And, when all else fails, consider a long-acting injectable

SAN DIEGO — Sorting through the myriad number of antipsychotic medications in the schizophrenia armamentarium is a daunting prospect for any clinician, but two readily available tools can help: number needed to treat, and number needed to harm. 

That advice was the primary take-home message from Leslie Citrome, MD, MPH, clinical professor of psychiatry and behavioral science at New York Medical College in Valhalla, New York, and Christoph Correll, MD, professor of psychiatry and molecular medicine at Hofstra Northwell School of Medicine in Hempstead, New York, who co-chaired a session at Psych Congress 2019.

Citrome explained that both tools are especially useful for clinicians treating patients with schizophrenia because there are so few head-t0-head studies of antipsychotic agents, but there are a wealth of studies comparing antipsychotic agents to placebo. One can extrapolate data from meta-analyses of those studies in order to calculate both the number needed to treat and number needed to harm. 

“In the case of number needed to treat, or NNT, we are seeking a low number — the lower the better,” he said. “An NNT of 2 would mean the drug offered a hugely important benefit, an NNT of less than 10 means the drug has potential benefit. When considering NNH, an NNH of more than 10 is desirable.” 

For example, he noted that Aristada (aripiprazole lauroxil) has an NNH for weight gain of 20, for somnolence 21, and 25 for akathisia — meaning it would require treating 20 patients to have one patient gain 7% or more of baseline weight, treat 21 patients to have one experience somnolence, and 25 to have one experience movement disorders. 

By comparison, treating less than 10 patients with olanzapine or quetiapine immediate release will mean that one will gain more than 7% of baseline body weight. 

Correll said the necessary comparisons can be culled from the landmark meta-analysis comparing 32 oral antipsychotic medications by Huhn et al published in Lancet last July.  

But deciding on a specific medication is only one small part of the challenge posed by treating schizophrenia. Perhaps the greatest barrier to success is non-adherence. “Non-adherence should be at the top of your list if a patient does not appear to be responding or relapses,” Citrome said, noting that one study found that 25% of patients stopped taking medications within 14 days of hospital discharge, 50% stopped by 1 year, and 75% by 2 years. 

The reasons for non-adherence can be divided into four buckets:

  • Treatment related: side-effects or lack of efficacy.
  • Societal related: stigma attached to illness or stigma caused by treatment side effects (e.g., tardive dyskinesia).
  • Environment/relationship related: lack of family or social support.
  • Practical problems: financial/transportation issues.

Correll noted that transitioning a patient to a long-acting injectable (LAI) requires clinicians to engage in motivational interviewing, to engage the patient by showing him or her the advantages of LAI versus oral medications. 

He noted that a study that evaluated how clinicians introduced LAIs to patients found that during an initial discussion, clinicians spent only 9% of the conversation discussing the benefit of LAI therapy. Another study found that when clinicians were asked if they discussed LAIs with patients, all said they did, but when patients were asked if LAIs were mentioned to them, only 33% said their provider discussed LAIs. 

In an interview with BreakingMED, Citrome said he believed that the main barrier to LAI use was a lack of knowledge among clinicians. The key, he said, is to make the case for convenience — a case that has to be made to both clinicians and patients. 

One Psych Congress attendee, Bethlehem, Pennsylvania psychiatrist J. Andrew Burkins, MD, told BreakingMED that he agreed that LAIs address many non-adherence issues. Aristada has a good program for supporting the transition to LAI, which makes it very simple,” he said. 

Finally, Citrome noted that any medication decision must involve the patient. “People have been telling that patient what to do all the time,” he said. “You need to empower the patient to make the decision with you.” 

Written by Peggy Peck, Editor-in-Chief, BreakingMED, is a service of @Point of Care, LLC, which provides daily medical news reports curated to serve the unique needs of busy physicians and other healthcare professionals.