Neuroleptic Treatment Research Articles

Metabolic Side Effects from Antipsychotic Treatment with Clozapine Linked to Aryl Hydrocarbon Receptor (AhR) Activation.

Metabolic syndrome (MetS) is the most common adverse drug reaction from psychiatric pharmacotherapy. Neuroreceptor blockade by the antipsychotic drug clozapine induces MetS in about 30% of patients. Similar to insulin resistance, clozapine impedes Akt kinase activation, leading to intracellular glucose and glutathione depletion. Additional cystine shortage triggers tryptophan degradation to kynurenine, which is a well-known AhR ligand. Ligand-bound AhR downregulates the intracellular iron pool, thereby increasing the risk of mitochondrial dysfunction. Scavenging iron stabilizes the transcription factor HIF-1, which shifts the metabolism toward transient glycolysis. Furthermore, the AhR inhibits AMPK activation, leading to obesity and liver steatosis. Increasing glucose uptake by AMPK activation prevents dyslipidemia and liver damage and, therefore, reduces the risk of MetS. In line with the in vitro results, feeding experiments with rats revealed a disturbed glucose-/lipid-/iron-metabolism from clozapine treatment with hyperglycemia and hepatic iron deposits in female rats and steatosis and anemia in male animals. Decreased energy expenditure from clozapine treatment seems to be the cause of the fast weight gain in the first weeks of treatment. In patients, this weight gain due to neuroleptic treatment correlates with an improvement in psychotic syndromes and can even be used to anticipate the therapeutic effect of the treatment.

Cerebrospinal Fluid Homovanillic and 5-Hydroxyindoleacetic Acids in a Large Pediatric Population; Establishment of Reference Intervals and Impact of Disease and Medication.

Cerebrospinal fluid (CSF) homovanillic (HVA), and 5-hydroxyindoleacetic acids (5-HIAA) are biomarkers of neurological diseases affecting the dopaminergic and serotoninergic pathways. Establishing reference intervals for these metabolites faces the challenges of a lack of healthy controls and a negative correlation with age, making stratified intervals unrealistic. We propose a pipeline to determine continuous reference intervals for HVA and 5-HIAA using an indirect method. We also studied the confounding effects of different variables and explored the impact of antiepileptic and neuroleptic treatments on HVA and 5-HIAA values. The study used least squares regression to fit age-concentration curves from a cohort of pediatric patients (n = 1533), where the residuals represent metabolite values excluding age effect. Presuming that HVA and 5-HIAA primary deficiencies characterize a distinct subpopulation, we fitted a two-component finite mixture model in age-normalized data and set reference intervals at the central 95% of the nondeficient population. Patients with primary genetic deficiencies of HVA and/or 5-HIAA consistently fall outside the proposed continuous reference intervals. Using the new continuous reference intervals reduces the number of secondary deficiencies detected compared with using stratified values. No correlations were observed between CSF HVA and 5-HIAA values across the studied drug categories (antiseizure and neuroleptic medications). In addition, biopterin values positively influenced both metabolite concentrations. The proposed continuous reference intervals caused a substantial reduction in the number of secondary deficiencies detected, most of which demonstrated no conclusive correlations between the diseases and altered HVA and 5-HIAA values.

Modeling the Determinants of Subjective Well-Being in Schizophrenia.

The ultimate goal of successful schizophrenia treatment is not just to alleviate psychotic symptoms, but also to reduce distress and achieve subjective well-being (SWB). We aimed to identify the determinants of SWB and their interrelationships in schizophrenia. Data were obtained from 637 patients with schizophrenia enrolled in multicenter, open-label, non-comparative clinical trials. The SWB under the Neuroleptic Treatment Scale (SWN) was utilized; a cut-off score of 80 indicated a high level of SWB at baseline and 6 months. Various machine learning (ML) algorithms were employed to identify the determinants of SWB. Furthermore, network analysis and structural equation modeling (SEM) were conducted to explore detailed relationship patterns. The random forest (RF) model had the highest area under the curve (AUC) of 0.794 at baseline. Obsessive-compulsive symptoms (OCS) had the most significant impact on high levels of SWB, followed by somatization, cognitive deficits, and depression. The network analysis demonstrated robust connections among the SWB, OCS, and somatization. SEM analysis revealed that OCS exerted the strongest direct effect on SWB, and also an indirect effect via the mediation of depression. Furthermore, the contribution of OCS at baseline to SWB was maintained 6 months later. OCS, somatization, cognition, and depression, rather than psychotic symptoms, exerted significant impacts on SWB in schizophrenia. Notably, OCS exhibited the most significant contribution not only to the current state of well-being but also to follow-up SWB, implying that OCS was predictive of SWB. The findings demonstrated that OCS management is critical for the treatment of schizophrenia.

