Lower-Dose Antipsychotics Benefit Patients with Schizophrenia in Long-Term Care

Nancy A. Melville

June 17, 2022

NEW ORLEANS — Patients with treatment-refractory schizophrenia in a long-term forensic facility showed significant stabilization following reduced doses of long-acting injectable antipsychotics, a study revealed.

Dr Mujeeb Shad

"There is an argument by some experts in the field that state hospital populations represent a different set of patients who require higher antipsychotic dosages, with no alternative, but I don't agree with that," study lead author Mujeeb U. Shad, MD, GME-psychiatry program director and adjunct professor at the University of Nevada, Las Vegas, said in an interview.

In reducing doses, "patients appeared to blossom, becoming more active and less 'zombie-like'; they started taking more interest in activities and their social [involvement] increased," he said.

The study was among several presenting pros and cons of high antipsychotic doses at the 2022 annual meeting of the American Psychiatric Association.

Higher doses of antipsychotics are often relied upon when patients with acute psychosis fail to respond to standard treatment, however evidence supporting the approach is lacking.

And while some studies in fact show no benefit from the higher-dose maintenance therapy over conventional or even lower doses of antipsychotics, evidence regarding forensic patients hospitalized in long-term psychiatric facilities is also scant.

Meanwhile, the need to restore competency among those patients can be more pressing than normal.

"In a forensic population where executive cognitive function is one of the key elements to restore competency to stand trial, the continuation of high-dose therapy with excessive dopamine blockade may further compromise preexisting executive dysfunction to delay competency restoration," Shad notes in the study.

The study describes a case series in which antipsychotic doses were lowered among 22 of Shad's patients who had been determined to be incompetent to stand trial and referred to a state hospital to restore their competency.

With the objective of regaining the mental fitness to stand trial and being discharged from the facility, those on high doses of therapy, defined as a dose greater than 50% of the average package-insert dose, had their doses reduced to conventional dosages.

The approach led to as many as 68% of the patients being stabilized and discharged after having their competency restored, without symptom relapse, following an average antipsychotic dose reduction of 44%.

The average time to discharge following the dose reduction was just 2.3 months, after an average total hospitalization time of 11 months.

The shortest hospitalization durations (less than 7 months) were observed among those who did not receive changes in doses as they were already achieving efficacy with standard dosages.

Among two patients who were treated subtherapeutically, dose increases were required and they had the longest overall hospitalization (14.5 months)

Additional Benefits of Reduced Dosages

Shad noted that, in addition to the earlier discharges, patients also had reductions in their polypharmacy, and in prolactin.

"We know that high prolactin level is such a huge problem, especially for female patients because it can cause osteoporosis, infertility, and abnormal menstruation, and the reductions in hyperprolactinemia can help reduce weight gain," he said.

Shad added that he let some of those effects be his guide in making dose reductions.

"I was trying to gradually minimize the dose while monitoring the patients for relapse, and I used extrapyramidal symptoms and prolactin levels as my guide, looking for a sweet spot with the dosing," he said.

"For example, if patients were taking an average of about 40-60 mg of a drug, I brought it down close to 20 mg, or close to the average package insert," Shad said.

Key concerns among clinicians about reducing antipsychotic doses include the emergence of discontinuation or rebound symptoms, including psychosis, akathisia, or Parkinsonian symptoms, and studies, including a recent meta-analysis have supported those concerns, urging caution in reducing doses below standard levels.

However, Shad said his series suggests that reducing doses gradually while carefully monitoring extrapyramidal symptoms and prolactin levels may indeed pay off.

"They're not the perfect guides, but they're good guides, and with the right approach, [some] may be able to do this," Shad said.

"However, the key to a successful dose reduction or discontinuation of an [antipsychotic medication] is to avoid abrupt discontinuation and follow a gradual dose reduction while monitoring symptoms and tolerability," he said.

Dr T. Scott Stroup

Commenting on the research, T. Scott Stroup, MD, a professor of psychiatry at Columbia University, New York, chimed in on the side of urging caution with higher doses and supporting possible benefits with the lower-dose approach.

"I agree that people who need antipsychotic medications should receive the lowest effective dose and that often this is identified by careful dose reduction," he said in an interview.

Shad and Stroup had no disclosures to report.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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