Assessing the Effectiveness of STAPP@Work, a Self-Management Mobile App, in Reducing Work Stress and Preventing Burnout: Single-Case Experimental Design Study.

BACKGROUND: Work-related stress and burnout remain common problems among employees, leading to impaired health and higher absenteeism. The use of mobile health apps to promote well-being has grown substantially; however, the impact of such apps on reducing stress and preventing burnout is limited. OBJECTIVE: This study aims to assess the effectiveness of STAPP@Work, a mobile-based stress management intervention, on perceived stress, coping self-efficacy, and the level of burnout among mental health employees. METHODS: The study used a single-case experimental design to examine the use of STAPP@Work among mental health employees without a known diagnosis of burnout (N=63). Participants used the app for 1 week per month repeatedly for a period of 6 months. Using a reversal design, the participants used the app 6 times to assess replicated immediate (1 week after use) and lasting (3 weeks after use) effects. The Perceived Stress Scale, the Coping Self-Efficacy Scale, and the Burnout Assessment Tool were used to measure the outcomes. Linear mixed models were used to analyze the data. RESULTS: After 6 months of app use for 1 week per month, the participants showed a statistically significant decrease in perceived stress (b=-0.38, 95% CI -0.67 to -0.09; P=.01; Cohen d=0.50) and burnout symptoms (b=-0.31, 95% CI -0.51 to -0.12; P=.002; Cohen d=0.63) as well as a statistically significant improvement in problem-focused coping self-efficacy (b=0.42, 95% CI 0-0.85; P=.049; Cohen d=0.42). Long-term use of the app provided consistent reductions in burnout symptoms over time, including in the level of exhaustion and emotional impairment. CONCLUSIONS: The use of an app-based stress management intervention has been shown to reduce burnout symptoms and enhance coping self-efficacy among mental health workers. Prevention of burnout and minimization of work-related stress are of utmost importance to protect employee health and reduce absenteeism.

Combining actigraphy and experience sampling to assess physical activity and sleep in patients with psychosis: A feasibility study.

Background: Sleep disorders and reduced physical activity are common in patients with psychosis and can be related to health-related outcomes such as symptomatology and functioning. Mobile health technologies and wearable sensor methods enable continuous and simultaneous monitoring of physical activity, sleep, and symptoms in one's day-to-day environment. Only a few studies have applied simultaneous assessment of these parameters. Therefore, we aimed to examine the feasibility of the simultaneous monitoring of physical activity, sleep, and symptoms and functioning in psychosis. Methods: Thirty three outpatients diagnosed with a schizophrenia or other psychotic disorder used an actigraphy watch and experience sampling method (ESM) smartphone app for 7 consecutive days to monitor physical activity, sleep, symptoms, and functioning. Participants wore the actigraphy watch during day and night and completed multiple short questionnaires (eight daily, one morning, and one evening) on their phone. Hereafter they completed evaluation questionnaires. Results: Of the 33 patients (25 male), 32 (97.0%) used the ESM and actigraphy during the instructed timeframe. ESM response was good: 64.0% for the daily, 90.6% for morning, and 82.6% for evening questionnaire(s). Participants were positive about the use of actigraphy and ESM. Conclusion: The combination of wrist-worn actigraphy and smartphone-based ESM is feasible and acceptable in outpatients with psychosis. These novel methods can help both clinical practice and future research to gain more valid insight into physical activity and sleep as biobehavioral markers linked to psychopathological symptoms and functioning in psychosis. This can be used to investigate relationships between these outcomes and thereby improve individualized treatment and prediction.

Movement Disorders and Mortality in Severely Mentally Ill Patients: The Curacao Extrapyramidal Syndromes Study XIV.

BACKGROUND AND HYPOTHESIS: There is a substantial gap in life expectancy between patients with severe mental illness (SMI) and the general population and it is important to understand which factors contribute to this difference. Research suggests an association between tardive dyskinesia (TD) and mortality; however, results are inconclusive. In addition, studies investigating associations between parkinsonism or akathisia and mortality are rare. We hypothesized that TD would be a risk factor for mortality in patients with SMI. STUDY DESIGN: We studied a cohort of 157 patients diagnosed predominantly with schizophrenia on the former Netherlands Antilles. TD, parkinsonism, and akathisia were assessed with rating scales on eight occasions over a period of 18 years. Twenty-four years after baseline, survival status and if applicable date of death were determined. Associations between movement disorders and survival were analyzed using Cox regression. Sex, age, antipsychotics, antidepressants and benzodiazepines at each measurement occasion were tested as covariates. STUDY RESULTS: Parkinsonism was a significant risk factor with an HR of 1.02 per point on the motor subscale of the Unified Parkinson's Disease Rating Scale (range 0-56). TD and akathisia were not significantly associated with mortality. CONCLUSIONS: Parkinsonism may be an important risk factor for mortality in SMI patients. This finding calls for more follow-up and intervention studies to confirm this finding and to explore whether treatment or prevention of parkinsonism can reduce excess mortality.

The effect on relapse rate and psychiatric symptomatology: Switching a combination of first- and second-generation antipsychotic polypharmacy to antipsychotic monotherapy in long-term inpatients with schizophrenia and related disorders. A pragmatic randomized open-label trial (SwAP trial).

