KCNT2-Related Disorders: Phenotypes, Functional, and Pharmacological Properties.

OBJECTIVE: Pathogenic variants in KCNT2 are rare causes of developmental epileptic encephalopathy (DEE). We herein describe the phenotypic and genetic features of patients with KCNT2-related DEE, and the in vitro functional and pharmacological properties of KCNT2 channels carrying 14 novel or previously untested variants. METHODS: Twenty-five patients harboring KCNT2 variants were investigated: 12 were identified through an international collaborative network, 13 were retrieved from the literature. Clinical data were collected and included in a standardized phenotyping sheet. Novel variants were detected using exome sequencing and classified using ACMG criteria. Functional and pharmacological studies were performed by whole-cell electrophysiology in HEK-293 and SH-SY5Y cells. RESULTS: The phenotypic spectrum encompassed: (a) intellectual disability/developmental delay (21/22 individuals with available information), ranging from mild to severe/profound; (b) epilepsy (15/25); (c) neurological impairment, with altered muscle tone (14/22); (d) dysmorphisms (13/20). Nineteen pathogenic KCNT2 variants were found (9 new, 10 reported previously): 16 missense, 1 in-frame deletion of a single amino acid, 1 nonsense, and 1 frameshift. Among tested variants, 8 showed gain-of-function (GoF), and 6 loss-of-function (LoF) features when expressed heterologously in vitro. Quinidine and fluoxetine blocked all GoF variants, whereas loxapine and riluzole activated some LoF variants while blocking others. INTERPRETATION: We expanded the phenotypic and genotypic spectrum of KCNT2-related disorders, highlighting novel genotype-phenotype associations. Pathogenic KCNT2 variants cause GoF or LoF in vitro phenotypes, and each shows a unique pharmacological profile, suggesting the need for in vitro functional and pharmacological investigation to enable targeted therapies based on the molecular phenotype. ANN NEUROL 2023;94:332-349.

Carbamazepine responsive episodic dystonia and hallucination due to pyruvate dehydrogenase E2 (DLAT) gene mutation.

Pyruvate Dehydrogenase (PDH) E2 deficiency due to Dihydrolipoamide acetyltransferase (DLAT) mutations is a very rare condition with only nine reported cases to date. We describe a 15-year-old girl with mild intellectual disability, paroxysmal dystonia and bilateral basal ganglia signal abnormalities on brain magnetic resonance imaging (MRI). Additionally, neurophysiological, imaging, metabolic and exome sequencing studies were performed. Routine metabolite testing, and GLUT1 and PRRT2 mutation analysis were negative. A repeat brain MRI revealed 'Eye-of-the-tiger-sign'. Exome sequencing identified homozygous valine to glycine alteration at amino acid position 157 in the DLAT gene. Bioinformatic and family analyses indicated that the alteration was likely pathogenic. Patient's dystonia was responsive to low-dose carbamazepine. On weaning carbamazepine, patient developed hallucinations which resolved after carbamazepine was restarted. PDH E2 deficiency due to DLAT mutation has a more benign course compared to common forms of PDH E1 deficiency due to X-linked PDHA1 mutations. All known cases of PDH E2 deficiency due to DLAT mutations share the features of episodic dystonia and intellectual disability. Our patient's dystonia and hallucinations responded well to low-dose carbamazepine.

Evaluation of Nav1.8 as a therapeutic target for Pitt Hopkins Syndrome.

Pitt Hopkins Syndrome (PTHS) is a rare syndromic form of autism spectrum disorder (ASD) caused by autosomal dominant mutations in the Transcription Factor 4 (TCF4) gene. TCF4 is a basic helix-loop-helix transcription factor that is critical for neurodevelopment and brain function through its binding to cis-regulatory elements of target genes. One potential therapeutic strategy for PTHS is to identify dysregulated target genes and normalize their dysfunction. Here, we propose that SCN10A is an important target gene of TCF4 that is an applicable therapeutic approach for PTHS. Scn10a encodes the voltage-gated sodium channel Nav1.8 and is consistently shown to be upregulated in PTHS mouse models. In this perspective, we review prior literature and present novel data that suggests inhibiting Nav1.8 in PTHS mouse models is effective at normalizing neuron function, brain circuit activity and behavioral abnormalities and posit this therapeutic approach as a treatment for PTHS.

