Long-acting injectable risperidone as an option in first-episode psychosis

What is already known on this topic

Appropriate use of antipsychotic medications for people experiencing early episode psychosis is critical for symptom control and for shaping attitudes towards medication as a support to recovery.1 Risperidone is an effective medication in treating early episode psychosis2 and long-acting injectable risperidone may increase early (12-week) adherence rates.3 However, long-acting medications are rarely used following a first episode of schizophrenia4 and the aim of the present study was to compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia.

Methods of the study

Eighty-three people with early episode schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)) in the Los Angeles area participated between March 2005 and September 2012. Exclusion criteria: habitual drug use or alcoholism; clinical contraindication to risperidone; evidence of neurological condition; premorbid mental retardation.

After a 3-week lead-in period of oral risperidone, participants were randomised to continue treatment with oral risperidone or take long-acting injectable risperidone. Participants were further randomly assigned to receive cognitive remediation (CR) or healthy-behaviours training (HBT). This paper examines secondary outcomes from the original trial (https://clinicaltrials.gov/show/NCT00333177), primarily symptom exacerbation or relapse as measured every 2 weeks using the expanded 24-item version of the Brief Psychiatric Rating Scale (BPRS). The authors applied an algorithm to classify changes through time in BPRS items of unusual thought content, hallucinations and conceptual disorganisation into remission followed by relapse, remission followed by significant exacerbation or persisting symptoms followed by significant exacerbation. Additional outcomes included psychiatric hospitalisation, control of psychotic symptoms and medication discontinuation.

Prescribers were not blinded and were permitted to adjust the dosage of oral or injectable risperidone to maximise clinical response. Participants' case managers, also not blinded, completed BPRS ratings. The follow-up was at 1-year.

What does this paper add

• This is the first report of a comparison of oral risperidone to long-acting injectable risperidone for people with first-episode schizophrenia.

• Compared to oral risperidone, long-acting injectable risperidone was associated with fewer exacerbations or relapses (mean time to event, 298.5 vs 218.6 days), lower average symptom on BPRS (p=0.01)), greater medication adherence (95% of the patients in the long-acting injectable risperidone group had excellent levels of adherence (<1.5 on a scale of 1–5, in which 1 indicates perfect adherence and 5, complete non-adherence), whereas only 33% of the patients on oral risperidone had excellent levels), and lower proportions of psychiatric hospitalisations (2 of 40 vs 8 of 43, p=0.05).

• Treatment discontinuation for adverse events was similar for oral and injectable risperidone (21% vs 10%).

• The two psychosocial interventions did not differentially impact outcomes. (eg, for the primary outcome, there was no significant three-way interaction among the psychosocial condition, medication condition, and relapse (p=0.88). The rate of return of psychosis was comparable in the two psychosocial treatments: 9 of 41 (22%) in the CR group and 7 of 42 (17%) in the HBT group; this was true for all secondary outcomes as well.

Limitations

• While prescribing the same medication to everyone demonstrates the relative efficacy of long-acting injectable to oral risperidone, without other medication comparators, the study cannot speak to risperidone's effectiveness compared to other medications.

• Participants' case managers conducted BPRS ratings. While the authors note advantages of using a semistructured rating scale with clear anchor points and of a clinician knowing a person well enough to detect subtle symptom changes, biased ratings may have influenced study findings.

What next in research

Future studies should compare long-acting injectable risperidone to other long-acting injectable and oral antipsychotics. To decrease rater bias, these trials should also include independent raters who are blind to the condition.

Do these results change your practices and why?

Yes. Information about medication choices, dosages and duration are limited for early episode psychosis1 and this report contributes knowledge to help people make well-informed choices. This study provides additional information that prescribers can share to inform treatment choice. A person might prefer the convenience of a twice monthly injection and the potentially greater protection against relapse because of assured adherence with injectable risperidone. On the other hand, some benefits of taking risperidone orally include the ability to change dosages or medication quickly based on efficacy and side effects and lower cost. People may also prefer oral medication to the process of injection, for example, in this study, three people (7%) who initially expressed a willingness to take injectable risperidone declined to accept the injectable as their random assignment.