A systematic review and pooled, patient-level analysis of predictors of mortality in neuroleptic malignant syndrome.

OBJECTIVE: Neuroleptic malignant syndrome (NMS) is a potentially fatal, idiosyncratic reaction to antipsychotics. Due to low incidence of NMS, research on risk factors of mortality associated with NMS is limited. METHODS: Two authors independently searched Medline/Embase/Cochrane/CINAHL/PsychINFO databases for case reports with author-defined NMS published in English until 05/30/2020. Demographic, clinical, treatment, and outcome data were independently extracted following PRISMA guidelines. NMS severity was rated using the Francis-Yacoub scale. Mortality risk factors were identified using a multivariable regression analysis including all characteristics that were significantly different between NMS cases resulting vs. not resulting in death. RESULTS: 683 cases with NMS were analyzed (median age = 36 years, males = 62.1%). In a multivariable model, independent predictors of NMS mortality were lack of antipsychotic discontinuation (odds ratio (OR) = 4.39 95% confidence interval (CI) = 2.14-8.99; p < 0.0001), respiratory problems (OR = 3.54 95%CI = 1.71-7.32; p = 0.0004), severity of hyperthermia (Unit-OR = 1.30, 95%CI = 1.16-1.46; p < 0.0001), and older age (Unit-OR = 1.05, 95%CI = 1.02-1.07; p = 0.0014). Even in univariate, patient-level analyses, antipsychotic formulation was not related to death (oral antipsychotic (OAP): n = 39/554 (7.0%) vs. long-acting injectable (LAI): n = 13/129 (10.1%); p = 0.2413). Similarly, death with NMS was not related to antipsychotic class (first-generation antipsychotic: n = 38/433 (8.8%) vs. second-generation antipsychotic: n = 8/180 (4.4%); p = 0.0638). Non-antipsychotic co-treatments were not associated with NMS mortality. CONCLUSION: Despite reliance on case reports, these findings indicate that presence of respiratory alterations, severity of hyperthermia, and older age should alert clinicians to a higher NMS mortality risk, and that antipsychotics should be stopped to reduce mortality, yet when NMS arises on LAIs, mortality is not increased vs. OAPs.

Risk Factors, Incidence, and Outcomes of Neuroleptic Malignant Syndrome on Long-Acting Injectable vs Oral Antipsychotics in a Nationwide Schizophrenia Cohort.

INTRODUCTION: Long-acting injectable antipsychotics (LAIs) are associated with multiple positive outcomes in psychosis, but it is unclear whether LAIs are associated with worse outcomes if neuroleptic malignant syndrome (NMS), a potentially lethal adverse effect, occurs. METHODS: We used nationwide and nationally representative databases of healthcare encounters in Finland to study the incidence and outcome predictors of NMS in patients diagnosed with schizophrenia/schizoaffective disorder between January 01, 1972 and December 31, 2017. Using a nested case-control design, we also explored differences by antipsychotic formulation (LAI vs oral antipsychotic [OAP]) and class (first-generation antipsychotic [FGA] vs second-generation antipsychotic [SGA]). RESULTS: One hundred seventy-two NMS cases and 1441 sex-, age-, and diagnosis-matched controls were included (age = 58.8 ± 13.1 years, males = 59.9%). Incidence of NMS was 1.99 (1.98-2.00) per 10 000 person-years. The likelihood of developing NMS did not differ by antipsychotic formulation (adjusted odds ratio [aOR]: 0.89, 95% confidence intervals [95% CI]: 0.59-1.33, for LAIs vs OAPs) or class (FGA-OAP vs SGA-OAP [aOR: 1.08, 95% CI: 0.66-1.76], FGA-LAI [aOR: 0.89, 95% CI: 0.52-1.53], SGA-LAI [aOR: 1.35, 95% CI: 0.58-3.12]). NMS risk factors included antipsychotic treatment change: increased number (odds ratios [OR]: 5.00, 95% CI: 2.56-9.73); decreased number/switch (OR: 2.43, 95% CI: 1.19-4.96); higher antipsychotic dose (>2DDDs-OR: 3.15, 95% CI: 1.61-6.18); co-treatment with anticholinergics (OR: 2.26, 95% CI: 1.57-3.24), lithium (OR: 2.16, 95% CI: 1.30-3.58), benzodiazepines (OR: 2.02, 95% CI: 1.44-3.58); and comorbid cardiovascular disease (OR: 1.73, 95% CI: 1.22-2.45). Within 30 days, 4.7% of cases with NMS died (15.1% within 1 year) without differences by antipsychotic formulation. NMS reoccurred in 5 of 119 subjects (4.2%), after a median = 795 (range = 77-839) days after rechallenge with antipsychotics. CONCLUSION: NMS remains a potentially life-threatening risk, yet these results should further contribute to mitigate concerns about LAI safety regarding NMS onset or outcomes, including mortality.