Disease Phenotypes in Refractory Musculoskeletal Pain Syndromes Identified by Unsupervised Machine Learning.

Overlapping chronic pain syndromes, including fibromyalgia, are heterogeneous and often treatment-resistant entities carrying significant socioeconomic burdens. Individualized treatment approaches from both a somatic and psychological side are necessary to improve patient care. The objective of this study was to identify and visualize patient clusters in refractory musculoskeletal pain syndromes through an extensive set of clinical variables, including immunologic, psychosomatic, wearable, and sleep biomarkers. Data were collected during a multimodal pain program involving 202 patients. Seventy-eight percent of the patients fulfilled the criteria for fibromyalgia, 77% had a concomitant psychiatric-mediated disorder, and 22% a concomitant rheumatic immune-mediated disorder. Five patient phenotypes were identified by hierarchical agglomerative clustering as a form of unsupervised learning, and a predictive model for the Brief Pain Inventory (BPI) response was generated. Based on the clustering data, digital personas were created with DALL-E (OpenAI). The most relevant distinguishing factors among clusters were living alone, body mass index, peripheral joint pain, alexithymia, psychiatric comorbidity, childhood pain, neuroleptic or benzodiazepine medication, and response to virtual reality. Having an immune-mediated disorder was not discriminatory. Three of five clusters responded to the multimodal treatment in terms of pain (BPI intensity), one cluster responded in terms of functional improvement (BPI interference), and one cluster notably responded to the virtual reality intervention. The independent predictive model confirmed strong opioids, trazodone, neuroleptic treatment, and living alone as the most important negative predictive factors for reduced pain after the program. Our model identified and visualized clinically relevant chronic musculoskeletal pain subtypes and predicted their response to multimodal treatment. Such digital personas and avatars may play a future role in the design of personalized therapeutic modalities and clinical trials.

Machine Learning-Enhanced Evaluation of Neuroleptics Efficacy and Management in Schizoaffective Disorder

Background Neuroleptics or antipsychotic medications are widely used in the treatment of various psychiatric disorders. However, they have been associated with the secondary development of obsessive-compulsive symptoms (OCS) in some patients. This case report examines two patients who developed obsessive-compulsive aspects secondary to neuroleptic treatment, analysed using visual data representations and machine learning. Objective To evaluate the development of OCS in patients treated with neuroleptics and to analyse their clinical outcomes using Y-BOCS and CGI-S scores, complemented by machine learning predictions. Methods Two patients treated with neuroleptics were assessed for the emergence of OCS using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Clinical Global Impression-Severity (CGI-S). Data were collected before and after the onset of OCS, and visualizations were employed to illustrate symptom progression and treatment effectiveness. Machine learning techniques were applied to predict OCS outcomes. Results Both patients developed significant OCS after the initiation of neuroleptic treatment. Their Y-BOCS and CGI-S scores increased, indicating the emergence and severity of OCS. Following treatment adjustments, both patients showed marked improvement in their scores. Machine learning models provided additional insights into the factors influencing OCS development. Conclusion These findings highlight the potential for neuroleptics to induce secondary OCS in patients, necessitating careful monitoring and management of these symptoms. Visual data analysis and machine learning provide powerful tools to understand and communicate these clinical changes.

Predictive Analysis of Neuroleptics-Induced Obsessive-Compulsive Symptoms Using Machine Learning

Background Neuroleptics, or antipsychotic medications, are widely used in the treatment of various psychiatric disorders. However, they have been associated with the secondary development of obsessive-compulsive symptoms (OCS) in some patients. This case report examines two patients who developed obsessive-compulsive aspects secondary to neuroleptic treatment. Objective To evaluate the development of OCS in patients treated with neuroleptics and to analyse their clinical outcomes. Methods Two patients treated with neuroleptics were assessed for the emergence of obsessive-compulsive symptoms using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Clinical Global Impression-Severity (CGI-S). Data were collected before and after the onset of OCS. Results Both patients developed significant OCS after the initiation of neuroleptic treatment. Their Y-BOCS and CGI-S scores increased, indicating the emergence and severity of OCS. Also include the bar plots, line plots, pair plots, heatmap, and box plots to present the findings visually. Explain each plot in the context of the patients' symptom progression and treatment adjustments. Conclusion These findings highlight the potential for neuroleptics to induce secondary obsessive-compulsive aspects in patients, necessitating careful monitoring and management of these symptoms.