Resolution of severe neurobehavioral difficulties in an individual with Primrose syndrome with sertraline.

Primrose syndrome (PS) is a rare genetic disease characterized by developmental delay, intellectual disability, sensorineural hearing loss, and dysmorphic features. PS is caused by de novo pathogenic variants in the ZBTB20 gene, which encodes a transcription factor modulating neurogenesis. We describe resolution with sertraline of neurobehavioral difficulties in a 17-year-old Hispanic male with PS with de novo heterozygous c.1916G > A (p.C639Y) variant of ZBTB20. Neurobehavioral difficulties included aggression towards self and others, irritability, tearfulness, and mood liability that did not respond to behavioral interventions or aripiprazole. Treatment with sertraline, a medication indicated for psychiatric disorders including anxiety and depression, led to the resolution of neurobehavioral difficulties after 2 weeks of initiation of medication. The treatment course suggests that selective serotonin reuptake inhibitors, such as sertraline, may be a useful tool for neurobehavioral difficulties in PS over antipsychotics that are accompanied by complex side effect profiles, and suggest that anxiety is the primary cause of the neurobehavioral difficulties in this patient.

Promyelinating drugs promote functional recovery in an autism spectrum disorder mouse model of Pitt-Hopkins syndrome.

Pitt-Hopkins syndrome is an autism spectrum disorder caused by autosomal dominant mutations in the human transcription factor 4 gene (TCF4). One pathobiological process caused by murine Tcf4 mutation is a cell autonomous reduction in oligodendrocytes and myelination. In this study, we show that the promyelinating compounds, clemastine, sobetirome and Sob-AM2 are effective at restoring myelination defects in a Pitt-Hopkins syndrome mouse model. In vitro, clemastine treatment reduced excess oligodendrocyte precursor cells and normalized oligodendrocyte density. In vivo, 2-week intraperitoneal administration of clemastine also normalized oligodendrocyte precursor cell and oligodendrocyte density in the cortex of Tcf4 mutant mice and appeared to increase the number of axons undergoing myelination, as EM imaging of the corpus callosum showed a significant increase in the proportion of uncompacted myelin and an overall reduction in the g-ratio. Importantly, this treatment paradigm resulted in functional rescue by improving electrophysiology and behaviour. To confirm behavioural rescue was achieved via enhancing myelination, we show that treatment with the thyroid hormone receptor agonist sobetirome or its brain penetrating prodrug Sob-AM2, was also effective at normalizing oligodendrocyte precursor cell and oligodendrocyte densities and behaviour in the Pitt-Hopkins syndrome mouse model. Together, these results provide preclinical evidence that promyelinating therapies may be beneficial in Pitt-Hopkins syndrome and potentially other neurodevelopmental disorders characterized by dysmyelination.

Continuous spike-wave of slow sleep in a patient with KCNB1-related epilepsy responsive to highly purified cannabidiol: a case report and comparison with literature.

KCNB1-associated encephalopathy is characterized by intellectual disability (ID), autism spectrum disorder and epilepsy. Specific treatments are still lacking. We describe a 12-year-old boy with severe ID and treatment-resistant seizures due to a pathogenic KCNB1 variant. His EEG showed a CSWS pattern. Aged 11, he started treatment with highly purified cannabidiol (CBD) and has been seizure free for 18 months, with significant EEG and social skills improvements. This suggests CBD may benefit CSWS, likely due to its anti-inflammatory properties. Some preclinical studies also indicate CBDs interact with voltage-gated channels, leading us to speculate its possible role for treating KCNB1 related encephalopathy.

Efficacy and tolerability of Brivaracetam in people with intellectual disability compared to those without intellectual disability.

