Effectiveness and implementation of a multidisciplinary lifestyle focused approach in the treatment of inpatients with mental illness (MULTI +): a stepped wedge study protocol.

BACKGROUND: People with mental illness have a reduced life expectancy compared to the general population. Despite the increasing evidence for the efficacy of lifestyle interventions there is little change in routine clinical care. This discrepancy is often referred to as the implementation gap and has caused a need for effectiveness and implementation research in real-world settings. Our study assesses the effectiveness and implementation of a multidisciplinary lifestyle focused approach in the treatment of inpatients with mental illness (MULTI +). METHODS: An open cohort stepped wedge cluster randomized trial in inpatients psychiatric wards of GGz Centraal, the Netherlands. The wards are divided into three clusters based on geographical region. These clusters are randomly allocated to one of the three pre-defined steps to integrate MULTI + . MULTI + can be tailored to fit individual psychiatric wards and includes 10 core components aimed at improving lifestyle factors. The primary outcome is to investigate the difference in the mean QRISK3 score of patients receiving MULTI + compared to patients receiving TAU. Secondary outcomes include somatic and mental health outcomes, lifestyle factors, and implementation factors. Findings will be analysed using mixed model analyses. DISCUSSION: The MULTI + study is the first large-scale study evaluating the long-term effects of a multidisciplinary, multicomponent approach aimed at improving lifestyle factors in routine inpatient mental health care. A limitation of this study is the risk of missing data due to the large-scale, real-world setting of this study. Furthermore, implementation monitoring and external events that may influence outcomes could be difficult to account for. Strengths of this study are the focus on effectiveness as well as implementation and the inclusion of both patient and health care professionals' perspectives. Effectiveness studies in routine clinical care can advance our knowledge on lifestyle interventions in real-world settings. TRIAL REGISTRATION: ClinicalTrials.gov registration. Identifier: NCT04922749 . Retrospectively registered 3th of June 2021.

[CYP2D6 and CYP2C19 genotyping: effectivity in psychiatric practice] / CYP2D6- en CYP2C19-genotypering: effectiviteit in de psychiatrische praktijk.

BACKGROUND: International guidelines recommend in patients with an in- or decreased CYP2D6 and CYP2C19 metabolism to adjust the dose of medication metabolized by these enzymes. This is in purpose to increase effectiveness and to lower the risk of side-effects of this medication. However, it is still unclear if dose adjustment based on genotype results in better clinical outcomes. AIM: To provide an update regarding CYP2D6 and CYP2C19 genotyping in psychiatry in relation to ethnic diversity.To provide an update regarding CYP2D6 and CYP2C19 genotyping in psychiatry in relation to ethnic diversity. METHOD: We conducted a comprehensive meta-analysis to the prevalence of non-normal metabolizers as the equivalent of the sum-prevalence of poor, intermediate and ultrarapid metabolizer CYP2D6 and CYP2C19 predicted phenotypes. For the prevalence and effectiveness study, a total of 166 Antilleans living in the Netherlands and 269 psychiatric patients (on the island Curaçao) were genotyped for CYP2D6 and CYP2C19. Of the psychiatric patients, 45 non-normal CYP2D6 metabolizers using medication metabolized by CYP2D6, were included for dose adjustment and were matched with 41 normal metabolizers. All 45 patients were using antipsychotic medication for a minimum of two years. Four months after dose adjustment they were reassessed. RESULTS: The mean total probability estimates of having a non-normal predicted phenotype worldwide were 36% and 62% for CYP2D6 and CYP2C19, respectively. There was a large interethnic variability (min-max 2.7-61.2% (CYP2D6) and minmax 31.7-80.1% (CYP2C19)). No significant difference was found in the phenotypes of psychiatric patients, Dutch Caribbean subjects from the general population, and European populations. There were no beneficial effects of dose adjustments to phenotype in the non-normal CYP2D6 metabolizers. CONCLUSION: More than 75% of the world population has a non-normal CYP2D6 and/or CYP2C19 phenotype. Dose adjustment to the CYP2D6 phenotype according to international guidelines in patients on long-term antipsychotic treatment showed no beneficial effect. Further research to CYP genotyping in psychiatry is warranted.