Clinical and Sociodemographic Correlations with Neurological Soft Signs in Hospitalized Patients with Schizophrenia: A Preliminary Longitudinal Study.

Schizophrenia is a severe, chronic neuropsychiatric disorder characterized by symptoms that profoundly impact behavior, cognition, perception, and emotions, leading to a reduced quality of life and physical impairment. Given the complexity of schizophrenia, there is a pressing need for clinical markers and tools to predict its course, enhance disease staging, facilitate early intervention, improve differential diagnosis, and tailor individualized treatment approaches. Previous studies focused on the relationship between neurological soft signs (NSS) and factors such as age, illness duration, and symptomatology, indicating NSS as state markers improving in parallel with psychotic symptom remission or predicting treatment resistance. However, there is a lack of consensus on NSS assessment tools, hindering routine clinical monitoring despite diagnostic and prognostic potential. The present longitudinal study involved 81 psychiatric inpatients diagnosed with schizophrenia. Patients were assessed at three time points: baseline, 1 month, and 6 months. The examination included the use of scales to evaluate psychotic and neurological symptoms, as well as the identification of adverse extrapyramidal reactions caused by neuroleptic treatment. The progression of NSS was correlated to both the symptomatology and the sociodemographic data of the patients. The main findings from the present investigation revealed a statistical correlation between NSS and psychopathological symptoms, especially with negative symptoms of schizophrenia. However, it is important to note that neuroleptic side effects only had a limited impact on NSS. Therefore, instead of being linked to extrapyramidal symptoms caused by neuroleptics, NSS appears to be more frequently related with symptoms of schizophrenia. Our findings provide further support for their strong association with the course of schizophrenia, independent of treatment side effects, thus emphasizing their potential as reliable assessment tools in both research and clinical settings.

Importance of the type of pharmacological treatment in patients with severe mental disorder

Introduction The use of long-acting treatments is a common clinical practice in psychiatry. No disease insight and the risk of treatment discontinuation in a significant portion of our patients, increase the demand for psychiatric emergency and hospital admissions. Treatment adherence must be facilitated, taking into account possible side effects and patient´s subjective satisfaction.Objectives-Evaluate the type of long-acting intramuscular treatment in selected patients. -Evaluate the differences in treatment satisfaction between different types of long-acting intramuscular treatments as well as frequency of psychiatric emergency and hospital admissions in the last year.MethodsWe select patients with different severe mental disorders who stay in a Medium Stay Unit, Sociosanitary Community Residence, Supervise house and Residence for the elderly in Albacete (Spain); all of them, with intramuscular neuroleptic treatment (zuclopenthixol dihydrochloride, aripiprazole long acting, palmitate paliperidone monthly, 3-monthly and 6-monthly) at least 1 year.We evaluate their sociodemographic characteristics, the satisfaction questionnaire with the treatment (TSQM-9) and the rate of psychiatric emergencies and admissions after current intramuscular treatment in last year.ResultsWe have selected 57 patients with an average age of 45.86. 78.94% with a diagnosis of schizophrenia, 12.28% with schizoaffective disorder, 5.26% bipolar disorder and 3.5% unspecified psychotic disorder.We can see in the graphics below that the longer duration of the intramuscular treatment, the greater satisfaction in all the items of the TSQM-9 questionnaire. 31% of the patients with zuclopenthixol dihydrochloride treatment, have gone to psychiatric emergencies and 28% of psychiatric admissions in the last year.18% of the patients with aripiprazole long acting, 17% with paliperidone palmitate long acting-monthly and 12% de 3-monthly have gone to psychiatric emergencies and 15%, 12% and 12% needed psychiatric admissions respectively. Patients with palmitate long acting-monthly have not emergencies or psychiatric admissions in the last year.Image:Image 2:Image 3:Conclusions- The longer long acting of the intramuscular treatments, the better patient satisfaction.- With the longer duration treatment (Palmitate paliperidone LD 6 month), we have lower psychiatric emergencies and hospital admissions.Disclosure of InterestNone Declared