INTRODUCTION: In England, nearly a quarter of people with intellectual disability (PwID) have epilepsy. Though 70 % of PwID have pharmaco-resistant seizures only 10 % are prescribed anti-seizure medication (ASMs) licenced for pharmaco-resistance. Brivaracetam (BRV) licenced in 2016 has had nine post-marketing studies involving PwID. These studies are limited either by lack of controls or not looking at outcomes based on differing levels of ID severity. This study looks at evidence comparing effectiveness and side-effects in PwID to those without ID prescribed Brivaracetam (BRV). METHODS: Pooled case note data for patients prescribed BRV (2016-2022) at 12 UK NHS Trusts were analysed. Demographics, starting and maximum dose, side-effects, dropouts and seizure frequency between ID (mild vs. moderate-profound (M/P)) and general population for a 12-month period were compared. Descriptive analysis, Mann-Whitney, Fisher's exact and logistic regression methods were employed. RESULTS: 37 PwID (mild 17 M/P 20) were compared to 102 without ID. Mean start and maximum dose was lower for PwID than non-ID. Mean maximum dose reduced slightly with ID severity. No difference was found between ID and non-ID or between ID groups (Mild vs M/P) in BRV's efficacy i.e. >50 % seizure reduction or tolerability. Mental and behavioural side-effects were more prevalent for PwID (27.0 % ID, 17.6 % no ID) but not significantly higher (P = 0.441) or associated with ID severity (p = 0.255). CONCLUSION: This is the first study on BRV, which compares ID cohorts with differing severity and non-ID. Efficacy, tolerability and side-effects reported are similar across differing ID severity to those with no ID.

Impact of the emotional development approach on psychotropic medication in adults with intellectual and developmental disabilities: a retrospective clinical analysis.

BACKGROUND: Compared with the general population, adults with an intellectual developmental disorder (IDD) are more likely to develop mental health problems and to receive high levels of psychotropic medication, particularly antipsychotics. The emotional development (ED) approach may help to better understand the nature of challenging behaviour (CB) and tailor treatment and support accordingly. The aim of this retrospective study was to investigate the impact of the ED approach on the prescription of psychotropic medication during inpatient psychiatric treatment. METHODS: The clinical data of 1758 patients were analysed within a retrospective study design over a period of 12 years. ED level was assessed (1) for the first time (INITIAL-SEO), (2) during a previous hospital stay (PAST-SEO) or (3) not at all (NO-SEO). The effects of the ED assessment and the respective intervention during the current admission on the number of psychotropics and the number and dosage of antipsychotics were analysed for the total sample, including those with CB, autism spectrum disorders and psychosis. Group differences were analysed by a chi-square test and a one-factorial analysis of variance. For analysing the impact of the application of the ED approach on psychotropic medication, a covariance model was applied. Changes between the subsamples were analysed by t-tests for dependent samples. RESULTS: The ED approach had a significant impact on reducing the overall amount of psychotropic medication and the dosage of antipsychotics in all patients with IDD. These effects were mainly attributable to those showing CB. In patients with autism spectrum disorders, the developmental approach reduced the number of antipsychotics. No effects could be observed in patients with psychosis; in this subsample, both the number and dosage of antipsychotics increased. CONCLUSIONS: The application of the ED approach in the current hospital stay reduced the number of psychotropic drugs and the number and dosage of antipsychotics, especially in those patients with IDD and CB, but also in those with autism spectrum disorders.

What do people with intellectual disabilities, their family members and paid carers understand about psychotropic medication? A rapid review.

BACKGROUND: People with intellectual disabilities are more likely to be prescribed psychotropic medication than the general population and are frequently prescribed multiple medications. Understanding people with intellectual disabilities and carer perspectives is essential to improving the quality of psychotropic medication prescribing and usage. METHOD: A rapid review explored people with intellectual disabilities' understanding of psychotropic medications, as well as family members and paid carers, and how this understanding can be improved. RESULTS: Twenty-one journal articles were included. Lack of understanding of medication was universal, with participants often unaware of adverse effects, alternatives, and rights around medication. There was also a lack of involvement in decision making for all participants. Some interventions aimed at people with intellectual disabilities or paid carers helped to improve knowledge. CONCLUSION: Evaluating how best to improve psychotropic medication understanding for people with intellectual disabilities, family members and paid carers should be a focus for future research.