[Thinking inside the box: improving the lifestyle of inpatients with severe mental illness]. / Thinking inside the box: leefstijl­verbetering bij mensen met een ernstige psychiatrische aandoening in de kliniek.

BACKGROUND: An unhealthy lifestyle plays an important role in the substantially reduced life-expectancy of inpatients with severe mental illness (SMI). However, there is a lack of evidence on the long-term effectiveness and implementation of lifestyle improvements in inpatient mental healthcare.
AIM: Increasing knowledge and understanding of (the implementation of) lifestyle changes in inpatients with SMI in longer-term clinical care.
METHOD: Cross-sectional research followed by an observational study to evaluate a multidisciplinary lifestyle enhancing treatment (MULTI) for both changes in health-related outcomes after 18 months compared to treatment as usual (TAU), and the implementation barriers and facilitators.
RESULTS: Patients were very sedentary and less physically active compared to people without SMI. After 18 months, MULTI showed significant improvements in total physical activity, cardiometabolic risk factors, psychosocial functioning and mediation use, compared to TAU. Physical health did not improve in TAU. The implementation of MULTI was hampered by organisational factors and facilitated by positive attitudes of healthcare professionals and patients towards MULTI and their own role in it.
CONCLUSION: Using a multidisciplinary integrated approach, it is possible to improve the lifestyle, and thus the health status, of SMI inpatients, within the current context of routine mental healthcare.

Efficacy of amantadine on behavioural problems due to acquired brain injury: A systematic review.

Objectives: To systematically review literature on efficacy of amantadine on behavior (irritability/aggression/agitation, emotional lability, apathy, impairment of executive functioning), participation, quality-of-life (QoL), and safety, in patients with acquired brain injury (ABI). Amantadine is widely used clinically, so comprehensive information on efficacy, participation, QoL and safety is relevant. Methods: We used PRISMA Guidelines. We searched PubMed/EMBASE/CINAHL (last search 28-8-2018) Two independent reviewers performed selection and data-extraction. Quality of studies was assessed, using CONSORT and Quality Assessment Tool for Quantitative Studies (QATFQS). Results: Eleven out of 500 studies were included. Of five RCTs, two reported significant effects on irritability/aggression, and one no effect. One RCT on cognition no effect. One prospective cohort study showed a significant effect on executive functioning. One retrospective study was inconclusive. One single-case experimental design (SCED) study reported significant effect on apathy and three case-reports indicated effects on behavior. QoL and societal participation were not measured. No safety issues emerged. Conclusion: Amantadine may be efficacious on irritability and aggression after ABI. Amantadine is a safe drug in the presence of adequate creatinine clearance. Future studies should use designs, suitable for the heterogeneous ABI population, like randomized SCEDs, and should include the effect on societal participation and QoL.

[Movement disorders as a prodromal sign in individuals at high risk of psychosis]. / Bewegingsstoornissen als prodroom bij personen met een sterk verhoogd risico op psychose.

BACKGROUND: The accurate prediction of a transition to psychosis in high-risk and ultra-high-risk (UHR) populations is important because timely preventive interventions may succeed in delaying or even averting psychosis. However, current screening programmes have very low predictive power. Therefore, if prodromal signs are to be really useful they need to be objective and have strong predictive power. We hypothesise that in the prodromal phase movement disorders (MD) are probably better than screening programmes at predicting the development of psychotic disorders. AIM: To determine, on the basis of published articles and personal experience, whether, in UHR populations, MD can predict a transition to psychosis more accurately that current screening programmes. METHOD: We studied the literature using Medline. RESULTS: Our strategy was to search the literature for studies concerning 1. children with schizotypal personality disorder, 2. UHR adolescents and 3. siblings of patients with schizophrenia. Studies relating to the first two groups showed that the severity of MD was related to the severity of the prodromal signs both at baseline and at follow-up. Patients with more (and more severe) MD had a higher risk of transition to a psychotic disorder than patients without MD. Studies relating to the third group showed that the frequency of mechanically measured md was significantly higher in the siblings of patients with schizophrenia than in healthy controls. CONCLUSION: MD are objective easy-to-measure prodromal signs which might be powerful predictors of a transition to psychosis in (U)HR populations.

