Comparative efficacy of akathisia treatments: A network meta-analysis.

OBJECTIVE: Akathisia, a common side effect of psychotropic medications, poses a significant challenge in neuropsychiatry, affecting up to 30% of patients on antipsychotics. Despite its prevalence, akathisia remains poorly understood, with difficulties in diagnosis, patient reporting, and treatment efficacy. This research aimed to shed light on effective interventions to improve akathisia management. METHODS: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted, encompassing controlled trials in English and Italian languages. Databases, such asPubMed, Scopus, and EMBASE, were searched until July 9, 2023. Treatment effectiveness was assessed using standardized mean differences (SMDs) in post-treatment akathisia scores. RESULTS: Thirteen studies involving 446 individuals met the inclusion criteria. Benzodiazepines, beta-blockers, and NaSSA demonstrated significant efficacy as compared with placebo. Anticholinergic, anticonvulsant, triptan, and other treatments did not show significant differences. Benzodiazepines ranked highest in P-scores (0.8186), followed by beta-blockers and NaSSA. CONCLUSIONS: Effective management of akathisia is crucial, with benzodiazepines, beta-blockers, and NaSSA offering evidence-based options. Treatment rankings provide guidance for clinicians. Future research should prioritize larger, more robust studies to address limitations associated with small sample sizes and publication bias. This research enhances our understanding of interventions for akathisia, offering promising options to improve patient quality of life and prevent complications related to non-adherence and mismanagement.

Appearance of extrapyramidal symptoms in adolescent psychiatry patients during COVID-19 infection.

Since the start of the pandemic, there has been an increase in the incidence of psychiatric morbidity among those infected with coronavirus disease 2019 (COVID-19) and those indirectly affected by COVID-19. There has been a considerable increase in the number of individuals with such psychiatric conditions as depression, acute stress disorders, anxiety, and posttraumatic stress disorder (PTSD). About one-third of patients with COVID-19 are reported to have developed short and long-term neuropsychiatric conditions such as delirium, agitation, altered consciousness, hypoxic encephalopathy encephalitis, dysexecutive syndrome, cerebrovascular complications (e.g., stroke), hypoxic encephalopathy, convulsions, neuromuscular dysfunction, demyelinating processes, or parkinsonism through several pathophysiological mechanisms. Nevertheless, as the pandemic progressed, data on neuropsychiatric manifestations implied that the pathologic capacity of COVID-19 and its association with the onset and/or exacerbation of psychiatric morbidity indicate that COVID-19 is potentially related to neuropsychiatric involvement. Patients with existing mental disorders under psychotropic treatment exposed to the COVID-19 infection have been represented by an increased risk of worsened psychiatric symptoms and expanded drug side effects. The present study aimed to describe five pediatric patients with various psychiatric illness that experienced COVID-19 infection and had potentially associated neuropsychiatric involvement, such as exacerbation of underlying psychiatric symptoms and extrapyramidal side effects. To the best of our knowledge, the present study is the first to describe adolescents with COVID-19 infection that presented with a series of manifestations in the form of an increase in extrapyramidal symptoms (EPS)  during exacerbation of underlying psychiatric disease.

The Extrapyramidal Symptom Rating Scale and Its Abbreviated Version: A Critical Review of Clinimetric Properties.

