Efficacy and tolerability of antidepressants for sub-threshold depression and for mild major depressive disorder

Isobel M Cameron, Ian C Reid, Steve A MacGillivray

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background
It is commonly assumed that robust evidence exists for the lack of efficacy of antidepressants at the milder end of the depression severity spectrum. In light of specific limitations of existing reviews, we assess if antidepressants are efficacious and tolerable for sub-threshold or mild Major Depressive Disorder (MDD).

Method
Systematic review and meta-analysis of Randomised Controlled Trials of adults with sub-threshold depression or mild MDD (initial baseline symptom severity of HRSD≤20) comparing an antidepressant with placebo or treatment as usual (TAU) however defined. A pre-specified protocol was published (Prospero reference: CRD42013004505).

Results
8 trials were included: 5 trials (453 participants) of sub-threshold depression and 3 trials (502 participants) of mild MDD. Trials of sub-threshold depression exhibited low risk of bias whereas those of mild MDD exhibited high risk. Two trials of sub-threshold depression were pooled (n=102) to assess efficacy and favoured antidepressants over placebo statistically but the difference was small and unlikely to be clinically meaningful: mean difference -1.39 (-2.41, -0.36). Due to heterogeneity, no trials of mild MDD could be pooled for efficacy. There was no difference between antidepressant treatment and placebo for drop out due to adverse events. The maximum proportion in those receiving antidepressants dropping out due to adverse events was 17%, with indication of a dose effect.

Limitations
Not all data from identified trials could be included in the meta-analyses due to a lack of availability of relevant data.

Conclusion
There is insufficient evidence to support or contest the efficacy of antidepressant medication for sub-threshold depression or mild MDD. More trials, with adequate follow up, are required to address this question.
Original languageEnglish
Pages (from-to)48-58
Number of pages11
JournalJournal of Affective Disorders
Volume166
Early online date9 May 2014
DOIs
Publication statusPublished - Sep 2014

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Major Depressive Disorder
Antidepressive Agents
Depression
Placebos
Meta-Analysis
Randomized Controlled Trials
Therapeutics

Keywords

  • systematic review
  • meta-analysis
  • depressive disorder
  • antidepressants

Cite this

Efficacy and tolerability of antidepressants for sub-threshold depression and for mild major depressive disorder. / Cameron, Isobel M; Reid, Ian C; MacGillivray, Steve A.

In: Journal of Affective Disorders, Vol. 166, 09.2014, p. 48-58.

Research output: Contribution to journalArticle

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abstract = "BackgroundIt is commonly assumed that robust evidence exists for the lack of efficacy of antidepressants at the milder end of the depression severity spectrum. In light of specific limitations of existing reviews, we assess if antidepressants are efficacious and tolerable for sub-threshold or mild Major Depressive Disorder (MDD).MethodSystematic review and meta-analysis of Randomised Controlled Trials of adults with sub-threshold depression or mild MDD (initial baseline symptom severity of HRSD≤20) comparing an antidepressant with placebo or treatment as usual (TAU) however defined. A pre-specified protocol was published (Prospero reference: CRD42013004505).Results8 trials were included: 5 trials (453 participants) of sub-threshold depression and 3 trials (502 participants) of mild MDD. Trials of sub-threshold depression exhibited low risk of bias whereas those of mild MDD exhibited high risk. Two trials of sub-threshold depression were pooled (n=102) to assess efficacy and favoured antidepressants over placebo statistically but the difference was small and unlikely to be clinically meaningful: mean difference -1.39 (-2.41, -0.36). Due to heterogeneity, no trials of mild MDD could be pooled for efficacy. There was no difference between antidepressant treatment and placebo for drop out due to adverse events. The maximum proportion in those receiving antidepressants dropping out due to adverse events was 17{\%}, with indication of a dose effect.LimitationsNot all data from identified trials could be included in the meta-analyses due to a lack of availability of relevant data.ConclusionThere is insufficient evidence to support or contest the efficacy of antidepressant medication for sub-threshold depression or mild MDD. More trials, with adequate follow up, are required to address this question.",
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N2 - BackgroundIt is commonly assumed that robust evidence exists for the lack of efficacy of antidepressants at the milder end of the depression severity spectrum. In light of specific limitations of existing reviews, we assess if antidepressants are efficacious and tolerable for sub-threshold or mild Major Depressive Disorder (MDD).MethodSystematic review and meta-analysis of Randomised Controlled Trials of adults with sub-threshold depression or mild MDD (initial baseline symptom severity of HRSD≤20) comparing an antidepressant with placebo or treatment as usual (TAU) however defined. A pre-specified protocol was published (Prospero reference: CRD42013004505).Results8 trials were included: 5 trials (453 participants) of sub-threshold depression and 3 trials (502 participants) of mild MDD. Trials of sub-threshold depression exhibited low risk of bias whereas those of mild MDD exhibited high risk. Two trials of sub-threshold depression were pooled (n=102) to assess efficacy and favoured antidepressants over placebo statistically but the difference was small and unlikely to be clinically meaningful: mean difference -1.39 (-2.41, -0.36). Due to heterogeneity, no trials of mild MDD could be pooled for efficacy. There was no difference between antidepressant treatment and placebo for drop out due to adverse events. The maximum proportion in those receiving antidepressants dropping out due to adverse events was 17%, with indication of a dose effect.LimitationsNot all data from identified trials could be included in the meta-analyses due to a lack of availability of relevant data.ConclusionThere is insufficient evidence to support or contest the efficacy of antidepressant medication for sub-threshold depression or mild MDD. More trials, with adequate follow up, are required to address this question.

AB - BackgroundIt is commonly assumed that robust evidence exists for the lack of efficacy of antidepressants at the milder end of the depression severity spectrum. In light of specific limitations of existing reviews, we assess if antidepressants are efficacious and tolerable for sub-threshold or mild Major Depressive Disorder (MDD).MethodSystematic review and meta-analysis of Randomised Controlled Trials of adults with sub-threshold depression or mild MDD (initial baseline symptom severity of HRSD≤20) comparing an antidepressant with placebo or treatment as usual (TAU) however defined. A pre-specified protocol was published (Prospero reference: CRD42013004505).Results8 trials were included: 5 trials (453 participants) of sub-threshold depression and 3 trials (502 participants) of mild MDD. Trials of sub-threshold depression exhibited low risk of bias whereas those of mild MDD exhibited high risk. Two trials of sub-threshold depression were pooled (n=102) to assess efficacy and favoured antidepressants over placebo statistically but the difference was small and unlikely to be clinically meaningful: mean difference -1.39 (-2.41, -0.36). Due to heterogeneity, no trials of mild MDD could be pooled for efficacy. There was no difference between antidepressant treatment and placebo for drop out due to adverse events. The maximum proportion in those receiving antidepressants dropping out due to adverse events was 17%, with indication of a dose effect.LimitationsNot all data from identified trials could be included in the meta-analyses due to a lack of availability of relevant data.ConclusionThere is insufficient evidence to support or contest the efficacy of antidepressant medication for sub-threshold depression or mild MDD. More trials, with adequate follow up, are required to address this question.

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