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Does Melatonin and Melatonin Agonists Improve the Metabolic Side Effects of Atypical Antipsychotics?: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

ABSTRACT: Atypical antipsychotics (AAPs) are increasingly used for the treatment of psychotic disorders but are known to be associated with metabolic abnormalities. This study is a systematic review and meta-analysis of randomized controlled trials (RCTs) studying the effectiveness of melatonin for the amelioration of AAP-induced metabolic syndrome. The MEDLINE (accessed via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials, PsycINFO, LILACS, CINAHL, and OpenGrey databases were searched for RCTs without language restrictions. Inclusion criteria were randomized, double-blind clinical trials comparing melatonin or melatonin agonists with placebo for the amelioration of AAP-induced effects at any age with selected components of metabolic syndrome as outcome measures. Two reviewers independently selected articles and assessed quality using Cochrane risk of bias and concealment tools. Of 53 records, five RCTs were eligible for the systematic review and three for the meta-analysis. The meta-analyses showed no statistically significant difference in any anthropometric or metabolic variable considered. Analysis according to psychiatric diagnosis from one RCT showed significant decreases in diastolic blood pressure (5.5 vs. -5.7 mmHg for the placebo and melatonin groups, respectively; p =0.001), fat mass (2.7 vs. 0.2 kg, respectively; p =0.032), and triglycerides (D) (50.1 vs. -20 mg/dl, respectively; p =0.08) in the bipolar group but not the schizophrenia group. Although limited to five RCTs with small sample sizes, evidence from RCT indicates that melatonin improves AAP-induced metabolic syndrome. This beneficial effect seems more significant in patients with bipolar disorder than those with schizophrenia. Further RCTs are needed to definitively establish the potential ameliorative effect of melatonin and to justify its efficacy as an add-on therapy to curtail AAP-induced metabolic syndrome.

SUBMITTER: Igwe SC

PROVIDER: S-EPMC6124875 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

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Does Melatonin and Melatonin Agonists Improve the Metabolic Side Effects of Atypical Antipsychotics?: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Igwe Stanley C SC Brigo Francesco F

Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology 20180801 3

Atypical antipsychotics (AAPs) are increasingly used for the treatment of psychotic disorders but are known to be associated with metabolic abnormalities. This study is a systematic review and meta-analysis of randomized controlled trials (RCTs) studying the effectiveness of melatonin for the amelioration of AAP-induced metabolic syndrome. The MEDLINE (accessed via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials, PsycINFO, LILACS, CINAHL, and OpenGrey databases ...[more]

PMID: 30121990

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Project description:BackgroundAtypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics.MethodsWe examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library), and data combined for analysis where there was clinical homogeneity, with a special reference to trial duration.ResultsIn five trials (2,206 patients) participants presented with a depressive episode, and in 25 trials (6,174 patients) the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5-6, but more adverse event withdrawals (NNH 12). With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6-12 weeks, but more adverse event withdrawals (NNH of about 22) in studies of 6-12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10). In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of >or=7% (mainly olanzapine trials), somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics were associated with lower rates of extrapyramidal symptoms, but higher rates of weight gain and somnolence.ConclusionAtypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo, and as effective as established drug therapies. Atypical antipsychotics produce fewer extrapyramidal symptoms, but weight gain is more common (with olanzapine). There is insufficient data confidently to distinguish between different atypical antipsychotics.

Dataset Information

Does Melatonin and Melatonin Agonists Improve the Metabolic Side Effects of Atypical Antipsychotics?: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Publications

Does Melatonin and Melatonin Agonists Improve the Metabolic Side Effects of Atypical Antipsychotics?: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

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