Aggressive behaviour and diabetes: A clinical case of atypical metabolic improvement during clozapine treatment.

Aggressive and violent behaviour is a challenging psychiatric emergency to manage, especially among vulnerable categories such as patients with Intellectual Developmental Disorder. Although there is some evidence that clozapine may be useful as an anti-violence compound, its use is limited by common metabolic complications. An adult patient presented with obesity, type II diabetes mellitus, compulsive food intake, severe Intellectual Developmental Disorder, and a treatment-resistant aggressive behaviour. Clozapine was administered resulting in reduced aggressive behaviour. Unexpectedly, a reduction in the food craving as well as a sustained improvement in both anthropometric parameters and glycemic control were observed during the clozapine treatment. Our case report, describes these findings for the first time, highlighting the need for more clinical research to investigate both the efficacy of clozapine in the Intellectual Developmental Disorder populations and its long-term effects with special regard to the metabolic outcomes in this type of patients.

[Pharmacotherapy in sexual behavior disorders and intellectual disability]. / Farmacotherapie bij seksuele gedragsstoornissen en verstandelijke beperking.

BACKGROUND: Sexual behavior disorders in intellectual disability form several challenges, despite evolutions in treatment options and risk assessment. The use of antilibidinal pharmacotherapy in this population is controversial and research is inconclusive about the most appropriate treatment strategy. AIM: To highlight pharmacotherapeutic management of sexual behavior disorders in intellectual disability, its medical and ethical considerations. METHOD: A literature review to provide an overview of the available literature, which was elaborated based on clinical experience. RESULTS: We found a lack of scientific evidence on the efficacy of pharmacotherapy specifically for sexual behavior disorders in people with intellectual disabilities. The routine use of antilibidinal medication is contraindicated. Medical and ethical guidelines have been published as well as contraindications for initiating androgen deprivation therapy in the general population. The necessity of pharmacotherapy should be closely monitored and supplemented with psychotherapeutic care to cultivate the patient’s sexual skills, attitudes and knowledge. A distinction should be made between sexual behavior disorders of the ‘paraphilic type’ and of the ‘sexually maladjusted or naive type’. CONCLUSION: Multidisciplinary evaluation, risk assessment and an individualized approach are the cornerstones of high-quality treatment of sexual behavior disorders in persons with intellectual disability.

A Farnesyltransferase Inhibitor Restores Cognitive Deficits in Tsc2+/- Mice through Inhibition of Rheb1.

Tuberous sclerosis complex (TSC) is caused by mutations in Tsc1 or Tsc2, whose gene products inhibit the small G-protein Rheb1. Rheb1 activates mTORC1, which may cause refractory epilepsy, intellectual disability, and autism. The mTORC1 inhibitors have been used for TSC patients with intractable epilepsy. However, its effectiveness for cognitive symptoms remains unclear. We found a new signaling pathway for synapse formation through Rheb1 activation, but not mTORC1. Here, we show that treatment with the farnesyltransferase inhibitor lonafarnib increased unfarnesylated (inactive) Rheb1 levels and restored synaptic abnormalities in cultured Tsc2+/- neurons, whereas rapamycin did not enhance spine synapse formation. Lonafarnib treatment also restored the plasticity-related Arc (activity-regulated cytoskeleton-associated protein) expression in cultured Tsc2+/- neurons. Lonafarnib action was partly dependent on the Rheb1 reduction with syntenin. Oral administration of lonafarnib increased unfarnesylated protein levels without affecting mTORC1 and MAP (mitogen-activated protein (MAP)) kinase signaling, and restored dendritic spine morphology in the hippocampi of male Tsc2+/- mice. In addition, lonafarnib treatment ameliorated contextual memory impairments and restored memory-related Arc expression in male Tsc2+/- mice in vivo Heterozygous Rheb1 knockout in male Tsc2+/- mice reproduced the results observed with pharmacological treatment. These results suggest that the Rheb1 activation may be responsible for synaptic abnormalities and memory impairments in Tsc2+/- mice, and its inhibition by lonafarnib could provide insight into potential treatment options for TSC-associated neuropsychiatric disorders.SIGNIFICANCE STATEMENT Tuberous sclerosis complex (TSC) is an autosomal-dominant disease that causes neuropsychiatric symptoms, including intractable epilepsy, intellectual disability (ID) and autism. No pharmacological treatment for ID has been reported so far. To develop a pharmacological treatment for ID, we investigated the mechanism of TSC and found that Rheb1 activation is responsible for synaptic abnormalities in TSC neurons. To inhibit Rheb1 function, we used the farnesyltransferase inhibitor lonafarnib, because farnesylation of Rheb1 is required for its activation. Lonafarnib treatment increased inactive Rheb1 and recovered proper synapse formation and plasticity-related Arc (activity-regulated cytoskeleton-associated protein) expression in TSC neurons. Furthermore, in vivo lonafarnib treatment restored contextual memory and Arc induction in TSC mice. Together, Rheb1 inhibition by lonafarnib could provide insight into potential treatments for TSC-associated ID.