Malignant syndromes: current advances.

Introduction: Many drugs are known to induce malignant syndromes. The most common malignant syndromes are induced by the use of antipsychotics and anesthetics and the withdrawal of anti-Parkinson drugs. As the clinical manifestations of antipsychotic malignant syndrome, Parkinson's disease hyperpyrexia syndrome and anesthetic-induced malignant syndrome are very similar, they are easily confused in the clinic.Areas covered: We reviewed articles published between 1960 and April 2021 describing malignant syndromes. This paper provides a detailed literature review of malignant syndromes and important guidance for the diagnosis and treatment of malignant syndromes to clinicians.Expert opinion: Although malignant syndromes are rare conditions with a low incidence, these conditions usually progress rapidly and can endanger patients' lives, meriting attention from clinicians. The typical clinical manifestations of malignant syndromes are hyperpyrexia, muscular rigidity, an altered mental status and increased levels of creatine kinase; however, the pathophysiology, treatment and prognosis of different malignant syndromes are quite different. Prompt diagnosis and treatment may significantly improve the prognosis of patients with malignant syndromes.

Neuroleptic malignant syndrome associated with long-acting injectable versus oral second-generation antipsychotics: Analyses based on a spontaneous reporting system database in Japan.

Long-acting injectable antipsychotics (LAI-APs) remain underutilized. One reason is the concern that LAI-APs might cause serious adverse events such as neuroleptic malignant syndrome (NMS) and lead to prolonged symptoms compared with oral treatment. Because the risk of NMS associated with LAI second-generation antipsychotics (LAI-SGAs) remains unclear, we compared reporting frequency, time to onset, and mortality of NMS between LAI- and oral SGAs using data from a Japanese spontaneous adverse event reporting database between April 2004 and September 2019. Of 5791 patients reporting adverse events due to LAI-SGAs or the equivalent oral SGAs, 768 (13%) developed NMS. LAI aripiprazole and LAI paliperidone were associated with a significantly lower reporting frequency of NMS than the equivalent oral SGAs (adjusted reporting odds ratio [95% confidence interval]: 0.35 [0.19-0.63] and 0.40 [0.27-0.59], respectively). Between 42% and 62% of the NMS associated with LAI- and oral SGAs other than LAI risperidone occurred within 30 days after initiation. The proportion of mortality due to NMS associated with oral aripiprazole was 13.1% and no deaths occurred in patients with NMS associated with LAI aripiprazole. The proportions of mortality due to NMS associated with oral risperidone/paliperidone, LAI risperidone, and LAI paliperidone were 8.8%, 4.2%, and 3.4%, respectively. Our findings showed that LAI-SGAs were not associated with a higher reporting frequency and mortality of NMS compared with oral SGAs, although clinicians need to closely monitor the occurrence of NMS not only during oral SGA treatment, but also, and in particular, in the early stage of LAI-SGA treatment.

Antipsychotics and Risk of Neuroleptic Malignant Syndrome: A Population-Based Cohort and Case-Crossover Study.