BACKGROUND: There is little evidence to support the use of antipsychotic polypharmacy, and there are concerns about safety and side effects. Nonetheless, it is commonly used in the treatment of long-term inpatients with schizophrenia. This study investigated the effects of switching from a combination of first- and second-generation antipsychotics (FGA and SGA) to monotherapy (FGA or SGA) on relapse rates and psychiatric symptomatology. METHODS: Institutionalized patients with chronic psychotic disorders using a combination of SGA and FGA (n = 136) participated in a randomized open-label trial. The SWITCH group discontinued either FGA or SGA, the STAY group continued combination treatment. Relapse and psychotic symptoms were measured at baseline and during follow-up at 3, 6, and 9 months. Psychiatric symptomatology was measured using the Brief Psychiatric Rating Scale (BPRS). Relapse was defined as (i) an increase in BPRS score of at least 2 points on any item, or (ii) an increase of at least 4 points in total BPRS score and an adjustment of antipsychotics. RESULTS: A logistic regression model, corrected for sex, showed that the probability of relapse was significantly lower in the SWITCH group: 0.29 (95% CI 0.13-0.62). The protective effect of switching to monotherapy was attributable to patients continuing clozapine as monotherapy. For patients who did not experience a relapse nor dropped out, BPRS total scores decreased significantly more in the SWITCH group (p = 0.0001). CONCLUSION: Switching from a combination of FGA and SGA to monotherapy in long-term inpatients does not increase the relapse rate and may even reduce it.

The polysemous concepts of psychomotricity and catatonia: A European multi-consensus perspective.

Current classification systems use the terms "catatonia" and "psychomotor phenomena" as mere a-theoretical descriptors, forgetting about their theoretical embedment. This was the source of misunderstandings among clinicians and researchers of the European collaboration on movement and sensorimotor/psychomotor functioning in schizophrenia and other psychoses or ECSP. Here, we review the different perspectives, their historical roots and highlight discrepancies. In 1844, Wilhelm Griesinger coined the term "psychic-motor" to name the physiological process accounting for volition. While deriving from this idea, the term "psychomotor" actually refers to systems that receive miscellaneous intrapsychic inputs, convert them into coherent behavioral outputs send to the motor systems. More recently, the sensorimotor approach has drawn on neuroscience to redefine the motor signs and symptoms observed in psychoses. In 1874, Karl Kahlbaum conceived catatonia as a brain disease emphasizing its somatic - particularly motor - features. In conceptualizing dementia praecox Emil Kraepelin rephrased catatonic phenomena in purely mental terms, putting aside motor signs which could not be explained in this way. Conversely, the Wernicke-Kleist-Leonhard school pursued Kahlbaum's neuropsychiatric approach and described many new psychomotor signs, e.g. parakinesias, Gegenhalten. They distinguished 8 psychomotor phenotypes of which only 7 are catatonias. These barely overlap with consensus classifications, raising the risk of misunderstanding. Although coming from different traditions, the authors agreed that their differences could be a source of mutual enrichment, but that an important effort of conceptual clarification remained to be made. This narrative review is a first step in this direction.

A systematic review of the prognostic value of motor abnormalities on clinical outcome in psychosis.

Schizophrenia spectrum disorders have heterogeneous outcomes and currently no marker predicts the course of illness. Motor abnormalities (MAs) are inherent to psychosis, the risk of psychosis, symptom severity, and brain alterations. However, the prognostic value of MAs is still unresolved. Here, we provide a systematic review of longitudinal studies on the prognostic role of MAs spanning individuals at clinical high risk for psychosis (CHR), patients with first-episode psychosis (FEP), and chronic schizophrenia. We included 68 studies for a total of 23,630 subjects that assessed neurological soft signs (NSS), hypo- or hyperkinetic movement disorders and/or catatonia as a prognostic factor on clinical and functional outcomes. We found increased levels of MAs, in particular NSS, parkinsonism, and dyskinesia, were related to deteriorating symptomatic and poor functional outcome over time. Collectively, the findings emphasize the clinical, prognostic and scientific relevance of MA assessment and detection in individuals with or at risk of psychosis. In the future, instrumental measures of MA are expected to further augment detection, early intervention and treatment strategies in psychosis.

Exploring the Relationship Between Movement Disorders and Physical Activity in Patients With Schizophrenia: An Actigraphy Study.