[The genetics of antipsychotic-related movement disorders]. / De genetica van antipsychotica-gerelateerde bewegingsstoornissen.

BACKGROUND: Treatment with antipsychotics is associated with movement disorders which are sometimes irreversible. It is therefore important to find ways of preventing the movements generated by the use of antipsychotics. Pharmacogenetic research is working on prevention strategies. The result of this research focus mainly on meta-analyses of association studies and genome-wide association studies (GWAS). AIM: To present a review of the main pharmacogenetic studies of antipsychotic-related movement disorders. METHOD: We reviewed the literature using Medline, Embase and PsycINFO. RESULTS: Evidence from pooled data derived from meta-analyses showed small odds ratios between tardive dyskinesia (TD) and genes encoding DRD2, DRD3, BDNF, COMT, 5-HTR2A, CYP2D6, and MnSOD (p-value < 0.05). These results were not confirmed in DRDs and mnSOD by the most recent meta-analyses. GWAS for TD and parkinsonism have revealed new genes. CONCLUSION: So far, we are unable to provide any clinically useful advice. New pharmacogenetic research and diagnostic systems are likely to create new opportunities.

[Risk factors for tardive movement disorders in schizophrenia]. / Risicofactoren van tardieve bewegingsstoornissen bij schizofrenie.

BACKGROUND: Tardive movement disorders are common among patients with schizophrenia. Risk factors for movement disorders are of the utmost importance in the context of preventive strategies. AIM: To achieve clearer classification of movement disorders in schizophrenia, to identify the risk factors involved and thereby develop strategies to prevent movement disorders. METHOD: We searched PubMed for prospective studies which had been performed in homogeneous target populations with schizophrenia and which contained well-defined definitions of the movement disorders. From these we selected studies in which risk factors were repeatedly identified. RESULTS: Tardive dyskinesia is well documented. Risk factors for developing tardive dyskinesia are use of antipsychotics, particularly those belonging to the first generation, 'not belonging to the Caucasian race', early extrapyramidal symptoms and older age. So far, there is very little conclusive evidence regarding the genetics of tardive movement disorders. CONCLUSION: With regard to tardive dyskinesia, not belonging to the Caucasian race and old age are two risk factors that can be quickly determined for the purpose of prevention. In this case it leads to the choice of medication with a low D2 affinity. Furthermore, it is advisable, after commencing treatment with an antipsychotic drug, to evaluate on a regular basis if the patient is showing (early) signs of TD. If TD does occur, there is a choice between medication with a low D-2 affinity or clozapine.

[Severe treatment-resistant tardive dystonia: is deep brain stimulation a treatment option]. / Ernstige, therapieresistente tardieve dyskinesie: is diepe hersenstimulatie een behandeloptie?