BACKGROUND: Neuroleptic malignant syndrome (NMS) is a rare and acute adverse drug reaction associated with antipsychotic therapy. However, few data on the risk and epidemiology of NMS are available. OBJECTIVES: The aim of this study was to ascertain the incidence risk and all-cause mortality of NMS associated with antipsychotic use, and to assess the association of recent antipsychotic exposure and NMS. METHODS: We did a population-based study using data from the Hong Kong Hospital Authority's Clinical Data Analysis and Reporting System database. Cases had a first diagnosis of NMS between 1 January 2004 and 30 November 2017. A case-crossover analysis was used to compare antipsychotic exposure 30 days before the diagnosis of NMS (index date) and a reference period 91-120 days before the index date. To adjust for potential time trends in antipsychotic exposure, we sampled from cases to match current cases and future cases, and further adjusted for select medications and acute medical conditions. RESULTS: 297,647 patients were prescribed antipsychotics, and the incidence risk of NMS was 0.11%. Of the 336 cases included in the case-crossover analysis, 20 (6%) died within 30 days after the index date; only one case had NMS recorded as the primary cause of death. When compared with the reference period, cases were more frequently prescribed multiple antipsychotics (15.8% vs 26.8%; standardized mean difference [SMD] 0.27) and short-acting injectable antipsychotics (3.6% vs 13.7%; SMD 0.37) during the 30 days prior to the diagnosis of NMS. Odds ratios for antipsychotic exposure in the case-crossover, case-crossover adjusted for time trend, and case-crossover adjusted for time trend and potential confounders analysis were 8.00 (95% confidence interval 3.42-18.69), 5.88 (2.46-14.04), and 4.77 (1.95-11.66). CONCLUSIONS: Our results suggest that recent use of antipsychotics is associated with NMS. Although a case-only design inherently controls for confounding by time-invariant factors, residual confounding by acute medical conditions with similar presentations to NMS cannot be fully excluded.

Neuroleptic malignant syndrome: evaluation of drug safety data from the AMSP program during 1993-2015.

Neuroleptic malignant syndrome (NMS) is a rare, but severe adverse drug reaction of drugs with anti-dopaminergic properties. The main symptoms are fever and rigor. In addition, other symptoms such as creatine kinase elevation, alteration of consciousness and various neurological symptoms may occur. A total of 52 NMS cases have been documented in the drug safety program 'Arzneimittelsicherheit in der Psychiatrie' from 1993 to 2015. We calculated incidences and analyzed imputed substances and additional risk factors to study the impact of changing therapy regimes. The overall incidence was 0.16‰. High-potency first-generation antipsychotics (FGAs) had the highest incidences, e.g. flupentixol with 0.61‰. Second-generation antipsychotics (SGAs) had lower incidences. Low-potency FGAs had very low incidences, comparable to SGAs, but in contrast to SGAs, had not been imputed alone in any case of NMS. Preexisting organic pathologies of the central nervous system, lithium treatment, infection/exsiccosis and the withdrawal of medication with anticholinergic properties or alcohol were found to be additional risk factors. With the increasing use of SGAs, one should always be aware of the risk of NMS. Better suited diagnostic criteria for 'atypical NMS' would lead to a better understanding and, therefore, to improved treatment possibilities.

Clozapine Rechallenge After Major Adverse Effects: Clinical Guidelines Based on 259 Cases.

BACKGROUND: Clozapine is widely prescribed for treatment-refractory schizophrenia, but its use is limited by many potentially life-threatening adverse effects. The risk of rechallenge after these complications has never been comprehensively assessed in controlled studies. Thus, clinical guidelines must rely on the published case reports. The number of such reports is likely to increase over time, and updated analyses of larger samples are needed, as they may lead to changes in clinical guidelines. STUDY QUESTIONS: How safe is the clozapine rechallenge after life-threatening adverse effects? STUDY DESIGN: The published case reports of clozapine rechallenge were identified in a MEDLINE search. We added 121 cases reported from 2012 through 2017 to the 138 cases reported from 1972 through 2011 analyzed by us in a previous publication. The 95% confidence intervals (CIs) of the successful rechallenge rate were calculated for each adverse effect with at least 5 published case reports. The rechallenge was considered a valid clinical option when the lower end of the CI range was at least 50%. RESULTS: A successful outcome was documented in 128/203 patients rechallenged after neutropenia (63.0%, CI, 56.0%-69.6%), 3/17 after agranulocytosis (17.7%, CI, 4.7%-44.2%), 11/17 after myocarditis (64.7%, CI, 38.6%-84.7%), and 7/7 after neuroleptic malignant syndrome (100%, CI, 56.1%-100%). Among the 15 patients with other clozapine-induced adverse effects, the rechallenge was successful in those with eosinophilia, cardiac complications other than myocarditis (QTc prolongation, pericarditis, cardiomyopathy, and atrial flutter), and gastrointestinal hypomotility. The rechallenge failed in patients who had developed pancreatitis or renal insufficiency. CONCLUSION: Clozapine rechallenge is a reasonable clinical option after return to baseline for patients who had developed neutropenia and neuroleptic malignant syndrome, but not after agranulocytosis or myocarditis. Data are insufficient to formulate rechallenge guidelines for any other clozapine-related adverse effects.

