Injectable vs Oral Antipsychotics: Which Do Patients Prefer?

Liam Davenport

June 25, 2020

Patients with schizophrenia appear to prefer long-acting injectable (LAI) antipsychotics compared with oral versions of these medications primarily because injectables are more convenient and give individuals more control over their lives, new research shows.

Patients also prefer injections once every 3 months to monthly injections, citing the need for fewer doctor visits and less pain as key reasons. They also reported a preference for deltoid vs gluteal injections, as they were faster and easier to administer, and less embarrassing.

Study investigator Srihari Gopal, MD, senior director at Janssen Research and Development in Titusville, New Jersey, told Medscape Medical News that stigma, which is a "is a really powerful force in mental health treatment," underlies these findings in terms of the disease itself and its management.

"It's one of the [key] reasons that schizophrenia patients decide to abandon their drugs and not go to the doctor," he added.

The study was scheduled to be presented at the Congress of the Schizophrenia International Research Society (SIRS) 2020, but the meeting was canceled because of the coronavirus pandemic.

Outdated Perceptions

The investigators note there is limited information on patient preference with regard to LAI vs oral antipsychotics in the management of schizophrenia.

They also note that LAIs have been shown to reduce the risk of relapse and rehospitalization because of treatment discontinuation, and may help to improve to medication adherence.

However, these medications are still underutilized in clinical practice. Gopal estimates that only around 1 in 10 patients with schizophrenia in the US take an LAI, although that figure varies considerably at a global level, and is as high as 1 in 2 in Spain.

This is the result of a number of factors that act as potential barriers to LAI use, not the least of which is misconceptions among caregiver and healthcare professionals about the drugs.

"When I first was in medical school, this was in the 1990s...there were really only first-generation antipsychotics available in a depot, or a long-acting form, and those had very severe side effects," said Gopal.

"They would tend to cause all sorts of movement disorders and would make patients feel really drowsy throughout the day, so they really hated taking them," he said, noting that these depot meds were oil-based, which was painful on injection and caused reactions.

While the newer generations of LAIs are water-based and have a much-improved adverse-effect profile, doctors "on my end of the age spectrum," Gopal said, "have all those negative connotations and memories in their minds about what these older LAIs were like."

"It's only the newer generation of doctors who were not around at the time that have a more forward-thinking attitude about the newer long-actings."

Differences by Country

To assess factors that determine patients' medication preferences in order to better understand expectations and reduce potential barriers to treatment, the researchers analyzed data on 1429 patients with schizophrenia who were participants in a double-blind, randomized, noninferiority study of paliperidone palmitate taken monthly vs once every 3 months.

Participants had a mean age of 38.4 years, and 55% were men. The majority (54%) were white, while 8% were black or African American, and 38% were from other races. About one eighth (12%) of the patients were from the US.

LAIs were preferred by 77% of patients, ranging from 84.2% among whites, 57.7% among blacks, and 71.2% from other races.

The highest preference for LAIs was in Europe, at 88%, vs 59.1% in the US and 70.7% in the rest of the world.

Interestingly, the preference for LAIs in the US was comparable across different races, at 59.6% among black patients, 58.8% among whites, and 57.1% for other races.

All study participants had a confirmed diagnosis of schizophrenia and a Positive and Negative Syndrome Scale total score of between 70 and 120 at baseline, with worsening symptoms.

They completed the Medication Preference Questionnaire on day 1, day 120, and at the end of the study, with the current analysis focusing on day 1 responses, as that was the only time when patients would not have received any study medication.

Patient Empowerment Key

The most common reason patients cited for preferring LAIs over oral antipsychotics were that they felt healthier (57%), could get back to their favorite activities (56%), and didn't have to think about taking their medication (54%).

In terms of their personal experiences, patients preferred LAIs to pills because they "are easier for me" (67% vs 18%) and offered a greater sense of control and relieved them from having to think about taking medication (64% vs 14%).

Finally, 50% of patients preferred LAI injections once every 3 months, vs 38% for monthly and 3% for daily injections. Main reason cited were fewer injections (96%), less pain (84%), and fewer doctor visits (80%).

The preferred site for LAI injection was deltoid muscle over gluteal muscle, at 59%, with faster administration (63%), easier use (51%), and the location being less embarrassing (44%) cited as the primary reasons.

"Overall, patient empowerment and quality-of-life-related goals were important for patients who preferred LAI antipsychotics," the investigators note.

Logistic regression analysis indicated that only race and country were significantly associated with medication preferences, with white patients significantly more likely than others to prefer LAIs vs oral medications (adjusted odds ratio [AOR], 2.39; P < .001). US patients were significantly less likely to prefer the drugs than those from other countries (AOR, 0.41; P < .001).

Gopal added that significant differences in patient preference for LAIs likely has a lot to do with the prevailing attitudes of doctors from different countries, with low LAI use corresponding to "more negative attitudes."

"Better understanding of patients' treatment priorities and perspective could help overcome barriers to LAI use and inform best course of personalized schizophrenia treatment for improved patient satisfaction and medication adherence," the investigators note.  

Approached for comment, Matej Markota, MD, a psychiatrist at the Mayo Clinic in Rochester, Minnesota who was not involved with the research, said that he agreed with the findings of the study.

He told Medscape Medical News that, in his clinical experience, the convenience of not having to take medications daily is an important factor that drives patient preference for LAI use over oral medications.

The study was funded by Janssen Research & Development, LLC. Gopal reports he is an employee of Janssen Research & Development, LLC, and owns stock/equity in Johnson & Johnson. Markota has disclosed no relevant financial relationships.

Congress of the Schizophrenia International Research Society (SIRS) 2020: Abstract S208.

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