Nortriptyline Compared With Amitriptyline for Migraine Prevention at SQUH

Inclusion Criteria: 1. Age 18 to 65 years at consent, of any sex or nationality, receiving care at Sultan Qaboos University Hospital and able to attend the required visits. 2. Migraine with or without aura diagnosed according to the International Classification of Headache Disorders, third edition, present for at least 12 months, with onset before age 50 years. 3. A history consistent with episodic migraine during the preceding three months and a prospective baseline showing 4.0 to 14.0 migraine days inclusive and fewer than 15 headache days per 28 days. 4. A clinical indication for preventive therapy agreed by the treating clinician and participant. 5. At least 23 valid diary days during the prospective 28-day baseline. Frequency thresholds will be assessed using standardized 28-day counts without rounding. 6. Ability to provide informed consent and complete an Arabic or English diary independently or with approved assistance that records the participant's own responses. 7. For participants who could become pregnant, a negative pregnancy test and agreement to an effective contraceptive approach or consistent abstinence where this reflects usual practice, from consent until 30 days after the last study dose. Exclusion Criteria: 1. Chronic migraine, another predominant headache disorder, suspected secondary headache, a trigeminal autonomic cephalalgia, or inability to distinguish migraine from other recurrent head pain. Hemiplegic migraine and migraine with brainstem aura are excluded. Typical visual or sensory aura is eligible. 2. Medication overuse headache or sustained acute medication use at overuse thresholds during the preceding three months. Use on 10 or more days per month of triptans, ergots, opioids, combination analgesics, or mixed acute drug classes, or on 15 or more days per month of simple analgesics or nonsteroidal anti-inflammatory drugs, will exclude participation. Baseline diary use meeting these thresholds will also exclude participation. 3. Previous clear treatment failure after an adequate course of either trial medicine, or previous clinically important intolerance, allergy, or contraindication to either medicine or its excipients. An adequate course is at least eight weeks at a tolerated dose of at least 25 mg nightly with insufficient benefit. Brief previous exposure without established failure is permissible if completed at least three months before screening and recorded. 4. Current migraine preventive medication or another treatment with substantial preventive activity that cannot safely be stopped. Oral preventive medicines must have been discontinued for at least four weeks and at least five elimination half-lives, whichever is longer, before baseline. OnabotulinumtoxinA or peripheral nerve blocks for prevention within four months, or a calcitonin gene-related peptide monoclonal antibody within six months or five half-lives, whichever is longer, will exclude participation. Preventive gepants follow the oral preventive washout rule. Effective treatment will not be withdrawn solely to enable enrollment when clinically inappropriate. 5. Current use of another antidepressant, a monoamine oxidase inhibitor, or a clinically important interacting medicine that cannot safely be avoided. All prescribed, nonprescribed, and herbal products will undergo pharmacist review. A prior monoamine oxidase inhibitor requires at least a 14-day interval, with any longer product-specific interval respected. Recent fluoxetine or another long-acting inhibitor requires an individualized documented washout. Psychiatric treatment will not be withdrawn simply to meet trial eligibility. 6. Previous myocardial infarction with ongoing risk, clinically significant ischemic or structural heart disease, heart failure, clinically important arrhythmia, unexplained syncope, congenital long QT syndrome, Brugada syndrome, or a family history suggesting an inherited arrhythmia without satisfactory specialist assessment. 7. Baseline corrected QT interval using Fridericia's formula above 450 milliseconds in men or 470 milliseconds in women, QRS duration of 120 milliseconds or greater, any degree of atrioventricular block including PR above 200 milliseconds, or another clinically significant electrocardiographic abnormality. A borderline or technically inadequate trace may be repeated and reviewed before eligibility is determined. 8. Uncontrolled epilepsy, previous serious drug-related seizure, untreated narrow-angle glaucoma, clinically important urinary retention, paralytic ileus, untreated hyperthyroidism, or a comparable condition increasing tricyclic treatment risk. 9. Severe hepatic disease, estimated glomerular filtration rate below 30 mL/min/1.73 m², or clinically significant uncorrected electrolyte disturbance. Alanine aminotransferase or aspartate aminotransferase above three times the local upper limit, or bilirubin above twice the upper limit unless a documented benign cause exists, requires exclusion or specialist clarification before reconsideration. 10. Bipolar I or II disorder, previous antidepressant-induced mania or hypomania, current psychosis, current suicidal intent or plan, a suicide attempt within the preceding year, or another psychiatric condition requiring treatment incompatible with the protocol. Stable anxiety or mild depressive symptoms alone will not exclude participation. 11. Current moderate or severe substance use disorder likely to affect safety or reliable participation. 12. Pregnancy, breastfeeding, planned pregnancy during participation, or inability to follow the agreed pregnancy prevention arrangements. 13. Participation in another interventional trial within the preceding 30 days or five investigational drug half-lives, whichever is longer. 14. A condition, planned procedure, or practical limitation preventing informed consent, reliable outcome assessment, or safe completion, with a specific reason documented by the investigator.