Antiseizure medications prescribing for behavioural and psychiatric concerns in adults with an intellectual disability living in England.

Antiseizure medications (ASMs) are the second most widely prescribed psychotropic for people with intellectual disabilities in England. Multiple psychotropic prescribing is prevalent in almost half of people with intellectual disabilities on ASMs. This analysis identifies limited evidence of ASM benefit in challenging behaviour management and suggests improvements needed to inform clinical practice.

Addressing Metabolic Comorbidity in Individuals With Intellectual and Developmental Disability on Antipsychotics: A Clinical Case Series.

PURPOSE/BACKGROUND: Individuals with intellectual and developmental disabilities (IDDs) are at increased risk for serious metabolic comorbidities, which is further exacerbated by the high rate of antipsychotic use in this population. There is currently a lack of literature on effective treatment options for antipsychotic-induced weight gain and metabolic abnormalities in IDD. This case series reports on the clinical use of metformin in patients with IDD on antipsychotics. METHODS/PROCEDURES: We conducted a retrospective review of patients in a novel clinical service at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada for adults with IDD experiencing antipsychotic-related weight gain and other metabolic aberrations. Charts were reviewed for weight and other metabolic outcome measures before and after commencing metformin treatment. FINDINGS/RESULTS: In 11 patients referred to this clinic, the mean weight loss while on metformin treatment was 11.1 kg, with over 50% of the sample achieving clinically meaningful weight loss of >7%. Additional adaptive changes were observed for fasting glucose, glycated hemoglobin, triglyceride, and high-density lipoprotein cholesterol levels. IMPLICATIONS/CONCLUSIONS: In line with its use in severe mental illness, metformin may be a safe, effective, and accessible treatment option for patients with IDD experiencing metabolic adverse effects of antipsychotic medication. Further research and randomized controlled trials are needed to examine the efficacy of metformin in this population.

Patterns of antiseizure medications prescribing in people with intellectual disability and epilepsy: A narrative review and analysis.

People with intellectual disabilities (PwID) have a bidirectional relationship with epilepsy. Nearly 25% of PwID have seizures and 30% people with epilepsy are thought to have a significant intellectual impairment. Furthermore, 70% of PwID are thought to have treatment-resistant epilepsy. In the United Kingdom, antiseizure medications (ASMs) are the second most widely prescribed psychotropic agent for PwID. However, it is unclear what the current evidence and patterns is on current prescribing of ASMs, including when and how a case is made to withdraw them. A narrative review along with an analysis of large-scale NHS Digital published data (2015-2020) on several aspects of ASM prescribing by general practices for PwID was undertaken. The review results and data analysis are consolidated and presented as 11 themes to provide a comprehensive overview of the study topic. Recent studies estimate that one-third and one-fifth of PwID are prescribed ASMs. A history of epilepsy is seen as the primary prescribing reason; however, often it is a legacy, and the indication is no longer clear. The proportion receiving ASMs continues to rise with age. This pattern of use does not correlate well with seizure onset. There are limited data on de-prescribing ASMs in PwID. The study population heterogenicity, associated polypharmacy, multimorbidity and higher sudden unexpected death in epilepsy risks are outlined. Suggestions are made from available evidence for improving prescribing practices for PwID and seizures, and key areas for further research in this complex clinical area are outlined.

