Deborah Brauser

May 25, 2011

May 25, 2011 (Honolulu, Hawaii) — Switching from the atypical antipsychotics olanzapine, quetiapine, or risperidone to the atypical antipsychotic aripiprazole may reduce metabolic risk in patients with schizophrenia, new research suggests.

In findings from the Comparison of Antipsychotics for Metabolic Problems (CAMP) study, presented here at the American Psychiatric Association (APA) 2011 Annual Meeting, more than 200 schizophrenic patients who were already taking olanzapine, quetiapine, or risperidone were randomly assigned to continue receiving their current medication or switch to aripiprazole.

Results showed that switching led to improvements in several metabolic measures, including larger reductions in weight gain, non-high-density lipoprotein (HDL) cholesterol, and serum triglycerides.

However, although rates of efficacy failure were similar between the switchers and nonswitchers, aripiprazole was associated with a higher rate of stopping the assigned treatment, report the investigators.

"The primary result showed that switching to aripiprazole was effective, especially in lowering the non-HDL cholesterol, albeit modestly. That was a significant finding," Scott Stroup, MD, MPH, director of the Program for Intervention Effectiveness Research at Columbia University Medical Center in New York City, told Medscape Medical News.

Dr. Scott Stroup

"I would tell clinicians that for some patients, perhaps many patients, switching medication is an effective strategy. But it's important to monitor them carefully. For those who can't switch successfully, it's okay to put them back on their previous medication and then look for other strategies, such as behavioral interventions," said Dr. Stroup.

Unique Mechanism

Unlike the other study medications, which are D2 receptor antagonists, aripiprazole is a D2 partial agonist. Its additional role as a partial agonist of the 5-HT2C receptor may lead to less weight gain compared with other atypical antipsychotics.

"The commonly used antipsychotic medications are associated with metabolic problems that are risk factors for cardiovascular disease [CVD]. And we know that people with schizophrenia are dying prematurely from CVD. So we wanted to try and find solutions to that problem," Dr. Stroup said.

The investigators enrolled 215 patients with schizophrenia or schizoaffective disorder (mean body mass index, 27; mean non-HDL cholesterol level, 130 mg/dL). The participants were then randomly assigned to continue taking their regular dosage of olanzapine, quetiapine, or risperidone (n = 106) for 24 weeks or to change over to aripiprazole (n = 109).

However, only 89 of the switchers and 98 of the nonswitchers were included in this analysis.

Another Effective Strategy

Results showed significantly decreased mean non-HDL cholesterol levels for the switchers compared with the nonswitchers (change, -20.2 mg/dL vs -10.8 mg/dL; P = .01).

The switching group also had larger reductions in weight (difference, 2.9 kg) and serum triglyceride levels (difference, 32.7 mg/dL) compared with the nonswitchers.

Efficacy failure rates did not significantly differ between the 2 groups (20.6% for the switchers vs 17% for the nonswitchers).

"We were concerned with balancing clinical stability with switching medicines to get these metabolic benefits. That's why we wanted to look at efficacy failure, which meant significant worsening of clinical status or substantial increases in symptoms or psychiatric hospitalization," explained Dr. Stroup.

"We weren't surprised with what we found for this as the study took place in close clinical monitoring. And we would intervene before someone would get very seriously ill."

However, "47.7% of the switchers and 27.4% of the stayers stopped the protocol-specified treatment before 24 weeks," write the investigators.

Dr. Stroup noted that this finding is consistent with those of other studies.

He also pointed out that the CAMP study took place during a behavioral intervention that focused on getting people to diet and exercise.

"So even those who didn't switch had some improvement. So there's some evidence that that's a useful approach as well."

Dr. Stroup reported that his team of investigators has also been doing research on metformin, "which can reduce weight," and statins for treating cholesterol problems.

"Switching to some other antipsychotics may also work, though we haven't tested that yet. There are a variety of strategies we need to be doing to help our patients. And I'd say that this study is an independent verification that switching is just another strategy that can work," he said.

Evidence-Based Alternative

"I thought this was an interesting and important contribution," session moderator Peter M. Thompson, MD, associate professor and director of the Southwest Brain Bank in the Division of Mood and Anxiety Disorders, Department of Psychiatry, at the University of Texas Health Science Center in San Antonio, told Medscape Medical News.

"The treatment of any of the severe mental illnesses that use neuroleptics involves a tremendous amount of medication and a lack of effectiveness, which is defined as treatment efficacy and stopping due to side effects," said Dr. Thompson, was not involved in this study.

He noted that in the National Institute of Mental Health–sponsored Clinical Antipsychotic Trials of Intervention Effectiveness study (N Engl J Med. 2005;353:1209-23), 74% of the patients discontinued use of their medication by 18 months of treatment because of intolerance.

"It didn't matter what you put them on, they stopped. And so you have to have choices for when the first medication doesn't work," said Dr. Thompson.

In addition, "We're becoming all too familiar with the consequences of the metabolic side effects of our medications. Clearly in the last 10 years, we've recognized that making people obese, which leads to diabetes, hyperlipidemia, and cardiovascular consequences, is a bad thing," he said.

"Now, keep in mind that not everyone gets obese. Only about 7% of people on olanzapine will gain more than 5 or 10 pounds. But for those affected, that has to be balanced with the benefit that they get."

Dr. Thompson pointed out that this study's data were "very concerning" regarding the discontinuation rates for the switchers.

"It shows that although aripiprazole is a good medication for a lot of people, for a lot of people it is not — either because it didn't work or they couldn't tolerate its side effects, which are usually parkinsonism and extrapyramidal side effects.

"Still, because of the metabolic side effects, having an evidence-based alternative to treatments that we know cause obesity is important. And this would be 1 such strategy," he concluded.

The study was jointly funded by the National Institute of Mental Health (NIMH) and by the Foundation for the National Institutes of Health. Dr. Stroup has disclosed no relevant financial relationships. Dr. Thompson reported having received research funding in the past from Cyberonics, Pfizer, GlaxoSmithKline, and the NIMH.

American Psychiatric Association (APA) 2011 Annual Meeting: Scientific and Clinical Report Session 22, No. 3. Presented May 16, 2011.