Subjective discomfort and lack of volitional drive with neuroleptic pharmacotherapy - a phenomenological case study

IntroductionIn comparison to extrapyramidal and metabolic side effects, the subjective aspects of neuroleptic treatment have been less extensively researched. Nevertheless, they are equally significant given their potential to influence adherence and functional outcome. Historically, terms such as “neuroleptic dysphoria,” “neuroleptic-induced psychic indifference,” and “neuroleptic-induced deficit syndrome” were used to characterize a range of unpleasant mood states on the one hand and a documented and observable motivational deficit on the other. The latter aligns with the findings from preclinical neuroscientific studies and animal models highlighting the significant involvement of mesolimbic dopamine in motivational processes. Despite an abundance of anecdotal data these adverse effects are often undetectable in large-scale clinical studies that utilize standardized assessment measures.ObjectivesTo present adverse subjective changes in arousal, mood and volitional drive resulting from neuroleptic intake from a patient’s perspective.MethodsThe subject is a patient, with no reported negative symptoms or lasting functional impairment described, who underwent a gradual 6-month discontinuation of risperidone in an outpatient setting following a complete recovery after a single psychotic episode. A semi-structured interview modelled after The Clinical Assessment Interview for Negative Symptoms (CAINS) was conducted. We aimed to elicit descriptions of the subjective experience while ensuring our approach remained non-suggestive.ResultsIn addition to describing potential akathisia and lethargy at higher doses, the subject reported a significant lack of motivation and a notably reduced willingness to exert effort towards achieving specific goals or engaging in activities that he still found rewarding or pleasurable. Furthermore, he consistently noted gradual improvements across various psycho-social aspects following the discontinuation of the medication. These adverse and unpleasant experiences were presented as the primary reason for wanting to discontinue pharmacological treatment.ConclusionsCertain adverse effects of antipsychotic medications can only be elucidated by the clinician through the examination of the patient’s subjective experiences. Medication induced dysphoria and volitional deficits have the potential to profoundly impact treatment adherence, leading to unrecommended discontinuation of neuroleptics, and can cause important functional impairment.Disclosure of InterestNone Declared

Efficacy and tolerability of half-yearly long acting injectable palmitate paliperidone after 12 months follow-up

IntroductionThis retrospective study analysed the clinical efficacy, tolerability and treatment satisfaction of patients who switched from receiving palmitate paliperidone monthly (PP1M) to palmitate paliperidone six-monthly (PP6M) after 12 months of follow-up. A total of 48 patients (31 men and 17 women) with recently diagnosed schizophrenia were included.ObjectivesTo assess the clinical efficacy, tolerability and treatment satisfaction in a sample of recently diagnosed schizophrenic patients who switched from receiving palmitate paliperidone monthly (PP1M) to palmitate paliperidone six-monthly (PP6M)MethodsThe sample included a total of 48 recently diagnosed schizophrenic (1-5 years) from three Mental Health units in the province of Toledo (Spain). The inclusion criteria were a diagnosis of schizophrenia (based on the ICD-10 criteria), the start of treatment with Long Acting Injectable Paliperidone Palmitate six-monthly (previously with palmitate paliperidone monthly), and the non-utilization of another neuroleptic treatment. A series of demographic variables were recorded, PANSS scale was used to to identify the presence and severity of psychopathology symptoms and the CGI scale was used to assessed the severity of the symptoms finally time to relapse was measured (primary outcome). The scales were again applied at baseline, 3 and 6 and 12 months after the start of treatmentResultsN=48 patients (31 males and 17 females), with a mean age of 31 years. 4.3 years of evolution of illness. During the follow-up period only 2 patients (4%) relapsed. Results showed an improvement in PANSS (baseline 50.8, 3 months 41.9, 6 months 37.3, 12 months 26.1), likewise and improvement in CGI was observed (baseline 4.1, 3 months 3.4, 6 months 2.9, 12 months 2.5).In terms of tolerability, no secundary effects were reported after treatment change, suggesting a good safety profile and predictable tolerability of PP6M. Patient satisfaction with treatment also improved over time. The study reports that 87% of patients accepted the switch from PP1M to PP6M, with reasons for switching including reduced frequency of administration and increased comfort. Most patients (95%) received antipsychotic monotherapy.ConclusionsIn conclusion, this study suggests that switching from PP1M to PP6M in patients with recently diagnosed schizophrenia was associated with maintained clinical stability, good tolerability and improved patient satisfaction with treatment. These findings support the efficacy and clinical utility of PP6M as a convenient and effective treatment option for patients with schizophrenia.Disclosure of InterestNone Declared