A case of Pitt-Hopkins syndrome: psychopharmacological approach for anxiety, insomnia, and agitation.

Pitt-Hopkins syndrome (PTHS) is a rare genetic disorder resulting from TCF4 gene mutations which is characterized by dysmorphic facial features, psychomotor delay, intellectual disability, breathing anomalies, and seizures. Psychiatric conditions are occasionally seen. We present the case report of a seven-year-old PTHS patient with anxiety, insomnia, and agitation. We discuss the psychopharmacological intervention options for this patient. The present case study reports on a 7-year-old female with PTHS, autism spectrum disorder (ASD), and intellectual disability. She had insomnia, crying spells and agitation complaints. For anxiety symptoms and agitation, risperidone, fluoxetine, and clonazepam treatment were given by the neurologist which caused behavioral disinhibition, paroxysmal agitation and no benefit. After admission to our hospital, aripiprazole and hydroxyzine were prescribed for anxiety and ASD-related irritability. She showed a minimal improvement but hyperventilation attacks were still ongoing. Hydroxyzine was stopped, and quetiapine was given to eliminate sleep disturbance. Her sleep period went up to eleven hours. For the anxiety symptoms, escitalopram was prescribed. She showed improvements in sleep, diminished hyperactivity and decreased frequency of abnormal breathing spells. Also, enhancement of social communication skills like increased eye contact and response to her name was observed. Patients with genetic syndromes may have various psychiatric complaints. Psychopharmacological interventions should be administered carefully for the side effects.

Deprescribing psychotropic medicines for behaviours that challenge in people with intellectual disabilities: a systematic review.

BACKGROUND: Clear evidence of overprescribing of psychotropic medicines to manage behaviours that challenges in people with intellectual disabilities has led to national programmes within the U.K. such as NHS England's STOMP to address this. The focus of the intervention in our review was deprescribing of psychotropic medicines in children and adults with intellectual disabilities. Mental health symptomatology and quality of life were main outcomes. METHODS: We reviewed the evidence using databases Medline, Embase, PsycINFO, Web of Science, CINAHL and Open Grey with an initial cut-off date of 22nd August 2020 and an update on 14th March 2022. The first reviewer (DA) extracted data using a bespoke form and appraised study quality using CASP and Murad tools. The second reviewer (CS) independently assessed a random 20% of papers. RESULTS: Database searching identified 8675 records with 54 studies included in the final analysis. The narrative synthesis suggests that psychotropic medicines can sometimes be deprescribed. Positive and negative consequences were reported. Positive effects on behaviour, mental and physical health were associated with an interdisciplinary model. CONCLUSIONS: This is the first systematic review of the effects of deprescribing psychotropic medicines in people with intellectual disabilities which is not limited to antipsychotics. Main risks of bias were underpowered studies, poor recruitment processes, not accounting for other concurrent interventions and short follow up periods. Further research is needed to understand how to address the negative effects of deprescribing interventions. TRIAL REGISTRATION: The protocol was registered with PROSPERO (registration number CRD42019158079).

Use of psychotropic medications in adults with intellectual disability: A systematic review and meta-analysis.

