KENSINGTON, MD — Ensuring high rates of medication adherence is one of the greatest challenges in treating schizophrenia patients at the VA and elsewhere.

A recent study in the American Journal of Psychiatry pointed out that relatively small randomized clinical trials are used to gauge the effectiveness of anti-psychotic drugs in patients who are both carefully selected and closely monitored. That is a very different situation from patients treated in daily clinical practice, according to the international authors, who question how generalizable evidence is to that situation.1

As a result, the authors sought to compare the clinical effectiveness between all oral and long-acting injectable (LAI) anti-psychotic medications used in the treatment of schizophrenia in the VHA.

The observational study used VA pharmacy data from 37,368 outpatient veterans with schizophrenia. Defined as outcome measures were all-cause anti-psychotic discontinuation and psychiatric hospitalizations, with oral olanzapine used as the reference group.

The multivariable analysis determined that reduced hazard of discontinuation compared to oral olanzapine was found with the following:

  • clozapine (hazard ratio=0.43),
  • aripiprazole long-acting injectable (LAI) (hazard ratio=0.71),
  • paliperidone LAI (hazard ratio=0.76),
  • antipsychotic polypharmacy (hazard ratio=0.77), and
  • risperidone LAI (hazard ratio=0.91).

On the other hand, oral first-generation antipsychotics (hazard ratio=1.16), oral risperidone (hazard ratio=1.15), oral aripiprazole (hazard ratio=1.14), oral ziprasidone (hazard ratio=1.13) and oral quetiapine (hazard ratio=1.11) were significantly associated with an increased risk of discontinuation compared with oral olanzapine.

While no treatment signaled reduced risk of psychiatric hospitalization compared with oral olanzapine, quetiapine was associated with a 36% worse outcome in terms of hospitalizations compared with the reference drug, the authors pointed out.

“In a national sample of veterans with schizophrenia, those treated with clozapine, two of the LAI second-generation antipsychotics, and antipsychotic polypharmacy continued the same antipsychotic therapy for a longer period of time compared with the reference drug,” the researchers explained. “This may reflect greater overall acceptability of these medications in clinical practice.”

Another study from the Cincinnati and Clarksburg, WV, VAMCs also discussed benefits of longer-acting injection formulations of schizophrenia medications.

In a presentation at the CPNP annual meeting, researchers advised that, in March 2020, VAMCs nationwide began canceling nonessential in-person appointments to reduce the spread of COVID-19. 2

“While long-acting injectables are a standard of care for improved adherence in patients with psychiatric disorders, administration requires in-person contact with a healthcare professional,” the authors noted. “Experts have suggested converting stable patients to longer-acting injection formulations to reduce potential exposure to COVID-19. Some published data supports the safety and effectiveness of converting to longer-acting injections, but rigid inclusion and exclusion requirements in those studies limit applicability to real-world situations.”

The authors described how, to reduce clinic exposures during the pandemic, pharmacists evaluated patient eligibility to switch to longer-acting injections based on Food and Drug Administration-approved labeling and made recommendations to patients’ providers.

Options under consideration included paliperidone palmitate monthly injection (PPMI) to paliperidone palmitate three-month injection (PP3MI group) and risperidone every two weeks to PPMI (PPMI group). In a novel proactive role, the pharmacist performed patient medical record reviews to identify appropriate candidates, provided drug information including appropriate dose conversions and coordinated care between nursing and mental health providers, according to the report.

Ultimately, of 102 patients evaluated, 41 were converted to longer-acting injections. Results indicated that clinic visits for injections during a 40-week period decreased from projected average of six (PP3MI group) and 13 (PPMI group) to actual average of two and six, respectively.

In fact, total clinic visits were reduced by 78% in the PP3MI group and 60% in the PPMI group, a total reduction from 420 projected visits to 101 actual visits, the authors noted. Of the six patients who had a psychiatric decompensation after transition, active substance use was found to have contributed in four of the cases. In terms of changes in average weight (-1.27 kg) and hemoglobin A1c (+0.07%)—both safety measures—more patients had weight loss than weight gain (19 vs. 6). None of the patient had documented positive tests for COVID-19 post-conversion.

“Converting patients to longer-acting injections reduced the number of clinic visits, which reduced potential exposure to COVID-19,” the researchers concluded. “There were no significant adverse safety outcomes, with very few psychiatric decompensations directly attributable to the conversion. This proactive approach to patient care represents a new practice strategy for the psychiatric pharmacy specialty.”

 

  1. Weiser M, Davis JM, Brown CH, Slade EP, Fang LJ, Medoff DR, Buchanan RW, Levi L, Davidson M, Kreyenbuhl J. Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs. Am J Psychiatry. 2021 Jul 14:appiajp202020111657. doi: 10.1176/appi.ajp.2020.20111657. Epub ahead of print. PMID: 34256606.
  2. Mellado P-Q, Brown M, Newbold M. Quality of Patient Care by Converting to Injectable Antipsychotics With Longer Duration of Actions During COVID-19 Pandemic. Presented at the 2021 CPNP Annual Meeting, April 19-23, 2021. Virtual.