To Increase-or Not to Increase-the Dose?

• Antidepressant nonresponse is common, with rates in the range of 30-40%¹
• Dose increase is a prevalent strategy following antidepressant treatment failure (ATF) in routine clinical practice²
• Results of randomized controlled trials (RCTs) of dose increase strategies have yielded conflicting results, and this topic has not been systematically and quantitatively reviewed

• Rink and colleagues³ performed a systematic literature review and meta-analysis of double-blind RCTs of dose increase following ATF
• The authors systematically searched CENTRAL, Embase, PubMed and PsychINFO
• They included RCTs of patients with unipolar depression randomized to either dose increase or unchanged continuation following ATF (as defined by the authors in each study)

• The authors excluded studies of antidepressant treatments below standard doses or of duration <3 weeks.
• The primary outcome was efficacy of dose increase versus continuation, expressed as standardized mean difference (SMD)
• Secondary outcomes were response and remission rates, as well as tolerability
• Data were analyzed using a random effects approach

• The authors identified 9 studies, comprising 1273 patients, that met the inclusion criteria
• 8 of 9 included studies were RCTs of SSRIs in adult patients
• Dose increase was associated with a small, nonsignificant effect (SMD=0.05)
• The effect of dose increase was also nonsignificant in subgroup analyses in 1) adult patients with major depression treated with SSRIs, and 2) studies with low risk of bias

• The authors identified 9 studies, comprising 1273 patients, that met the inclusion criteria
• 8 of 9 included studies were RCTs of SSRIs in adult patients
• Dose increase was associated with a small, nonsignificant effect (SMD=0.05)
• The effect of dose increase was also nonsignificant in subgroup analyses in (1) adult patients with major depression treated with SSRIs, and (2) studies with low risk of bias

• The authors found there is no clinically or statistically significant effect of antidepressant dose increase after ATF
• A limitation of the present study is the lack of data on non-SSRI antidepressants
• The authors concluded that increasing the dose of SSRIs is not beneficial to adults who failed to respond to an antidepressant treatment trial of 3- to 6-weeks’ duration