Optimal dose of aripiprazole for augmentation therapy of antidepressant-refractory depression: preliminary findings based on a systematic review and dose-effect meta-analysis
<p><strong>Background:</strong> Aripiprazole augmentation is proven effective for antidepressant-refractory depression, but its licensed dose range is wide and optimal dosage remains unclear.</p> <p><strong>Aims:</strong> To find the optimal dosage of aripi...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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Cambridge University Press
2021
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| _version_ | 1826308558240612352 |
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| author | Furukawa, Y Hamza, T Cipriani, A Ostinelli, E |
| author_facet | Furukawa, Y Hamza, T Cipriani, A Ostinelli, E |
| author_sort | Furukawa, Y |
| collection | OXFORD |
| description | <p><strong>Background:</strong> Aripiprazole augmentation is proven effective for antidepressant-refractory depression, but its licensed dose range is wide and optimal dosage remains unclear.</p>
<p><strong>Aims:</strong> To find the optimal dosage of aripiprazole augmentation.</p>
<p><strong>Methods:</strong> Multiple electronic databases were searched (from inception to February 16, 2021) to identify all assessor-blind, randomised controlled trials evaluating aripiprazole augmentation therapy in adults (≥18 years old, both sexes) with major depressive disorder showing inadequate response to at least one antidepressant treatment. Random-effects, one-stage dose-effect meta-analysis model with restricted
pubic splines was conducted. Outcomes were efficacy (treatment response defined as 50% or greater reduction in depression severity), tolerability (dropouts due to adverse effects), and acceptability (dropouts for any reason), after 8 weeks of treatment (range 4–12 weeks).</p>
<p><strong>Results:</strong> Ten studies met the inclusion criteria. All were individually-randomised, placebo-controlled, multi centred, parallel studies including 2,625 participants in total. The maximum target dose-efficacy curve showed an increase up to doses between 2 mg (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.15- 1.85) and 5 mg (OR 1.93, 95%CI 1.33-2.81), and then a non-increasing trend through the higher licensed dose up to 20 mg (OR 1.90, 95%CI 1.52-2.37). Tolerability showed a similar trend with greater uncertainty. Acceptability showed no significant difference through the examined dose range. Certainty of evidence was low to moderate.</p>
<p><Strong>Conclusions:</strong> Low-dose aripiprazole as augmentation treatment might achieve the optimal balance between efficacy, tolerability, and acceptability in the acute treatment of antidepressant-refractory depression. However, the small number of included studies and the overall moderate to high risk of bias seriously compromise the reliability of the results. Further research is required to investigate the benefits of low versus high dose.</p> |
| first_indexed | 2024-03-07T07:21:15Z |
| format | Journal article |
| id | oxford-uuid:6133b16c-362b-47a2-b577-dc192c0e6329 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:21:15Z |
| publishDate | 2021 |
| publisher | Cambridge University Press |
| record_format | dspace |
| spelling | oxford-uuid:6133b16c-362b-47a2-b577-dc192c0e63292022-10-12T08:56:51ZOptimal dose of aripiprazole for augmentation therapy of antidepressant-refractory depression: preliminary findings based on a systematic review and dose-effect meta-analysisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6133b16c-362b-47a2-b577-dc192c0e6329EnglishsymplecticCambridge University Press2021Furukawa, YHamza, TCipriani, AOstinelli, E<p><strong>Background:</strong> Aripiprazole augmentation is proven effective for antidepressant-refractory depression, but its licensed dose range is wide and optimal dosage remains unclear.</p> <p><strong>Aims:</strong> To find the optimal dosage of aripiprazole augmentation.</p> <p><strong>Methods:</strong> Multiple electronic databases were searched (from inception to February 16, 2021) to identify all assessor-blind, randomised controlled trials evaluating aripiprazole augmentation therapy in adults (≥18 years old, both sexes) with major depressive disorder showing inadequate response to at least one antidepressant treatment. Random-effects, one-stage dose-effect meta-analysis model with restricted pubic splines was conducted. Outcomes were efficacy (treatment response defined as 50% or greater reduction in depression severity), tolerability (dropouts due to adverse effects), and acceptability (dropouts for any reason), after 8 weeks of treatment (range 4–12 weeks).</p> <p><strong>Results:</strong> Ten studies met the inclusion criteria. All were individually-randomised, placebo-controlled, multi centred, parallel studies including 2,625 participants in total. The maximum target dose-efficacy curve showed an increase up to doses between 2 mg (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.15- 1.85) and 5 mg (OR 1.93, 95%CI 1.33-2.81), and then a non-increasing trend through the higher licensed dose up to 20 mg (OR 1.90, 95%CI 1.52-2.37). Tolerability showed a similar trend with greater uncertainty. Acceptability showed no significant difference through the examined dose range. Certainty of evidence was low to moderate.</p> <p><Strong>Conclusions:</strong> Low-dose aripiprazole as augmentation treatment might achieve the optimal balance between efficacy, tolerability, and acceptability in the acute treatment of antidepressant-refractory depression. However, the small number of included studies and the overall moderate to high risk of bias seriously compromise the reliability of the results. Further research is required to investigate the benefits of low versus high dose.</p> |
| spellingShingle | Furukawa, Y Hamza, T Cipriani, A Ostinelli, E Optimal dose of aripiprazole for augmentation therapy of antidepressant-refractory depression: preliminary findings based on a systematic review and dose-effect meta-analysis |
| title | Optimal dose of aripiprazole for augmentation therapy of antidepressant-refractory depression: preliminary findings based on a systematic review and dose-effect meta-analysis |
| title_full | Optimal dose of aripiprazole for augmentation therapy of antidepressant-refractory depression: preliminary findings based on a systematic review and dose-effect meta-analysis |
| title_fullStr | Optimal dose of aripiprazole for augmentation therapy of antidepressant-refractory depression: preliminary findings based on a systematic review and dose-effect meta-analysis |
| title_full_unstemmed | Optimal dose of aripiprazole for augmentation therapy of antidepressant-refractory depression: preliminary findings based on a systematic review and dose-effect meta-analysis |
| title_short | Optimal dose of aripiprazole for augmentation therapy of antidepressant-refractory depression: preliminary findings based on a systematic review and dose-effect meta-analysis |
| title_sort | optimal dose of aripiprazole for augmentation therapy of antidepressant refractory depression preliminary findings based on a systematic review and dose effect meta analysis |
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