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Atypical antipsychotic augmentation in SSRI treatment refractory obsessive-compulsive disorder: a systematic review and meta-analysis.

Veale D, Miles S, Smallcombe N, Ghezai H, Goldacre B, Hodsoll J - BMC Psychiatry (2014)

Bottom Line: Two studies found aripiprazole to be effective in the short-term.There was a small effect-size for risperidone or anti-psychotics in general in the short-term.We found no evidence for the effectiveness of quetiapine or olanzapine in comparison to placebo.

View Article: PubMed Central - PubMed

Affiliation: The Institute of Psychiatry, King's College London and South London and Maudsley NHS Foundation Trust, 16 De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. david.veale@kcl.ac.uk.

ABSTRACT

Background: In 2006, the National Institute of Clinical and Health Excellence (NICE) guidelines for Obsessive Compulsive Disorder (OCD) recommended anti-psychotics as a class for SSRI treatment resistant OCD. The article aims to systematically review and conduct a meta-analysis on the clinical effectiveness of atypical anti-psychotics augmenting an SSRI.

Methods: Studies that were double-blind randomized controlled trials of an atypical antipsychotic against a placebo, for a minimum of 4 weeks, in adults with OCD, were included. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores were the primary outcome measure. Inclusion criteria included Y-BOCS score of 16 or more and at least one adequate trial of a SSRI or clomipramine for at least 8 weeks prior to randomization. Data sources included Medline, Embase, PsycINFO, Cochrane Database of Systematic Reviews (CDSR), trial registries and pharmaceutical databases and manufacturers up to September 2013. Forest-plots were drawn to display differences between drug and placebo on the Y-BOCS.

Results: Two studies found aripiprazole to be effective in the short-term. There was a small effect-size for risperidone or anti-psychotics in general in the short-term. We found no evidence for the effectiveness of quetiapine or olanzapine in comparison to placebo.

Conclusions: Risperidone and aripiprazole can be used cautiously at a low dose as an augmentation agent in non-responders to SSRIs and CBT but should be monitored at 4 weeks to determine efficacy.

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Related in: MedlinePlus

Meta-analysis of quetiapine treatment vs placebo for obsessive-compulsive disorder.
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Related In: Results  -  Collection

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Fig4: Meta-analysis of quetiapine treatment vs placebo for obsessive-compulsive disorder.

Mentions: Analyses were conducted using “metan” and associated commands in STATA, version 11 [27,28]. The command combined the outcome of each drug to give an overall difference on the original Y-BOCS scale (shown along the x-axis of Figures 1, 2, 3, 4 and 5), summary effect-size and 95% confidence intervals (C.I.), using a random effects meta-analysis model of continuous data, with each study change score weighted by the inverse of the variance [29]. We used a random effects model as we assumed that the included studies are a random sample of the population of studies. Forest plots (see Figures 1–5) were created – each line depicting estimates and confidence intervals for each study, and plotting symbol size representing the weight of each study entered into the meta-analysis. Further, as the clinical populations and treatments had varying factors, we expected treatment effects to be heterogeneous. For each Forest plot of studies separated according to antipsychotic trialed, a Z-score was computed to demonstrate the significance of the overall effect of a drug in comparison to a placebo. For investigating the effects of risperidone, a categorical meta-analysis was also conducted to determine the odds ratio for responding in comparison to not responding on the Y-BOCS. One of the studies found 0 responders in the placebo arm [12]. STATA performs poorly for studies with a very low or very high event rate and so by default changes zero frequencies to 0.5 in order to give a minimum variance unbiased estimate. As this procedure can influence weighted mean differences, the categorical analysis has been included for research comparison purposes but is to be considered with caution.Figure 1


Atypical antipsychotic augmentation in SSRI treatment refractory obsessive-compulsive disorder: a systematic review and meta-analysis.

Veale D, Miles S, Smallcombe N, Ghezai H, Goldacre B, Hodsoll J - BMC Psychiatry (2014)

Meta-analysis of quetiapine treatment vs placebo for obsessive-compulsive disorder.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4262998&req=5

Fig4: Meta-analysis of quetiapine treatment vs placebo for obsessive-compulsive disorder.
Mentions: Analyses were conducted using “metan” and associated commands in STATA, version 11 [27,28]. The command combined the outcome of each drug to give an overall difference on the original Y-BOCS scale (shown along the x-axis of Figures 1, 2, 3, 4 and 5), summary effect-size and 95% confidence intervals (C.I.), using a random effects meta-analysis model of continuous data, with each study change score weighted by the inverse of the variance [29]. We used a random effects model as we assumed that the included studies are a random sample of the population of studies. Forest plots (see Figures 1–5) were created – each line depicting estimates and confidence intervals for each study, and plotting symbol size representing the weight of each study entered into the meta-analysis. Further, as the clinical populations and treatments had varying factors, we expected treatment effects to be heterogeneous. For each Forest plot of studies separated according to antipsychotic trialed, a Z-score was computed to demonstrate the significance of the overall effect of a drug in comparison to a placebo. For investigating the effects of risperidone, a categorical meta-analysis was also conducted to determine the odds ratio for responding in comparison to not responding on the Y-BOCS. One of the studies found 0 responders in the placebo arm [12]. STATA performs poorly for studies with a very low or very high event rate and so by default changes zero frequencies to 0.5 in order to give a minimum variance unbiased estimate. As this procedure can influence weighted mean differences, the categorical analysis has been included for research comparison purposes but is to be considered with caution.Figure 1

Bottom Line: Two studies found aripiprazole to be effective in the short-term.There was a small effect-size for risperidone or anti-psychotics in general in the short-term.We found no evidence for the effectiveness of quetiapine or olanzapine in comparison to placebo.

View Article: PubMed Central - PubMed

Affiliation: The Institute of Psychiatry, King's College London and South London and Maudsley NHS Foundation Trust, 16 De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. david.veale@kcl.ac.uk.

ABSTRACT

Background: In 2006, the National Institute of Clinical and Health Excellence (NICE) guidelines for Obsessive Compulsive Disorder (OCD) recommended anti-psychotics as a class for SSRI treatment resistant OCD. The article aims to systematically review and conduct a meta-analysis on the clinical effectiveness of atypical anti-psychotics augmenting an SSRI.

Methods: Studies that were double-blind randomized controlled trials of an atypical antipsychotic against a placebo, for a minimum of 4 weeks, in adults with OCD, were included. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores were the primary outcome measure. Inclusion criteria included Y-BOCS score of 16 or more and at least one adequate trial of a SSRI or clomipramine for at least 8 weeks prior to randomization. Data sources included Medline, Embase, PsycINFO, Cochrane Database of Systematic Reviews (CDSR), trial registries and pharmaceutical databases and manufacturers up to September 2013. Forest-plots were drawn to display differences between drug and placebo on the Y-BOCS.

Results: Two studies found aripiprazole to be effective in the short-term. There was a small effect-size for risperidone or anti-psychotics in general in the short-term. We found no evidence for the effectiveness of quetiapine or olanzapine in comparison to placebo.

Conclusions: Risperidone and aripiprazole can be used cautiously at a low dose as an augmentation agent in non-responders to SSRIs and CBT but should be monitored at 4 weeks to determine efficacy.

Show MeSH
Related in: MedlinePlus