Paliperidone 3-Month Injection for Treatment of Schizophrenia: A Narrative Review

Given the typical age onset of schizophrenia, there are tremendous economic and social impacts that extend beyond the person and their families. One critical determinant of the diseases' impact is the patient's adherence to antipsychotic drug treatment. Approved in 2015 for the treatment of schizophrenia, paliperidone palmitate (Invega Trinza, a 3-month injection, noted as PP3M) is a second-generation long-acting injectable antipsychotic medication. Among the different formulations offered for palmitate paliperidone, including the 1 and 3-month formulations, the longer duration 3-month formulation was better at preventing relapse in schizophrenic patients. To date, different formulations of palmitate paliperidone that have been studied on relapse episodes of schizophrenia include once-daily extended-release oral paliperidone (ORAL paliperidone), once-monthly paliperidone palmitate (PP1M), and once-every-3-months paliperidone palmitate (PP3M). Post-hoc analyses show that patients who were withdrawn from PP1M paliperidone had the least risk of relapse, followed by patients withdrawn from PP3M and patients withdrawn from ORAL paliperidone. PP3M was better at preventing relapse compared to ORAL paliperidone. The results demonstrated that 50% of patients who were withdrawn from ORAL paliperidone, PP1M, or PP3M remained relapse-free for ~2, 6, and 13 months, respectively. Compared to PP1M, PP3M is just as safe and effective and has the added advantage of increased adherence related to a longer dose interval, decreasing the risk of relapse.

Case Report: Cariprazine in a Patient With Schizophrenia, Substance Abuse, and Cognitive Dysfunction

This case report describes a 30-year old male diagnosed with schizophrenia at the age of 23, and with a long history of drug abuse. He had previously received a wide range of antipsychotic drug treatment regimens, all with some degree of effect, but never with complete symptom relief. He was also suffering from persistent cognitive and negative symptoms. At the time of admission in our clinic, he was on Quetiapine (QUE) and Haloperidol (HAL). It was therefore decided to substitute HAL for Cariprazine (CAR)—an agent with a novel pharmacological and clinical profile—in the hope of gaining increased efficacy, particularly in the cognitive and negative symptom domains. Within 3 weeks of the switch from HAL to CAR the patient clearly improved, and notably so in the aforementioned symptom areas. A number of subsequent adjustments of antipsychotic dosages and adjunct medications during the ensuing months resulted in an apparently more stable alleviation of positive as well as negative and cognitive symptoms, including markedly improved personal and social capabilities. Interestingly, some time after initiating CAR treatment the patient also reported that from being a heavy smoker (60 cig/d) he had cut down and eventually ceased smoking entirely; furthermore, he has remained clean of other substance abuse since his first admission in 2020. The joint treatment with CAR in combination with QUE thus seems to have improved the patient's cognitive functioning as well as possibly his susceptibility to substance abuse.

Monitoring of Adverse Drug Reaction-Related Parameters in Children and Adolescents Treated With Antipsychotic Drugs in Psychiatric Outpatient Clinics

Aim: To assess the frequency of monitoring of adverse drug reaction (ADR) related parameters in children and adolescents treated with antipsychotic drugs in psychiatric outpatient clinics and the considerations when monitoring was not performed.Methods: This retrospective follow-up study included 100 randomly selected outpatients aged ≤18 years who had a first prescription of an antipsychotic drug recorded in the electronic medical records of psychiatric outpatient clinics between 2014 and 2017. They were followed for up to 3 years. This study assessed the frequency of monitoring for physical parameters (weight, height, body mass index, waist circumference, pulse, blood pressure, and an electrocardiogram) and laboratory parameters (glucose, lipids, and prolactin) before the first prescription of an antipsychotic drug as well as during its use. Monitoring frequencies were stratified by the patient characteristics (sex, age, cardiovascular risk factors, and use of other psychotropic drugs), and by location of antipsychotic drug initiation (psychiatric outpatient clinic or elsewhere). Additionally, this study assessed the considerations mentioned in the medical records for not monitoring ADR-related parameters.Results: Overall, physical parameters were monitored more frequently (weight: 85.9% during the first half-year) than laboratory parameters (glucose and cholesterol: both 23.5%). There were no significant differences in monitoring at least one physical as well as in monitoring at least one laboratory parameter during the baseline period and during the total follow-up of antipsychotic drug treatment between the patient characteristics. In total, 3% of the children and adolescents were never monitored for any physical parameter, and 54% were never monitored for any laboratory parameter. For a minority of the children (14.8%) who were never monitored for laboratory parameters, considerations were recorded in their medical records, including refusal by the child or parents and monitoring performed by the general practitioner or elsewhere.Conclusion: Monitoring frequencies of ADR-related parameters in children and adolescents treated with antipsychotic drugs in psychiatric outpatient clinics varied and especially monitoring of laboratory parameters was infrequent. Considerations why monitoring was not performed were rarely recorded. The optimal method of monitoring and documentation thereof should become clear to optimize the benefit-risk balance of antipsychotic drug treatment for each child.

Acute and Chronic Depressive Disorders in Head and Neck Cancer Patients

The review focuses on depressive disorders in cancer patients. The article summarizes the findings of domestic and foreign studies on depression prevalence, clinical symptoms and treatment in head and neck cancer patients. Early detection of affective disorder and timely administration of antipsychotic drug treatment is shown to be important for this patient category.

