Lowering antipsychotic dose can improve symptoms in schizophrenia
By Lorraine L. Janeczko
NEW YORK (Reuters Health) - Reducing the dose of risperidone and olanzapine can improve cognitive function and negative symptoms in patients with stable schizophrenia, new research from China suggests.
"The dosage for the schizophrenia maintenance stage is still controversial, and there are different recommendations in different treatment guidelines. In clinical work, many clinicians have not known the best dose for patients during the maintenance treatment period. So it was important for us to do this study to examine which dose is better," said Dr. Yuping Ning of Guangzhou Medical University.
"These results may help patients with stable schizophrenia improve negative symptom and cognitive function through a simple and effective means: careful dose reduction of antipsychotics," she told Reuters Health by email
Dr. Ning and her colleagues randomly assigned 75 adult patients with schizophrenia who were stable on risperidone (4 mg or more per day) or olanzapine (10 mg or more per day) to receive half their dose of antipsychotic or to continue as before.
After a year, the patients in the dose-reduction group had fewer negative symptoms and better cognitive performance without experiencing an increased risk of relapse, the researchers report in the Journal of Psychopharmacology, online March 1.
The dose-reduction group improved significantly more than the maintenance group in Positive and Negative Syndrome Scale negative subscale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, working memory and total score of MATRICS Consensus Cognitive Battery.
"This study is supportive of the majority of findings in the literature," said Dr. Russell L. Margolis, a professor of psychiatry and behavioral sciences at Johns Hopkins Medicine in Baltimore.
"The results provide additional evidence that, on average, high doses of antipsychotics may be unnecessary and even detrimental, and they provide further encouragement to keep doses of antipsychotics less than maximal," he told Reuters Health by email.
"There is a strong tendency in hospitalized patients, at least in the United States, for the rapid escalation of antipsychotic doses to relatively high levels. This is driven in part by the pressure to reduce hospital length of stay, as clinicians fear under-dosing will delay discharge," Dr. Margolis added.
"When faced daily, or even hourly, with an acutely ill patient, clinicians understandably feel motivated to act, by increasing drug dose, when in fact simply allowing more time for a lower dose to have an effect may be equally effective in most patients,” he said. “Once the patient is in outpatient care and reasonably stable, outpatient clinicians are reluctant to reduce doses for fear of precipitating a relapse."
Dr. Juan Gallego, an assistant professor of psychiatry at Weill Cornell Medical College in New York City, told Reuters Health by phone, "It was important to do this study because even though we may have an understanding that high doses of antipsychotics worsen negative symptoms and side effects, in reality, we rarely try to decrease the dose at this level to see if the patient will benefit from this. It's good to have a proper study doing this with these two antipsychotics over a long period of time."
"Do not be afraid to try to reduce the dose on your patients, specifically in the context of patients having side effects and negative symptoms," he advised.
Dr. Donald Goff, a professor of psychiatry at NYU Langone Health in New York City, said, "A strength of the study is that the dose-reduction was randomized, which makes this finding more compelling than the results of some naturalistic studies. However, because the raters and subjects were aware of whether or not the dose was reduced, expectations may have influenced ratings of negative symptoms and performance on cognitive tests and hence biased the results."
"While clinicians can conclude that the lowest effective dose of an antipsychotic drug should be used, the process of identifying the lowest effective dose must be done very carefully because too low a dose can result in relapse," he told Reuters Health by email.
Dr. Ning said her team is planning further related research.
"We'll prolong the observation time on the current study. We’ll focus on cognitive function and symptomatology after dose reduction of second-generation antipsychotics in first-onset schizophrenic patients," she said.
SOURCE: https://bit.ly/2DVwAey
J Psychoparmacol 2018.
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