BACKGROUND: The Extrapyramidal Symptom Rating Scale - Abbreviated (ESRS-A) is an abbreviated version of the Extrapyramidal Symptom Rating Scale (ESRS) with instructions, definitions, and a semi-structured interview that follows clinimetric concepts of measuring clinical symptoms. Similar to the ESRS, the ESRS-A was developed to assess four types of drug-induced movement disorders (DIMD): parkinsonism, akathisia, dystonia, and tardive dyskinesia (TD). SUMMARY: The present review of the literature provides the most relevant clinimetric properties displayed by the ESRS and ESRS-A in clinical studies. Comprehensive ESRS-A definitions, official scale, and basic instructions are provided. ESRS inter-rater reliability was evaluated in two pivotal studies and in multicenter international studies. Inter-rater reliability was high for assessing both antipsychotic-induced movement disorders and idiopathic Parkinson's disease. Guidelines were also established for inter-rater reliability and the rater certification processes. The ESRS showed good concurrent validity with 96% agreement between Abnormal Involuntary Movement Scale (AIMS) for TD-defined cases and ESRS-defined cases. Similarly, concurrent validity for ESRS-A total and subscores for parkinsonism, akathisia, dystonia, and dyskinesia ranged from good to very good. The ESRS was particularly sensitive for detecting DIMD-related movement differences following treatment with placebo, antipsychotics, and antiparkinsonian and antidyskinetic medications. ESRS measurement of drug-induced extrapyramidal symptoms was shown to discriminate extrapyramidal symptoms from psychiatric symptoms. KEY MESSAGES: The ESRS and ESRS-A are valid clinimetric indices for measuring DIMD. They can be valuably implemented in clinical research, particularly in trials testing antipsychotic medications, and in clinics to detect the presence, severity, and response to treatment of movement disorders.

The factor structure of extrapyramidal symptoms evaluated using the Drug-Induced Extrapyramidal Symptoms Scale in patients with schizophrenia: Results from the 2016 REAP AP-4 study.

INTRODUCTION: Drug-induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychiatry. This study aimed to examine the factor structure of drug-induced extrapyramidal symptoms observed in patients with schizophrenia and assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). METHODS: The participants were 1478 patients with a diagnosis of schizophrenia whose EPS was assessed using the DIEPSS in India, Indonesia, Japan, Malaysia, and Taiwan in the 2016 REAP AP-4 study. The records of the participants were randomly divided into two subgroups: the first for exploratory factor analysis of the eight DIEPSS items, and the second for confirmatory factor analysis. RESULTS: The factor analysis identified three factors: F1 (gait and bradykinesia), F2 (muscle rigidity and tremor), and F3 (sialorrhea, akathisia, dystonia, and dyskinesia). CONCLUSION: The results suggest that the eight individual items of the DIEPSS could be composed of three different mechanisms: acute parkinsonism observed during action (F1), acute parkinsonism observed at rest (F2), and central dopaminergic mechanisms with pathophysiology other than acute parkinsonism (F3).

Mid-life extrapyramidal symptoms predict cognitive impairment 23 years later.

OBJECTIVES: The prevalence of dementia is growing rapidly worldwide. The early identification and treatment of cognitive decline could reduce the burden on the health care system. Our objective was to investigate whether factors measured at an examination at age 50 predict cognitive impairment (CI) 23 years later. MATERIALS & METHODS: In 1993 we enrolled a randomly selected sample of 798 men, 50 years of age, from the general population. They all underwent a physical examination, provided blood samples and filled out questionnaires addressing lifestyle and psychosocial factors. Cognitive testing was offered to all participants still alive in 2016, at age 73. RESULTS: A total of 333 men participated in the cognitive study, of which 80 (24.0%) performed at a level corresponding to mild cognitive impairment, and four (1.2%) at a level consistent with severe cognitive impairment. After the first step in the multivariable analysis, hypertension, heavy smoking, high intake of alcohol, financial stress, difficulty falling asleep, and cogwheel rigidity were associated with cognitive impairment. After further adjustment, only wide waist circumference measured in cm (OR 1.04, 95% CI 1.00-1.08, p = .04), leg pendulousness (OR 41.97, 95% CI 3.27-538.62, p = .004) and self-assessed hidden irritability (OR 2.18, 95% CI 1.10-4.32, p = .03) at baseline, remained as being associated with cognitive impairment 23 years later. CONCLUSIONS: Extrapyramidal symptoms such as leg pendulousness, at the age of 50, may be an indicator for very early identification of future cognitive decline.

Driving fitness in clinically stable outpatients with chronic schizophrenia.

