare (15% of cases) after 1 year of stable remission. Respondents uniformly expressed confidence in their ability to regain a remission after breakthrough symptoms of depression recur; only 1 (2%) viewed such recovery as an uncommon event.

When asked about the need to raise SSRI dosages following an initial remission, about half the sample found this often to be necessary during long-term SSRI pharmacotherapy.

Clinicians were asked whether they agreed or disagreed with the statement: "Failure to sustain a clinical response to SSRIs during continued treatment for depression is a relatively rare event in my experience." Nearly half the sample disagreed with this statement, suggesting that many practitioners commonly observe some loss of SSRI antidepressant efficacy over time. Respondents were also asked to indicate whether they noted any differences in their experiences of relapse using fluoxetine versus sertraline versus paroxetine. Partial or complete relapse was noted to occur using all 3 medications, with no statistical differences in the reporting of any individual SSRI.

When asked to compare observations of relapse using SSRIs versus TCAs, 40% of the sample expressed the belief that depressive symptoms were more likely to recur with SSRIs than TCAs; however, one third of respondents expressed uncertainty about whether differences exist in this area.

Table I provides information on different somatic therapies that respondents reported using in efforts to regain an attenuating response to SSRIs. Increasing the dosage of SSRI was the most commonly reported strategy attempted, followed by changing medications to a different SSRI or to a non-SSRI antidepressant. Among augmentation strategies, the addition of a tricyclic antidepressant to the existing SSRI was the most frequently reported addition, followed by lithium. Respondents believed that of the clinical strategies listed in Table I, increasing the dose of SSRI was most often likely to result in an improved antidepressant response.

Other effective strategies noted by clinicians, along with those described in Table I, included lowering the dose of SSRI or drug washouts (n = 3), additions of bupropion (n = 3), anxiolytics (n = 2), trazodone (n = 1), valproic acid (n = 1), carbamazepine (n = 1), or more frequent psychotherapy visits (n = 1).

Finally, clinicians were asked to identify clinical features they believed to be associated with cases of relapse during long-term SSRI antidepressant treatment. As described in Table II, the most frequently cited factors included: none (n = 29), histories of dysthymia (n = 25) or chronic major depression (n = 16), prior SSRI failure (n = 17), atypical depressive features (n = 14), and substance abuse (n = 14).