Movement side effects of antipsychotic drugs in adults with and without intellectual disability: UK population-based cohort study.

OBJECTIVES: To measure the incidence of movement side effects of antipsychotic drugs in adults with intellectual disability and compare rates with adults without intellectual disability. DESIGN: Cohort study using data from The Health Improvement Network. SETTING: UK primary care. PARTICIPANTS: Adults with intellectual disability prescribed antipsychotic drugs matched to a control group of adults without intellectual disability prescribed antipsychotic drugs. OUTCOME MEASURES: New records of movement side effect including acute dystonias, akathisia, parkinsonism, tardive dyskinaesia and neuroleptic malignant syndrome. RESULTS: 9013 adults with intellectual disability and a control cohort of 34 242 adults without intellectual disability together contributed 148 709 person-years data. The overall incidence of recorded movement side effects was 275 per 10 000 person-years (95% CI 256 to 296) in the intellectual disability group and 248 per 10 000 person-years (95% CI 237 to 260) in the control group. The incidence of any recorded movement side effect was significantly greater in people with intellectual disability compared with those without (incidence rate ratio 1.30, 95% CI 1.18 to 1.42, p<0.001, after adjustment for potential confounders), with parkinsonism and akathisia showing the greatest difference between the groups. Neuroleptic malignant syndrome, although occurring infrequently, was three times more common in people with intellectual disability-prescribed antipsychotic drugs (incidence rate ratio 3.03, 95% CI 1.26 to 7.30, p=0.013). Differences in rates of movement side effects between the groups were not due to differences in the proportions prescribed first and second-generation antipsychotic drugs. CONCLUSIONS: This study provides evidence to substantiate the long-held assumption that people with intellectual disability are more susceptible to movement side effects of antipsychotic drugs. Assessment for movement side effects should be integral to antipsychotic drug monitoring in people with intellectual disability. Regular medication review is essential to ensure optimal prescribing in this group.

Acute Presentation of Nonmotor Symptoms in Parkinson's Disease.

There are a few syndromes involving the nonmotor symptoms of Parkinson's disease and other movement disorders that can quickly lead to severe morbidity and mortality, and, as such, need rapid identification and management. Among these are neuroleptic malignant syndrome, serotonin syndrome, dopamine agonist withdrawal syndrome, and dystonic storm. It is important to maintain a high index of suspicion for these disorders as lack of identification can lead to death. Many of these acutely occurring nonmotor syndromes are primarily the result of imbalances in dopaminergic and serotonergic systems due to changes in pharmacologic management of psychiatric disorders or Parkinson's disease. We discuss these acutely occurring nonmotor symptoms in order to raise awareness and also to highlight how these extremes in symptoms may uniquely shed light on the pathophysiology of Parkinson's disease.

A systematic review of sex and age factors in neuroleptic malignant syndrome diagnosis frequency.

OBJECTIVE: To examine sex and age distributions in neuroleptic malignant syndrome (NMS) patients based on a systematic literature review. METHOD: EMBASE and PubMed databases were searched to identify any observation of NMS published from January 1, 1998 through November 1, 2014 that was accessible and interpretable (using language translation software). Redundant and equivocal reports were excluded. Sex ratio and age distributions were examined using standard graphical techniques and measures of association. RESULTS: Twenty-eight independent sex ratio estimates were included. Males predominated in most (75%) estimates with an overall median sex ratio of 1.47 (95% CI, 1.20-1.80). NMS incidence peaked at age 20-25 years and declined steadily thereafter, with males consistently outnumbering females at all but the oldest age intervals. CONCLUSION: NMS patients are 50% more likely to be males, and NMS is most likely to occur in young adulthood.

Akinetic crisis in dementia with Lewy bodies.

