Recurrence is more likely if treatment has not resulted in full remission of symptoms.4 In fact, current guidelines for antidepressant use recommend 4 to 6 months of continuing treatment after symptom resolution to prevent relapse.

Combined evidence from many randomized controlled trials indicates that continuing antidepressant medications after recovery substantially reduces (halves) the chances of relapse. This preventive effect probably lasts for at least the first 36 months of use.[62]

Anecdotal evidence suggests that chronic disease is accompanied by recurrence after prolonged treatment with antidepressants (tachyphylaxis). Psychiatric texts suggest that physicians respond to recurrence by increasing dosage, complementing the medication with a different class, or changing the medication class entirely.

The reason for recurrence in these cases is as poorly understood as the change in brain physiology induced by the medications themselves. Possible reasons may include aging of the brain or worsening of the condition. Most SSRI psychiatric medications were developed for short-term use (a year or less) but are widely prescribed for indefinite periods.[63]