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Jury Still Out on Best Oral Antipsychotic for Multi-Episode Schizophrenia

July 23, 2019

By Will Boggs MD

NEW YORK—Most oral antipsychotics are effective for acute treatment of multi-episode schizophrenia in adults, but it's not clear which, if any, is best, according to a new network meta-analysis comparing 32 drugs.

"All antipsychotics have their individual advantages and disadvantages, and none is optimal," Dr. Maximilian Huhn of the School of Medicine, Technical University of Munich, in Germany, told Reuters Health by email. "This (study) shows, that the 'ideal' drug has not been found yet."

Many guidelines favor the newer antipsychotics over the older, less costly ones. But none have been compared in a comprehensive network meta-analysis, Dr. Huhn and colleagues note in The Lancet, online July 11.

The team used data from 402 studies that enrolled more than 53,000 participants to compare 17 first-generation antipsychotics and all 15 licensed second-generation antipsychotics in the acute treatment of adults with schizophrenia.

Overall, 26 (81%) of the 32 antipsychotics produced significant symptom improvement compared with placebo. Clozapine, amisulpride, zotepine, olanzapine and risperidone reduced overall symptoms significantly more than any other drugs.

In the 10 studies of eight antipsychotics with adequate quality-of-life data, five antipsychotics significantly improved quality of life.

Twenty (63%) oral antipsychotics significantly lowered discontinuation rates, compared with placebo. But 12 (46%) of 26 antipsychotics studied caused significantly more weight gain than placebo.

Two-thirds of antipsychotics were associated with significantly increased use of antiparkinsonian medication, nine were associated with significantly elevated prolactin levels, seven of 14 studied caused significantly more QTc prolongation, 18 were associated with significantly increased sedation, and nine were associated with significantly increased anticholinergic side effects, compared with placebo.

The researchers' confidence in the evidence for 75% of the comparisons with placebo was low or very low, and their confidence in the evidence for comparisons of two antipsychotic drugs was low or very low for 92%.

"Clinicians can see that many antipsychotic treatment options for the acute phase of schizophrenia are available, including older and newer antipsychotics," Dr. Huhn said. "They differ in their individual efficacy and side effect profile. We hope that doctors can use the efficacy and side effects panels presented in the publication to choose the best suited drug for the individual patient."

"When interpreting the data, one should consider that the overall quality is rather low," he said. "Especially the evidence for older antipsychotics is based on sparse data."

Dr. Joshua T. Kantrowitz of New York State Psychiatric Institute and Columbia University, in New York City, who studies schizophrenia treatment, told Reuters Health by email, "There is little difference between most antipsychotics in treating schizophrenia symptoms, but there are differences in side effects. Whenever possible, it is helpful to have a frank discussion with a patient before using a specific agent, and then choosing an antipsychotic that is most acceptable to that patient. For example, for some patients, weight gain is more palatable than Parkinson-like symptoms."

"For reasons that are not fully understood, serious side effects such as weight gain are less common with the less effective antipsychotics," he said. "Usually, the safer antipsychotics are worth trying first, as they do work well for many people."

The study did not have commercial funding. Dr. Huhn and a coauthor report financial ties to antipsychotic manufacturers.


Lancet 2019.

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