Psych News Alert: Researchers Propose Olanzapine and Perphenazine as First-Line Schizophrenia Treatments

Along with aripiprazole and risperidone, olanzapine and perphenazine should be considered first-line antipsychotics for patients with schizophrenia, according to a clinical perspective published in Schizophrenia.

“Clinicians face challenges in balancing efficacy and side effects when prescribing antipsychotics to treatment-naive patients,” wrote Matej Markota, M.D., and colleagues at Mayo Clinic in Rochester, Minnesota. “Existing algorithms approach this issue by assigning high significance to a few side effects, such as weight gain and/or tardive dyskinesia, commonly leading to exclusion of agents such as olanzapine and first-generation antipsychotics (FGAs), respectively, as first-line treatments.”

In the article, Markota and colleagues suggested physicians should focus instead on three overlapping factors:

• Overall efficacy, particularly long-term efficacy since schizophrenia is a disorder requiring long-duration treatment.
• All-cause discontinuation as a surrogate for side-effect burden rather than weighing one or two side effects.
• Mortality risk, which factors in medication effectiveness, discontinuation rate, and long-term burden of reported side effects, such as the cardiovascular implications of excess weight gain.

When considering those factors, the researchers noted that clinical trials have shown olanzapine demonstrates superior efficacy as well as low discontinuation rates compared with risperidone or aripiprazole. Olanzapine does have a high risk of weight gain, but available data does not suggest it increases mortality relative to other medications. Given its demonstrated effects on hostility, the researchers believe olanzapine is a preferred first-line choice for patients for whom aggression may be a concern, with clozapine as a second-line medication.

Meanwhile, perphenazine has typically been overlooked due to the risks of extrapyramidal symptoms like tardive dyskinesia (TD) among first-generation antipsychotics. “However, there is considerable variability in TD risk within FGA and second-generation antipsychotic classes, a nuance frequently ignored by other algorithms,” Markota and colleagues wrote. “Perphenazine has one of the lowest known risks of TD among FGAs.” This medication also has a favorable metabolic and weight gain profile, they noted.

Markota and colleagues stressed that their medication rationale was for a “general” patient: “[W]hen idiographic factors of individuals dictate a different approach, the considerations discussed here should defer to individualized plans, and patients and practitioners should engage in shared decision-making at every step.”

For related information, see the Psychiatric News article “Clozapine Found Most Effective in Patients With Schizophrenia and Conduct Disorder.”

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