Older Antipsychotics Trump Newer Agents for Schizophrenia

Newer Not Necessarily Better, Researchers Say

Fran Lowry

June 16, 2011

June 16, 2011 (Boca Raton, Florida) — In a large population-based cohort study, conventional depot antipsychotics turned out to be superior to risperidone long-acting injection, Danish researchers reported here at the New Clinical Drug Evaluation Unit (NCDEU) 51st Annual Meeting, sponsored by the American Society of Clinical Psychopharmacology.

"Newer does not necessarily mean better," Jimmi Nielsen, MD, PhD, from Aalborg Psychiatric Hospital, Aalborg, Denmark, told Medscape Medical News.

"People tend to think that new equals improved, but as we found, the conventional depot antipsychotic formulation was more effective and it also was much cheaper."

Risperidone long-acting injection (RLAI), the first atypical depot antipsychotic, is widely used in Europe and the United States, and its superiority to placebo and oral antipsychotics has been shown in several randomized controlled trials, Dr. Nielsen said.

"Only a few studies have compared RLAI with the conventional depot formulation, so we decided to look at this issue in a large population using our Danish nationwide registers," he said.

Further Investigation Warranted

Dr. Nielsen and his team looked at data from 1996 to 2007. In all, there were 8310 patients (mean age, 42 years; 57% male) with an International Classification of Diseases, 10th revision, diagnosis for schizophrenia who were followed for 41,637 patient-years. Of these, 2712 were receiving RLAI, and 6523 were receiving conventional depot antipsychotics.

The investigators assessed the effectiveness of the 2 formulations in terms of time to all-cause discontinuation, along with bed-days and number of admissions for patients switched from conventional depot to RLAI.

The study found that RLAI treatment was associated with a shorter mean time to all-cause discontinuation.

After adjustment for age, sex, time, percentage of prior psychiatric hospitalizations, long-term institutionalization, dosage of concomitant oral antipsychotic medication, and frequency of outpatient contacts, patients receiving RLAI stopped their treatment at a mean of 433 ± 617 days, whereas those receiving conventional depot antipsychotics stopped their treatment at a mean of 792 ± 915 days (hazard ratio, 1.34; 95% confidence interval [CI], 1.27 - 1.42; P < .001).

In the 969 patients who were switched from conventional depot antipsychotics to RLAI, there was a significant increase in the number of admissions, which went from a mean of 3.3 before the switch (95% CI, 3.0 - 3.6) to 4.0 after the switch (95% CI, 3.5 - 4.5; P < .003).

Additionally, the number of bed-days increased in patients who were switched. Before the switch, the mean number of bed-days was 147.2 (95% CI, 128.0 - 166.4); after, the mean number of bed-days was 180.0 (95% CI, 154.3 - 205.7; P < .02).

"We think these findings warrant further investigation, especially in light of the fact that RLAI is more costly than conventional depot antipsychotics," Dr. Nielsen said.

Better Adherence

Daniel Safer, MD, from Johns Hopkins Medical Institutions, Baltimore, Maryland, told Medscape Medical News that he was struck by the large number of patients in the study.

"This is a very fine study, and I'm very impressed with the number of patients. It really shows that the first generation of antipsychotics are similar, if not superior, in effectiveness to the second generation," he said.

"Some of these drugs last a long time, longer than what the company claims," Dr. Safer added.

"One of the old ones, called fluphenazine or Prolexa, lasts up to 6 weeks but the company recommends giving it every 2 weeks. But I have patients that I see about once a month, and give them a shot of Prolexa and it's fine. I think that's important because the adherence is better for chronic schizophrenics."

Dr. Nielsen reports financial relationships with Astra Zeneca, BMS, Chempaq, Eli Lilly, Janssen Cilag, Lundbeck, and Pfizer. Dr. Safer has disclosed no relevant financial relationships.

New Clinical Drug Evaluation Unit (NCDEU) 51st Annual Meeting, sponsored by the American Society of Clinical Psychopharmacology. Abstract # 64. Presented June 15, 2011.

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