BACKGROUND: Severe tardive dyskinesia or dystonia (TD) are side-effects of dopamine-blocking agents, most of which are antipsychotics. A small subgroup of patients develop a severe debilitating treatment-resistant form of TD. AIM: To assess the effects and side-effects of deep brain stimulation (DBS) in this subgroup of TD patients. METHOD: We searched PubMed and Embase using the search terms 'tardive' and 'deep brain stimulation'. We found 19 articles containing data referring to 52 patients. Using the Burke Fahn Marsden Dystonia Rating Scale (BFMDRS), the Abnormal Involuntary Movement Scale (AIMS) and the Extrapyramidal Symptoms Rating Scale (ESRS) we calculated the average improvement in the patients' condition. RESULTS: On all the scales the improvement was statistically significant (p < 0.00001), the average improvement being 67% to 78%. In only 4% of the patients was there a deterioration in the psychiatric disorder. CONCLUSION: DBS seems to be an effective treatment for treatment-resistant TD and the side-effects seem to be limited. However, the evidence is limited because our conclusion is based on case-reports and on small-scale trials without randomisation or blinding.

[Instrumental registration of psychomotor symptoms in schizophrenia: has the time come to use the technique in clinical practice?]. / Instrumenteel meten van psycho-motorische symptomen bij schizofrenie: klaar voor de praktijk?

BACKGROUND: In clinical practice, psychomotor deficits are currently assessed by means of observation scales. However, instrumental (including mechanical and electronic) measurement techniques might also be valuable in clinical practice. AIM: To discuss the added value of using instrumental registration of psychomotor functioning into clinical practice. METHOD: We investigated the main pros and cons of instrumental registration by searching the literature systematically and we discuss our findings using concrete examples. RESULTS: Compared to observation scales, instrumental registration yields more reliable and sensitive information about the psychomotor functioning of patients. Another advantage of instrumental registration is that it gives us an opportunity to study affected sub-processes and underlying mechanisms. However, the validity of these measurements depends on whether instrumental registration can adequately reflect aspects of a movement that can be observed clinically. CONCLUSION: Clinical practice could benefit substantially from using instrumental registration of psychomotor disturbances in schizophrenia. However, more time and money needs to be invested in research before the new technique is fully validated and ready for use in clinical practice.

[Risk factors for inactivity in patients in long-term care with severe mental illness]. / Risicofactoren voor inactiviteit bij patiënten met ernstige psychiatrische aandoeningen in de langdurige zorg.

BACKGROUND: Inactivity is a major problem in long-stay patients with severe mental illness. Very little research has been done into the variables that can predict and explain this inactivity. AIM: To find associations between inactivity and the variables (psychiatric, pharmacological, lifestyle and comorbidity) of patients with severe mental health illness.methods A cross-sectional study was performed at "Zon en Schild", a centre for mental health care in Amersfoort in the Netherlands. The study included 100 long-stay psychiatric patients hospitalized throughout the period February 2011 till July 2011. All of these patients were being treated with antipsychotics and were long-term inpatients at a psychiatric clinic. At the out-patient clinic of "Zon en Schild"; they were screened for inactivity via a subscale of the Nurses"; Observation Scale for Inpatient Evaluation (NOSIE-30). Data were collected and analysed by means of a validated questionnaire, physical examination and patient records. Simple and multiple regression analyses were performed in order to find associated factors associated with inactivity. RESULTS: We found that 31.3% of the variance predicted by the multiple regression analysis model for inactivity was associated with the variables parkinsonism, negative symptoms, metabolic syndrome, diabetes, body-mass index (BMI), first-generation antipsychotics and combination of first- and second-generation antipsychotics. Age (ß=0.235, p=0.04) and a combination therapy involving traditional and atypical antipsychotics (ß=0.317, p=0.04) were significantly associated with inactivity. CONCLUSION: Age and the combination of first- and second-generation antipsychotics were associated with inactivity. Cross-sectional studies do not demonstrate any causal links, but can generate a hypothesis. One possible hypothesis for the surprising link between inactivity and the combination of traditional and atypical antipsychotics is that the combination of antipsychotics promotes and fosters inactivity.key words clinical, epidemiology, inactivity, long-term care, schizophrenia.

[Staging and profiling of psychiatric disorders]. / Stagering en profilering van psychiatrische stoornissen.

