Frenquel, a Blocking Agent Against Experimental LSD‐25 and Mescaline Psychosis

A combination of dextromethorphan and quinidine (AVP-923) reduces pseudobulbar affect—uncontrollable episodes of laughing or crying—in people with amyotrophic lateral sclerosis (ALS). In a 28-day trial, patients taking the combination showed a 3.3-point greater improvement on a lability scale compared with dextromethorphan alone and a 3.7-point greater improvement compared with quinidine alone. They also had fewer episodes overall and better quality-of-life and relationship scores. Adverse effects were mostly mild or moderate; 24% of those on the combination discontinued treatment due to side effects, versus 6% and 8% for the individual components.

Study at a glance

Abstract

Background: Patients with ALS commonly exhibit pseudobulbar affect. Methods: The authors conducted a multicenter, randomized, double-blind, controlled, parallel, three-arm study to test a defined combination of dextromethorphan hydrobromide (DM) and quinidine sulfate (Q) (AVP-923) for the treatment of pseudobulbar affect in ALS. Q inhibits the rapid first-pass metabolism of DM. The effects of AVP-923 (30 mg of DM plus 30 mg of Q) given twice daily for 28 days were compared with those of its components. Patients were evaluated on days 1, 15, and 29. The primary efficacy variable was the change from baseline in the Center for Neurologic Study Lability Scale (CNS-LS) score. Secondary efficacy variables were laughing/crying episode rates and changes in Visual Analog Scales for Quality of Life (QOL) and Relationships (QOR). Efficacy was evaluated in intention-to-treat subjects who were not poor metabolizers of DM (n = 65 for AVP-923, n = 30 for DM, and n = 34 for Q). Safety was assessed in all randomized subjects (n = 140). Results: AVP-923 patients experienced 3.3-point greater improvements in CNS-LS than DM patients (p = 0.001) and 3.7-point greater improvements than Q patients (p < 0.001). AVP-923 patients exhibited lower overall episode rates, improved QOL scores, and improved QOR scores (p < 0.01 for all endpoints). Adverse effects were mostly mild or moderate; treatment-related discontinuation was 24% for AVP-923, 6% for DM, and 8% for Q. Conclusions: AVP-923 palliates pseudobulbar affect in ALS. Overall benefits of treatment are reflected in fewer episodes of crying and laughing and improvements in overall quality of life and quality of relationships.