Clinical experience with paliperidone palmitate in a specialty hospital in the Philippines: A short report

Objectives@#This study aimed to describe the clinical outcomes related to theintroduction of Paliperidone Palmitate in a specialty hospital in the Philippines.@*Methodology@#Cross-sectional study among patients with Schizophrenia seen at thepsychiatry service of a specialty hospital catering to war veterans who were initiated onPaliperidone Palmitate. We reviewed and abstracted baseline patient data from themedical record of eligible patients. Outcome of treatment was collected through a one-time objective assessment of the patient by a third-party psychiatrist using theStructured Clinical Interview for Symptoms of Remission (SCI-SR) tool.@*Results@#A total of 30 patients were recruited for the study from August 2020 and June2021, the majority of whom were males (80%), residents of the National Capital Region(50%) and single (20%). The median duration from schizophrenia diagnosis to initiation of Paliperidone treatment was 19.50 years (IQR: 16.60 – 33.50). In eight patients (22.67%),other antipsychotic drugs were discontinued following initiation of Paliperidonetreatment; in the remaining 22 participants (73.33%), Paliperidone was taken concurrentlywith other antipsychotic drugs. The median duration from the initiation of Paliperidonetreatment to follow-up assessment was 27.20 months (IQR: 24.73 – 30.50), with allparticipants having at least 6 months of treatment. At follow-up assessment, allparticipants were classified to be in remission.@*Conclusion@#In this study among patients with schizophrenia seen in a specialtyhospital in the Philippines, we found evidence that clinical outcomes with PaliperidonePalmitate were comparable to those given a combination of oral and long- actingantipsychotics.

Protocolo Clínico e Diretrizes Terapêuticas (PCDT) complementares de esquizofrenia no Estado de Goiás - versão 2022 / Clinical protocol and complementary therapeutic guidelines (PCDT) for schizophrenia in the State of Goiás - version 2022

Protocolo estadual que complementa o PCDT do Ministério da Saúde e ambos devem ser considerados como referência diagnóstica e terapêutica pelos profissionais de saúde, em Goiás, para o tratamento de pessoas com o transtorno de esquizofrenia. A esquizofrenia é um transtorno mental grave que ocorre em cerca de 1% da população, independente de nível sociocultural. É caracterizada por períodos de intensas distorções do pensamento e da percepção (surtos) e pela inadequação e embotamento do afeto. Ao longo do tempo, pode aparecer prejuízos cognitivos em uma parcela significativa dos pacientes , principalmente os que não seguem tratamento regular

State protocol that complements the Ministry of Health's PCDT and both should be considered as a diagnostic and therapeutic reference by health professionals in Goiás for the treatment of people with schizophrenia disorder. Schizophrenia is a serious mental disorder that occurs in around 1% of the population, regardless of sociocultural level. It is characterized by periods of intense distortions of thought and perception (outbreaks) and by inadequacy and blunting of affect. Over time, cognitive impairment may appear in a significant portion of patients, especially those who do not follow regular treatment

Pica y traumatismo craneoencefálico en un paciente adolescente: recuperación <> con paliperidona / Pica and traumatic brain injury in an adolescent: complete improvement with paliperidone

Presentamos el caso clínico de un adolescente varón de 15 años derivado a Psiquiatría Infanto-Juvenil por realizar ingestas repetitivas de sustancias no nutritivas como gomas de borrar, escamas psoriásicas o incluso pintura de la pared. Entre sus antecedentes somáticos de interés, conviene destacar la Enfermedad de Kawasaki y psoriasis, además de haber sufrido un traumatismo craneoencefálico (TCE) tras lo cual presentó una exacerbación del cuadro. Tras el fracaso en el manejo conductual realizado por parte de su madre y teniendo en cuenta sus rasgos de personalidad caracterizados por una elevada suspicacia y desconfianza hacia los demás, se decide iniciar tratamiento con paliperidona oral produciéndose una rotunda mejoría clínica. Durante todo el seguimiento posterior hasta su mayoría de edad, se ha mantenido la desaparición de la pica. Presentamos el primer caso clínico publicado en la bibliografía actual de un adolescente con el diagnóstico de pica y un TCE previo y una adecuada respuesta a paliperidon

We present a case report of a 15-year-old male adolescent who was referred to our consultation of Children and Adolescent Psychiatry due to persistent eating of non-nutritive substances like rubber, psoriatic scale or wall paint. The patient had the previous diagnostic of Kawasaki Disease and psoriasis. In addition, he had suffered a traumatic brain injury, after which he presented an exacerbation of the clinic. After behaviour therapy failure realized by his mother and taking into account his personality features with high suspicion and distrust of others, he was prescribed paliperidone oral treatment and pica disappeared. During all subsequent follow-up until the age of majority, the disappearance of pica has been maintained. We describe the first case report in the current bibliography of an adolescent with the diagnosis of pica, a previous traumatic brain injury and a good response to oral paliperidone.

The Community Mental Health Program in Calabarzon: Preliminary report from an internal review of an innovative service integration initiative for Schizophrenia

@#The Community Mental Health Program (CMHP) of the Center for Health Development Calabarzon is an initiative that aims to integrate mental health into primary care to facilitate person-centered and holistic services. At the core of CMHP is a referral pathway between health centers and tertiary-level mental health services for the diagnosis and continuing management of persons with mental health conditions, as well as the use of an innovative medication (specifically for schizophrenia). This commentary presents lessons learned from a one-year implementation of CMHP in four pilot sites in the provinces of Rizal and Laguna, which stakeholders in mental health may consider in the design of community-based mental health programs to further the mandate of the Mental Health Act.

High Doses of Drugs Extensively Metabolized by CYP3A4 Were Needed to Reach Therapeutic Concentrations in Two Patients Taking Inducers / Dos pacientes que tomaban inductores necesitaron dosis altas de medicamentos metabolizados en gran medida por el CYP3A4 para alcanzar concentraciones terapéuticas

ABSTRACT Introduction: In the last 20 years of clinical practice, the senior author has identified these 2 rare cases in which the patients needed extremely high doses of drugs metabolized by CYP3A4 to reach and maintain serum therapeutic concentrations. Methods: The high metabolic ability of these 2 patients was demonstrated by the low concentration-to-dose ratios (C/D ratios) of several drugs metabolized by CYP3A4. Results: Case 1 was characterized by a history of high carbamazepine doses (up to 2,000 mg/day) and needed 170 mg/day of diazepam in 2 days to cooperate with dental cleaning. The high activity of the CYP3A4 isoenzyme was manifested by fast metabolism for quetiapine and diazepam, which took more than 1 year to normalize after the inducer, phenytoin, was stopped. Case 2 was also very sensitive to CYP3A4 inducers as indicated by very low C/D ratios for carbamazepine, risperidone and paliperidone. The carbamazepine (2,800 mg/day) and risperidone (20 mg/day) dosages for this second patient are the highest doses ever seen for these drugs by the senior author. Risperidone induction appeared to last for many months and metabolism was definitively normal 3 years after stopping carbamazepine. On the other hand, olanzapine C/D ratios were normal for induction. Conclusions: The literature has never described similar cases of very high doses of drugs metabolized by CYP3A4. We speculate that these 2 patients may have unusual genetic profiles at the nuclear receptor levels; these receptors regulate induction of drugs.

RESUMEN Introducción: Durante sus últimos 20 años de práctica, el último autor ha identificado estos 2 infrecuentes casos que necesitaban dosis extremadamente altas de medicaciones metabolizadas por el CYP3A4 para alcanzar y mantener concentraciones séricas terapéuticas. Métodos: La gran capacidad metabólica de estos 2 pacientes se demostró por los bajos cocientes entre concentración y dosis (C/D) de varias medicaciones metabolizadas por el CYP3A4. Resultados: El caso 1 se caracterizaba por una historia de altas dosis de carbamazepina (1.500 mg/día) y la necesidad de tomar 170 mg de diazepam en 2 días para facilitar una limpieza dental. La gran actividad de la isoenzima CYP3A4 se manifestó por una gran capacidad metabólica de quetiapina y diazepam, cuya normalización tardó más de 1 año tras la toma de un inductor, fenitoína. El caso 2 tambien era muy sensible a la inducción, lo cual se demuestra por los bajos cocientes C/D de carbamazepina, risperidona y paliperidona. Las dosis de carbamazepina (2.800 mg/día) y risperidona (20 mg/día) de este segundo paciente son las más altas nunca vistas por el último autor. La inducción de risperidona duró muchos meses y su metabolismo era normal 3 años después de interrumpir la carbamazepina. El cociente C/D de olanzapina era normal para la inducción. Conclusiones: Nunca se habían descrito casos similares de dosis tan altas de medicaciones metabolizadas por el CYP3A4. Se especula con que estos pacientes podrían tener unos perfiles genéticos inusuales en los receptores nucleares que regulan la inducción de medicamentos.

Eficácia, segurança e efetividade comparada de palmitato de paliperidona e outros antipsicóticos injetáveis de efeito prolongado para tratamento de esquizofrenia: revisão rápida de evidências / Efficacy, safety and effectiveness in the real world for paliperidone palmitate compared to the others long acting injectable antipsychotics for schizophrenia treatment: rapid review of evidence

Tecnologia: Palmitato de Paliperidona (PP) é um antipsicótico injetáveis de efeito prolongado (AIEP). Indicação: Tratamento sintomático da esquizofrenia. Objetivo: Comparar a eficácia, segurança e efetividade terapêutica entre PP e outros AIEP para o tratamento de esquizofrenia em adultos. Pergunta: O PP é mais eficaz e seguro que os outros AIEP (Decanoato de Haloperidol, Enantato de Flufenazina, Decanoato de Zuclopentixol, Risperidona-IEP) para o tratamento sintomático de esquizofrenia em adultos? Métodos: Levantamento bibliográfico, com estratégias estruturadas de busca, na base de dados PUBMED. Foi feita avaliação da qualidade metodológica das revisões sistemáticas (RS), ensaios clínicos randomizados (ECR) e dos estudos observacionais de efetividade no mundo real (EOEMR) com as ferramentas Assessing the Methodological Quality of Systematic Reviews (AMSTAR), Delphi List e Newcastle-Ottawa Scale (NOS), respectivamente. Resultados: Foram selecionadas 3 RS, 1 ECR e 3 EOEMR. Conclusão: PP (de aplicação mensal) tem similar eficácia e segurança com a Risperidona-IEP para o tratamento de esquizofrenia, exceto que provoca menor incidência de sintomas extrapiramidais. PP e Decanoato de Haloperidol são similares na eficácia e segurança para o tratamento de esquizofrenia, inclusive no risco de sintomas extrapiramidais (discinesias tardias e parkinsonismo), exceto que PP tem menor incidência de acatisia. PP é similar aos outros AIEP nos vários desfechos de eficácia e segurança terapêutica, inclusive mortalidade

Technology: Paliperidone palmitate (PP) is a long-acting injectable (LAI) antipsychotics. Indication: Symptomatic treatment of schizophrenia. Objective: To compare the therapeutic efficacy, safety and effectiveness in the real world between PP and other LAI antipsychotics for the treatment of schizophrenia in adults. Question: Is PP more effective and safer than other LAI antipsychotics (Haloperidol Decanoate, Fluphenazine Enanthate, Zuclopentixol Decanoate, Risperidone-LAI), for the symptomatic treatment of schizophrenia? Methods: Bibliographic survey, with structured search strategies, in the PUBMED database. Na evaluation was made of the methodological quality of systematic reviews (SR), randomized clinical trials (RCT) and observational studies (OS) of effectiveness in the real world with Assessing the Methodological Quality of Systematic Reviews (AMSTAR), Delphi List and Newcastle-Ottawa Scale (NOS) tools, respectively. Results: 3 SR, 1 RCT and 3 OE were included. Conclusion: PP (monthly dose presentation) has similar efficacy and safety with Risperidone-LAI for the treatment of schizophrenia, except that it causes a lower incidence of extrapyramidal symptoms. PP and Haloperidol Decanoate are similar in efficacy and safety for the treatment of schizophrenia, including the risk of extra-pyramidal symptoms (tardive dyskinesias and parkinsonism), except that PP has a lower incidence of akathisia. PP has similar outcomes of efficacy and safety to the other LAI antipsychotics, including mortality risk

Efficacy and safety of paliperidone palmitate 3-month formulation in Latin American patients with schizophrenia: A subgroup analysis of data from two large phase 3 randomized, double-blind studies

Objective: To analyze the efficacy and safety of paliperidone palmitate 3-monthly (PP3M) in Latin American patients with schizophrenia vs. rest-of-world (ROW). Methods: We analyzed data from two multinational, double-blind (DB), randomized, controlled phase 3 studies including patients with schizophrenia (DSM-IV-TR) previously stabilized on PP1M/PP3M (open-label [OL] phase). Patients were randomized to PP3M or PP1M (noninferiority study A) and PP3M or placebo (study B) in DB phase. The subgroup analysis included Latin American (Argentina, Brazil, Colombia, Mexico) patients. Primary efficacy endpoints were relapse-free rates (study A) and time-to-relapse (study B). Results: In study A, 63/71 (88.7%) and in study B 38/43 (88.4%) Latin American patients completed the DB phase. In study A, relapse-free percentage was similar in Latin America (PP3M: 97%, PP1M: 100%) and ROW (PP3M: 91%, PP1M: 89%). In study B, median time-to-relapse was not estimable in the Latin American subgroup for either placebo or PP3M groups, nor for the ROW PP3M group; the median time-to-relapse in the ROW placebo group was 395 days. Caregiver burden improved in patients switching from oral antipsychotics (OL baseline) to PP3M/PP1M in DB phase (Involvement Evaluation Questionnaire score mean ± SD change, -9.4±15.16; p < 0.001). Treatment emergent adverse events with PP3M during DB phase were similar in Latin America (study A: 24/34 [70.6%]; study B: 15/21 [71.4%]) and ROW (study A: 318/470 [67.7%]; study B: 84/139 [60.4%]) subgroups. Conclusion: PP3M was efficacious and showed no new safety concerns in patients with schizophrenia from Latin America, corroborating ROW findings. Clinical trial registration: NCT01515423, NCT01529515

The Long-Acting Injectable Antipsychotics in Clinical Practice / 신경정신의학

Symptomatic relapse is observed frequently and often associated with social and/or occupational decline that can be difficult to reverse in patients with schizophrenia. Several atypical antipsychotics, including risperidone, olanzapine, paliperidone, and aripiprazole, have become available as long-acting injectable antipsychotics (LAIs), and new evidence has been accumulating. LAIs appear to have a significant role in at least a group of schizophrenia patients. Improving the adherence, continuous availability, managing changes in receptor sensitivity, and lowering the requirement of cumulative doses are some of the major advantages of LAIs. Patients with first episode psychosis, dopamine super-sensitivity syndromes, and comorbid substance abuse might particularly benefit. Delaying the initiation of LAI until the establishment of non-adherence is not recommended. The results of clinical trials comparing LAIs with oral antipsychotics (OAPs) are inconsistent because they are influenced considerably by the study design. On the other hand, several barriers to LAIs use in current practice include clinical lack of knowledge, and negative attitudes about LAIs. This article tries to help clinicians better characterize the role of LAIs in the treatment of schizophrenia.

Korean Medication Algorithm for Bipolar Disorder 2018: Comparisons with Other Treatment Guidelines

The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2018 (KMAP-BP 2018) with other recently published guidelines for treating bipolar disorder. We reviewed a total of five recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2018 with those of other guidelines. For initial treatment of mania, there were no significant differences across treatment guidelines. All guidelines recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or a combination of an MS with an AAP as a first-line treatment strategy for mania. However, the KMAP-BP 2018 did not prefer monotherapy with MS or AAP for psychotic mania. Quetiapine, olanzapine and aripiprazole were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Most guidelines advocated newer AAPs as first-line treatment options for all phases while lamotrigine was recommended for depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. As research evidence accumulated over time, recommendations of newer AAPs (such as asenapine, cariprazine, paliperidone, lurasidine, long-acting injectable risperidone and aripiprazole once monthly) became prominent. KMAP-BP 2018 guidelines were similar to other guidelines, reflecting current changes in prescription patterns for bipolar disorder based on accumulated research data. Strong preference for combination therapy was characteristic of KMAP-BP 2018, predominantly in the treatment of psychotic mania and severe depression. Further studies were needed to address several issues identified in our review.

Aripiprazole-induced Hepatitis: A Case Report

Aripiprazole is an atypical antipsychotic that acts as a partial agonist of dopamine type 2 receptors as well as 5-HT1A receptors. It is used in the treatment of schizophrenia and in type 1 bipolar disorder for mania. Because aripiprazole is well tolerated with few side effects it is used off-label in other psychotic disorders. The prevalence of abnormal liver function tests with antipsychotic use is 32%, with clinically significant effects in 4% of cases. No cases of aripiprazole-induced liver injury have been published. We report a 28-year-old female who presented with non-affective first-episode psychosis and who was treated with aripiprazole. Initially she was medicated with 10 mg per day, with an increase to 20 mg per day on the 12th day of hospitalization. Nine days after she became icteric, with nausea and had a vomiting episode. Laboratory analysis revealed a very high level of alanine aminotransferase, and minor to moderately high levels of aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and bilirubin. Aripiprazole was tapered and paliperidone was started with the improvement of clinical and laboratory findings.

The Impact of Paliperidone Palmitate on Hospitalization in Patients with Schizophrenia: A Retrospective Mirror-image Study

OBJECTIVE: Whether long-acting injectable antipsychotics (LAI) are superior to oral antipsychotics remains a controversial question, and results vary depending on the study design. Our study was performed to compare outcomes of oral anti-psychotics and paliperidone palmitate (PP) in clinical practice by investigating the numbers of admissions and bed days. METHODS: We performed a retrospective observational mirror-image study at a single medical center, reviewing medical charts to obtain the clinical data. Forty-six patients with a diagnosis of schizophrenia or schizoaffective disorder who had received at least two doses of PP were included in the analysis. The Wilcoxon signed-rank test was used to compare the numbers of bed days and admissions 1 year before starting PP with those numbers at 1 year after. RESULTS: The mean number of admissions fell from 0.83 to 0.17 per patient (p < 0.0002), and the median fell from 1 to 0. The mean number of bed days decreased significantly, from 24.85 to 8.74 days (p < 0.006). The outcomes remained similar in sensitivity analyses set up with different mirror points. CONCLUSION: Our results indicate that initiating PP reduced the mean numbers of hospital admissions and bed days compared with prior oral medication. LAIs may thus be cost effective in practice; its use bringing about cost reductions greater than its purchase cost.

Change in Cognitive Function after Antipsychotics Treatment : A Pilot Study of Long-Acting Injectable versus Oral Form / 대한정신분열병학회지

OBJECTIVES: This study investigated whether long-acting injectable (LAI) paliperidone is different from its oral form in terms of the effect on cognitive function in schizophrenia spectrum and other psychotic disorders. METHODS: We reviewed the medical records of patients in Seoul National University Bundang Hospital who were diagnosed as having schizophrenia and/or other psychotic disorders based on DSM-5 from 2016 to 2017. Seven patients were treated with oral paliperidone and 11 were treated with paliperidone palmitate. All patients underwent clinical and neuropsychological assessment, including the Korean version of the MATRICS Consensus Cognitive Battery (MCCB) at their first visit or within one month of their initial treatment. MCCB was repeated within three to 12 months after the initial assessment. RESULTS: There was no significant difference between the two groups in most cognitive domains including speed of processing, attention and vigilance, working memory, verbal learning, visual learning and reasoning and problem solving domain. However, patients treated with paliperidone palmitate showed better improvement in social cognition domain than those taking oral paliperidone. The standardized values of social cognition domain scores had significantly improved over time in patients under paliperidone palmitate, demonstrating a significant time-by-group interaction. CONCLUSION: Our results show that long-acting injectable paliperidone could be helpful in some aspects of improving cognitive function in schizophrenia spectrum and other psychotic disorders. Further studies with other antipsychotics are necessary to generalize the results.

Effects of Risperidone and Paliperidone on Brain-Derived Neurotrophic Factor and N400 in First-Episode Schizophrenia / 中华医学杂志(英文版)

<p><b>Background</b>Risperidone and paliperidone have been the mainstay treatment for schizophrenia and their potential role in neuroprotection could be associated with brain-derived neurotrophic factor (BDNF) and N400 (an event-related brain potential component). So far, different effects on both BDNF and N400 were reported in relation to various antipsychotic treatments. However, few studies have been conducted on the mechanism of risperidone and paliperidone on BDNF and N400. This study aimed to compare the effects of risperidone and paliperidone on BDNF and the N400 component of the event-related brain potential in patients with first-episode schizophrenia.</p><p><b>Methods</b>Ninety-eight patients with first-episode schizophrenia were randomly divided into the risperidone and paliperidone groups and treated with risperidone and paliperidone, respectively, for 12 weeks. Serum BDNF level, the latency, and amplitude of the N400 event-related potential before and after the treatment and Positive and Negative Syndrome Scale (PANSS) scores were compared between the two groups.</p><p><b>Results</b>A total of 94 patients were included in the final analysis (47 patients in each group). After the treatment, the serum BDNF levels in both groups increased (all P < 0.01), while no significant difference in serum BDNF level was found between the groups before and after the treatment (all P > 0.05). After the treatment, N400 amplitudes were increased (from 4.73 ± 2.86 μv and 4.51 ± 4.63 μv to 5.35 ± 4.18 μv and 5.52 ± 3.08 μv, respectively) under congruent condition in both risperidone and paliperidone groups (all P < 0.01). Under incongruent conditions, the N400 latencies were shortened in the paliperidone group (from 424.13 ± 110.42 ms to 4.7.41 ± 154.59 ms, P < 0.05), and the N400 amplitudes were increased in the risperidone group (from 5.80 ± 3.50 μv to 7.17 ± 5.51 μv, P < 0.01). After treatment, the total PANSS score in both groups decreased significantly (all P < 0.01), but the difference between the groups was not significant (P > 0.05). A negative correlation between the reduction rate of the PANSS score and the increase in serum BDNF level after the treatment was found in the paliperidone group but not in the risperidone group.</p><p><b>Conclusions</b>Both risperidone and paliperidone could increase the serum BDNF levels in patients with first-episode schizophrenia and improve their cognitive function (N400 latency and amplitude), but their antipsychotic mechanisms might differ.</p>

Bilateral Pretibial Edema Associated with Paliperidone Palmitate Long-acting Injectable: A Case Report

Peripheral edema is observed as an adverse effect of the usage of antipsychotics in the literature. This case report describes a 36-year-old female patient with the diagnosis of paranoid schizophrenia who presented with pretibial edema following initiation of long-acting injectable paliperidone palmitate. Pretibial edema developed within the second week of treatment and completely disappeared after its discontinuation.

Five Month-Persistent Extrapyramidal Symptoms following a Single Injection of Paliperidone Palmitate: A Case Report

Long-acting injectable (LAI) antipsychotics are useful in the treatments for schizophrenic patients with poor adherence due to their maintaining feature of therapeutic plasma level without daily administrations. However, their long-lasting property can cause complicated problems such as a long-lasting side effect. We report a patient who experienced LAI-induced extrapyramidal symptoms (EPSs) for 5 months after a single injection. During that period, every trial to ameliorate this condition turned out to be a failure. The 3-month formulation of paliperidone palmitate is now close at hand. We have to be aware of possible long-lasting adverse events and confirm the tolerability to LAI before use.

Comparison of Hematologic Variability between Clozapine Monotherapy and Augmentation Therapy with Atypical Antipsychotics for Schizophrenia: Results from a 6-Month Retrospective Follow-Up Study / 대한정신분열병학회지

OBJECTIVES: Clozapine is an antipsychotic agent commonly prescribed in patients with treatment-resistant schizophrenia. A drawback of using clozapine is risk of hematologic side effects ranging from mild neutropenia to fatal agranulocytosis. In clinical settings, other atypical antipsychotic agents are frequently combined with clozapine because some treatment-resistant patients would not respond to clozapine alone. Unfortunately, other atypical antipsychotics may also cause hematologic side effects, and the combination therapy might aggravate the possible neutropenic side effects. The purpose of this study was to investigate the difference in the incidence of hematologic side effects between clozapine monotherapy and augmentation therapy. METHODS: We retrospectively reviewed the medical records of 114 patients who were diagnosed with schizophrenia and being prescribed with clozapine in a single university hospital. White blood cell count (WBC) and absolute neutrophil count (ANC) were identified every 1 month in clozapine monotherapy group and clozapine-atypical antipsychotics augmentation therapy group. RESULTS: Compared with clozapine monotherapy group, augmentation therapy group showed no significant differences in WBC and ANC for the first 6 months of combination. Amisulpride augmentation showed temporary increases in WBC and ANC, especially compared with paliperidone augmentation. CONCLUSION: Augmentation of amisulpride to clozapine might be associated with temporary increases in WBC and ANC during the first 3 months of combination. Further investigations should be carried out to clarify the clinical significance of our findings.

Comparison of Hematologic Variability between Clozapine Monotherapy and Augmentation Therapy with Atypical Antipsychotics for Schizophrenia: Results from a 6-Month Retrospective Follow-Up Study / 대한정신분열병학회지

OBJECTIVES: Clozapine is an antipsychotic agent commonly prescribed in patients with treatment-resistant schizophrenia. A drawback of using clozapine is risk of hematologic side effects ranging from mild neutropenia to fatal agranulocytosis. In clinical settings, other atypical antipsychotic agents are frequently combined with clozapine because some treatment-resistant patients would not respond to clozapine alone. Unfortunately, other atypical antipsychotics may also cause hematologic side effects, and the combination therapy might aggravate the possible neutropenic side effects. The purpose of this study was to investigate the difference in the incidence of hematologic side effects between clozapine monotherapy and augmentation therapy. METHODS: We retrospectively reviewed the medical records of 114 patients who were diagnosed with schizophrenia and being prescribed with clozapine in a single university hospital. White blood cell count (WBC) and absolute neutrophil count (ANC) were identified every 1 month in clozapine monotherapy group and clozapine-atypical antipsychotics augmentation therapy group. RESULTS: Compared with clozapine monotherapy group, augmentation therapy group showed no significant differences in WBC and ANC for the first 6 months of combination. Amisulpride augmentation showed temporary increases in WBC and ANC, especially compared with paliperidone augmentation. CONCLUSION: Augmentation of amisulpride to clozapine might be associated with temporary increases in WBC and ANC during the first 3 months of combination. Further investigations should be carried out to clarify the clinical significance of our findings.

The Effects on Metabolic Syndrome Parameters of Atypical Antipsychotic Agents in Schizophrenics Patients : 3 Years Retrospective Follow Up / 대한정신분열병학회지

OBJECTIVES: Pharmacological treatment is critical on relapse prevention in patients with schizophrenia. However, atypical antipsychotic agents are known to cause weight gain more than typical agents despite their various effects. In addition, they are known to affect blood sugar, blood pressure, cholesterol, cardiac function, and sexual function. This study was designed to examine the effects on metabolic parameters when schizophrenic patients have been taken atypical antipsychotic agents. METHODS: This was a trial in 137 patients with DSM-IV-TR schizophrenia who were admitted or treated in mental hospital. Anthropometric measurement and blood testing were conducted at baseline, 12 month, 36 month, and sociodemographic and treatment history were collected from medical records. We conducted height, weight, waist circumference, blood pressure, FBS, total cholesterol, HDL, triglyceride, and QTc interval. Metabolic syndrome was diagnosed by ATPIIIa criteria. RESULTS: Aripiprazole showed the significant difference in the impact on weight, blood pressure, waist circumference, total cholesterol, HDL, triglyceride than paliperidone and olanzapine at 1-year and 3-year period. Olanzapine showed the significant increase of weight and triglyceride than paliperidone at 3-year period. The prevalence of metabolic syndrome increased in paliperidone at 1-year and in olanzapine at 3-year period compared to aripiprazole significantly. CONCLUSION: We concluded that aripiprazole has less impact on the abdominal obesity, FBS, blood pressure, and cholesterol than paliperidone and olanzapine. Olanzapine showed the increase of long-term metabolic risk than other agents. There was needed the routine screening and multidisciplinary management of medical problems in schizophrenic patients for the prevention of metabolic syndrome.

Prevalence of Metabolic Syndrome in Patients with Schizophrenia in Korea: A Multicenter Nationwide Cross-Sectional Study

OBJECTIVE: We designed a nationwide study with limited exclusion criteria to investigate the prevalence of metabolic syndrome (MetS) in Korea and its relationship with antipsychotic medications. METHODS: This multicenter, cross-sectional, and observational study included patients diagnosed with schizophrenia or schizoaffective disorder. Sixteen hospitals enrolled 845 patients aged 18 to 65 years prescribed any antipsychotic medication between August 2011 and August 2013. MetS was diagnosed using the criteria of the modified Adult Treatment Panel III of the National Cholesterol Education Program with the Korean abdominal obesity definition (waist circumference ≥85 cm in women, ≥90 cm in men). RESULTS: The prevalence of MetS in all patients was 36.5% and was significantly higher in men than women (men, 40.8%; women, 32.2%) and was significantly correlated with age [odds ratio (OR) 1.02] and duration of illness (OR 1.03). The prevalence of MetS across antipsychotic drugs in the major monotherapy group was as follows: 18.8% for quetiapine, 22.0% for aripiprazole, 33.3% for both amisulpride and paliperidone, 34.0% for olanzapine, 35% for risperidone, 39.4% for haloperidol, and 44.7% for clozapine. CONCLUSION: The prevalence of MetS is very high in patients with schizophrenia or schizoaffective disorder. Screening and monitoring of MetS is also strongly recommended.

Efficacy and Tolerability of Paliperidone Extended-release in the Treatment of First-episode Psychosis: An Eight-week, Open-label, Multicenter Trial

OBJECTIVE: We investigated the efficacy and tolerability of paliperidone extended-release (ER) tablets in patients with first-episode psychosis (n=75). METHODS: This was an 8-week, open-label, multicenter trial. The primary outcome variable was scores on the Positive and Negative Syndrome Scale (PANSS); secondary measures included the Scale for the Assessment of Negative Symptoms (SANS), the Cognitive Assessment Interview (CAI), and the Global Assessment of Functioning (GAF). To assess safety, we measured drug-related adverse events, weight, lipid-related variables, and prolactin and administered the Simpson–Angus Rating Scale (SARS), the Abnormal Involuntary Movement Scale (AIMS), the Barnes Akathisia Scale (BAS), the Arizona Sexual Experiences Scale (ASEX), and the Udvalg for Kliniske Undersogelser side effect rating scale (UKU). RESULTS: The administration of paliperidone ER resulted in significant improvement in the PANSS, SANS, CAI, and GAF scores (p<0.001) over time. This improvement was evident as early as 1 week. The most frequent adverse events were akathisia, somnolence, anxiety, and sedation, which were well tolerated. Modest increases in weight and lipid profiles were also noted. Prolactin levels were substantially increased at the endpoint in both male and female patients. CONCLUSION: These results indicate that paliperidone ER is effective and is characterized by good tolerability in the treatment of positive and negative symptoms and cognitive functioning in first-episode psychosis.