Antipsychotic Switch Rates Suggest 'Suboptimal' FEP Prescribing

High rates of antipsychotic switching in first episode psychosis (FEP) suggests first-line prescribing is less than optimal and does not follow recent clinical guidance.

In a large-scale, real-world analysis of UK prescribing patterns, researchers found more than two thirds of patients who received antipsychotics for FEP switched medication and almost half switched drugs three times.

Although this is "one of the largest real-world studies examining antipsychotic treatment strategies," it reflects findings from previous, smaller studies showing "antipsychotic switching in first episode psychosis is high," said study investigator Aimee Brinn, Institute of Psychiatry, Psychology & Neuroscience at King's College London in London, England.

This may reflect reports of poor efficacy and suggests that first-line prescribing is "suboptimal," Brinn noted. In addition, olanzapine remains the most popular antipsychotic for prescribing despite recent guidelines indicating it is "not ideal...due to its dangerous metabolic side effects," she added.

The findings were presented at the Congress of the Schizophrenia International Research Society (SIRS) 2022.

Real-World Data

The response to, and tolerability of, antipsychotics differs between patients with FEP; and prescribing patterns "reflect clinician and patient-led decision-making," Brinn told meeting attendees.

Since randomized controlled trials "do not necessarily reflect prescribing practice in real-world clinical settings," the researchers gathered data from a large mental health care electronic health record dataset.

The investigators examined records from the South London and Maudsley NHS Foundation Trust (SLaM), which has a catchment area of 1.2 million individuals across four boroughs of London. The group sees approximately 37,500 active patients per week.

The team used the Clinical Interactive Record Search tool to extract data on 2309 adults with FEP who received care from a SLaM early intervention in psychosis service between April 1, 2008, and March 31, 2019.

They found that 12 different antipsychotics were prescribed as first-line treatment. The most common were olanzapine (43.9%), risperidone (24.7%), and aripiprazole (19.9%).

Results showed that over 81,969.5 person-years of follow-up, at a minimum of 24 months per patient, 68.8% had an antipsychotic switch. The most common first treatment switch, in 17.9% of patients, was from olanzapine to aripiprazole.

Of patients who switched to aripiprazole, 48.4% stayed on the drug, 26% switched back to olanzapine, and 25.6% received other treatment. Overall, 44.7% of patients switched medication at least three times.

Among patients with FEP who did not switch, 42.2% were prescribed olanzapine, 26.2% risperidone, 23.3% aripiprazole, 5.6% quetiapine, and 2.7% amisulpride.

During the post-presentation discussion, Brinn was asked whether the high rate of first-line olanzapine prescribing could be because patients started treatment as inpatients, and were then switched once they were moved to community care.

"We found that a lot of patients would be prescribed olanzapine for around 7 days at the start of their prescription and then switch," Brinn said, adding it is "likely" they started as inpatients. The investigators are currently examining the differences between inpatient and outpatient prescriptions to verify whether this is indeed the case, she added.

"Pulling Out the Big Guns Too Fast?"

Commenting on the findings for Medscape Medical News, Thomas W. Sedlak, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, Maryland, said the study raises a "number of questions."

Both olanzapine and risperidone "tend to have higher treatment effect improvements than aripiprazole, so it's curious that a switch to aripiprazole was common," said Sedlak, who was not involved with the research.

"Are we pulling out the 'big guns' too fast or inappropriately, especially as olanzapine and risperidone carry greater risk of weight gain?" he asked. In addition, "now that olanzapine is available with samidorphan to mitigate weight gain, will that shape future patterns, if it can be paid for?"

Sedlak noted it was unclear why olanzapine was chosen so often as first-line treatment in the study and agreed it is "possible that hospitalized patients had been prescribed a 'stronger' medication like olanzapine compared to never-hospitalized patients."

He also underlined that it is "not clear if patients in this FEP program are representative of all FEP patients."

"For instance, if the program is well known to inpatient hospital social workers, then the program might be disproportionately filled with patients who have had more severe symptoms," Sedlak said.

The study was supported by Janssen-Cilag. The investigators and Sedlak have disclosed no relevant financial relationships.

Congress of the Schizophrenia International Research Society (SIRS) 2022: Abstract T168. Presented April 7, 2022.

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