Effects of antipsychotics on amino acid levels in patients with first-episode schizophrenia: A prospective study

Background and objectives Alterations in the molecular mechanisms of specific amino acids (AAs) may be implicated in the pathophysiology of schizophrenia (SZ). However, little is known about antipsychotic drugs influence on levels of AAs. This study aimed to further explore antipsychotics' effects on AAs and serum lipid levels in first-episode SZ. Methods Eighty subjects with the International Classification of Diseases, Tenth Edition (ICD-10) criteria-defined SZ were enrolled. The levels of 31 AAs were measured in plasma samples using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results Ten AAs (i.e., citrulline, sarcosine, tyrosine, leucine, proline, hydroxyproline, kynurenine, tryptophan, valine and isoleucine) were observed to be higher and three AAs (i.e., GABA, aminobutyric acid and asparaginic acid) were lower in 80 patients with first-episode SZ after various antipsychotics treatment. In addition, there were 1 out of 31 AAs altered after olanzapine treatment and there were only 2 out of 31 AAs altered after risperidone treatment. Furthermore, serum triglyceride (TG) was markedly upregulated after olanzapine treatment, while Apolipoprotein A1 (ApoA1) was generally upregulated after risperidone treatment in patients with first-episode SZ. Conclusions Taken together, antipsychotic treatment can affect the plasma levels of AAs in patients with first-episode SZ, and olanzapine and risperidone have differential effects on the levels of AAs. (AU)

AMPlifying metabolic screening for inpatients on antipsychotic medications with a nurse-driven protocol.

INTRODUCTION: Patients on antipsychotic medications are at higher risk of developing metabolic syndrome; nevertheless, metabolic screening for patients on antipsychotics is suboptimal. METHODS: This project developed and implemented AMP (Antipsychotic Metabolic screening Protocol), a nurse-driven protocol on inpatient psychiatric units that allowed nursing staff to collect all components of a metabolic screening. Nurses working on units with AMP were surveyed pre- and post-implementation on perception of AMP and empowerment. RESULTS: AMP significantly increased overall metabolic screening as well as the most frequently missing component (lipid panel). The screening rates pre-intervention were similar to those found in the literature (on average, only two-thirds of patients were screened). However, AMP improved the rate such that nine out of every ten patients on the units were screened. Nurses had a negative perception and no change in empowerment from AMP implementation. CONCLUSIONS: AMP can be used to increase metabolic screening for patients on antipsychotics. Further research is needed to better understand adoptability of nurse-driven protocols in the psychiatric inpatient setting as well as other applications, such as smoking cessation or safety sitters.

Schizophrenia and medication adherence: Associated factors.

BACKGROUND: Schizophrenia is a chronic condition that requiring maintenance treatment with antipsychotic medication. Medication adherence is essential to improve the symptoms of this health problem reduce relapses and readmissions and achieve treatment goals. The rate of challenges associated with medication adherence in schizophrenia is reported to be 26.5-85.1 %. PURPOSE: This study was conducted to determine factors associated with medication adherence in individuals diagnosed with schizophrenia. METHODS: A descriptive correlational research design was used. The study was completed with a total of 162 participants diagnosed with schizophrenia, between February-June 2021, at a Community Mental Health Center. Regression analysis (Model: enter and stepwise) was used to determine associated factors. RESULTS: The mean medication adherence score of individual diagnosed with schizophrenia indicated that more than half of the participants (52 %) had poor medication adherence. In individual diagnosed with schizophrenia, medication attitudes, level of internalized stigma, the status of regular attendance to appointments, belief in recovery, and using medicines as prescribed were complicating factors for medication adherence (p < 0.05). CONCLUSIONS: Medication adherence in individuals with diagnosed schizophrenia may be multifactorial. Mental health professionals should consider associated factors and implement a personalized treatment plan in this direction for strengthening adherence to medication treatment.

Correlation between desynchrony of hippocampal neural activity and hyperlocomotion in the model mice of schizophrenia and therapeutic effects of aripiprazole.

AIMS: The hippocampus has been reported to be morphologically and neurochemically altered in schizophrenia (SZ). Hyperlocomotion is a characteristic SZ-associated behavioral phenotype, which is associated with dysregulated dopamine system function induced by hippocampal hyperactivity. However, the neural mechanism of hippocampus underlying hyperlocomotion remains largely unclear. METHODS: Mouse pups were injected with N-methyl-D-aspartate receptor antagonist (MK-801) or vehicle twice daily on postnatal days (PND) 7-11. In the adulthood phase, one cohort of mice underwent electrode implantation in field CA1 of the hippocampus for the recording local field potentials and spike activity. A separate cohort of mice underwent surgery to allow for calcium imaging of the hippocampus while monitoring the locomotion. Lastly, the effects of atypical antipsychotic (aripiprazole, ARI) were evaluated on hippocampal neural activity. RESULTS: We found that the hippocampal theta oscillations were enhanced in MK-801-treated mice, but the correlation coefficient between the hippocampal spiking activity and theta oscillation was reduced. Consistently, although the rate and amplitude of calcium transients of hippocampal neurons were increased, their synchrony and correlation to locomotion speed were disrupted. ARI ameliorated perturbations produced by the postnatal MK-801 treatment. CONCLUSIONS: These results suggest that the disruption of neural coordination may underly the neuropathological mechanism for hyperlocomotion of SZ.

Antipsychotic Medication Continuation vs Taper and Discontinuation in Patients With Schizophrenia and Other Nonaffective Psychotic Disorders.

Schizophrenia is a major mental illness that is managed with long-term antipsychotic medication as a standard of care. Antipsychotic medications, however, are associated with many subjective and objective adverse effects. These adverse effects have driven the study of risk-mitigation strategies such as targeted intermittent therapy and dose reduction and drug discontinuation. Randomized controlled trials (RCTs) of these strategies have been synthesized in meta-analysis; both strategies have been associated with no functional benefits and with an increased risk of relapse. The RCTs, however, have been criticized because, in many, patients were abruptly switched to the target dose or too rapidly tapered, thereby predisposing the RCT to failure of the intervention. Two important RCTs examined gradual individualized dose reduction and discontinuation. One, conducted in first-episode psychosis patients who were free from positive symptoms for 6 months, found that, at 18-month follow-up, dose reduction was associated with a higher risk of relapse (number needed to harm [NNH] = 5) and with no functional benefits. However, after return to routine clinical care, at a 7-year follow-up, the dose reduction group had better functional outcomes and similar clinical outcomes relative to the maintenance treatment group. The other RCT, conducted in patients with relapsing psychosis, found that, at a 2-year follow-up, dose reduction was associated with a higher risk of relapse (NNH = 5) and with no improvements in social, cognitive, quality of life, satisfaction, and other domains. Many large nationwide observational studies have found that antipsychotic discontinuation by patients with first-episode psychosis and schizophrenia is associated with increased relapse, rehospitalization, suicide mortality, cardiovascular mortality, and all-cause mortality. There is also the ethical matter that attempts to identify the few who may benefit from antipsychotic dose reduction and discontinuation may compromise the health and stability of the many who require long-term maintenance treatment.

Sex-related cortical asymmetry in antipsychotic-naïve first-episode schizophrenia.

Schizophrenia has been considered to exhibit sex-related clinical differences that might be associated with distinctly abnormal brain asymmetries between sexes. One hundred and thirty-two antipsychotic-naïve first-episode patients with schizophrenia and 150 healthy participants were recruited in this study to investigate whether cortical asymmetry would exhibit sex-related abnormalities in schizophrenia. After a 1-yr follow-up, patients were rescanned to obtain the effect of antipsychotic treatment on cortical asymmetry. Male patients were found to show increased lateralization index while female patients were found to exhibit decreased lateralization index in widespread regions when compared with healthy participants of the corresponding sex. Specifically, the cortical asymmetry of male and female patients showed contrary trends in the cingulate, orbitofrontal, parietal, temporal, occipital, and insular cortices. This result suggested male patients showed a leftward shift of asymmetry while female patients showed a rightward shift of asymmetry in these above regions that related to language, vision, emotion, and cognition. Notably, abnormal lateralization indices remained stable after antipsychotic treatment. The contrary trends in asymmetry between female and male patients with schizophrenia together with the persistent abnormalities after antipsychotic treatment suggested the altered brain asymmetries in schizophrenia might be sex-related disturbances, intrinsic, and resistant to the effect of antipsychotic therapy.

Clozapine Use Among People With Psychotic Disorders Who Experience Specific Indications for Clozapine.

Objective: To examine rates of clozapine use among people with psychotic disorders who experience specific indications for clozapine.Methods: Records data from 11 integrated health systems identified patients aged 18 years or older with recorded International Classification of Diseases, Tenth Revision, Clinical Modification, diagnoses of schizophrenia, schizoaffective disorder, or other psychotic disorder who experienced any of the 3 events between January 1, 2019, and December 31, 2019, suggesting indications for clozapine: a diagnosis of self-harm injury or poisoning, suicidal ideation diagnosed or in response to standardized assessments, and hospitalization or emergency department (ED) care for psychotic disorder despite treatment with 2 or more antipsychotic medications. Prescription dispensing data identified all clozapine use prior to or in the 12 months following each indication event. Analyses were conducted with aggregate data from each health system; no individual data were shared.Results: A total of 7,648 patients with psychotic disorder diagnoses experienced at least 1 indication event. Among 1,097 experiencing a self-harm event, 32 (2.9%) had any prior clozapine use, and 10 (0.9%) initiated clozapine during the following 12 months. Among 6,396 with significant suicidal ideation, 238 (3.7%) had any prior clozapine use, and 70 (1.1%) initiated clozapine over 12 months. Among 881 with hospitalization or ED visit despite pharmacotherapy, 77 (8.7%) had any prior clozapine treatment, and 41 (4.7%) initiated clozapine over 12 months. Among those with significant suicidal ideation, rates of both prior clozapine treatment and subsequent initiation varied significantly by race and ethnicity, with rates among Hispanic and non-Hispanic Black patients lower than among non Hispanic White patients.Conclusions: Initiating clozapine treatment is uncommon among people with psychotic disorders who experience events suggesting clozapine is indicated, with even lower rates among Black and Hispanic patients.

An algorithm for pharmacological treatment of mania during hospitalisation.

Current evidence for pharmacological treatment of mania during hospitalisation is insufficient as there are no larger well-designed randomised trials of comparative medical treatments of mania during inpatient stays. Moreover, there is considerable variation in pharmacological medication in clinical practice during hospitalisation for mania. Based on a hospital data overview, a systematic search of the literature and a three-day consensus meeting, this narrative review proposed an algorithm for optimised pharmacological treatment of mania during hospitalisation and its subsequent scientific evaluation.

[Clinical reflexes in the face of an atypical neuropsychiatric picture]. / Réflexes cliniques devant un tableau neuropsychiatrique atypique.

A 59-year-old man who had been presenting with a variety of neuropsychiatric symptoms for several weeks. Despite repeated visits to somatic emergencies, as well as a thorough work-up including complementary examinations and specialist opinions, no organic diagnosis was established. The patient was treated symptomatically with neuroleptics and benzodiazepines, which led to a significant improvement in symptoms.

Incorporating clinician insight and care plans into an audit and feedback initiative for antipsychotic prescribing to Medicaid-enrolled youth in Philadelphia.

BACKGROUND: Audit and feedback (A/F), which include initiatives like report cards, have an inconsistent impact on clinicians' prescribing behavior. This may be attributable to their focus on aggregate prescribing measures, a one-size-fits-all approach, and the fact that A/F initiatives rarely engage with the clinicians they target. METHODS: In this study, we describe the development and delivery of a report card that summarized antipsychotic prescribing to publicly-insured youth in Philadelphia, which was introduced by a Medicaid managed care organization in 2020. In addition to measuring aggregate prescribing behavior, the report card included different elements of care plans, including whether youth were receiving polypharmacy, proper medication management, and the concurrent use of behavioral health outpatient services. The A/F initiative elicited feedback from clinicians, which we refer to as an "audit and feedback loop." We also evaluate the impact of the report card by comparing pre-post differences in prescribing measures for clinicians who received the report card with a group of clinicians who did not receive the report card. RESULTS: Report cards indicated that many youth who were prescribed antipsychotics were not receiving proper medication management or using behavioral health outpatient services alongside the antipsychotic prescription, but that polypharmacy was rare. In their feedback, clinicians who received report cards cited several challenges related to antipsychotic prescribing, such as the logistical difficulties of entering lab orders and family members' hesitancy to change care plans. The impact of the report card was mixed: there was a modest reduction in the share of youth receiving polypharmacy following the receipt of the report card, while other measures did not change. However, we documented a large reduction in the number of youth with one or more antipsychotic prescription fill among clinicians who received a report card. CONCLUSIONS: A/F initiatives are a common approach to improving the quality of care, and often target specific practices such as antipsychotic prescribing. Report cards are a low-cost and feasible intervention but there is room for quality improvement, such as adding measures that track medication management or eliciting feedback from clinicians who receive report cards. To ensure that the benefits of antipsychotic prescribing outweigh its risks, it is important to promote quality and safety of antipsychotic prescribing within a broader care plan.

Evidence for Therapeutic Drug Monitoring of Atypical Antipsychotics.

Second-generation antipsychotics (SGAs), also known as atypical antipsychotics, are a newer class of antipsychotic drugs used to treat schizophrenia, bipolar disorder, and related psychiatric conditions. The plasma concentration of antipsychotic drugs is a valid measure of the drug at its primary target structure in the brain, and therefore determines the efficacy and safety of these drugs. However, despite the well-known high variability in pharmacokinetics of these substances, psychiatric medication is usually administered in uniform dosage schedules. Therapeutic drug monitoring (TDM), as the specific method that can help personalised medicine in dose adjustment according to the characteristics of the individual patient, minimizing the risk of toxicity, monitoring adherence, and increasing cost-effectiveness in the treatment, thus seems to be an elegant tool to solve this problem. Non-response to therapeutic doses, uncertain adherence to medication, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM of SGAs. This review aims to summarize an overview of the current knowledge and evidence of the possibilities to tailor the dosage of selected SGAs using TDM, including the necessary pharmacokinetic parameters for personalised pharmacotherapy.

Long-term persistence of the risk of agranulocytosis with clozapine compared with other antipsychotics: a nationwide cohort and case-control study in Finland.

BACKGROUND: Agranulocytosis is a life-threatening side-effect of clozapine, the only approved drug for treatment-resistant schizophrenia. The long-term profile of this complication has not yet been well established. Here we aim to describe the risk of clozapine-induced agranulocytosis over the long term. METHODS: We used the entire population of Finland to identify people diagnosed with schizophrenia or schizoaffective disorder between 1972 and 2014 and developed a Kaplan-Meier model of time to diagnosis of agranulocytosis during clozapine versus non-clozapine treatment over a 22-year observation period (1996 to 2017). Next, we developed a nested case-control model for agranulocytosis matching by sex, age, time since diagnosis, and being in the incident cohort on a 1 to 5 ratio. Various durations of use for clozapine and non-clozapine antipsychotic treatment were compared to the modal antipsychotic use duration, deriving adjusted odds ratios (aORs) in a multivariable regression model. Recurrence and lethality rates for clozapine-induced agranulocytosis were described. These data reflect on all individuals with lived experience of schizophrenia in Finland during the study time, although individuals with lived experience were not included in the design of the study. FINDINGS: We identified 61 769 people with schizophrenia or schizoaffective disorder (14 037 individuals treated with clozapine and 47 732 individuals treated with non-clozapine antipsychotics), with a mean age of 46·67 years (IQR 34·44-57·61), of whom 30 721 (49·7%) were female and 31 048 (50·3%) were male (data on ethnicity not available). Among those, 398 individuals were diagnosed with agranulocytosis (231 individuals treated with clozapine and 167 individuals treated with non-clozapine antipsychotics), representing a cumulative incidence of agranulocytosis for 1·37% (95% CI 0·58-3·16) on clozapine and 0·13% (0·04-0·23) on non-clozapine antipsychotics. In the case (n=398) versus control (n=1987) model, the risk of clozapine-induced agranulocytosis decreased steeply over time from an aOR of 36·01 (95% CI 16·79-77·22) for less than 6 months on clozapine to 4·38 (1·86-10·34) for clozapine use of 54 months or more. Only one of 3559 individuals starting clozapine died because of clozapine-induced agranulocytosis. INTERPRETATION: The risk of clozapine-induced agranulocytosis decreases steeply over time but might be persistently greater than that of non-clozapine antipsychotics. This long-term risk excess seems small in absolute terms compared with the known magnitude of the advantages of clozapine in relevant outcomes, including life expectancy. Given the widespread underuse of clozapine, relaxing the long-term neutrophil monitoring could favour the advantages of long-term clozapine use, including greater life expectancy, without incurring the intolerable risk of clozapine-induced agranulocytosis. FUNDING: Northwell Health and Sigrid Jusèlius Foundation.

Metabolic Syndrome in people treated with Antipsychotics (RISKMet): A multimethod study protocol investigating genetic, behavioural, and environmental risk factors.

INTRODUCTION: The RISKMet project aims to: (1) identify risk factors for metabolic syndrome (MetS) by comparing patients with and without MetS; (2) characterise patients treated with second-generation antipsychotics (SGAs) about MetS diagnosis; (3) study behavioural patterns, including physical activity (PA) and dietary habits, in patients and healthy individuals using a prospective cohort design. METHOD: The RISKMet project investigates MetS in individuals treated with SGAs, focusing on both adult and paediatric populations. The study utilizes a case-control design to examine potential risk factors for MetS, categorizing participants as MetS+ considered as "Cases" and MetS- considered as "Controls" matched by sex and age. The evaluation of factors such as MetS, lifestyle habits, and environmental influences is conducted at two time points, T0 and T3, after 3 months. Subsequently, the project aims to assess body parameters, including physical examinations, and blood, and stool sample collection, to evaluate metabolic markers and the impact of SGAs. The analysis includes pharmacological treatment data and genetic variability. Behavioural markers related to lifestyle, eating behaviour, PA, and mood are assessed at both T0 and T3 using interviews, accelerometers, and a mobile app. The study aims to improve mental and physical well-being in SGA-treated individuals, establish a biobank for MetS research, build an evidence base for physical health programs, and develop preventive strategies for SGA-related comorbidities. CONCLUSIONS: This project innovates MetS monitoring in psychiatry by using intensive digital phenotyping, identifying biochemical markers, assessing familial risks, and including genetically similar healthy controls. STUDY REGISTRATION NUMBER: ISRCTN18419418 at www.isrctn.com.

Cognitive Outcomes in Nonacute Patients With Schizophrenia Treated With Long-Acting Injectable Antipsychotics Versus Oral Antipsychotics.

BACKGROUND: Patients with schizophrenia often face challenges related to cognitive function, affecting their daily functioning and overall quality of life. The choice of antipsychotic treatment may play a crucial role in determining cognitive outcomes. STUDY QUESTION: Our study aimed to investigate whether there was a difference in cognitive ability between the patients with schizophrenia receiving oral antipsychotics (OAP) versus long-acting injectable antipsychotics (LAI-APs). STUDY DESIGN: We conducted a cross-sectional study using analytical methods between January 1, 2020, and January 1, 2022. Participants were divided into 2 groups: patients undergoing treatment with OAP and patients undergoing treatment with LAI-AP. All participants underwent version A of Brief Assessment of Cognition in Schizophrenia (BACS). MEASURES AND OUTCOMES: The primary objective was to compare cognitive function in patients with schizophrenia treated with LAI antipsychotics versus OAP using BACS. Primary outcome measures include overall BACS score, with secondary measures focusing on specific cognitive domains. This study contributes to the understanding of the cognitive effects of different antipsychotic formulations in schizophrenia treatment. RESULTS: Although there was a slightly higher intelligence quotient in the LAI-AP group (102.2 vs. 101.32, P = 0.5401), it was not statistically significant. Olanzapine was the most commonly prescribed antipsychotic, with 48% of patients in the LAI-AP group and 40% in the OAP group. The LAI-AP group outperformed in all BACS evaluations. The most notable difference was in the token motor task (57.78 ± 17.03 vs. 50.04 ± 18.82, P = 0.0335), while the Tower of London test showed the smallest difference (17.26 ± 2.61 vs. 15.48 ± 3.47, P = 0.0046). Regression analysis revealed no significant variance in intelligence quotient scores; however, a significant discrepancy in BACS scores was evident, favoring the LAI treatment for better cognitive outcomes. CONCLUSIONS: The use of long-acting antipsychotic treatment in individuals with schizophrenia offers promising advantages in preserving cognitive function.

Risk assessment for aggressive behaviour in schizophrenia.