BACKGROUND AND PURPOSE: Dementia with Lewy bodies (DLB) is characterised by neuroleptic hypersensitivity. It is unclear, however, whether the neuroleptic hypersensitivity implies an increased incidence of neuroleptic malignant syndrome (NMS) or of akinetic crisis (AC), which are expressions of the same possibly lethal clinical event, and whether AC in DLB can appear independently of neuroleptic treatment. In our prospective study, we assessed the incidence of AC in a cohort of DLB as compared with that in patients with Parkinson disease (PD). METHODS: In total, 614 patients with PD and 236 DLB were recruited and followed during 2005-2013. AC was diagnosed as sudden akinetic state unresponsive to dopaminergic rescue drugs, dysphagia and serological alterations without recovery for 48 h or more requiring hospital admission. Exposure to neuroleptics was specifically evaluated, because of the high implicit risk in DLB. RESULTS: 24 patients with PD (3.9%) and 16 patients with DLB (6.8%) developed AC. 77 (32.6%) DLB and 32 (5.2%) PD were exposed to typical neuroleptics, but only 8 DLB and 3 PD presented with AC. Disease duration before AC was lower in DLB than in PD group (p<0.01). Outcome was fatal in 8 patients with (50%) DLB and 3 (12.5%) PD (p=0.05). When age and use of neuroleptics were adjusted for into a Cox proportional hazards model predicting time to AC, the HR of patients with DLB was 13.0 (95% CI 4.23 to 39.9; p<0.001). CONCLUSIONS: AC in DLB can appear independently of neuroleptic treatment, occurs earlier and is more frequently fatal than in PD.

Neuroleptic Malignant Syndrome: Complications, Outcomes, and Mortality.

OBJECTIVE: Our study objective was to identify real-world rates of complications, mortality, and outcomes in patients with neuroleptic malignant syndrome (NMS) over the last decade in the United States. METHODS: A total of 1346 patients were obtained from the nationwide inpatient sample for the years 2002-2011. Common complications known to be associated with NMS were identified. Multivariable regression analyses were used to identify predictors of mortality. RESULTS: The most prevalent complication was rhabdomyolysis (30.1%). Other common complications were acute respiratory failure (16.1%), acute kidney injury (17.7%), sepsis (6.2%), and other systemic infections. Unadjusted mortality rate was 5.6%. Older age, acute respiratory failure, acute kidney injury, sepsis, and comorbid congestive heart failure were significant predictors of mortality. Acute respiratory failure was the strongest independent mortality predictor (p < 0.001). CONCLUSION: In our large sample population-based study on NMS, we were able to identify the rates of several preselected complications and the mortality. The identification of independent mortality predictors in this study can guide physicians in the management and prognostication of this rare syndrome.

[The Neuroleptic Malignant Syndrome]. / Das maligne neuroleptische Syndrom (MNS)--Eine systematische Übersicht.

BACKGROUND: Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening medication-induced syndrome. Core symptoms are hyperthermia, diaphoresis, rigidity, impaired consciousness, and creatinine kinase elevation. Additionally, patients show vegetative dysregulation including blood pressure fluctuations. The purpose of this paper is to summarize current findings, to facilitate diagnostics and to distinguish NMS from other syndromes. METHODS: We performed a systematic review of the literature. We included scientific publications, books and guidelines. RESULTS: In this review we summarize the current diagnostic criteria, differential diagnosis, pathogenesis and therapeutic options. CONCLUSION: Clinical symptoms of NMS are heterogeneous and it is difficult to diagnose early states. Early interventions are important to ensure fast and complete recovery. Since NMS is a rare condition, publications on NMS-therapy are based on single-case reports, meta-analysis or expert opinions. Core symptoms should be considered: Exposure to dopamine-antagonists, hyperthermia, diaphoresis, rigidity, mental status alteration, creatinine kinase elevation, and vegetative dysregulation.

Second-generation antipsychotics and neuroleptic malignant syndrome: systematic review and case report analysis.

BACKGROUND: Neuroleptic malignant syndrome (NMS) is a rare, severe, idiosyncratic adverse reaction to antipsychotics. Second-generation antipsychotics (SGAs) were originally assumed to be free from the risk of causing NMS, however several cases of NMS induced by SGAs (SGA-NMS) have been reported. OBJECTIVES: The aim of this study was to systematically review available studies and case reports on SGA-NMS and compare the presentation of NMS induced by different SGAs. DATA SOURCES: Citations were retrieved from PubMed up to November 2013, and from reference lists of relevant citations. STUDY ELIGIBILITY CRITERIA: Eligibility criteria included (a) primary studies reporting data on NMS, with at least 50 % of the sample receiving SGAs; or (b) case reports and case reviews reporting on NMS induced by SGA monotherapy, excluding those due to antipsychotic withdrawal. STUDY APPRAISAL AND SYNTHESIS METHODS: A standardized method for data extraction and coding was developed for the analysis of eligible case reports. RESULTS: Six primary studies and 186 individual cases of NMS induced by SGAs were included. Primary studies suggest that SGA-NMS is characterized by lower incidence, lower clinical severity, and less frequent lethal outcome than NMS induced by first-generation antipsychotics. Systematic analysis of case reports suggests that even the most recently marketed antipsychotics are not free from the risk of inducing NMS. Furthermore, clozapine-, aripiprazole- and amisulpride-induced NMS can present with atypical features more frequently than other SGA-NMS, i.e. displaying less intense extrapyramidal symptoms or high fever. LIMITATIONS: Case reports report non-systematic data, therefore analyses may be subject to bias. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Clinicians should be aware that NMS is virtually associated with all antipsychotics, including those most recently marketed. Although apparently less severe than NMS induced by older antipsychotics, SGA-NMS still represent a relevant clinical issue.

