Dose escalation for insufficient response to standard-dose selective serotonin reuptake inhibitors in major depressive disorder: systematic review

BACKGROUND: Although selective serotonin reuptake inhibitors (SSRIs) are frequently used for major depressive disorder, only 50-60% of patients respond to a standard dose. For non-responders, dose escalation is often applied. AIM: To systematically review the evidence for dose escalation of SSRIs. METHOD: A systematic literature search in MEDLINE, EMBASE, CINAHL and PsycInfo was performed. Randomised controlled trials and meta-analyses investigating dose escalation of SSRIs were identified. Relevant articles were retrieved and critically appraised. Results were summarised in an evidence table. Pooling was not justified because of heterogeneity of the identified studies. RESULTS: Eight true dose-escalation studies and three meta-analyses were identified. The available data provided no unequivocal base for dose escalation. Dose escalation before 4 weeks of treatment at a standard dose appeared to be ineffective. CONCLUSIONS: Dose escalation of SSRIs is equivocally supported by evidence of randomised controlled trials; methodological difficulties in the studies may account for this lack of evidence