Efficacy, Safety and Tolerability of Clonazepam 0.25 mg and Propranolol 10/20 mg Fixed-dose Combination among Anxiety Disorder Patients: A Randomized, Double-blind, Multicentric, Active-controlled, Phase IV Study

Background and aim: Although monotherapy of anti-anxiety drugs is effective in controlling anxiety, due to the progressive nature of the disease, it is often associated with a lack of effectiveness over time.So, this study was carried out to assess the efficacy, safety, and tolerability of clonazepam 0.25 mg and propranolol 10/20 mg fixed-dose combination among anxiety disorder patients.Materials and methods: This was a randomized, double-blind, multicenter, actively-controlled, phase IV study conducted among individuals having established diagnosis of anxiety, total Hamilton Rating Scale for Anxiety (HAM-A) score 17, Clinical Global Impressions Severity (CGI-S) score >4 in the week prior to inclusion.The study participants were randomized to receive either the test or the reference drug once daily for 8 weeks.At the last study visit, the degree of a patient's anxiety was assessed by using the HAM-A and CGI-S scores.Results: At week 8, it was observed that there was a decrease in HAM-A score in all the groups.Between the group analysis, at visit 3, there was a reduction in the HAM-A score compared with the randomization visit.The investigator-rated scale and patient-rated global improvement were highest in group B followed by group C compared with group A. Also, there was a notable reduction in group A at week 8 in the CGI-S score as compared with baseline in group B. Conclusion:The combination of clonazepam and propranolol was effective, safe, and well-tolerated.Hence, it can be a significant armamentarium in anxiety disorder management.Clinical significance: The clonazepam 0.25 mg and propranolol 10/20 mg fixed-dose combination showed a significant decrease in the HAM-A score across patients with anxiety disorders and was found to be clinically effective, safe, and well-tolerated.