Acute affective symptoms during antidepressant tapering indicate withdrawal reactions rather than relapse: Results from a prospective longitudinal cohort study.

INTRODUCTION It remains contested if rapid onset of affective symptoms during antidepressant tapering reflects pharmacological withdrawal effects or relapse of an underlying mental disorder.

Methods

A prospective cohort (n=32) of adult primary care patients from Switzerland was assessed repeatedly over 26 weeks after initiation of antidepressant tapering. Dose reductions and within-person change in withdrawal symptoms (DESS affective and discriminatory physical symptom subscales), depressive (PHQ-9) and anxiety symptoms (GAD-7) were assessed over six intervals, resulting in 187 measurements for each variable.

Results

Over the 26-week observation period, within-person change in PHQ-9 and GAD-7 scores were strongly associated with concurrent change in DESS affective scores (r≈0.6), and both were also moderately associated with DESS physical scores (r≈0.3). Dose reductions were accompanied by significant increases in DESS affective, PHQ-9 and GAD-7, while scores in both DESS affective and GAD-7 significantly declined during intervals without dose reductions. Within-person change in DESS physical score was independently associated with changes in DESS affective and both PHQ-9 and GAD-7 scores. Adjusting for DESS physical scores substantially attenuated the within-person increase in DESS affective, PHQ-9 and GAD-7 scores during periods with dose reductions.

Conclusion

During antidepressant tapering, affective symptoms reflect a periodic course of increasing intensity after dose reductions and decreasing intensity after stabilizations of dosage that is accompanied by change in discriminatory physical withdrawal symptoms. Although causality cannot be inferred, this pattern indicates withdrawal reactions rather than relapse of mental disorders. These findings are relevant for researchers evaluating discontinuation trials and clinicians seeing patients during antidepressant tapering.