Clinical trial NCT06838104: Effect of Melatonin on Schizophrenic Symptoms: a Randomized Placebo-Controlled Trial
Official title: Effect of Melatonin on Positive and Negative Symptoms of Schizophrenic Patients: a Randomized Placebo-Controlled Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Schizophrenia Disorders
Psychotic Disorder
Keywords: Antipsychotic Therapy
Positive Symptoms
Negative Symptoms
Lead sponsor: Lahore General Hospital
Sponsor class: OTHER_GOV
First posted: 2025-02-20
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Schizophrenia is a chronic mental health disorder that affects thoughts, emotions, and behaviors. It includes positive symptoms such as hallucinations and delusions, as well as negative symptoms like reduced motivation, social withdrawal, and blunted emotional expression.

This study is a randomized, placebo-controlled trial designed to evaluate the effect of melatonin on schizophrenia symptoms. Melatonin, a natural hormone that regulates sleep, has antioxidant properties and potential neuroprotective effects.

A total of 76 patients diagnosed with schizophrenia according to DSM-5 criteria will be randomly assigned to receive either melatonin (6 mg daily) or a placebo for eight weeks while continuing their standard risperidone-based antipsychotic therapy. Symptoms will be assessed at baseline and after 8 weeks using the Positive and Negative Syndrome Scale (PANSS), a validated tool for measuring schizophrenia severity. The primary outcome will be changes in PANSS scores, evaluating whether melatonin leads to significant improvement compared to placebo.

The study hypothesizes that melatonin will significantly reduce positive and negative symptoms compared to placebo. Findings from this research may help determine whether melatonin can be used as an adjunctive treatment in schizophrenia, potentially improving clinical outcomes and quality of life for patients.

Detailed description: Schizophrenia is a chronic psychiatric disorder characterized by a combination of positive symptoms (hallucinations, delusions, disorganized thinking) and negative symptoms (social withdrawal, reduced motivation, and blunted affect). While antipsychotic medications remain the primary treatment, they often fail to address negative symptoms, which are strongly associated with poor functional prognosis and reduced quality of life. Emerging evidence suggests that melatonin, a neurohormone primarily responsible for sleep regulation, possesses antioxidant and neuroprotective properties that may contribute to symptom improvement in schizophrenia.

This randomized, placebo-controlled trial aims to evaluate the efficacy of melatonin supplementation as an adjunct to standard antipsychotic therapy (risperidone 6-8 mg/day) in patients diagnosed with schizophrenia. The study will enroll 76 patients, randomly assigned to receive either melatonin (6 mg daily, administered as two 3 mg tablets before bedtime) or a placebo identical in shape, size, color, and taste for eight weeks. Participants will continue their standard antipsychotic regimen throughout the study period.

The primary outcome of the study is the change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 8, assessing the overall impact of melatonin on symptom severity. The secondary outcomes include changes in PANSS negative symptom subscale scores, evaluating whether melatonin improves motivation, emotional expression, and social engagement.

To ensure methodological rigor, patients will be assessed at baseline and after eight weeks using the PANSS scoring system. Randomization will be performed using a lottery method, and the study will follow a double-blind design, ensuring that neither patients nor investigators are aware of the treatment allocation. Safety monitoring will include adverse event reporting, particularly evaluating the incidence of excessive sedation, dizziness, headache, and gastrointestinal disturbances.

This study aims to provide clinical evidence regarding the role of melatonin as an adjunctive treatment for schizophrenia. If proven effective, melatonin supplementation could offer a low-cost, well-tolerated intervention to enhance treatment outcomes in schizophrenia patients, particularly those experiencing persistent negative symptoms.

Eligibility criteria: Inclusion Criteria:

* Patients aged between 18 to 50 years.
* Patients diagnosed with schizophrenia according to DSM-5 criteria, exhibiting both positive negative symptoms.
* Patients who score less than 6 on the Calgary Depression Scale for Schizophrenia (CDSS), indicating no significant depressive episode, will be considered eligible.

Exclusion Criteria:

* Patients with a known hypersensitivity or allergy to melatonin or any of its excipients.
* Patients with a current or past diagnosis of major depressive disorder, bipolar disorder, or obsessive-compulsive disorder, unless these are in full remission and do not require active pharmacological treatment.
* Patients with any unstable or serious medical condition (e.g., cardiovascular, hepatic, renal, or respiratory diseases) that could interfere with the study outcomes or pose additional risk to the patient.
* Married women of reproductive age, unless they use a reliable non-hormonal contraception method.
* Patients with neurological disorders, such as epilepsy, Parkinson's disease, or traumatic brain injury, which may mimic psychiatric symptoms.
* Use of antiepileptic, antihypertensive, anticoagulant, or anti-platelet drugs.
* Use of inhibitors or stimulants of hepatic isoenzymes that metabolize melatonin or olanzapine (e.g., omeprazole, rifampin, fluvoxamine, ciprofloxacin, carbamazepine, modafinil).
* History of addictive disorders.

Primary outcomes:
measure: Change in Positive and Negative Syndrome Scale (PANSS) Total Score
timeFrame: Baseline (Week 0) and Week 8
Secondary outcomes:
measure: Change in PANSS Negative Symptom Subscale Score
timeFrame: Baseline (Week 0) and Week 8
Other outcomes:
Locations:
city: Lahore
country: Pakistan
facility: Lahore General Hospital, Lahore
state: Punjab
Study officials:
affiliation: Lahore General Hospital, Lahore
name: Muhammad Irfan Jamil
role: PRINCIPAL_INVESTIGATOR
References: