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

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.

A Bibliometric Analysis of Scientific Production on Second-Generation Anti- Psychotic Drugs in Malaysia

Objective: We carried out a bibliometric study on the scientific papers related to second generation anti-psychotic drugs (SGAs) in Malaysia. Methods: With the SCOPUS database, we selected those documents made in Malaysia whose title included descriptors related to SGAs. We applied bibliometric indicators of production and dispersion, as Price’s law and Bradford’s law, respectively. We also calculated the participation index of the different countries. The bibliometric data were also been correlated with some social and health data from Malaysia (total per capita expenditure on health and gross domestic expenditure on R&D). Results: We found 105 original documents published between 2004 and 2016. Our results fulfilled Price’s law, with scientific production on SGAs showing exponential growth (r = 0.401, vs. r = 0.260 after linear adjustment). The drugs most studied are olanzapine (9 documents), clozapine (7), and risperidone (7). Division into Bradford zones yields a nucleus occupied by the Medical Journal of Malaysia, Singapore Medical Journal, Australian and New Zealand Journal of Psychiatry, and Pharmacogenomics. Totally, 63 different journals were used, but only one in the top four journals had an impact factor being greater than 3. Conclusion: The publications on SGAs in Malaysia have undergone exponential growth, without evidence a saturation point.

Evaluation of antipsychotic effect of methanolic extract of Ocimum sanctum leaves on laboratory animals.

Ocimum sanctum (Lamiaceae) commonly known as tulsi, is well known for its excellent nutritional and medicinal values throughout the world. The present study was undertaken to test the effect of methanolic extract of Ocimum sanctum leaves (50, 100 and 200mg/kg, p.o) on psychosis employing Ketamine induced stereotypic behaviour in mice and Pole climbing avoidance in rats. Haloperidol (1mg/kg, i.p.) and Olanzapine (5mg/kg, i.p.) are established antipsychotic drugs used as standard drugs in the present study. Effect of methanolic extract of Ocimum sanctum leaves (OS), on brain dopamine levels was also estimated. Methanolic extract of Ocimum sanctum leaves (50, 100 and 200mg/kg, p.o), significantly reduced the Ketamine induced falling, weaving, head bobbing and turning behavior in mice. Furthermore, it significantly delayed the latency time taken by the rats to climb the pole. Haloperidol (1mg/kg; i.p.) and Olanzapine (5mg/kg, i.p.) significantly reduced the Ketamine induced stereotypic behavior in mice and condition avoidance behavior in rats. Interestingly, Brain dopamine level was significantly reduced by methanolic extract of Ocimum sanctum leaves. These findings, when taken together indicate that methanolic extract of Ocimum sanctum leaves possesses anti-psychotic like property.