Amitriptyline in the preventive treatment of persistent COVID-19 related headache: 50% responder rate and response predictors in a series of 66 patients

Abstract text (incl. figure legends and references)

Background

Headache is a frequent symptom of coronavirus disease 2019 (COVID-19). In most cases, it is transient, but in an 8-16% it adopts a chronic pattern. Herein we describe our experience in a real-world setting with amitriptyline (AMT) and we explore the possible response predictors.

Methods

Patients with confirmed COVID-19 that were referred due to headache were included. The 50% responder rate of AMT was determined as the proportion of patients who presented a 50% reduction in the number of headache days per month between weeks 8-12 of treatment, compared to the month prior to the AMT onset. We conducted a regression model to evaluate which variables were associated with a higher probability of response.

Results

Sixty-six patients had used AMT, 92.4% female, aged 48.11 (standard deviation (SD): 11.5) years, 34.8% with prior history of migraine and 15.2% with prior history of tension-type headache. Patients had prior history of anxiety (43.9%), depression (28.8%), sleep disorders (37.9%), and other painful conditions (27.3%).

Median time between the COVID-19 infection and the AMT use was 6.1 (inter-quartile range (IQR): 4.1-9.6) months.

The median monthly frequency of headache at the moment of AMT use was 30 (IQR: 28-30). AMT was the first preventive treatment in 80.3%.

The 50% responder rate between weeks 8-12 of AMT use was 45.5%. The variables that remained associated with a 50% responder rate in the multivariate analysis were prior history of other painful conditions (odds ratio (OR): 0.142; 95% confidence interval (CI): 0.027-0.755); number of prior preventive medications (OR: 0.349; 95% CI: 0.158-0.771) and hemicranial headache (OR: 0.159; 95% CI: 0.32-0.798).

Conclusion

Amitriptyline was effective in treating patients with persistent post-covid-19 headache six months after the acute phase. Prior history of painful conditions, the number of preventive medications and hemicranial headache were associated with a lower probability of response.