Objective: Serum melatonin, a biomarker of circadian rhythm, can upregulate Growth-associated protein 43 (GAP-43) which is involved in neural regeneration and plasticity. The present study was conducted to investigate the adequacy of the first-line antipsychotic drugs to improve sleep and circadian rhythm disruptions by assessing the effect of haloperidol and risperidone on serum melatonin and GAP-43 in schizophrenia. Methods: In this cohort study, 100 schizophrenic patients were recruited, and clinical evaluations were done using the Positive and Negative Syndrome Scale (PANSS) and the Pittsburgh sleep quality index (PSQI). The patients with predominantly positive symptoms taking haloperidol (Group I) and patients with predominantly negative symptoms taking risperidone (Group II) were admitted and serum melatonin, arylalkylamine N-acetyltransferase, GAP-43 and urinary melatonin were estimated. After 8 weeks, all clinical and biochemical parameters were repeated. Results: Serum melatonin (2:00 hours) was significantly decreased in both haloperidol (2.42; 95% confidence interval [95% CI]: 0.67−4.17; p = 0.008) and risperidone group (3.40; 95% CI: 0.54−6.25; p = 0.021). Urinary melatonin was significantly decreased in both haloperidol (p = 0.005) and risperidone group (p = 0.014). PSQI score was significantly increased in both haloperidol (p = 0.001) and risperidone group (p = 0.003). Serum GAP-43 was significantly decreased in both haloperidol and risperidone group (p ＜ 0.001). PANSS decreased significantly in both the groups and there was a significant negative correlation between serum melatonin at 2:00 hours and PANSS (r = −0.5) at baseline. Conclusion Monotherapy with haloperidol and risperidone can achieve symptomatic improvement but cannot improve sleep and circadian rhythm disturbances in schizophrenia.

BACKGROUND: AND PURPOSE: The role of low-frequency repetitive transcranial stimulation (rTMS) in drug-resistant epilepsy (DRE) has been conflicting and inconclusive in previous clinical trials. This meta-analysis evaluated the efficacy of rTMS on seizure frequency and epileptiform discharges in DRE. METHODS: A standard meta-analysis protocol was registered in the International Prospective Register of Ongoing Systematic Reviews (PROSPERO: CRD42018088544). After performing a comprehensive literature search using specific keywords in MEDLINE, the Cochrane database, and the International Clinical Trial Registry Platform (ICTRP), reviewers assessed the eligibility and extracted data from seven relevant clinical trials. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed in the selection, analysis, and reporting of findings. A random-effects model was used to estimate the effect size as the mean difference in seizure frequency and interictal epileptiform discharges between the groups. Quality assessment was performed using a risk-of-bias assessment tool, and a meta-regression was used to identify the variables that probably influenced the effect size. RESULTS: The random-effects model analysis revealed a pooled effect size of −5.96 (95% CI= −8.98 to −2.94), significantly favoring rTMS stimulation (p=0.0001) over the control group with regard to seizure frequency. The overall effect size for interictal epileptiform discharges also significantly favored rTMS stimulation (p < 0.0001), with an overall effect size of −9.36 (95% CI=−13.24 to −5.47). In the meta-regression, the seizure frequency worsened by 2.00±0.98 (mean±SD, p=0.042) for each week-long lengthening of the posttreatment follow-up period, suggesting that rTMS exerts only a short-term effect. CONCLUSIONS This meta-analysis shows that rTMS exerts a significant beneficial effect on DRE by reducing both the seizure frequency and interictal epileptiform discharges. However, the meta-regression revealed only an ephemeral effect of rTMS.