BACKGROUND: Diagnostic issues are at the heart of medicine. Although the existing systems to classify mental disorders have been of tremendous value to Psychiatry, there is growing pressure to reform psychiatric diagnosis. In other areas in medicine staging and profiling has been a fruitful strategy to model the diagnosis of complex disorders. AIM: To examine whether staging and profiling may be a fruitful model for the diagnosis of psychiatric disorders. RESULTS: Clinical staging and profiling may help to reform our current static, descriptive and largely categorical classification of mental disorders and arrive at a diagnostic system that is developmental, that can accommodate better the continuous nature of most mental health problems and that is sensitive to etiologic and prognostic risk factors. CONCLUSION: Looking beyond the forthcoming revisions of DSM and ICD, clinical staging and profiling provide the necessary framework for a more fundamental reform of psychiatric diagnosis.

Movement disorders are associated with schizotypy in unaffected siblings of patients with non-affective psychosis.

BACKGROUND: Movement disorders and schizotypy are both prevalent in unaffected siblings of patients with schizophrenia and both are associated with the risk of developing psychosis or schizophrenia. However, to date there has been no research into the association between these two vulnerability factors in persons with an increased genetic risk profile. We hypothesized that unaffected siblings of patients with non-affective psychosis have more movement disorders and schizotypy than healthy controls and that these co-occur. METHOD: In a cross-sectional design we assessed the prevalence and inter-relationship of movement disorders and schizotypy in 115 unaffected siblings (mean age 27 years, 44% males) and 100 healthy controls (mean age 26 years, 51% males). Movement disorders were measured with the Abnormal Involuntary Movement Scale (AIMS), the Unified Parkinson Disease Rating Scale (UPDRS), the Barnes Akathisia Rating Scale (BARS), and one separate item for dystonia. Schizotypy was assessed with the Structured Interview for Schizotypy--Revised (SIS-R). RESULTS: There were significant differences in the prevalence of movement disorders in unaffected siblings versus healthy controls (10% v. 1%, p<0.01) but not in the prevalence of schizotypy. Unaffected siblings with a movement disorder displayed significantly more positive and total schizotypy (p=0.02 and 0.03 respectively) than those without. In addition, dyskinesia correlated with positive schizotypy (r=0.51, p=0.02). CONCLUSIONS: The association between movement disorders (dyskinesia in particular) with positive and total schizotypy in unaffected siblings suggests that certain vulnerability factors for psychosis or schizophrenia cluster in a subgroup of subjects with an increased genetic risk of developing the disease.

Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions.

Despite accumulating evidence pointing to a genetic basis for tardive dyskinesia, results to date have been inconsistent owing to limited statistical power and limitations in molecular genetic methodology. A Medline, EMBASE and PsychINFO search for literature published between 1976 and June 2007 was performed, yielding 20 studies from which data were extracted for calculation of pooled estimates using meta-analytic techniques. Evidence from pooled data for genetic association with tardive dyskinesia (TD) showed (1) in COMT(val158met), using Val-Val homozygotes as reference category, a protective effect for Val-Met heterozygotes (OR=0.63, 95% CI: 0.46-0.86, P=0.004) and Met carriers (OR=0.66, 95% CI: 0.49-0.88, P=0.005); (2) in Taq1A in DRD2, using the A1 variant as reference category, a risk-increasing effect for the A2 variant (OR=1.30, 95% CI: 1.03-1.65, P=0.026), and A2-A2 homozygotes using A1-A1 as reference category (OR=1.80, 95% CI: 1.03-3.15, P=0.037); (3) in MnSOD Ala-9Val, using Ala-Ala homozygotes as reference category, a protective effect for Ala-Val (OR=0.37, 95% CI: 0.17-0.79, P=0.009) and for Val carriers (OR=0.49, 95% CI: 0.24-1.00, P=0.047). These analyses suggest multiple genetic influences on TD, indicative of pharmacogenetic interactions. Although associations are small, the effects underlying them may be subject to interactions with other loci that, when identified, may have acceptable predictive power. Future genetic research will take advantage of new genomic knowledge. Molecular Psychiatry (2008) 13, 544-556; doi:10.1038/sj.mp.4002142; published online 8 January 2008.

