Amitriptyline to Prevent Headache After Traumatic Brain Injury
Condition: Brain Injuries; Post-Traumatic Headache
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Post-Traumatic Headache; Headache; Wounds and Injuries
Intervention: Amitriptyline
Intervention description: Participants with headache will be enrolled within the first 12 weeks after injury and will be randomly assigned to 2 groups (see Table 1 for summary of protocol). Group 1 will be assessed within 3 months of injury (baseline, Day 0) (when they will receive their initial ramp-up dosage containers; see Table 2 for dosing), Day 30 and Day 60 (to monitor compliance and distribute study drug), and for final outcome on Day 90. Group 2 will be assessed within 3 months of injury (baseline, Day 0) but will not receive medication until their Day 30 visit. Those in group 2 who report headache at Day 30 will receive their initial dosage container and will then be reassessed at Day 60 (to monitor compliance and distribute study drug) and Day 90 (final outcome).
Intervention MeSH terms: Amitriptyline
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Traumatic brain injury; Post-traumatic headache; Drug therapy

Summary:

      The investigators propose to conduct a 2-arm, open-label pilot study to determine if early
      treatment with amitriptyline will decrease the frequency and severity of headaches after mild
      traumatic brain injury (TBI). Amitriptyline is a tricyclic antidepressant that is commonly
      available and inexpensive. It is used as a first-line drug for primary headache prevention in
      a very low dose range of 10-50 mg.

        -  Specific Aim 1 is to conduct a 2-arm open-label study to examine the effect of
           preventive treatment with amitriptyline on the frequency and severity of headache after
           mild TBI.

        -  Specific Aim 2 is to collect data needed for design of a Phase 3 study, including an
           estimate of effect size, headache variability, and desirable drug treatment start date.

        -  Specific Aim 3 is to examine the feasibility of using headache diaries with individuals
           with mild TBI.

        -  Specific Aim 4 is to establish the safety and tolerability of amitriptyline for the
           prevention of headache after mild TBI.

      The investigators hypothesize that early preventive treatment with amitriptyline will avert
      the development of chronic post-traumatic headache (PTH) as compared to rates of headache
      from a recent natural history study on PTH after mild TBI.

      The investigators propose to enroll inpatient subjects from a Level I trauma center as well
      as from outpatient clinics and from the general community with a diagnosis of mild TBI.
      Subjects will be screened for current headache. After baseline assessment, 72 subjects with
      current headache will be randomized to one of 2 groups. Group 1 will immediately begin
      amitriptyline and or Group 2 will be followed and begin amitriptyline at Day 30. All subjects
      will be asked to complete a daily headache diary beginning on Day 1 of the study. A detailed
      medical history and headache survey will be completed. Subjects will have a scheduled stepped
      increase in the drug dosage every week for 3 weeks to the maximum study dosage of 50 mg.
      Weekly telephone calls will monitor for adverse events and compliance with the drug and
      headache diary. Clinic visits will occur at 30, 60 and 90 days. The 30 day clinic visit will
      include cognitive testing to assess for differences between groups and initiation of drug
      treatment for Group 2. Both 30 and 60 day visits will include review of headache diary,
      potential adverse effects, and pill counts. The 90 day visit will be for outcome assessment.
      In addition, the headache survey will be repeated by telephone at Day 180.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Acute mild TBI (Glasgow Coma Scale of 13-15 on emergency department evaluation, any
             period of loss of consciousness (LOC) < than 30 minutes, alteration of consciousness
             or post-traumatic amnesia (not to exceed 24 hours)

          -  Ability to give consent

          -  Ages 18-60

          -  Access to a telephone

          -  Current headache (new headache or headache worse than prior to injury)

        Exclusion Criteria:

          -  Does not speak English

          -  Diagnosed seizure disorder

          -  Myocardial infarction in prior 6 months

          -  Cardiac arrhythmia requiring medication treatment

          -  Prolonged Q-T interval on electrocardiogram

          -  Psychosis

          -  Intoxication on hospital admission sufficient enough to cloud the diagnosis of mild
             TBI

          -  Incarceration or homelessness

          -  Allergy to amitriptyline

          -  Current treatment with amitriptyline or other tricyclic antidepressant

          -  Currently taking any medication not recommended for use with amitriptyline due to the
             potential for Q-T interval prolongation. Examples of this include: Class I, I-A or II
             antiarrhythmics, TCA's, MAOI's, selected fluoroquinolones (gatifloxacin,
             moxifloxacin), selected antipsychotic medications (haloperidol, risperidone,
             quetiapine), selected antiretroviral medications, cisapride, chloroquine,
             chlorpromazine, prochlorperazine, promethazine, citalopram, fluoxetine, erythromycin,
             methadone

          -  History of glaucoma

          -  History of prostate disease or current urinary retention