Yet Another Poor Showing for Atypical Antipsychotics

The New England Journal of Medicine published another study from the CATIE group, this time testing second generation (aka SGA or “atypical”) antipsychotic medications on patients with Alzheimer’s Disease.

Let’s start off by quoting the authors’ conclusion from the abstract: “Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer’s disease.”

Olanzapine (Zyprexa), risperidone (Risperdal), and quetiapine (Seroquel) showed no significant advantage as a group (combining the three medications into one group) over placebo in efficacy on the primary outcome measure, the Clinical Global Impressions Improvement Scale. 32% of patients on olanzapine were rated as having at least minimal improvement compared to 26% for quetiapine, 29% for risperidone, and 21% for placebo. When comparing olanzapine to placebo, the difference is statistically significant (barely, with p = .05). The authors did not report effect size differences, but across the CGI-I, Neuropsychiatric Inventory, and Brief Psychiatric Rating Scale, they appear to all be in about the .25-ish range (according to my mental calculations based on reported means and standard deviations), suggesting very modest improvement for drug versus placebo.

Another important measure was discontinuation of treatment. Overall, there was not a significant difference between placebo and medication on how frequently treatment was discontinued by clinicians.

How about safety? Over 12 weeks, 11% of both the olanzapine and risperidone groups gained over 7% of their body weight, compared to 3% of placebo patients. All medications resulted in significantly greater increase in body mass index compared to placebo. Both olanzapine and risperidone were significantly more likely to cause extrapyramidal symptoms compared to placebo. Remember that one reason SGAs were supposedly superior to older antipsychotic meds was because SGAs would cause extrapyramidal symptoms at a very low rate. Hmmm...

Thank you NIMH for funding this study! The bad news continues to flow about second generation antipsychotics. Link to the study abstract here. Feel free to read more about atypical antipsychotics here, here, here, and here.