Effect of haloperidol and risperidone on serum melatonin and GAP-43 in patients with schizophrenia: A prospective cohort study
RITUPARNA MAITI 1, BISWA RANJAN MISHRA 2*, MONALISA JENA 1, ARCHANA MISHRA 3, SANTANU NATH 2
1Department of Pharmacology, AIIMS, Bhubaneswar, India, 2Department of Psychiatry, AIIMS, Bhubaneswar, India, 3Department of Pharmacology, AIIMS, New Delhi, India
Received: June 19, 2020; Revised: August 23, 2020; Accepted: September 7, 2020; Published online: September 7, 2020.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Abstract
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 (AANAT), 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%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.
Keywords: Schizophrenia, Melatonin, Haloperidol, Risperidone, GAP-43


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