The role of dopamine D3, 5-HT2A and 5-HT2C receptor variants as pharmacogenetic determinants in tardive dyskinesia in African-Caribbean patients under chronic antipsychotic treatment: Curacao extrapyramidal syndromes study IX.

Tardive dyskinesia (TD) is associated with polymorphisms of the dopamine D(3), serotonin 2A and 2C receptors (DRD3, HTR2A and HTR2C, respectively). This study investigated the possible relationship between TD and the polymorphisms Ser9Gly (DRD3), 102T>C (HTR2A), -1438G>A(HTR2A) and Cys23Ser (HTR2C) in African-Caribbean inpatients. One hundred and twenty-six patients under chronic antipsychotic treatment were genotyped. The assessment of TD was carried out with the abnormal involuntary movement scale (AIMS). The relationships between the carriership of the least frequent alleles and the respective orofaciolingual dyskinesia (TDof) (sum of the items 1-4 of the AIMS), limb-truncal dyskinesia (TDlt) (sum of items 5-7 of the AIMS) and TD (sum of items 1-7 of the AIMS) were analyzed with ANCOVA, comparing means with age as a covariate and stratification for carriers and non-carriers of the mutations. In addition, we conducted pre-planned t-tests to compare AIMS values of carriers of the combinations of alleles versus the corresponding non-carriers. In the study population, females with 9Ser carriership exhibited higher AIMS values than non-carriers. Male subjects with 9Ser carriership in combination with 23Ser or -1438A carriership exhibited higher AIMS values. In male patients also, the combination of 23Ser and -1438A carriership increased TD. The study clearly shows that the African-Caribbean population differs from the Caucasian population with regard to the association of TD with the polymorphisms studied and suggests that the association of TD with the studied polymorphisms of the 5-HT(2C) and probably of the 5-HT(2A) receptor are the result of a changed susceptibility of the patients, independent of the action of the antipsychotics on these receptors.

The course of tardive dystonia in Afro Caribbean patients, a population-based study: the Curacao extrapyramidal syndromes study: VII.

Tardive dystonia (TDt) is a severe side effect of long-term use of antipsychotics. Previous publications suggested that TDt persist but the results are distorted by referral bias. In a population-based nine-year follow-up study (one baseline, six follow-ups) of chronic psychiatric patients (N=194) on a Caribbean island, the course of prevalent and incident TDt was measured with the Fahn-Marsden rating scale. Of the 26 patients (mean age 53.3 yrs) with TDt at baseline, 64% recovered, 20% persisted, and in 16% the course was intermittent. The severity of baseline TDt was significantly higher in persistent cases versus those who recovered (t=3.01, P<0.008). Of the 27 incident cases (cumulative 9-year incidence: 16.1%; mean age 57.6 yrs), 80% recovered, 8% persisted, and in 12% the course was intermittent. Predominantly affected were hands, eyes (blepharospasm), neck and mouth. The natural course of TDt is better than previously suggested but severe cases tend to persist.

[Number needed to treat: a useful tool for estimating the effectiveness of a treatment]. / Number needed to treat: een nuttige maat voor de effectiviteit van een behandeling.

The concepts developed in evidence-based medicine, together with clinical experience, are the major principles on which clinical decisions are made. One of the concepts is number needed to treat (NNT), which means the number of patients who have to be treated either to prevent one additional unfavourable outcome or to achieve one additional favourable outcome. The NNT is dependent on the baseline risk (the risk of occurrence at baseline): the higher the baseline risk, the lower will be the NNT (which is more favourable). In contrast, the relative risk reduction is fairly independent of the baseline risk. NNT and number needed to harm provide numerical arguments for deciding whether a particular treatment does more good than harm.