Psychosis following traumatic brain injury: A case study and a brief overview

IntroductionPsychosis resulting from traumatic brain injury (TBI) is a relatively uncommon but potentially severe and disabling outcome. The complex relationship between TBI and the onset of psychosis is marked by significant scientific uncertainty and differing opinions.ObjectivesTo investigate the occurrence of psychosis following traumatic brain injury (TBI) and explore the intricate relationship between TBI and the development of psychosis.MethodsA comprehensive case report was conducted on a 38-year-old patient who, after a severe TBI at the age of 23, exhibited signs of psychosis. Developmental history, family background, clinical assessments, magnetic resonance imaging (MRI), and electroencephalogram (EEG) results were analyzed.ResultsThe patient, at the time of writing aged 38, was born at full term with a regular presentation and uneventful delivery, with no indications of perinatal or obstetric complications. Developmentally, he reached all milestones within the expected range, and there were no significant premorbid characteristics. There was no family history of schizophrenia in a first- or second-degree relative; a paternal cousin had had psychosis-like symptoms, but reportedly remained well without any medication.At the age of 23, the patient was knocked from his motorcycle by a car and sustained a severe traumatic brain injury (TBI), with initial loss of consciousness and was in a coma state for approximatively a month, with later sequelae of cerebellar syndrome and predominant right-sided pyramidal syndrome.Magnetic resonance imaging (MRI) a year following the TBI showed sequelae of bifrontal and temporal contusion lesions.An EEG did not indicate any evidence of epilepsy, and a repeat EEG 14 years later revealed no diagnostic abnormality.A year after the accident, his surroundings have noticed social withdrawal, a turning inward with a religious fervor, and persecutory remarks focused on his brother. At the age of 26, he presented to a psychiatric service having auditory hallucinations. He was deluded, believing himself to be a prophesied redeemer figure who is expected to appear and bring justice and righteousness to the world. He had an inappropriate affect. A diagnosis of schizophrenia was made, and neuroleptics prescribed. His auditory hallucinations faded, but the subsequent course was of repeated episodes of florid psychosis requiring maintenance neuroleptic treatment, eventually haloperidol decanoate (150mg monthly).ConclusionsPsychosis following TBI is an uncommon yet potentially severe consequence, carrying the risk of significant debilitation. The relationship between TBI and psychosis is complex, but notable distinctions exist in clinical, epidemiological, and neurobiological aspects when compared to primary psychotic disorders.Disclosure of InterestNone Declared

Association of somatic comorbidity and treatment adherence in patients with psychotic disorder

BackgroundIncreased risk for somatic comorbidity in individuals with schizophrenia has been well established. In addition, psychiatric patients with somatic illnesses are more likely to have more psychiatric readmissions. Increased burden of treatment related to chronic somatic comorbidities may be associated with lower adherence to psychiatric medication. MethodsCross-sectional study of 275 patients with schizophrenia spectrum disorder. A general practitioner performed a complete physical health checkup for all participants, including a complete medical examination and laboratory tests. Patients’ adherence, attitudes, insight, and side-effects were evaluated using the Attitudes toward Neuroleptic Treatment Scale. Overall symptomatology was measured using the Brief Psychiatric Rating Scale. Regression analysis was used to investigate interactions and associations among health beliefs, disease burden, and treatment adherence. Separate regression models were utilized to account for the complexity of health behavior and treatment adherence pathways. ResultsPatients’ somatic comorbidity and health behavior were not associated with adherence or attitudes toward antipsychotic treatment. High dose of antipsychotics and obesity were related to the need for medical interventions, while a healthy diet reduced the risk. Higher BPRS score and older age were associated with having somatic symptoms. Somatic comorbidities had no negative effects on treatment adherence or attitudes. ConclusionThis study focuses on exploring possible associations between health beliefs and treatment adherence pathways in patients with psychotic disorders. Contrary to our hypotheses, we found no evidence to support our health belief and diseases burden models and their associations.

