Schizophrenia care during COVID-19: Reducing hospitalization and treatment burden with LAI antipsychotics
History and presentation
This is the case of a 21-year-old female university student in her final-year studies in Xi’an, mainland China. She first presented to our Early Psychosis Clinic 2 years ago, after a first episode of psychosis precipitated by stress from academic studies and interpersonal relationships. She was brought to a psychiatrist in Xi’an due to symptoms of strong paranoia, referential ideation and verbal auditory hallucinations, and was started on medications. Her family subsequently brought her to our clinic in Hong Kong.
The patient was started on oral risperidone (4 mg nocte) and given education about psychosis and the importance of maintenance therapy. With good adherence to treatment, her symptoms gradually subsided and functioning normalized. Six months later, she returned to Xi’an to continue her studies while being maintained on oral risperidone, visiting our clinic for follow-up during holidays. She remained in remission for 1.5 years.
Early relapse trigged by COVID-19 life changes
The patient returned to Hong Kong in February 2020 as classes were suspended due to the coronavirus disease 2019 (COVID-19) outbreak. With life routines coming to a halt, she began to experience a low mood.
The patient found a part-time job in early March 2020 and had become partially adherent to oral risperidone since then. Her mother, who worked until late at night, was initially unaware of her decreased medication adherence.
With interpersonal relationships in the part-time job causing stress, the patient began to experience verbal auditory hallucinations similar to those in her first-episode psychosis. She had also become fearful of going out and had stopped working part-time. Her mother thus brought her to our clinic for earlier follow-up.
Treatment and response
The early relapse necessitated prompt control of symptoms. However, admission was not absolutely necessary as the patient did not show violent behaviours, self-harm or suicidal ideation.
Although continuation of oral risperidone could be an option due to its previously established efficacy in the patient, its use at this juncture would require close supervision by her mother to ensure consistent intake. It would, however, be challenging for her mother to take leave from work given the socioeconomic impact of COVID-19.
A second option would be early admission for hospital nurses to supervise her medication intake. However, the patient would then be isolated from her family due to visiting restrictions implemented as part of the COVID-19 control measure.
A third option would be to switch treatment to a long-acting injectable (LAI) antipsychotic in an outpatient setting. This could ensure consistent medication intake without daily supervision, thus reducing the burden of treatment on the patient’s family while eliminating the need for hospitalization.
Upon discussion and agreement with the patient and her mother, treatment was switched from oral risperidone 4 mg/day to LAI paliperidone palmitate once-monthly (PP1M) 100 mg in mid-April 2020, along with weekly follow-up to monitor response.
The patient was almost in total remission by late April 2020. In the most recent follow-up visit in early May 2020, both the patient and her mother expressed satisfaction with PP1M treatment. The patient remained in near-total remission, with the verbal auditory hallucinations turning into muffled voices of brief duration that were perceived only occasionally. She was no longer fearful and was able to resume her final-year dissertation work.
A switch of treatment to paliperidone palmitate 3-monthly (PP3M) 350 mg injection as maintenance therapy would be considered if the patient remains well after another four injections of PP1M.
Life changes brought by the COVID-19 pandemic (eg, social disengagement, academic underachievement, employment issues) are stressful events which, together with inconsistent medication intake, may increase the risk of schizophrenia relapse. With community rehabilitation and day hospital services being temporarily suspended or scaled down due to the outbreak, patients with schizophrenia are receiving less support. As a result, some are showing signs of early relapse requiring intervention.
Increased time spent at home during the COVID-19 pandemic can also lead to increased conflicts between patients and their family members. A high level of expressed emotions (EE) (ie, emotional overinvolvement, critical comments and/or hostility) from a family member towards a patient with schizophrenia is indeed a reliable predictor of schizophrenia relapse, according to a study conducted in Hong Kong Chinese patients.1 At 9 months, schizophrenia relapse rate was 60 percent in the high EE group vs 11.1 percent in the low EE group (p<0.01), with a relapse risk ratio of 5.4 (95 percent confidence interval [CI], 1.38 to 21.1).1 A more recent study in Hong Kong reported similar findings, with a 12-month relapse rate of 33.3 percent vs 7.9 percent in the high vs low EE group (p=0.0019) and an odds ratio for relapse of 6.3.2
Another challenge in schizophrenia management during this time is the suspension of home visits by case managers. While tele-assessments are provided, difficulties exist in fully evaluating a patient’s mental state and medication adherence without face-to-face assessment.
These challenges can be partially addressed by switching treatment from an oral to a LAI antipsychotic (eg, PP1M or PP3M), which provides durable efficacy and high transparency in medication intake. In our patient, switching from oral risperidone to PP1M enabled prompt control of symptoms without the need of hospitalization or daily supervision of medication intake by family caregivers.
In a real-world study in 29,823 patients with schizophrenia from a Swedish nationwide cohort, LAI antipsychotics demonstrated a substantially lower risk of psychiatric rehospitalization vs their equivalent oral formulations (hazard ratio [HR], 0.78; 95 percent CI, 0.72 to 0.84).3 The risk of psychiatric rehospitalization was the lowest with PP1M monotherapy (HR, 0.51; 95 percent CI, 0.41 to 0.64), compared with no antipsychotic treatment, among 20 oral or injectable antipsychotics evaluated.3
Another study showed comparable 48-week relapse-free rates between PP3M and PP1M (91.2 percent vs 90 percent) in adults with schizophrenia after clinical stabilization with 17 weeks of PP1M treatment.4 Median postwithdrawal time to relapse was 395 days with PP3M, 172 days with PP1M, and 58 days with daily extended-release oral paliperidone among adults with schizophrenia.5 The durable effect of PP1M and PP3M on relapse prevention supports extended follow-up intervals and a reduced frequency of home visits by case managers during the COVID-19 pandemic, and provides a buffer against potential medication interruptions.
Paliperidone is the major active metabolite of risperidone.6 Patients previously stabilized on oral risperidone or oral paliperidone can be switched to PP1M, and subsequently to PP3M, based on an established dose conversion guide. 7,8 While treatment switching should be based on careful evaluation of the pros and cons of each option available, it is equally important to reassure patients and their caregivers about the similar efficacy offered by the change in route of administration and absorption, and educate them about the possible advantages of LAI second-generation antipsychotics, to increase their acceptance of treatment. Although treatment switching in an inpatient setting ensures symptom stabilization before discharge, this case shows that switching from an oral to a LAI antipsychotic in an outpatient setting can also provide prompt symptom control and functional recovery.