This important study, co-authored by Dilip Jeste the current president of the American Psychiatric Association, is worth reviewing in greater detail.
The study was modeled to capture clinical practice. Entry to the study was broad and not limited to a specific diagnostic category. It is characterized as a study of “older adults” and I admit to some chagrin that this meant anyone over 40. Diagnoses included schizophrenia, schizoaffective disorder, and psychosis associated with mood disorder, PTSD or dementia. It was open to individuals who were either already taking an atypical neuroleptic or had a psychiatrist who was recommending this.
Individuals were admitted to the study if they were willing to be randomized to at least 2 of the drugs studied: olanzapine, risperidone, aripiprazole, or quetiapine. So a person who was only willing to take, for example, olanzapine and aripirazole, for example could be included but a person who was only willing to take risperidone could not. These four drugs were selected because they are the most commonly prescribed atypical neuroleptics. Subjects were then assigned to one of the drugs using a technique called equipoise-stratified randomization. Each subject had a list of acceptable drugs and was then randomized to one of the drugs along with all others who had an identical list.
Assessment was single blinded; subjects and their treating physicians knew which drug they were taking but the raters did not. Ratings were done at baseline and periodically over 2 years. They were assessed on a variety of measures including time to discontinuation of initial drug, Brief Psychiatric Rating Scale (BPRS) and its psychosis subscale, drug side effects, and metabolic parameters. A total of 332 individuals consented to the study and completed at least a baseline visit.
The primary outcome – similar to what was used in the CATIE study – was time to discontinuation of the first drug used. The percentage of patients who stopped the first drug used ranged from 78.6% for quetiapine to 81.5% for aripirazole. The average time until discontinuation was 26 weeks. Most people who stopped the first drug were started on another one so early discontinuation does not appear to be secondary to remission of symptoms. Reasons stated for discontinuation included side effects (51.6%) and lack of effectiveness (26.9%).
What was most striking to me is this line from the study: there was
“no significant change in psychopathology with any of the study atypical antipsychotics“
They did not even report the numbers in their report.
Also of note, they discontinued the use of quetiapine after 3.5 years due to a high incidence of adverse side effects.
The one year incidence of metabolic syndrome was 36.5%.
The authors discussion is so compelling, rather than paraphrasing, I will just quote directly:
“the results of our study are sobering.”
“there was no significant improvement in BPRS total or psychosis subscale scores over a 6 month period.”
“the overall risk-benefit ratio for the atypical antipsychotics in patients over age 40 was not favorable, irrespective of diagnosis and drug.”
And finally,
“Shared decision making, involving detailed discussions with the patients and their family members or legal guardians about the risks and benefits of atypical antipsychotics and possible treatment alternatives, as well as of no pharmacologic treatment is warranted.” (bolding mine).
We often discuss the serious side effects of these drugs in the context of their presumptive benefit. To reiterate, unless I missed something, in this study they did not find any benefit.
I want to give a nod to 1boringoldman for also alerting me to this study. His comments on this and many other topics are worth reading.
I wrote previously about another large a study that suggested that these drugs have relatively weak effects. I am curious to see what the impact of these studies is on accepted practice within psychiatry. Yesterday, the APA Board of trustees voted to approve the new DSM-5. This will undoubtedly gain significant attention within and outside of our field. The time and expense that will be devoted to the role out of this edition is enormous. From my vantage point, it seems more important to put our energies into a serious consideration of the impacts and efficacy of the treatments we so readily prescribe than to a diagnostic manual that has so many problems.