INTRODUCTION: Driving motorized vehicles is an integral part of individual mobility and a key parameter for employment and social integration. This naturalistic, cross-sectional study investigated the associations between driving fitness, residual symptomatology, olanzapine equivalent, and extrapyramidal symptoms (EPS) in long term stable outpatients with schizophrenia. METHODS: Beside sociodemographic data, and driving habits, residual symptoms, and EPS were assessed using the Positive and Negative Syndrome Scale (PANSS), and the Modified Simpson Angus Scale (MSAS). PANSS symptoms were analyzed using the Wallwork/Fortgang five-factor model. MSAS cut-off scores ≥3 were defined as positive for EPS. Driving skills were assessed using the Vienna Test System and an expert evaluation. RESULTS: 50 patients were included into the study. Mean PANSS total scores indicated mild residual symptomatology and EPS were not present in 48% of study participants. 44% passed the driving fitness assessment and were considered as competent to drive, 20% were judged to be partially competent and 36% to be incompetent to drive. With the exception of disorganization (r = -0·287, p = 0·048) residual symptoms of schizophrenia did not correlate with driving fitness. However, moderate negative correlations were detected between driving fitness and the severity of EPS (r = -0·554, p = 0·000), age (r = -0·413, p = 0·003) as well as olanzapine equivalent doses (r = -0·432, p = 0·002). These results were not corrected for multiple comparison. DISCUSSION: The present findings indicate that up to two thirds of clinically stable outpatients with chronic schizophrenia may be (partially) competent to drive. Both the presence of EPS as well as the dosage of antipsychotic medication seem to be of particular relevance in this regard.

Efficacy of Combination Haloperidol, Lorazepam, and Diphenhydramine vs. Combination Haloperidol and Lorazepam in the Treatment of Acute Agitation: A Multicenter Retrospective Cohort Study.

BACKGROUND: Antipsychotic and sedative combinations are commonly used for treating agitation in the emergency department despite limited evidence regarding their comparative safety and efficacy. OBJECTIVES: To compare the efficacy and safety of combination haloperidol, lorazepam, and diphenhydramine (B52) to combination haloperidol and lorazepam (52) in treating acute agitation. METHODS: This multicenter, retrospective cohort study included adult patients ≥ 18 years of age who received either B52 or 52 at a Banner Health facility between August 2017 and September 2020. Patients were excluded if they had a pre-existing movement disorder or were withdrawing from alcohol. The primary outcome was administration of additional agitation medication(s) within 2 h of B52 or 52. Secondary outcomes included incidence of extrapyramidal symptoms, length of stay, and additional safety measures. RESULTS: There was no difference in administration frequency of additional agitation medication(s) (B52: n = 28 [14%] vs. 52: n = 40 [20%]; p = 0.11). Patients who received 52 were more likely to require an antimuscarinic medication within 2 days (15 vs. 6 patients, p = 0.04). Of the patients who received an antimuscarinic medication, none had documented extrapyramidal symptoms. The 52 group had shorter length of stay (13.8 vs. 17 h; p = 0.03), lower incidence of hypotension (7 vs. 32 patients; p < 0.001), and oxygen desaturation (0 vs. 6 patients; p = 0.01), and fewer physical restraints (53 vs. 86 patients; p = 0.001) compared with the B52 group. CONCLUSIONS: Both the B52 and 52 combinations infrequently required repeat agitation medication; however, the B52 combination resulted in more oxygen desaturation, hypotension, physical restraint use, and longer length of stay.

Cerebrospinal fluid α synuclein concentrations in patients with positive AD biomarkers and extrapyramidal symptoms.