Relationship between medication burden and medication experience in stable patients with schizophrenia: the mediating effect of medication belief

BackgroundIndividuals with schizophrenia require prolonged antipsychotic medication treatment. But more than 50% of individuals with schizophrenia experience adverse medication experiences during their antipsychotic treatments. Such individuals often adjust or discontinue medication, leading to disease relapse and impaired social functioning. Psychiatric nurses should pay close attention to the medication experiences of individuals with schizophrenia. This research explore the relationship between medication burden and medication experience, as well as the mediating effect of medication belief in stable patients with schizophrenia.MethodsA convenience sample of hospitalized stable patients with schizophrenia were selected from Daqing Third Hospital and Baiyupao Hospital from September 2023 to December 2023. A survey was conducted with them using a questionnaire consisting of general information questionnaire, The Subjective Well-being Under Neuroleptic Treatment Scale(SWN), The Living with Medicines Questionnaire(LMQ), Beliefs about Medicines Questionnaire-Specific (BMQ-Specific). Pearson correlation analysis was used to explore the correlation between LMQ, BMQ-Specific and SWN scores, and multiple linear regression analysis was used to explore the influencing factors of medication experience in patients with schizophrenia. AMOS 24.0 was used to construct the structural equation modeling(SEM), and the mediation effect of the SEM was tested using Bootstrap method.ResultsAccording to the sample size calculation requirements of structural equation model, a total of 300 samples were required in this study, and 400 effective questionnaires were actually collected in this study, which met the sample size requirements for constructing structural equation models. Bootstrap test showed that the mediation effect was significant. The total effect of medication burden on medication experience was significant (Z=-12.146, 95%CI (-0.577, -0.417), P < 0.001). The indirect effect of medication burden on medication experience, that is, the mediating effect of medication belief was significant (Z=-4.839, 95%CI (-0.217, -0.096), P < 0.001). The direct effect of medication burden on medication experience was significant (Z=-7.565, 95%CI (-0.437, -0.257), P < 0.001). This model belongs to partial mediation model.ConclusionsPsychiatric nurses can enhance the patients’ medication experience by reducing medication burden and strengthening medication beliefs. Therefore, the results also provide theoretical references and decision-making foundations for psychiatric nursing professionals to develop appropriate management strategies for individuals with schizophrenia.

DRD4 VNTR 4/4 homozygosity as a genetic biomarker for treatment selection in patients with schizophrenia

ObjectiveThere seems to be an association between the DRD4 48-bp VNTR polymorphisms and antipsychotic treatment response, but there is a rare reference to confirm this finding. Hence, the present study tried to investigate the association between DRD4 48-bp VNTR polymorphisms and the treatment response of antipsychotics in patients with schizophrenia in Taiwan, using a propensity score matching (PSM) method. MethodsA total of 882 participants were enrolled in this study and completed informed consent, research questionnaires, including demographic information and the revised Chinese version Beliefs about Voices Questionnaire, and blood sampling. For descreasing of the selection bias and confounding variables, the PSM nearest neighbor matching method was used to select 765 paitents with schizophrenia (ratio of 1:8 between 85 persistent auditory hallucination and 680 controls) with matched and controlled the age and gender. ResultsSchizophrenia patients with DRD4 4 R homozygosity had a lower rate of good antipsychotic treatment response than the other DRD4 genotype carriers (DRD4 non-4/4). Among those 4 R homozygosity carriers, 60 cases of 503 (11.9%) retain persistent auditory hallucinations. Furthermore, this subgroup of patients is accounted for up to 70.6% of cases with poor neuroleptic treatment response. ConclusionsA poor treatment outcome for patients with the 4 R homozygosity had presented,that comparing with those DRD non-4/4 genotype carriers. DRD4 VNTR 4 R homozygosity could be a genetic biomarker to predict poor antipsychotic treatment response in schizophrenia. Patients with DRD 4/4 probably receive novel antipsychotic medications preferentially or in combination with alternative therapy, such as psychotherapy or milieu therapy.

