Denbufylline in dementia: A double-blind controlled study

The xanthine derivative denbufylline has been evaluated in the treatment of cognitive dysfunction in 110 patients with vascular or mixed dementia (VD) and 226 patients with dementia of the Alzheimer type (DAT). After a run-in period of 4 weeks, during which all patients received placebo, the patients were randomly allocated to denbufylline 25, 50 or 100 mg or to placebo given twice daily for 16 weeks. By the end of the study (completed by 68% of the patients), but also at enrollment, the scores obtained on the Mini-Mental State Examination (MMSE) were higher among those who had received denbufylline than among those who had received placebo, but the differences were not statistically significant; a dose effect of denbufylline was not observed and there was no significant difference in the mean scores of the digit substitution subtest (DSST) of the Wechsler memory test. The responses of patients with VD were similar to those of patients with DAT. When patients were compared in terms of those who received denbufylline versus those who received placebo, improvement in the MMSE scores was observed in 46% of the patients who received placebo and 67% among those who received denbufylline (p < 0.05). An inverse relationship was found between the improvement that occurred during the run-in period and that observed by the end of the study, had the patients received denbufylline or placebo. No major adverse event was ascribed to denbufylline. In conclusion, denbufylline was not deemed efficacious in the treatment of DAT or VD, although patients who received denbufylline tended to improve in terms of cognitive scores, but the effects were not statistically significant. MMSE scores were found to be higher among patients who received denbufylline when these latter were combined as a single group, regardless of their diagnosis or dosage regimen. A placebo effect was observed in about half the patients who completed the study.