Extrapyramidal symptoms (EP) are not uncommon in Alzheimer's Disease (AD); when present, they negatively influence the course of the disorder. A large proportion of AD patients shows concomitant Lewy bodies' pathology post mortem. Total α Synuclein (αSyn) concentrations are frequently increased in the cerebrospinal fluid (CSF) of AD patients, but are decreased in Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). αSyn CSF concentrations in AD patients with EP (EP+) have not been reported so far. αSyn and the four Neurochemical Dementia Diagnostics (NDD) CSF biomarkers, (Aß1-42, Aß42/40, Tau, and pTau181), interpreted according to the Erlangen Score algorithm, were measured in patients with positive NDD results and presence of extrapyramidal symptoms (NDD + / EP+; n = 26), in patients with positive NDD results and absence of extrapyramidal symptoms (NDD+ / EP-; n = 54), and in subjects with negative NDD results (NDD-; n = 34). Compared to the NDD- controls (379.8 ± 125.2 pg/mL), NDD+ patients showed, on average, highly significantly increased CSF αSyn (519 ± 141.3 pg/mL, p < 0.01), but without differences between NDD+ / EP+ and NDD+ / EP- subgroups (p = 0. 38). Moderate but highly significant association was observed between concentrations of αSyn and Tau (r = 0.47, p < 0.01) and pTau181 (r = 0.65, p < 0.01). Adjusted for diagnoses, age, and sex, subjects with more advanced neurodegeneration on neuroimaging showed significantly lower αSyn concentrations (p < 0.02). In the setting AD versus controls, the area under the receiver operating characteristic (ROC) curve was 0.804 [0.712; 0.896] with the sensitivity and the specificity of 0.863 and 0.618, respectively. αSyn in AD patients does not differentiate between subjects with- and without EP. Its increased average concentration reflects probably neurodegenerative process, and is not specific for any pathophysiologic mechanisms. Further studies are necessary to explain the role of CSF αSyn as a potential biomarker.

Leptospira Triggered Anti-N-Methyl-d-Aspartate Receptor Encephalitis.

Primary neuroleptospirosis although rare but has been reported in the literature in the form of case reports and case series. However, there are no reports of autoimmune encephalitis triggered by leptospirosis in the literature, although four cases of acute disseminated encephalomyelitis, which is also considered to have autoimmune etiology have been reported. We are reporting an adolescent girl, who developed anti-N-methyl-d-aspartate receptor encephalitis after the resolution of systemic symptoms of leptospirosis. Her symptoms including neuropsychiatric and extrapyramidal features and sleep disturbances resolved completely after immunotherapy. As recently autoimmune encephalitis triggered by various infections are getting reported more frequently around the world, the clinicians need to consider this clinical possibility, even in patients with leptospirosis, who develop neurological symptoms while systemic clinical features are subsiding. Early recognition and timely administration of immunotherapy have the potential to completely reverse the neurological symptoms.

Dyskinesia is most centrally situated in an estimated network of extrapyramidal syndrome in Asian patients with schizophrenia: findings from research on Asian psychotropic prescription patterns for antipsychotics.

BACKGROUND: Network analysis provides a new viewpoint that explicates intertwined and interrelated symptoms into dynamic causal architectures of symptom clusters. This is a process called 'symptomics' and is concurrently applied to various areas of symptomatology. AIMS: Using the data from Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), we aimed to estimate a network model of extrapyramidal syndrome in patients with schizophrenia. METHODS: Using data from REAP-AP, extrapyramidal symptoms of 1046 Asian patients with schizophrenia were evaluated using the nine items of the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The estimated network of the ordered-categorical DIEPSS items consisted of nodes (symptoms) and edges (interconnections). A community detection algorithm was also used to identify distinctive symptom clusters, and correlation stability coefficients were used to evaluate the centrality stability. RESULTS: An interpretable level of node strength centrality was ensured with a correlation coefficient. An estimated network of extrapyramidal syndrome showed that 26 (72.2%) of all possible 35 edges were estimated to be greater than zero. Dyskinesia was most centrally situated within the estimated network. In addition, earlier antipsychotic-induced extrapyramidal symptoms were divided into three distinctive clusters - extrapyramidal syndrome without parkinsonism, postural instability and gait difficulty-dominant parkinsonism, and tremor-dominant parkinsonism. CONCLUSIONS: Our findings showed that dyskinesia is the most central domain in an estimated network structure of extrapyramidal syndrome in Asian patients with schizophrenia. These findings are consistent with the speculation that acute dystonia, akathisia, and parkinsonism could be the risk factors of tardive dyskinesia.

Long-term safety and tolerability of aripiprazole lauroxil in patients with schizophrenia.

