Loss of responsiveness on reinstatement of antidepressants after treatment interruption - A systematic review.

Background: The societal burden of depression continues to increase despite the greater use of antidepressants. It is not clear why wider antidepressant prescribing has not reduced the impact of depression at a population level. One possible explanation is that intermittent use of antidepressants at an individual level might reduce responsiveness to antidepressants.

Methods: We searched EMBASE and PubMed from the beginning of records to June 2024 for articles describing loss of response to antidepressants (in any psychiatric condition) occurring as a result of interruption in treatment. We did not restrict our search with respect to language or date.

Results: We found 6869 articles of potential interest, of which 5360 were excluded after initial screening by title, and 1453 were excluded as duplicates. We ultimately included 12 studies that provided data on 594 participants. Non-response was reported in 4%-57% of people who stopped and restarted antidepressant treatment that was previously effective.

Conclusion: Non-continuous consumption of antidepressants leads to a loss of responsiveness in an important proportion of people. Intermittent adherence to antidepressants may lessen their effectiveness and explain the relationship between wider antidepressant use and increased societal burden of depression.