Malignant Neuroleptic Syndrome: From Diagnosis to Management. Experience at Ar-Razi Hospital

Malignant Neuroleptic Syndrome (MNS) is a diagnostic and therapeutic emergency that poses a threat to a patient's life. It represents a rare but severe complication of neuroleptic treatment. It can occur with any antipsychotic, regardless of dosage or administration route. Its exact cause remains unknown. We present a series of 20 cases of MNS in patients hospitalized at Ar-Razi Hospital over a 3-year period, spanning from January 2018 to October 2021. We describe the clinical characteristics of MNS in these patients, the treatments received, the management, and the outcome of this syndrome. The clinical presentation of MNS is heterogeneous, with some patients not meeting all the criteria for MNS. 85% of the patients experienced a favorable outcome without complications. Early recognition of MNS can save lives. In the presence of fever, altered consciousness, generalized rigidity, tachycardia, and labile blood pressure in a patient taking antipsychotics, consider malignant neuroleptic syndrome and discontinue any suspect medication.

Subjective assessment of brexpiprazole in patients with schizophrenia: a prospective observational study.

To investigate the subjective assessments of an antipsychotic treatment with brexpiprazole. This was a 14-week prospective observational study. Nineteen patients participated in the study between February 2019 and January 2020. Patients had a mean age of 40.6±14.2 years and a Clinical Global Impressions-Severity of Illness scale (CGI-S) score of 4.6±1.2 at the initiation of brexpiprazole treatment. The Subjective Well-being under Neuroleptic drug treatment Short form, Japanese version (SWNS-J) total score significantly improved from 68.1±22.3 in week 2 to 79.5±21.0 in week 14 (p=0.0084). The SWNS-J subscales of self-control and social integration status also significantly improved from 14.0±4.7 and 13.9±6.0 in week 2 to 17.0±4.7 and 16.0±5.1 in week 14, respectively (p=0.0053 and 0.012, respectively). No significant improvements were observed in any other SWNS-J subscales or the Drug Attitude Inventory-10 (DAI-10) in the 14-week observation period. Moreover, the SWNS-J total score did not correlate with the DAI-10 (r=0.31, p=0.19), or CGI-S (r=-0.18, p=0.47) scores. The present results suggest that brexpiprazole might improve subjective well-being, although this may not necessarily reflect psychopathological improvements. To enhance medication adherence, it is important to perform subjective assessments on patients over time.

Giant faecaloma as a complication of neuroleptic treatment – case report.

A faecal impaction is a condition that is well known as a complication of long-term neuroleptic treatment. Rarely can provide life-threatening complications such as gastrointestinal obstruction. Long-term consolidation of faecal masses can lead to create a well-formed, hard intraluminal conglomerate (faecaloma). Fecaloma can be successfully conservatively treated. In some cases endoscopic methods may be effective. Rarely surgical treatment is required. Prophylaxis of faecal impaction is important to patients undergoing neuroleptic therapy. Indispensable is to monitor the patient's condition for constipation and obstruction of the gastrointestinal tract. In this case study, we want to present a case of a giant faecaloma, which appeared as a complication of neuroleptic treatment.

Augmentation Therapies as Treatments for Coexisting Somatic Problems in Schizophrenia-A Systematic Review.

The aim of this review is to appraise the data from available randomized clinical trials (RCT) regarding the possible combinations of neuroleptic and non-antipsychotic treatment which could enhance antipsychotic therapy efficacy whilst simultaneously addressing somatic symptoms in individuals with schizophrenia. A systematic search of the PubMed database up to February 2022 was conducted. Inclusion criteria: randomized controlled trials using augmentation therapy in chronic schizophrenia in adults, written in English, and only studies with psychometric assessments of schizophrenia were incorporated. Exclusion criteria: non-clinical, first episode of schizophrenia, patients on medication other than antipsychotics augmented, and not adjunctive therapy. Overall, 37 studies of 1931 patients with schizophrenia who received a combination of antipsychotic medication with other drugs were selected. A statistically significant reduction of negative and positive symptoms of schizophrenia, measured with the PANSS scale, when using a combination of antipsychotic treatment along with aspirin, simvastatin, N-acetylcysteine, or pioglitazone was found. A combination of antipsychotic medication with aspirin, simvastatin, N-acetylcysteine, or pioglitazone seems to be effective in the reduction of symptoms of schizophrenia in adults, but long-term studies are required to confirm this effect.

