Food refusal occurs in a significant number of patients with dementia of the Alzheimer type (DAT). Some patients do not respond to antidepressant therapy and are at risk of malnutrition. Since dronabinol has been found to be effective in treatment of anorexia in AIDS, we investigated its effect in DAT. A placebo controlled crossover design, with each treatment period lasting six weeks, was used to investigate the effects of dronabinol on food refusal and disruptive behavior. Fifteen patients with a diagnosis of probable DAT who were refusing food, but not choking on food or liquids, were enrolled in the study. Eleven patients completed both study periods; one patient who died of a heart attack two weeks before the end of the study was also included in the analysis. The study was terminated in three patients; one developed a grand mal seizure after the first dronabinol dose and two developed serious intercurrent infections. Most subjects had severe dementia (mean Mini-mental State Examination score of 4) and were completely dependent in activities of daily living (mean Katz ADL score of 5.7). Body weights of study subjects increased during both dronabinol and placebo periods but the increase was significantly greater during the dronabinol treatment that during the placebo periods. Caloric intake and skin fold thickness were not affected by dronabinol treatment. Dronabinol treatment decreased the severity of disturbed behavior and this effect persisted during the placebo period in patients who received dronabinol first and placebo second. Dronabinol also significantly decreased negative affect, while positive affect remained unchanged. Side-effects, which were more common during the dronabinol treatment than during placebo periods, included euphoria, somnolence and tiredness. None of these side-effects required discontinuation of therapy. These results indicate that dronabinol may be useful not only for treatment of anorexia but also to improve disturbed behavior and negative mood in patients with DAT.
A placebo-controlled crossover design, with each treatment period lasting 6 weeks, was used to investigate effects of dronabinol in 15 patients with a diagnosis of probable Alzhemer's disease who were refusing food. Eleven patients completed both study periods; one patient who died of a heart attack 2 weeks before the end of the study was also included in the analysis. The study was terminated in 3 patients: one developed a grand mal seizure and 2 developed serious intercurrent infections. Body weight of study subjects increased more during the dronabinol treatment than during the placebo periods. Dronabinol treatment decreased severity of disturbed behavior and this effect persisted during the placebo period in patients who received dronabinol first. Adverse reactions observed more commonly during the dronabinol treatment than during placebo periods included euphoria, somnolence and tiredness, but did not require discontinuation of therapy. These results indicate that dronabinol is a promising novel therapeutic agent which may be useful not only for treatment of anorexia but also to improve disturbed behavior in patients with Alzheimer's disease.
Food refusal occurs in a significant number of patients with dementia of the Alzheimer type (DAT). Some patients do not respond to antidepressant therapy and are at risk of malnutrition. Since dronabinol has been found to be effective in treatment of anorexia in AIDS, we investigated its effect in DAT. A placebo controlled crossover design, with each treatment period lasting six weeks, was used to investigate the effects of dronabinol on food refusal and disruptive behavior. Fifteen patients with a diagnosis of probable DAT who were refusing food, but not choking on food or liquids, were enrolled in the study. Eleven patients completed both study periods; one patient who died of a heart attack two weeks before the end of the study was also included in the analysis. The study was terminated in three patients; one developed a grand mal seizure after the first dronabinol dose and two developed serious intercurrent infections. Most subjects had severe dementia (mean Mini-mental State Examination score of 4) and were completely dependent in activities of daily living (mean Katz ADL score of 5.7). Body weights of study subjects increased during both dronabinol and placebo periods but the increase was significantly greater during the dronabinol treatment that during the placebo periods. Caloric intake and skin fold thickness were not affected by dronabinol treatment. Dronabinol treatment decreased the severity of disturbed behavior and this effect persisted during the placebo period in patients who received dronabinol first and placebo second. Dronabinol also significantly decreased negative affect, while positive affect remained unchanged. Side-effects, which were more common during the dronabinol treatment than during placebo periods, included euphoria, somnolence and tiredness. None of these side-effects required discontinuation of therapy. These results indicate that dronabinol may be useful not only for treatment of anorexia but also to improve disturbed behavior and negative mood in patients with DAT.
