The literature on persistent antidepressant withdrawal symptoms is sparse. This systematic review is the first to examine the prevalence, duration, severity, risk/protective factors and treatment strategies for post-acute withdrawal syndrome (PAWS) following the discontinuation of antidepressant medications.

We searched PubMed, Web of Science and PsycInfo, focusing on newer-generation antidepressants. The electronic database search was complemented with handsearching reference lists of pivotal studies. We included original studies in adults reporting on PAWS and providing data about epidemiology and clinical management of withdrawal symptoms persisting for at least 6 weeks.

The literature search yielded 1286 results, with 26 records assessed for eligibility, and seven studies fulfilled our selection criteria. Prevalence data were sparse, with one small cohort study reporting a 15% prevalence rate for PAWS in patients with panic disorder and agoraphobia. The duration of PAWS varied considerably across studies, ranging from 1.5 to 166 months. Long-term paroxetine use emerged as a potential risk factor for the development of PAWS. There was no reliable evidence to support the effectiveness of various treatment strategies, including the reinstatement of antidepressant medication, the use of benzodiazepines and the provision of cognitive-behavioral therapy.

The current evidence on PAWS is sparse and predominantly of low certainty. The presence of withdrawal symptoms, lasting several months and possibly even years in some patients, underscores the need for further research with rigorous methodology. Large prospective cohort studies are needed to assess the epidemiology of PAWS, while randomized controlled trials are quired to test the efficacy of clinical interventions to treat PAWS.

CRD42023461793