OBJECTIVE: Safety and tolerability of long-term treatment with the long-acting antipsychotic aripiprazole lauroxil (AL) were evaluated in patients with schizophrenia. METHODS: This was an international, multicenter, phase 3, 52-week safety study of 2 fixed doses of AL (441 mg or 882 mg intramuscular every 4 weeks). Safety endpoints included adverse events (AEs) and extrapyramidal symptoms (EPS) including akathisia, injection-site reactions (ISRs), and clinically relevant changes in metabolic and endocrine values. RESULTS: Of 478 patients entering this study, 236 (49%) continued from a previous 12-week, phase 3 efficacy study of AL, and 242 (51%) were newly enrolled. Overall, 77% and 23% of patients received AL 882 mg (N = 368) and 441 mg (N = 110), respectively. AEs occurred in 50.4% of patients; most were mild (28.7%) or moderate (18.2%). The most common AEs were insomnia (8.4%) and increased weight (5.0%). Akathisia was reported as an AE in 3.8% of the overall population, with higher rates in patients initiating AL on study entry than those continuing on AL. EPS-related AEs occurred in 9.4% of patients, and AEs related to metabolic parameters were reported in 4.6% of patients. Weight gain was minimal (0.8 kg), and no clinically relevant changes were observed for metabolic parameters. The overall incidence of ISRs was 3.8%; most were associated with the initial injections in patients receiving their first injection in this study. CONCLUSION: Long-term treatment with AL is generally well tolerated, with a safety profile consistent with that of oral aripiprazole. It is a suitable option for patients with schizophrenia.

Polypharmacy in a hospitalized psychiatric population: risk estimation and damage quantification.

BACKGROUND: Polypharmacy increases the risk of pharmacological interactions, prevalence of secondary effects and with this the lack of adherence to treatment. It is estimated that between 10 and 40% of patients hospitalized in psychiatric institutions are prescribed more than one antipsychotic. The objective of the present study was to identify the prevalence of polypharmacy, evaluate adverse effects associated to the use of psych drugs and to estimate the risk in specific groups. METHODS: We carried out a longitudinal, retrospective study that included the analysis of all discharged patients (n = 140) in the first trimester of the year in a psychiatric hospital in Mexico. The information was classified into 7 sections: sociodemographic, diagnosis, clinical follow-up information, prescribed drugs, adverse reactions, substance abuse, laboratory and complementary results. Risk estimation was obtained with Odds Ratios, to correlate continuous variables Pearson's correlation was used. Student's T and Mann Whitney's U were used to compare 2 independent samples; multiple and linear regressions were carried out. RESULTS: The mean number of drugs used during hospitalization was 7.8 drugs per patient. The mean prescribed psych drugs was 4.07. The mean antipsychotic dose was the risperidone equivalent of 5.08 mg. 29.2% of patients had at least one secondary effect associated to the use of drugs, 17.8% presented extrapyramidal symptoms. 81.4% of patients were prescribed 6 or more drugs (polypharmacy) and were 5 times more likely to suffer a secondary effects (OR 6.24). 14.2% had polypharmacy while receiving antipsychotics and had more than twice the risk of presenting extrapyramidal symptoms (OR 3.05). For each added psych drug, hospital stay increased by 6.56 days. CONCLUSIONS: Despite international guideline recommendations where reasoned and conciliatory prescription of psych drugs is advised, there is still a high prevalence of polypharmacy in patients hospitalized in psychiatric institutions. In the present study 4 out of 5 patients received polypharmacy decreasing tolerability, treatment adherence and increasing the risk and costs secondary to an increased hospital stay.

Inhibition of Recombinant Human Acetylcholinesterase Activity by Antipsychotics.