BACKGROUND: Aggressive or violent behaviour is often associated with people with schizophrenia in common perceptions of the disease. Risk assessment methods have been used to identify and evaluate the behaviour of those individuals who are at the greatest risk of perpetrating aggression or violence or characterise the likelihood to commit acts. Although many different interventions have been developed to decrease aggressive or violent incidences in inpatient care, staff working in inpatient settings seek easy-to-use methods to decrease patient aggressive events. However, many of these are time-consuming, and they require intensive training for staff and patient monitoring. It has also been recognised in clinical practice that if staff monitor patients' behaviour in a structured manner, the monitoring itself may result in a reduction of aggressive/violent behaviour and incidents in psychiatric settings. OBJECTIVES: To assess the effects of structured aggression or violence risk assessment methods for people with schizophrenia or schizophrenia-like illnesses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ISRCTN registry, ClinicalTrials.gov, and WHO ICTRP, on 10 February 2021. We also inspected references of all identified studies. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing structured risk assessment methods added to standard professional care with standard professional care for the evaluation of aggressive or violent behaviour among people with schizophrenia. DATA COLLECTION AND ANALYSIS: At least two review authors independently inspected citations, selected studies, extracted data, and appraised study quality. For binary outcomes, we calculated a standard estimation of the risk ratio (RR) and its 95% confidence interval (CI). For continuous outcomes, we calculated the mean difference (MD) and its 95% CI. We assessed risk of bias in the included studies and created a summary of findings table using the GRADE approach. MAIN RESULTS: We included four studies in the review. The total number of participants was not identifiable, as some studies provided number of participants included, and some only patient days. The studies compared a package of structured assessment methods with a control group that included routine nursing care and drug therapy or unstructured psychiatric observations/treatment based on clinical judgement. In two studies, information about treatment in control care was not available. One study reported results for our primary outcome, clinically important change in aggressive/violent behaviour, measured by the rate of severe aggression events. There was likely a positive effect favouring structured risk assessment over standard professional care (RR 0.59, 95% CI 0.41 to 0.85; 1 RCT; 1852 participants; corrected for cluster design: RR 0.59, 95% CI 0.37 to 0.93; moderate-certainty evidence). One trial reported data for the use of coercive measures (seclusion room). Compared to standard professional care, structured risk assessment may have little or no effect on use of seclusion room as days (corrected for cluster design: RR 0.92, 95% CI 0.27 to 3.07; N = 20; low-certainty evidence) or use of seclusion room as secluded participants (RR 1.83, 95% CI 0.39 to 8.7; 1 RCT; N = 20; low-certainty evidence). However, seclusion room may be used less frequently in the standard professional care group compared to the structured risk assessment group (incidence) (corrected for cluster design: RR 1.63, 95% CI 0.49 to 5.47; 1 RCT; N = 20; substantial heterogeneity, Chi2 = 0.0; df = 0.0; P = 0.0; I2 = 100%; low-certainty evidence). There was no evidence of a clear effect on adverse events of escape (RR 0.2, 95% CI 0.01 to 4.11; 1 RCT; n = 200; very low-certainty evidence); fall down (RR 0.33, 95% CI 0.04 to 3.15; 1 RCT; n = 200; very low-certainty evidence); or choking (RR 0.2, 95% CI 0.01 to 4.11; 1 RCT; n = 200; very low-certainty evidence) when comparing structured risk assessment to standard professional care. There were no useable data for patient-related outcomes such as global state, acceptance of treatment, satisfaction with treatment, quality of life, service use, or costs. AUTHORS' CONCLUSIONS: Based on the available evidence, it is not possible to conclude that structured aggression or violence risk assessment methods are effective for people with schizophrenia or schizophrenia-like illnesses. Future work should combine the use of interventions and structured risk assessment methods to prevent aggressive incidents in psychiatric inpatient settings.

Aripiprazole-induced quasi-neuroleptic malignant syndrome: two case reports.

BACKGROUND: Significant elevation of creatine kinase levels (above three digits) and leucocytosis in the absence of muscle rigidity, tremors, or autonomic dysfunction can pose a real challenge in the context of antipsychotic treatment as an early herald of neuroleptic malignant syndrome. CASE PRESENTATION: We present here two cases of adult male patients of Black British heritage, ages 51 years and 28 years, respectively. Both received a diagnosis of schizoaffective disorder and presented with massive increase of creatine kinase blood level after aripiprazole depot administration, one with pernicious increase associated with silent neuroleptic malignant syndrome, and the second with asymptomatic benign enzyme elevation. CONCLUSION: Though aripiprazole use is less likely to cause neuroleptic malignant syndrome, on rare occasions it can produce massive symptomatic or asymptomatic increase in serum creatine kinase enzyme levels, raising the need for close monitoring, especially at the initial doses of the drug.