Safety and efficacy of aripiprazole 2-month ready-to-use 960 mg: secondary analysis of outcomes in adult patients with bipolar I disorder in a randomized, open-label, parallel-arm, pivotal study

Objective Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable antipsychotic formulation for administration every 2 months. A 32-week trial evaluated the safety, tolerability, and pharmacokinetics of Ari 2MRTU 960 in clinically stable adults with schizophrenia or bipolar I disorder (BP-I) (per DSM-5 criteria). This secondary analysis evaluated the safety and efficacy of Ari 2MRTU 960 in the subpopulation of patients with BP-I. Methods Patients with BP-I were randomized to receive Ari 2MRTU 960 (n = 40) every 56 ± 2 days (4 injections scheduled) or aripiprazole once-monthly 400 mg (AOM 400; n = 41) every 28 ± 2 days (8 injections scheduled). Data were collected during August 2019–July 2020 across 16 US sites. Primary safety endpoints included reported adverse events (coded by the Medical Dictionary for Regulatory Activities preferred term), injection site reactions (assessments included a Visual Analog Scale [VAS] to evaluate patient-reported injection-site pain), and motoric symptoms. Secondary endpoints for efficacy included change from baseline at Week 32 in the Young Mania Rating Scale (YMRS), Montgomery–Åsberg Depression Rating Scale (MADRS), Clinical Global Impression – Bipolar Version (CGI-BP), and Subjective Well-being under Neuroleptic Treatment – Short Form (SWN-S) scores, and Clinical Global Impression – Improvement (CGI-I) at Week 32. Results The incidence of treatment-emergent adverse events (TEAEs) was similar between Ari 2MRTU 960 (82.5% [33/40]) and AOM 400 (87.8% [36/41]; p = .5468). The most frequently reported TEAE was increased weight (Ari 2MRTU 960: 25.0% [10/40]; AOM 400: 26.8% [11/41]; p = 1). Injection-site pain was experienced by more patients in the Ari 2MRTU 960 group (25% [10/40]) versus the AOM 400 group (7.3% [3/41]; p = .0622). Mean (standard deviation [SD]) VAS scores for patient-reported injection-site pain following the last injection were 1.2 (2.07) for Ari 2MRTU 960 group and 1.3 (2.19) for AOM 400 (p = .9479) (VAS scale range 0–100 [no pain–extreme pain]). No notable improvement or decline from baseline was observed in motoric symptoms in either treatment group. Patients in both treatment groups remained clinically stable for the entire 32-week trial duration, with minimal difference between treatment groups in the least squares (LS) mean change from baseline at Week 32 in the YMRS Total (p = .8995), MADRS Total (p = .3185), and CGI-BP scores (p = .8485), and in mean CGI-I score (p = .7960). LS mean change from baseline in SWN-S score was greater for Ari 2MRTU 960 than for AOM 400 at Week 32 (p = .0169). Conclusions Ari 2MRTU 960 was well tolerated in patients with BP-I, with efficacy similar to AOM 400. Trial registration ClinicalTrials.gov identifier: NCT04030143.

Antipsychotic Medication Influences the Discriminative Value of Acylethanolamides as Biomarkers of Substance Use Disorder.

Plasma acylethanolamides (NAEs), including the endocannabinoid anandamide (AEA), have been proposed as circulating biomarkers of substance use disorders. However, the concentration of these lipid transmitters might be influenced by the use of drugs prescribed for either the treatment of addiction or the associated psychiatric co-morbidities such as psychosis. As an example, neuroleptics, used for attenuation of psychotic symptoms and sedation, might theoretically interfere with the monoamine-mediated production of NAEs, obstructing the interpretation of plasma NAEs as clinical biomarkers. To solve the lack of information on the impact of neuroleptics on the concentration of NAEs, we evaluated the concentrations of NAEs in a control group and compared them to those present in (a) substance use disorders (SUD) patients that are not prescribed with neuroleptics, and (b) SUD patients (both alcohol use disorder and cocaine use disorder patients) using neuroleptics. The results demonstrate that SUD patients exhibited greater concentrations of NAEs than the control population, affecting all species with the exception of stearoylethanolamide (SEA) and palmitoleoylethanolamide (POEA). Neuroleptic treatment enhanced the concentrations of NAEs, especially those of AEA, linoleoylethanolamide (LEA), and oleoylethanolamide (OEA). This effect of neuroleptic treatment was observed independently of the drug addiction that motivated the demand for treatment (either alcohol or cocaine). This study remarks the need to control the current use of psychotropic medication as a potential confounding variable when considering the use of NAEs as biomarkers in SUD.