BACKGROUND/AIMS: Extrapyramidal symptoms (EPS) are representative side effects of antipsychotics, caused by their inhibitory action on dopaminergic nerves in nigrostriatal pathways. EPS could be also caused by direct augmentation of cholinergic effects, for example, by acetylcholinesterase (AChE) inhibition. We investigated the potential inhibitory effects of 26 clinically available antipsychotics on the activity of recombinant human AChE (rhAChE) to predict the role of antipsychotic-induced AChE inhibition in EPS onset. METHOD: The degree of rhAChE activity inhibition was calculated using the 5,5'-dithio-bis-(2-nitrobenzoic acid) method. RESULTS: At a concentration of 10-5 mol/L, haloperidol, bromperidol, timiperone, nemonapride, pimozide, risperidone, blonanserin, aripiprazole, and brexpiprazole inhibited rhAChE activity by >20%. Risperidone, aripiprazole, and brexpiprazole inhibited rhAChE activity in a concentration-dependent manner, and their effects were more potent than those of other antipsychotics. The inhibitory effects of these 3 drugs were evident from 10-6 mol/L, and their pIC50 values were 4.74 ± 0.04, 4.80 ± 0.04, and 4.93 ± 0.06, respectively. Notably, the concentration range in which aripiprazole inhibited rhAChE activity (≥10-6 mol/L) overlapped with its clinically achievable blood levels. CONCLUSION: Aripiprazole may cause EPS at clinical dosages by augmenting cholinergic effects via AChE inhibition, in addition to its suppressive effect on dopaminergic neurons.

Drug-Induced Extrapyramidal Symptoms Scale of the Norwegian version: inter-rater and test-retest reliability.

Background: The Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) is a multidimensional rating scale designed for the fast, easy and reliable assessment of extrapyramidal symptoms (EPSs) induced by antipsychotics. Aim: The aim of this study was to validate the level of inter-rater and test-retest reliability of the Norwegian translation of this scale. Methods: A total of 125 video clips showing a variety of or no signs of EPSs were used in the present study. The participants recorded were Japanese psychiatric patients receiving first- and/or second-generation antipsychotics. A total of 103 patients (47 males and 56 females), diagnosed with schizophrenia (n = 68) or mood disorders (n = 35) appeared in the video clips. Their mean age was 48.7 ± 16.3 years (range 18-80) at the time of video recording. Inter-rater agreement was assessed with five raters and test-retest reliability with three. Results: Inter-rater reliability analyses showed interclass correlation coefficients (ICCs) ranging from 0.74 to 0.93 for each individual item. Test-retest reliability analysed independently for each rater ranged from 0.71 to 0.96. Conclusions: Inter-rater and test-retest agreement exhibited satisfactory ICC levels above 0.70. The Norwegian version of the DIEPSS is a reliable instrument for the assessment of drug-induced EPSs.

Optimization of maintenance therapy of Risperidone with CYP2D6 genetic polymorphisms through an extended translational framework-based prediction of target occupancies/clinical outcomes.

Risperidone, one of the second-generation antipsychotics, can efficiently target dopamine D2 and serotonin 5-HT2A receptors. There actually exists significant implication of CYP2D6 genetic polymorphisms on the metabolic kinetics of risperidone, little is known about the extent of CYP2D6 impacting human D2 and 5-HT2A receptor occupancies as well as the clinical efficacy and efficacy in schizophrenia treatment. Here we assessed the influences of CYP2D6 gene polymorphisms on human target occupancies/clinical outcomes and optimized the maintenance therapy of risperidone. A translational framework, previously developed using in vitro and in vivo information in rats, was used as the basis for integrating the effects of CYP2D6 genetic polymorphisms on target occupancies and clinical outcomes. D2 occupancy as a biomarker was related to Positive and Negative Syndrome Scale (PANSS) response and Simpson-Angus Scale (SAS). The population approach was applied to characterize pharmacokinetic and pharmacodynamic (PK/PD) profiles of risperidone. Non-compartment analysis method was performed to calculate the steady state PK/PD parameters of both risperidone and 9-hydroxyrisperidone. The predictive power of this extended translational framework was determined by comparing the predictions of target occupancies and clinical outcomes with the reported human values of risperidone at clinically suggested dosage of 4.0 mg/day. This extended translational framework was adequately used to predict human target occupancies and clinical outcomes. At the steady state, D2 ROs were 75.8%, 79.3% and 86.0% for CYP2D6 poor metabolizer (PM), intermediate metabolizer (IM) and extensive metabolizer (EM), respectively; 5-HT2A ROs were 96.4%, 97.2% and 98.4% for CYP2D6 PM, IM and EM, respectively; PANSS changes from placebo were -5.3, -7.7 and -11.3 for CYP2D6 PM, IM and EM, respectively; SAS changes from placebo were 0.13, 0.15 and 0.18 for CYP2D6 PM, IM and EM, respectively. The predictions of human D2, 5-HT2A RO, PANSS and SAS changes for risperidone with CYP2D6 genetic polymorphisms were well in line with the reported values in clinic. 5.0, 4.0 and 2.5 mg/day were the equivalent dosages of risperidone for CYP2D6 PM, IM and EM, respectively. The optimized maintenance therapy of risperidone was provided through the Three-Step method and the dosage range was 2.5-5.0 mg/day for three CYP2D6 gene groups in the present study. Taken together, our findings demonstrate that this extended translational framework not only differentiates the effects of CYP2D6 genetic polymorphisms on target occupancies and clinical outcomes, but also constitutes a scientific basis to optimize the maintenance therapy of neuropsychiatric patients in clinic.

