Withdrawal from controlled carbamazepine therapy followed by further carbamazepine treatment in patients with dementia

Background: The aim of this study was to assess the effects of withdrawal f rom placebo and carbamazepine administered for agitation associated with de mentia and to assess safety, tolerability, and efficacy of subsequent ongoi ng carbamazepine therapy. Method: We previously reported the results of a 6-week, randomized, paralle l-group study of placebo versus carbamazepine in 51 nursing home patients w ith dementia who were agitated; 47 subjects completed that study. This repo rt first presents the results of withdrawal from that experimental treatmen t assessed by (blinded) observations 3 weeks later (N = 45 remaining). The primary outcome measure was the Brief Psychiatric Rating Scale. Secondary o utcome measures addressed other aspects of behavior, cognition, function, s afety, and tolerability. Patients were then treated with carbamazepine for an additional 6 weeks (N = 32 remaining) or 12 weeks (N = 25 remaining), wi th the same assessments performed. Results: Patients who had previously shown behavioral improvement with carb amazepine therapy reverted to their baseline state after washout, whereas t here was no change in the patients previously treated with placebo. There w ere 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 oth er adverse events resulting in dropout. Neither of the deaths, and only 1 s erious adverse experience, was judged to be related to carbamazepine. There were a variety of nonserious adverse experiences during the trial. Behavio r ratings showed ongoing improvement in agitation and aggression, as well a s 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 treatmen t was not associated with unexpected toxicity and was associated with impro vement in measures of agitation and aggression that appeared to continue fo r up to 12 weeks. These findings confirm and extend results from earlier pl acebo-controlled studies.