Effect of add-on ramelteon therapy on sleep and circadian rhythm disruption in patients with schizophrenia: A randomized controlled trial.

The sleep and circadian rhythm disruptions in schizophrenia are attributed to a decrease in nocturnal melatonin level which may worsen if treated with conventional sedative drugs. This study was planned to evaluate the effects of add-on ramelteon on sleep and circadian rhythm disturbances in schizophrenia. A randomized, rater-blinded clinical trial was conducted on 120 patients with schizophrenia. Patients were categorized into predominantly positive (PG) or negative (NG) symptoms depending on Positive and Negative Syndrome Scale (PANSS) scoring, and then they were randomized into control (haloperidol/risperidone) or test (add-on ramelteon) groups. After recruitment, baseline serum melatonin, serum AANAT, urinary melatonin and Pittsburgh Sleep Quality Index (PSQI) were evaluated. Patients were reassessed after 4 weeks of therapy with antipsychotics with or without ramelteon. A significantly greater increase in night-time melatonin level (PG: 10·19; 95%CI: 1·42 to 18·97; p = 0·024; NG: 18·74; 95%CI: 8·48 to 29·0; p = 0·001), decrease in PSQI scores (PG: -1·57; 95%CI: -2·59 to -0·55; p = 0·003; NG: -2·49; 95%CI: -4·59 to -0·39; p = 0·021), increase in urinary melatonin (PG: 0·20; 95% CI: 0·056 to 0·35; p = 0·008; NG :0·15; 95% CI: 0·01 to 0·29; p = 0·034), increase in serum AANAT (PG: 4·61; 95%CI: 1·34 to 7·87; p = 0·007; NG:3·46; 95%CI: 1·30 to 5·63; p = 0·002) and improvement in PANSS score were found in patients receiving add-on ramelteon. The increase in serum melatonin and decrease in PSQI score were greater with predominantly negative symptom group in comparison to positive symptom group. Ramelteon may be considered as an add-on therapy with antipsychotic drugs for sleep and circadian rhythm disturbances in schizophrenia.

Effect of lurasidone vs olanzapine on neurotrophic biomarkers in unmedicated schizophrenia: A randomized controlled trial.

Neurotrophic factors like Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin 3 (NT3) and Nerve Growth Factor (NGF), play a role in neuroplasticity and neurogenesis contributing to the pathogenesis of schizophrenia. The objective of the present study was to investigate and compare the effect of olanzapine and lurasidone on the change in serum neurotrophins in patients with schizophrenia. The present study was a randomized, open-label, active-controlled, parallel design clinical trial. After randomization baseline evaluations of serum BDNF, NGF, NT3, Positive and Negative Syndrome Scale (PANSS) scoring, Social and Occupational Functioning Assessment Scale (SOFAS) scoring of 101 unmedicated schizophrenia patients were done. Patients were reassessed after 6 weeks of monotherapy with olanzapine or lurasidone. Serum BDNF increased after treatment with both the drug groups but rise with olanzapine was found to be significantly higher (916.22; 95 %CI: 866.07 to 966.37; p < 0.001) in comparison to lurasidone. Increase in levels NGF and NT3 was also observed but there was no significant difference between the groups (NGF: 2.32; CI: 3.54 to -3.53; p = 0.57 and NT3: 0.99; CI: 2.11 to 0.14; p = 0.086). The difference in improvement in PANSS and SOFASS with both the drugs was not statistically significant. Both the drugs alleviate the symptoms of schizophrenia but olanzapine was better tolerated. Our findings suggest that increase in serum BDNF with olanzapine monotherapy is significantly higher than that with lurasidone but there is no significant difference in change in serum NGF and NT3. TRIAL REGISTRATION: ClinicalTrials.gov identifier: (NCT03304457).