Extrapyramidal symptoms resulting from risperidone use in a four year old child: A case report.

Extrapyramidal symptoms (EPS) are the major constraint in the use of antipsychotic agents. It is usually forewarned whenever therapy with these agents is considered. In this case, we present a child diagnosed with relapsed Wilm's tumour, who developed EPS just after a short duration of initiation of risperidone prescribed as an appetite stimulant. The patient became symptom free after management and risperidone was discontinued. Although risperidone has been approved to treat different indications in adolescents and children, scarce scientific evidence and our case report, are suggestive of further studies to establish safety of risperidone use in preschool children.

Factors associated with expression of extrapyramidal symptoms in users of atypical antipsychotics.

PURPOSE: The aim of this study was to investigate factors associated with the occurrence of extrapyramidal symptoms (EPS) in users of second-generation antipsychotics (SGA). METHODS: Observational cross-sectional study based on a random sample of subjects from three outpatient clinics. Inclusion criteria were age between 18 and 65 years, of both genders, with a diagnosis of schizophrenia and under the use of a single SGA agent. Subjects who had received i.m. long-acting antipsychotics in the past were excluded. The families of eligible patients were contacted by phone and, if willing to participate in the study, a household visit was scheduled. Informed consent was obtained from all study subjects and their next of kin. The risk of EPS associated with sociodemographic, clinical features and medications used was analyzed by logistic regression. RESULTS: The study population consisted of 213 subjects. EPS were observed in 38.0% of subjects. The more commonly used SGA were olanzapine (76, 35.7%), risperidone (74, 34.3%), quetiapine (26, 12.2%), and ziprasidone (23, 10.8%). Among the drugs used as adjunctive therapy for schizophrenia, benzodiazepines were the most prevalent (31.5%), followed by carbamazepine (24.4%) and antidepressants (20.2%). Multivariate analysis showed that the risk of EPS was associated with the use of carbamazepine (odds ratio 3.677, 95% CI 1.627-8.310). We found no evidence that the type of SGA modified the risk of EPS. CONCLUSION: The occurrence of EPS in SGA users is a common finding, with no difference of antipsychotics studied in relation to the risk of extrapyramidal manifestations. The adjunctive use of carbamazepine may predispose the user of SGA to the occurrence of EPS.

Physical Health and Drug Safety in Individuals with Schizophrenia.

