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

DOI: https://doi.org/10.1186/s10194- 019- 1051- 7

Abstract-Summary Despite the very high prevalence of PTH, there are no evidence-based guidelines for PTH treatment.

Included studies involved acute and preventive pharmacological treatment of headache attributed to traumatic injury to the head in adherence to the International Classification of Headache Disorders (ICHD) criteria.

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5 Future Directions

None of the seven included studies were randomized clinical trials (RCTs) or

used a placebo-controlled study design.

We found that there is a lack of high-quality evidence-based studies on the phar-

macological treatment of PTH.

Extended: We address methodological limitations and provide recommendations

for future research.

For each study, two investigators (E.L.L and A.I) recorded data on study design, assessment methods, inclusion criteria, exclusion criteria, age, gender, total number of subjects, headache phenotype, outcome measures and other data relevant for the scope of this review.

It would be interesting if future RCTs and high-quality open-label studies included secondary endpoints set to investigate drug efficacy on factors such as health-related quality of life, work productivity and levels of anxiety and depression.

Introduction Despite a very high prevalence of PTH, there are no evidence-based guidelines for acute or preventive pharmacological treatment of PTH.

Current pharmacological treatments for PTH are based on acute or preventive medications used for primary headache disorders [11, 158], since PTH often mim- ics a migraine-like or tension-type headache-like phenotype [159].

Side effects to pharmacological treatment may conflict with PTH comorbidities

such as depression and anxiety.

We review the current literature on acute and preventive treatment of PTH and

provide a useful overview for clinicians.

Methods The search was limited to articles on human subjects published in English.

We also reviewed the reference lists of relevant primary articles and reviews to

identify studies that were missed in the search process.

One investigator (E.L.L) screened all articles by title and abstract. Following this, two investigators (E.L.L and A.I.) performed a full-text screening

and determined which articles should be included.

Another investigator (H.M.A) subsequently reassessed all the included articles. For each study, two investigators (E.L.L and A.I) recorded data on study design, assessment methods, inclusion criteria, exclusion criteria, age, gender, total number of subjects, headache phenotype, outcome measures and other data relevant for the scope of this review.

Results A retrospective cross-sectional emergency department (ED) based study investi- gated the treatment response of intravenous acute migraine therapies in an adoles- cent (aged 8–21 years) group consisting of 254 subjects [160].

A patient satisfaction survey was conducted post-intervention (82% follow-up response rate) with 26% of subjects reporting that peripheral nerve blocks had cured their headache.

Following metoclopramide treatment, 32% of subjects reported complete imme- diate headache resolution while 44% achieved partial and 24% no headache relief, respectively.

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Post-concussion Syndrome

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A prospective ED-based open-label study investigated headache relief in 21 patients treated with intravenous metoclopramide 20  mg and diphenhydramine 25 mg after acute PTH attributed to TBI [161].

This study found that headache frequency decreases with 2.6 days (−15.5%, P = 0.009) at follow-up compared to baseline after the subjects started on prophy- lactic treatment.

Discussion We found a lack of quality studies on both acute and preventive pharmacological treatment of PTH.

The primary and secondary endpoints varied between the included studies, mak-

ing treatment comparisons unfeasible.

The preventive treatment study [62] included 44 children with a mean time

period since TBI of 7 months (range: 1–29 months).

Data analysis can be greatly enhanced, if consensus guidelines for controlled

trials of acute and preventive treatment of PTH are provided.

Future open-label studies and RCTs should require included subjects to fulfill

the ICHD criteria for PTH to reduce population heterogeneity.

It would be interesting if future RCTs and high-quality open-label studies included secondary endpoints set to investigate drug efficacy on factors such as health-related quality of life, work productivity and levels of anxiety and depression.

Conclusion This systematic review has shown a low level of evidence to support any pharmaco- logical treatment of PTH.

High-quality RCTs and open-label studies are needed to provide robust evidence

of clinical utility.

Future studies should include multidimensional outcome scales that cover mul-

tiple symptom domains.

Acknowledgement A machine generated summary based on the work of Larsen, Eigil Lindekilde; Ashina, Håkan; Iljazi, Afrim; Al-Khazali, Haidar Muhsen; Seem, Kristoffer; Ashina, Messoud; Ashina, Sait; Schytz, Henrik Winther 2019 in The Journal of Headache and Pain.

Psychiatric and cognitive comorbidities of persistent post- traumatic headache attributed to mild traumatic brain injury