Intervention: Amitriptyline
Trial phase: Phase 3
ATC code: N06AA09 | N06CA01
SMILES: CN(C)CCC=C1c2ccccc2CCc2ccccc21
Sex: All
Age groups: Child
Healthy volunteers: No
Participants at risk: 144
Group description: Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved.
Eligibility criteria:
Inclusion Criteria:

Migraine with or without aura (International Classification of Headache Disorders, 2nd Edition (ICHD-II) or chronic migraine (ICHD-II revised)
Migraine frequency based upon prospective headache diary of 28 days must be ≥ 4. Migraine frequency defined as any migraine during one day in the 28 day baseline period (1)
PedMIDAS Disability Score > 10, indicating at least mild disruption in daily activities and < 140, indicating extreme disability that may require more comprehensive, multi-component therapy

Females or males 8-17 years, inclusive

Migraine frequency is defined as the period from the onset to the stop time of painful migraine symptoms not to exceed 24 hours with the clock starting at midnight. If painful symptoms last longer than 24 hours, this is considered a new and distinct migraine headache. If painful symptoms recur within 24 hours of initial onset, this is considered part of the initial migraine episode and would be counted as one migraine.

Exclusion Criteria:

Continuous migraine defined as an unrelenting headache for a 28 day period
Weight less than 30 kg or greater than 120 kg
Unwilling to avoid taking non-specific acute medication such as NSAIDS (e.g., ibuprofen), more than 3 times per week, or migraine specific acute medications such as triptans more than 6 times per month
Currently taking other prophylactic anti-migraine medication within a period equivalent to 2 weeks of that medication before entering the screening phase, or the use of Botulinum toxin (Botox®) within 3 months of entering the screening phase
Subjects who have previously failed an adequate trial of AMI or TPM for prophylaxis of at least 3 months duration at doses recommended for migraine relief because of lack of efficacy or adverse events(2)
Current use of disallowed medications/products: opioids, antipsychotics, antimanics, barbiturates, benzodiazepines, muscle relaxants, sedatives, tramadol, nutraceuticals, SSRIs, or SSNRIs
Known history of allergic reaction or anaphylaxis to AMI or TPM
Abnormal findings on ECG at baseline, particularly lengthening of the QT interval greater than or equal to 450 msec
Subject is pregnant or has a positive pregnancy test
Subject is sexually active and not using a medically acceptable form of contraception
Diagnosis of epilepsy or other neurological diseases
History of kidney stones
Inability to swallow pills after using behavioral techniques if indicated between screening visit and baseline visit (3)
Present psychiatric disease as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM IV) (e.g. psychosis, bipolar disorder, major depression, generalized anxiety disorder), alcohol or drug dependence, or documented developmental delays or impairments (e.g., autism, cerebral palsy, or mental retardation) that, in the opinion of the site investigator, would interfere with adherence to study requirements or safe participation in the trial

Any and all other diagnoses or conditions which in the opinion of the site investigator, that would prevent the patient from being a suitable candidate for the study or interfere with the medical care needs of the study subject

(2)"Previously failed an adequate trial of AMI or TPM" is defined as: dosage of 1mg/kg/day of AMI or 2 mg/kg/day of TPM; trial of at least 3 months duration; efficacy of having at least a 50% decrease in migraine frequency in response to drug therapy; or unable to tolerate taking the medication due to treatment-related side effects.

(3)Subjects who cannot swallow pills at the time of the screening visit will be given a training session using behavioral techniques. Upon return for baseline visit, if the subject continues to be unable to swallow pills, the subject will be excluded from the study.