Comparison of Efficacy Between Combination of Amitriptyline-propranolol and Pizotifen for Migraine Prophylaxis.

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare efficacy and observe common adverse effects of a combination of amitriptyline-propranolol and pizotifen as prophylactic treatments for migraine. The main question it aims to answer is: • Does pizotifen more effective than the combination of amitriptyline-propranolol in migraine prophylaxis? Participants will be asked to : Maintain the provided headache diary accordingly Take supplied drugs as described during clinical visits Contact principle investigator if there is any issues regarding drug use and/or their adverse effects

Official Title
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Comparison of Efficacy Between Combination of Amitriptyline-propranolol and Pizotifen for Migraine Prophylaxis: A Single-blind Randomized Controlled Trial

Conditions
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Migraine

Intervention / Treatment
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* Drug: Pizotifen
* Drug: Amitriptyline-propranolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient of migraine (with typical aura or without aura) according to ICHD-3 (International Classification of Headache Disorder, 3rd edition) criteria. Age at entry: 18 to 50 years (to minimize the risks related to adverse effects of study drugs such as drowsiness, weight gain, A-V conduction block, postural hypotension) Patients not on any prophylactic medications. Patients willing to take part in the study. Patients being able to fill a headache diary successfully & reliably. Exclusion Criteria: Age <18 years or >50 years Patients having headache other than migraine, complicated migraine, ophthalmoplegic migraine, catamenial migraine, basilar migraine. Patients on prophylactic medication. Co-morbidities such as heart failure, hepatic or renal impairment, diabetes, bronchial asthma, malignancy, intracranial vascular aneurysm, pregnancy & breastfeeding etc. Patients having known hypersensitivity to amitriptyline, propranolol or pizotifen

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Amitriptyline-Propranolol<br>Combination of amitriptyline and propranolol. Initial 2 weeks: Amitriptyline 10 mg at bedtime Propranolol 20mg twice daily Next 2 weeks: Amitriptyline 25 mg at bedtime Propranolol 20mg three times daily Next 8 weeks: Amitriptyline 25 mg at bedtime Propranolol 40mg twice daily | Drug: Amitriptyline-propranolol<br>* Amitriptyline will be given at bedtime only, starting at 10 mg daily and gradually increasing to 25 mg daily. Propranolol will be started in 40 mg daily in divided doses, which gradually increases to 80 mg daily in divided doses<br>|
| Experimental: Pizotifen<br>Pizotifen Initial 2 weeks: Pizotifen 0.5 mg at bedtime Next 2 weeks: Pizotifen 1 mg at bedtime Next 8 weeks: Pizotifen 1.5 mg at bedtime | Drug: Pizotifen<br>* Pizotifen will be given only at night time to avoid daytime somnolence. Starting dose will be 0.5mg then gradually increased to 1.5 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of headache per month | Comparison of reduction of frequency of headache attack in immediate last month with initial baseline one month without any medication. These values will be compared between two study groups | 12 weeks | 
| Duration of headache per month | Comparison of reduction of total duration of headache attack in immediate last month with initial baseline one month without any medication. These values will be compared between two study groups | 12 weeks | 
| Severity of headache | Comparison of reduction of severity of headache attack in immediate last month with initial baseline one month without any medication using visual analogue scale. The visual analogue scale is numbered from 0 to 10. 0 stands for no pain, 1-3 for mild pain, 4-6 for moderate pain and 7-9 for severe pain and 10 for very severe unbearable pain. These values will be compared between two study groups | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse effects of drugs | Adverse effects (e.g., somnolence, dizziness, dry mouth, weight gain, constipation, bradycardia) of study drugs will be observed | 12 weeks |