Clinical efficacy of escitalopram combined with botulinum toxin A in patients with generalized anxiety disorder and comorbid headache.

[BACKGROUND] Generalized anxiety disorder (GAD) is a common mental disorder that happens comorbidly with other diseases. Headache is a common anxiety comorbidity. Previous reports have shown that the selection of therapeutic drugs for GAD patients and comorbid headache is challenging. Therefore, our study aimed to investigate the clinical efficacy of escitalopram combined with botulinum toxin A (BoNT/A) in patients with GAD and comorbid headache and seek an alternative treatment strategy for the comorbidity of GAD and headache.

[METHODS] A prospective, randomized controlled, double-blind study was performed. The eligible GAD patients with comorbid headache were randomly assigned to the BoNT/A group and the placebo group. All the patients were given oral escitalopram therapy (10-20 mg/day) for the whole duration of the study. The BoNT/A group was given local injections of BoNT/A (50 U per person), whereas the placebo group was given local saline (0.9% NaCl) injections at the beginning and 3 months after the experiments. All participants were followed up for 6 months and relevant information was collected at months 0, 1, 2, 3, and 6. Primary outcomes included the following: (1) the Generalized Anxiety Disorder 7 (GAD-7); (2) the Self-rating Anxiety Scale (SAS); (3) the Hamilton Anxiety Rating Scales (HAMA); (4) days with headache per month; (5) visual analogue scale (VAS).

[RESULTS] A total of 101 patients (the sex ratio of female to male: 3.39:1) were finally included. Compared with the placebo group, the BoNT/A group showed a significant decrease in GAD-7 scores, SAS scores, HAMA scores, days with headache per month, and VAS scores at months 1, 2, 3, and 6 of follow-up (all p < 0.05). The average time to complete remission of anxiety symptoms (HAMA< 7 points) in the BoNT/A group was less than the placebo group (2 months vs. 3 months). At the same time, the results of the survival analysis showed a clear beneficial effect of BoNT/A relative to placebo on the time to remission of anxiety (log-rank test, p < 0.001). Mean daily doses of escitalopram at the sixth month in the BoNT/A group was smaller than the placebo group (12.5 mg vs. 16.04 mg, p < 0.001). The number of patients who relapsed (HAMA total score ≥ 14 points) at 6 months of follow-up in the BoNT/A group was less than the placebo group (2.2% vs. 14.9%, p < 0.05). The rates of response (HAMA subtraction rate ≥ 50%) were 93.8% for the BoNT/A group and 75.5% for the placebo group (p < 0.05), and the rates of remission (HAMA < 7 points) were 87.5% for the BoNT/A group and 64.2% for the placebo group (p < 0.01) at the sixth month.

[CONCLUSION] The combination of escitalopram with BoNT/A is a significantly effective intervention in improving clinical efficacy and reducing the recurrence in patients with GAD and comorbid headache, and we believe that this approach will be an additional treatment strategy for future treatment of comorbid headache in GAD. Therefore, we recommend that escitalopram combined with BoNT/A should be given as early as possible in GAD patients and comorbid headache.