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Table 1 Overview of included studies

From: Acute and preventive pharmacological treatment of post-traumatic headache: a systematic review

Source Patient Population, Baseline Study Design TBI Severity Intervention Follow-up Eligible Outcome Measures Major Findings
Chan et al. (2015) [12] 254 children and adolescents, 124 Ma, 130 Fa, mean age 13.8 years Single-center, ED, tertiary children’s hospital, retrospective mTBI Acute Pharmacological Treatment.
IV therapies included one of the following four options:
- ketorolac only (n = 55)
- ketorolac and metoclopramide / prochlorperazine (n = 132)
- metoclopramide or prochlorperazine (n = 30)
- ondansetron only (n = 37)
The dosages used were not reported.
Thirty-seven percent of the subjects were pretreated with either acetaminophen or ibuprofen.
None Treatment success defined as ≥50% reduction in pain intensity as measured on a numeric rating scale from 0 to 10. Treatment success: - Ketorolac only: 80%
- Ketorolac plus metoclopramide or prochlorperazine: 89%
- Metoclopramide or prochlorperazine only: 93%
- Ondansetron only: 78%
Dubrovsky et al. (2014) [10] 28 children, 6 Ma, 22 Fa, mean age 14.6 years Single-center, tertiary referral center, retrospective mTBI Acute Pharmacological Treatment.
- GON block (2% lidocaine with epinephrine)
- Peripheral nerve blocks of the lesser occipital nerve and supraorbital nerve (only a subgroup of patients)
Follow-up was conducted using a patient satisfaction survey. Five patients lost to follow-up.
The exact time from intervention to follow-up could not be extracted properly.
Good therapeutic effect defined as headache relief lasting longer than 24 h or requested repeat blocks. - 93% with good therapeutic effect
- 71% reported complete headache resolution immediately following the intervention
- At the follow-up assessment (82% follow-up response rate), 26% of patients reported that peripheral nerve blocks had cured their headache
Erickson (2011) [15] 100 military personnel, 99 Ma, 1 Fa, mean age 28.7 years Single-center, clinic-based, retrospective mTBI Acute Pharmacological Treatment.
- Triptans (n = 73)
- Non-triptans (NSAIDs, acetaminophen, opioids and combination drugsb, n = 33)
The dosages were not reported.
Notably, 23% used more than one abortive medication.
Preventive Pharmacological Treatment.
One of the following therapies were prescribed:
- Tricyclic antidepressants (amitriptyline or nortriptyline, n = 48) 25–50 mg/day
- Topiramate 100 mg/day (n = 29)
- Propranolol LA 80 mg/day (n = 18)
- Valproate extended release 500 mg/day (n = 5)
3 months after treatment start, none lost to follow-up.
At 3 months post-baseline, 66 of 100 subjects (34% medication discontinuation rate) were still taking the prophylactic treatment that was prescribed at baseline.
Acute Pharmacological Treatment.
- Headache relief within two hours after intake (not further specified
Preventive Pharmacological Treatment.
- Headache frequency defined as number of days in the previous month with a headache lasting > 30 min
- Headache-related disability as determined by MIDAS
Acute Pharmacological Treatment.
- Triptans (n = 73 and a 70% responder rate) were more effective compared to non-triptans (n = 33 and a 42% responder rate) in terms of headache relief within two hours after intake (P = 0.01)
Preventive Pharmacological Treatment.
- The decrease in headache frequency was significant for subjects treated with topiramate (n = 29, P = 0.02), but not for any other of the prescribed prophylactic treatments
- 57% overall decrease in headache-related disability among all subjects as measured by MIDAS
Friedman et al. (2018) [11] 21 adults, 5 M, 16 F, mean age 45 years Single-center, ED, prospective NS Acute Pharmacological Treatment.
IV metoclopramide 20 mg + dephenhydramine 25 mg.
48 h + 7 days, 2 patients lost to follow-up. “Sustained headache relief for 48 h”, defined as mild headache or no headache sustained for 48 h since ED discharge without use of rescue medication. - At 48 h since ED discharge, 63% reported sustained headache relief for 48 h, while 37% continued to experience moderate to severe headaches
- At the 1-week follow-up, 53% reported no or rare headache occurrence
Kuczynski et al. (2013) [14] 44 children, 15 M, 29 F, mean age 14.1 years Single-center, clinic-based, retrospective mTBI Preventive Pharmacological Treatment.
The list of prophylactic treatments used included:
- Amitriptyline 5 mg to 1 mg/kg (n = 18)
- Topiramate 12.5–200 mg/day (n = 6)a
- Melatonin 3–10 mg/day (n = 12)
- Nortriptyline (n = 9)a and flunarizine (n = 8)a doses were not specified
- 17 subjects received more than one treatment i.e. physical therapy and biofeedback therapy
The mean follow-up rate was every 5.5 weeks until headache symptoms had resolved. None lost to follow-up. Treatment success defined as ≥50% reduction in headache frequency and whether prophylactic treatments were continued for 3 months after headache resolution and subsequently gradually discontinued. Treatment success:
- Amitriptyline: 72%
- Melatonin: 75%
Seeger et al. (2015) [9] 15 children, 5 M, 10 F, mean age 15.5 years Single-center, clinic-based, retrospective mTBI Acute Pharmacological Treatment.
Administration of GON block was done with 2,5 mL 2% lidocaine (50 mg) + 0.5 ml methylprednisolone acetate (20 mg) or 2.5 ml triamcinolone (25 mg).
Follow-up assessment was conducted at a mean of 5.6 months after treatment start, 1 patient lost to follow-up. Full treatment response defined as ≥50% reduction in headache frequency. Full treatment response:
- 64% (9 of 14 patients)
- Mean headache frequency was reduced from 26 days per month to 18 days per month
Cushman et al. (2019) [13] 277 children and adults, 139 Ma, 138 Fa, mean age 23.0 yearsa Single-center, academic sports medicine practice, retrospective mTBI Preventive Pharmacological Treatment.
Patients were classified into three groups:
- No medication (n = 123)
- Amitriptyline (median dose: 20 mg, n = 94)
- Gabapentin (median dose: 900 mg, n = 60)
Follow-up data was collected over 1 year after treatment start. Study inclusion was dependent on at least one follow-up assessment. Self-reported headache score, ranging from 0 to 6 (0 = no symptoms, 5–6 = severe symptoms). - In both medication groups (gabapentin and amitriptyline), headache scores improved over time
- However, headache scores improved similarly in the no medication group
  1. M males, F females, mTBI mild traumatic brain injury, NS not specified, ED emergency department, PTH post-traumatic headache, IV intravenous, GON greater occipital nerve, NSAIDs nonsteroidal anti-inflammatory drugs
  2. aData has been calculated based on data provided in the studies
  3. bIncludes Excedrin, Cafergot, and Midrin
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