BACKGROUND: While antipsychotic medications are the mainstay of therapy for individuals with schizophrenia and psychotic disorders, their use is associated with adverse effects on physical health that require the attention and care of prescribers. METHODS: We used the ADAPTE process to adapt existing guideline recommendations from the National Institute for Health and Care Excellence (NICE) and Scottish Intercollegiate Guidelines Network (SIGN) guidelines on the dosing of antipsychotics and antipsychotic polypharmacy, screening for adverse effects of antipsychotics, and management of metabolic and extrapyramidal side effects to the Canadian context. RESULTS: Prescribers are encouraged to use the lowest effective dose and to avoid the routine use of multiple antipsychotics. Scheduled monitoring of body mass index, waist circumference, blood pressure, glucose, lipids, prolactin, electrocardiograms, and extrapyramidal symptoms is recommended. Lifestyle interventions are recommended to mitigate antipsychotic-induced weight gain. Prescribers should follow Canadian guidelines on the treatment of obesity, dyslipidemia, and diabetes. Recommendations on antipsychotic drug choice are made for users particularly concerned about extrapyramidal symptoms. CONCLUSION: Careful monitoring and attention by prescribers may mitigate adverse effects associated with antipsychotic medications.

The possibility of the treatment for long-acting injectable antipsychotics induced severe side effects.

We present the case of a 47-year-old man with schizophrenia who developed acute and persistent circulatory failure after receiving injections of paliperidone palmitate. We measured blood concentrations of paliperidone and performed resection of hip tissues, where paliperidone palmitate was suspected to be present, in order to reduce the side effects. Unfortunately, the resection could not save the patient from prolonged and severe side effects and he died of multiple organ failure. We suggest that resection of the tissues suspected of containing paliperidone palmitate can help reduce its severe side effects. However, identifying the site of injection is essential.

Incidence of tardive dyskinesia in older adult patients treated with olanzapine or conventional antipsychotics.

BACKGROUND: The risk of persistent tardive dyskinesia (TD) was compared in patients with acute psychosis or agitation aged 55 years or older who were treated with olanzapine (OLZ) or conventional antipsychotic (CNV) drug therapy. METHODS: Patients without TD were randomized to treatment with OLZ (2.5-20 mg/d; n = 150) or CNV (dosed per label; n = 143). Following a 6-week drug tapering/initiation period, patients without TD were treated with OLZ or CNV for up to 1 year. The a priori defined primary outcome end point was persistent TD defined as Abnormal Involuntary Movement Scale (AIMS) scores = 2 on at least 2 items or ≥3 on at least 1 item (items 1-7) lasting at least for 1 month (Criterion A). Post hoc analyses assessed persistent TD meeting the criterion of moderate severity defined as AIMS score ≥3 on at least 1 item persisting for 1 month (Criterion B) and probable TD defined as elevated AIMS scores (Criterion A or B) not persisting for 1 month. Treatment groups were compared using Kaplan-Meier curve with log-rank exact test. RESULTS: On average, patients were 78 years of age; the predominant diagnosis was dementia (76.7% in the OLZ group and 82.5% in the CNV group). Approximately, 40.6% of patients in the CNV group received haloperidol. No significant difference in time to developing persistent TD was observed during treatment with OLZ or CNV (cumulative incidence: OLZ, 2.5% [95% confidence interval [95% CI]: 0.5-7.0]; CNV, 5.5% [95% CI: 2.1-11.6], P = .193). The exposure-adjusted event rates per 100 person-years were not significantly different between treatment groups: OLZ (2.7) and CNV (6.3; ratio: 0.420; 95% CI: 0.068-1.969). Post hoc analyses revealed a significantly lower risk of at least moderately severe persistent TD persisting for 1 month (P = .012) and probable TD not persisting for 1 month (Criterion A, P = .030; Criterion B, P = .048) in OLZ-treated patients. For those patients without significant extrapyramidal symptoms at baseline, significantly more patients in the CNV treatment group developed treatment-emergent parkinsonism than for patients in the OLZ treatment group (CNV: 70%, 35 of 50 patients; OLZ 44%, 25 of 57 patients; P = .011). No significant difference between the groups was observed for treatment-emergent akathisia (CNV: 6%, 7 of 117 patients; OLZ: 10%, 13 of 130 patients; P = .351). CONCLUSION: The cumulative incidence of persistent TD was low and the risk of persistent TD did not differ significantly among predominantly older adult patients having dementia with acute psychosis or agitation treated with OLZ or CNV.