BACKGROUND: The aim of this study was to assess the effects of withdrawal from placebo and carbamazepine administered for agitation associated with dementia and to assess safety, tolerability, and efficacy of subsequent ongoing carbamazepine therapy. METHOD: We previously reported the results of a 6-week, randomized, parallel-group study of placebo versus carbamazepine in 51 nursing home patients with dementia who were agitated; 47 subjects completed that study. This report first presents the results of withdrawal from that experimental treatment assessed by (blinded) observations 3 weeks later (N = 45 remaining). The primary outcome measure was the Brief Psychiatric Rating Scale. Secondary outcome measures addressed other aspects of behavior, cognition, function, safety, and tolerability. Patients were then treated with carbamazepine for an additional 6 weeks (N = 32 remaining) or 12 weeks (N = 25 remaining), with the same assessments performed. RESULTS: Patients who had previously shown behavioral improvement with carbamazepine therapy reverted to their baseline state after washout, whereas there was no change in the patients previously treated with placebo. There were no other significant effects of washout. During subsequent therapy with carbamazepine at a modal dose of 300 mg/day, there were 2 deaths and 4 other adverse events resulting in dropout. Neither of the deaths, and only 1 serious adverse experience, was judged to be related to carbamazepine. There were a variety of nonserious adverse experiences during the trial. Behavior ratings showed ongoing improvement in agitation and aggression, as well as in other aspects of psychopathology. CONCLUSION: The washout data provided independent confirmation of efficacy found in the prior placebo-controlled phase of this trial. Ongoing treatment was not associated with unexpected toxicity and was associated with improvement in measures of agitation and aggression that appeared to continue for up to 12 weeks. These findings confirm and extend results from earlier placebo-controlled studies.
RCT Entities:
BACKGROUND: The aim of this study was to assess the effects of withdrawal from placebo and carbamazepine administered for agitation associated with dementia and to assess safety, tolerability, and efficacy of subsequent ongoing carbamazepine therapy. METHOD: We previously reported the results of a 6-week, randomized, parallel-group study of placebo versus carbamazepine in 51 nursing home patients with dementia who were agitated; 47 subjects completed that study. This report first presents the results of withdrawal from that experimental treatment assessed by (blinded) observations 3 weeks later (N = 45 remaining). The primary outcome measure was the Brief Psychiatric Rating Scale. Secondary outcome measures addressed other aspects of behavior, cognition, function, safety, and tolerability. Patients were then treated with carbamazepine for an additional 6 weeks (N = 32 remaining) or 12 weeks (N = 25 remaining), with the same assessments performed. RESULTS:Patients who had previously shown behavioral improvement with carbamazepine therapy reverted to their baseline state after washout, whereas there was no change in the patients previously treated with placebo. There were no other significant effects of washout. During subsequent therapy with carbamazepine at a modal dose of 300 mg/day, there were 2 deaths and 4 other adverse events resulting in dropout. Neither of the deaths, and only 1 serious adverse experience, was judged to be related to carbamazepine. There were a variety of nonserious adverse experiences during the trial. Behavior ratings showed ongoing improvement in agitation and aggression, as well as in other aspects of psychopathology. CONCLUSION: The washout data provided independent confirmation of efficacy found in the prior placebo-controlled phase of this trial. Ongoing treatment was not associated with unexpected toxicity and was associated with improvement in measures of agitation and aggression that appeared to continue for up to 12 weeks. These findings confirm and extend results from earlier placebo-controlled studies.
Authors: Amy T Page; Rhonda M Clifford; Kathleen Potter; Darren Schwartz; Christopher D Etherton-Beer Journal: Br J Clin Pharmacol Date: 2016-06-13 Impact factor: 4.335