OBJECTIVE: This study presents the proportion of adults with intellectual disability using psychotropic medications including antipsychotics, antidepressants, anxiolytics, hypnotics and sedatives, and psychostimulants. METHODS: A search was performed in PubMed, Embase, PsycINFO, Web of Science, and Scopus up to 31 December 2021. Articles were included if they reported the proportion of adults with intellectual disability using psychotropic medications. Frequency of use was estimated using a random effects meta-analysis. Meta-regression analysis was used to assess the association between study-level characteristics and variability in estimates, when heterogeneity was considerable. RESULTS: Twenty-four articles were included in pooled analysis. The pooled prevalence of psychotropic medications was 41% (95% confidence interval: 35-46%). Pooled prevalences of subclasses were as follows: antipsychotics 31% (27-35%), antidepressants 14% (9-19%), anxiolytics 9% (4-15%), hypnotics/sedatives 5% (2-8%), and psychostimulants 1% (1-2%). Heterogeneity was considerable between studies, except for psychostimulants. There was no significant association between assessed characteristics and variability in prevalence estimates. CONCLUSION: Two-fifths of adults with intellectual disability were prescribed psychotropic medications. Antipsychotics and antidepressants were used by one-third and one-seventh of adults, respectively. There was considerable variability between studies, and further investigation is required to determine the source of variability. More studies are needed to better characterise prescribed psychotropic medications, including effectiveness and adverse effects, to ensure appropriate use of these drugs.

Training support workers about the overmedication of people with intellectual disabilities: an Australian pre-post pilot study.

BACKGROUND: There is evidence that psychotropic medications are overprescribed and overused to manage behaviours of concern for people with intellectual disabilities. Disability support workers and support staff lack education and training on the administration and safety of psychotropic medication use. This study aimed to test the applicability and preliminary efficacy of SPECTROM, an education programme developed in the UK, in an Australian context. METHODS: The training comprises two parts: Module 1 encompasses psychotropic medications, their use and side effects. Module 2 focuses on non-pharmacological interventions for supporting people with behaviours of concern. Thirty-three participants attended the training course and completed pre-training and post-training surveys on the Psychotropic Knowledge Questionnaire and Management of Aggression and Violence Attitude Scale-Revised at four time points: pre-training, 2 weeks, 3 months and 5 months post-training. RESULTS: Psychotropic Knowledge Questionnaire scores showed statistically significant post-training improvement at all post-training time points (P < 0.05). Management of Aggression and Violence Attitude Scale-Revised scores were high at pre-training and did not change significantly at any of the post-training survey time points. A 2-week post-training feedback questionnaire reported 80% agreement that the training programme was appropriate, useful and valid. Only 36% of participants completed questionnaires at all time points. CONCLUSIONS: SPECTROM training increased staff knowledge of psychotropic medications, yet loss of participants was high. Further refinement of the applicability of the training for the Australian context and evaluation of the feasibility of implementation, clinical and cost-effectiveness of the programme are required.

Medicine use in people with intellectual disabilities: a Finnish nationwide register study.

BACKGROUND: People with intellectual disability (ID) are a vulnerable group in our society; many of them depend on other people for assistance in their everyday lives. Compared with the general population, people with ID have poorer general health and, therefore, need more healthcare services and use more medicines. The aim of this study is to define the population of all Finnish people with ID using administrative data and to compare their medicine use and expenditure on medicines to those of the age-matched and sex-matched controls. METHODS: People with ID and their age-matched and sex-matched controls (1:1) were extracted from nationwide healthcare and social allowance registers. Administrative register data on all prescription medicine purchases in 2019 were used to determine the prevalence of medicine use in both groups on a general level and by medicine categories. The differences in the prevalence of medicine use between the two groups were analysed using the logistic regression model. In addition, we studied the total expenditure on reimbursable medicine purchases covered by the National Health Insurance between people with ID and control group. RESULTS: The subpopulation of people with ID consisted 37 196 individuals, of whom 82.7% purchased prescription medicines in 2019. The corresponding share of individuals purchasing prescription medicines in the control group was 70.3%. The differences in the prevalence of medicine use between the two populations were highest in the younger age groups (0-6, 7-12 and 13-17). In the study population, 28.1% (OR = 12.28; 95% CI: 11.54-13.07) of the people used antipsychotics, making it the most used medicine category in people with ID. In the control group, 3.3% of people used antipsychotics. Compared with the control group, the use of antiepileptics, drugs for constipation, mineral supplements and anxiolytics was four to seven times higher among people with ID. Furthermore, the median expenditure on medicine use among people with ID was four times higher than in the control group. CONCLUSIONS: Compared with the control group, people with ID used more medicines, especially psychotropics, and their expenditure on medicine use was higher.