Botulinum toxin type A is a protein and neurotoxin that hinders the reception of neurotransmitter signals (most notably acetylcholine) to neurons and muscles throughout the brain and body, thereby producing the analgesic effect. Also, this toxin is well tolerated in patients with chronic daily headache.

Psychiatric comorbidities, including depression and anxiety, are clinical entities associated with chronic daily headache (CDH). Botulinum toxin A (BTA) is a Food and Drug Administration approved drug for the treatment of chronic migraine, a subtype form of CDH. This study aimed to investigate the potential efficacy and safety of BTA for controlling psychiatric symptoms in CDH patients.

A prospective, open-label, pilot study (n = 30; 7 males, 23 females) was performed. A single low-dose of BTA (40–120 U) was injected into the pericranial muscle at multiple sites. Participants were evaluated before and 1, 4, 8, 12, 16, 20 and 24 weeks after BTA treatment. Primary outcomes included: (1) headache severity, determined by a visual analog scale; (2) depression and anxiety severity, assessed via the Hamilton Depression and Anxiety Rating Scales (HAM-D and HAM-A, respectively); (3) headache frequency per month and (4) single headache episode duration.

Headache severity was significantly ameliorated one week after treatment. Depression and anxiety symptoms were significantly reduced one month after treatment. At month four, the headache incidence per month decreased from 28.83 ± 2.95 to 17.57 ± 11.30 d (p < 0.001), and the single headache duration decreased from 12.03 ± 9.47 to 6.63 ± 8.98 h (p < 0.001). Furthermore, the percentage of patients who required analgesics significantly decreased. BTA was well tolerated, and the adverse events were mild and transient.

BTA treatment alleviated the severity and frequency of CDH, with improvements in depression and anxiety. These novel findings indicate that BTA may represent an effective and safe intervention to target psychiatric comorbidities in CDH.