Neuroleptic malignant syndrome or catatonia? Trying to solve the catatonic dilemma.

RATIONALE: A substantial overlap exists between catatonic phenomena and features of neuroleptic malignant syndrome. OBJECTIVES: The objective of this study is to examine whether catatonia can be distinguished from neuroleptic malignant syndrome and to identify symptoms that may have discriminatory power. METHODS: We conducted a literature search to identify relevant studies up to and including the year 2012. A total of 386 studies containing 490 case reports were included. To evaluate the discriminant value of each feature, we performed binominal regression analyses with the diagnosis as the dependent variable. First, all features were entered into the model as independent variables. In a second step, a stepwise backwards analysis was conducted to eliminate criteria with low discriminant value. RESULTS: The most common symptoms in patients with neuroleptic malignant syndrome were fever (87.7 %), rigor (85.9 %), laboratory evidence of muscle injury (70.5 %), and tachycardia (62.1 %) and in patients with catatonia were mutism (78.0 %), rigor (73.0 %), stupor (54.0 %), and agitation (49.0 %). Eleven variables with statistically significant discriminatory power remained after statistical analysis: diaphoresis (odds ratio (OR) 10.011), rigor (OR 9.550), fever (OR 7.317), tremor (OR 4.064), laboratory evidence of muscle injury (OR 3.542), leukocytosis (OR 3.081), negativism (OR 0.262), posturing (OR 0.241), waxy flexibility (OR 0.223), stupor (OR 0.158), and stereotypy (OR 0.122). CONCLUSIONS: Catatonia and neuroleptic malignant syndrome can be distinguished, at least on a descriptive level. There is a strong syndromal overlap. Our findings might be influenced by the fact that they are based on case reports, which reflect the respective authors' clinical opinion of the patient's condition.

Age and adverse drug reactions from psychopharmacological treatment: data from the AMSP drug surveillance programme in Switzerland.

QUESTION UNDER STUDY: The frequency of severe adverse drug reactions (ADRs) from psychotropic drugs was investigated in hospitalised psychiatric patients in relation to their age. Specifically, the incidence of ADRs in patients up to 60 years was compared to that of patients older than 60 years. METHODS: Prescription rates of psychotropic drugs and reports of severe ADRs were collected in psychiatric hospitals in Switzerland between 2001 and 2010. The data stem from the drug surveillance programme AMSP. RESULTS: A total of 699 patients exhibited severe ADRs: 517 out of 28,282 patients up to 60 years (1.8%); 182 out of 11,446 elderly patients (1.6%, ns). Logistic regression analyses showed a significantly negative relationship between the incidence of ADRs and patients' age in general and in particular for weight gain, extrapyramidal motor system (EPMS) symptoms, increased liver enzymes and galactorrhoea. A significantly negative relationship was observed for age and the dosages of olanzapine, quetiapine, risperidone, valproic acid and lamotrigine. When comparing age groups, frequency of ADRs was lower in general for antipsychotic drugs and anticonvulsants, in particular for valproic acid in the elderly. Weight gain was found to be lower in the elderly for antipsychotic drugs, in particular for olanzapine. For the group of mood-stabilising anticonvulsants (carbamazepine, lamotrigine and valproic acid) the elderly exhibited a lower incidence of reported allergic skin reactions. CONCLUSION: The results suggest that for psychiatric inpatients the incidence of common severe ADRs (e.g., weight gain or EPMS symptoms) arising from psychotropic medication decreases with the age of patients.