Intermittent selective serotonin reuptake inhibitors for premenstrual syndromes: A systematic review and meta-analysis of randomised trials

Background: Intermittent (luteal phase) dosing of selective serotonin reuptake inhibitors is one treatment strategy for premenstrual syndromes such as premenstrual dysphoric disorder. This avoids the risk of the antidepressant withdrawal syndrome associated with long-term continuous dosing. Aims: To compare intermittent dosing to continuous dosing in terms of efficacy and acceptability. Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, PubMed and CINAHL for randomised trials of intermittent compared with continuous dosing of selective serotonin reuptake inhibitors in premenstrual syndromes. We extracted response rates, dropout rates and changes in symptom scores. We used random effects meta-analyses to pool study-level data and calculated odds ratio for dichotomous data and standardised mean difference for continuous data. Risk of bias was assessed using the Cochrane risk-of-bias tool. The study was registered with PROSPERO (CRD42020224176). Results: A total of 1841 references were identified, with eight studies being eligible for analysis, consisting of a total of 460 participants. All included studies provided response rates, six provided dropout rates and five provided symptom scores. There was no statistically significant differences between intermittent and continuous dosing in terms of response rate (odds ratio: 1.0, 95% confidence interval (CI): 0.23-4.31, I-2 = 71%), dropout rate (odds ratio 1.26, 95% CI: 0.39-4.09, I-2 = 33%) or symptom change (standardised mean difference: 0.04, 95% CI: -0.27 to 0.35, I-2 = 39%). All studies had a moderate or high risk of bias. Conclusion: Since intermittent dosing avoids the potential for withdrawal symptoms, it should be considered more commonly in this patient population.