M41. TRAJECTORIES AND PREDICTORS OF OUTCOME IN SCHIZOPHRENIA: THE BENEFICIAL ROLE OF AMISULPRIDE

Background Schizophrenia is a serious illness and treatment with antipsychotic drugs remains one of the most effective types of treatment. The course of schizophrenia, however, is highly heterogeneous and currently it is not possible to predict which patient will respond adequately to which antipsychotic drug. The aim of our study was to define trajectories regarding response to antipsychotic drug treatment in patients with schizophrenia spectrum disorders. A second aim was to evaluate demographic factors and antipsychotic drugs as predictors for the different trajectories. Methods Best Intro is a randomized, rater-blind, head-to-head comparison of amisulpride, aripiprazole and olanzapine. Adult patients with a diagnosis in the schizophrenia spectrum (ICD-10 diagnoses F20-29) were included. Participants had symptoms of ongoing psychosis as determined by a score of four or more on at least one of the following PANSS (Positive and Negative Syndrome Scale) items: P1 (delusions), P3 (hallucinations), P5 (grandiosity), P6 (suspiciousness/persecution) or G9 (unusual thought content). Patients were followed over a period of 52 weeks and the assessment points were at baseline, after one week, three weeks, six weeks, three months, six months, nine months, and 12 months. Totally 359 patients were assessed for eligibility, and 144 of them were enrolled and randomized to one of the study drugs. We used the R statistical program to define trajectories of antipsychotic response. Results We identified three different trajectories regarding the reduction of PANSS total score, with Bayesian information criterion (BIC) = 6157 (BIC for two groups=6164 and for four groups=6171). A large group of patients (N=106, 74%) showed a trajectory of good improvement in PANSS total score over the first 26 weeks of follow-up and maintained it after one year with a total of 35% reduction in PANSS total score (Good response group). A second group of patients (N=19, 13%) followed a trajectory of quick response (already at one week) and a large reduction of PANSS total score (Strong response group). After one year, the reduction of PANSS total score was 58%. There was a difference in the starting point for PANSS total score in these two groups with a higher value at baseline in the Strong response group, but the ending point was quite similar. A third group of patients (N= 19, 13%) followed a trajectory of poor improvement and a 9% reduction in PANSS total score over the studied period (Slight response group). The demographic variables age, sex, civil status and living alone, or drug naivety did not predict participants grouping in the various trajectories. Furthermore, we examined the predictive value of different antipsychotic drug treatment for the different trajectories with the “Intention to treat” method. There was a statistically significant difference in favor of amisulpride treatment for belonging to the Strong response group, while olanzapine strongly predicted the belonging to the Slight response group. There was no significant difference among the antipsychotic drugs regarding the Good response group. Discussion Most patients (74%) with a schizophrenia spectrum diagnosis showed a good response during the one year follow-up and another 13% showed a remarkable strong improvement. That means that a total of 87% of patients had a satisfactory course of illness during the first year. Use of amisulpride predicts a better course compared to aripiprazole and olanzapine. This finding can be useful for clinicians when selecting antipsychotic drugs for their patients.

M210. GRIN2B METHYLATION IS RELATED TO PANSS EXCITED COMPONENT (PANSS-EC) IN SCHIZOPHRENIA

Background Among the adversities found in schizophrenia, the dysfunctions in the glutamatergic system, specifically the N-methyl-D-aspartate receptor (NMDAR) are apparent. GRIN2B (coding a NMDAR subunit) has a critical role in synaptic plasticity and important participation in CNS neurodevelopment, this gene is closely associated with behavioural and cognitive impairments. One of the mechanisms that may underlie the deficiencies seen in the glutamatergic system in psychosis is DNA methylation as it is known to regulate gene expression. As part of a major study investigating the relationship of DNA methylation with schizophrenia and its symptom response to antipsychotic drug treatment, we determined whether methylation of the GRIN2B promoter region was associated with specific symptoms of schizophrenia determined by the Positive and Negative Syndrome Scale (PANSS). Methods Blood samples were collected from schizophrenia patients (n = 79) on admission to the study. Bisulphite conversion and pyrosequencing were used to determine methylation levels in 5 CpG sites in the GRIN2B promoter. PANSS score and the five factor subscores (Wallwork et al, 2012) at baseline and at 6 weeks was collected, and the change in PANSS following treatment was determined. Results Mean methylation at the five CpG sites was not associated with overall PANSS score or with the change in PANSS. However, a highly significant positive correlation of mean methylation with the baseline excited factor score (r=0.342, p=0.002), but with no other PANSS subscore, was found. No significant correlation with changes in PANSS, or in changes in subscores, over the treatment period was found. Discussion This is the first evidence showing GRIN2B methylation correlation with the excited component (EC) of schizophrenia symptoms. PANSS-EC is used to assess agitated patients (Lindenmayer et al., 2008, Montoya et al., 2011), and is valuable in identifying risks associated with agitation and aggression related to primary psychiatric disturbances. This result suggests that this GRIN2B epigenetic signature may relate to agitation and aggressive behaviour in schizophrenia.