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A brief discussion of dose increase versus unchanged continuation of antidepressants after initial treatment failure in patients with depression.
A brief discussion of dose increase versus unchanged continuation of antidepressants after initial treatment failure in patients with depression.
• 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
REFERENCES
1. Reeve S, Sheaves B, Freeman D. The role of sleep dysfunction in the occurrence of delusions and hallucinations: a systematic review. Clin Psychol Rev. 2015;42:96–115.
2. Li SX, Lam SP, Zhang J, et al. Sleep disturbances and suicide risk in an 8-year longitudinal study of schizophreniaspectrum disorders. Sleep. 2016;39:1275–1282.
3. Reeve S, Sheaves B, Freeman D. Sleep disorders in early psychosis: incidence, severity, and association with clinical symptoms. Schizophr Bull. 2018. [Epub ahead of print]