Low physical activity (PA) and sedentary behavior (SB) are major contributors to mental health burden and increased somatic comorbidity and mortality in people with schizophrenia and related psychoses. Movement disorders are highly prevalent in schizophrenia populations and are related to impaired functioning and poor clinical outcome. However, the relationship between movement disorders and PA and SB has remained largely unexplored. Therefore, we aimed to examine the relationship between movement disorders (akathisia, dyskinesia, dystonia, and parkinsonism) and PA and SB in 216 patients with schizophrenia and related psychoses. Actigraphy, the St. Hans Rating Scale for extrapyramidal syndromes, and psychopathological ratings (PANSS-r) were applied. Data were analyzed using multiple linear regression, adjusting for sex, age, negative symptoms, and defined daily dose of prescribed antipsychotics. Parkinsonism was significantly associated with decreased PA (ß = -0.21, P < .01) and increased SB (ß = 0.26, P < .001). For dystonia, only the relationship with SB was significant (ß = 0.15, P < .05). Akathisia was associated with more PA (ß = 0.14, P < .05) and less SB (ß = -0.15, P < .05). For dyskinesia, the relationships were non-significant. In a prediction model, akathisia, dystonia, parkinsonism and age significantly predicted PA (F(5,209) = 16.6, P < .001, R2Adjusted = 0.27) and SB (F(4,210) = 13.4, P < .001, R2Adjusted = 0.19). These findings suggest that movement disorders, in particular parkinsonism, are associated with reduced PA and increased SB in patients with psychotic disorders. Future studies should take movement disorders into account when examining PA and SB, to establish the clinical value of movement disorders in activating people with psychotic disorders to improve their mental and somatic health.

Meta-analysis of probability estimates of worldwide variation of CYP2D6 and CYP2C19.

Extensive migration has led to the necessity of knowledge regarding the treatment of migrants with different ethnical backgrounds. This is especially relevant for pharmacological treatment, because of the significant variation between migrant groups in their capacity to metabolize drugs. For psychiatric medications, CYP2D6 and CYP2C19 enzymes are clinically relevant. The aim of this meta-analysis was to analyze studies reporting clinically useful information regarding CYP2D6 and CYP2C19 genotype frequencies, across populations and ethnic groups worldwide. To that end, we conducted a comprehensive meta-analysis using Embase, PubMed, Web of Science, and PsycINFO (>336,000 subjects, 318 reports). A non-normal metabolizer (non-NM) probability estimate was introduced as the equivalent of the sum-prevalence of predicted poor, intermediate, and ultrarapid metabolizer CYP2D6 and CYP2C19 phenotypes. The probability of having a CYP2D6 non-NM predicted phenotype was highest in Algeria (61%) and lowest in Gambia (2.7%) while the probability for CYP2C19 was highest in India (80%) and lowest in countries in the Americas, particularly Mexico (32%). The mean total probability estimates of having a non-NM predicted phenotype worldwide were 36.4% and 61.9% for CYP2D6 and CYP2C19, respectively. We provide detailed tables and world maps summarizing clinically relevant data regarding the prevalence of CYP2D6 and CYP2C19 predicted phenotypes and demonstrating large inter-ethnic differences. Based on the documented probability estimates, pre-emptive pharmacogenetic testing is encouraged for every patient who will undergo therapy with a drug(s) that is metabolized by CYP2D6 and/or CYP2C19 pathways and should be considered in case of treatment resistance or serious side effects.

Movement disorder and sensorimotor abnormalities in schizophrenia and other psychoses - European consensus on assessment and perspectives.

Over the last three decades, movement disorder as well as sensorimotor and psychomotor functioning in schizophrenia (SZ) and other psychoses has gained greater scientific and clinical relevance as an intrinsic component of the disease process of psychotic illness; this extends to early psychosis prediction, early detection of motor side effects of antipsychotic medication, clinical outcome monitoring, treatment of psychomotor syndromes (e.g. catatonia), and identification of new targets for non-invasive brain stimulation. In 2017, a systematic cooperation between working groups interested in movement disorder and sensorimotor/psychomotor functioning in psychoses was initiated across European universities. As a first step, the members of this group would like to introduce and define the theoretical aspects of the sensorimotor domain in SZ and other psychoses. This consensus paper is based on a synthesis of scientific evidence, good clinical practice and expert opinions that were discussed during recent conferences hosted by national and international psychiatric associations. While reviewing and discussing the recent theoretical and experimental work on neural mechanisms and clinical implications of sensorimotor behavior, we here seek to define the key principles and elements of research on movement disorder and sensorimotor/psychomotor functioning in psychotic illness. Finally, the members of this European group anticipate that this consensus paper will stimulate further multimodal and prospective studies on hypo- and hyperkinetic movement disorders and sensorimotor/psychomotor functioning in SZ and other psychotic disorders.

Age-Related Parkinsonian Signs in Microdeletion 22q11.2.

BACKGROUND: The recurrent hemizygous 22q11.2 deletion associated with 22q11.2 deletion syndrome has been identified as a genetic risk factor for early-onset PD. However, little is known about early motor signs in this condition. OBJECTIVES: We examined the presence, severity and possible factors associated with parkinsonism in adults with 22q11.2 deletion syndrome and without PD. METHODS: We compared motor signs between 82 adults with 22q11.2 deletion syndrome and 25 healthy controls, using the MDS-UPDRS part III, and three-dimensional motion-tracker technology to quantify components of bradykinesia. RESULTS: Median MDS-UPDRS part III total and bradykinesia subscores were significantly higher in 22q11.2 deletion syndrome (median age: 26 years; range, 17-65) than in controls (P = 0.000; P = 0.000, respectively). Age was a significant contributor to bradykinesia subscore (B = 0.06; P = 0.01) and to the electronic bradykinesia component, velocity (B = -0.02; P = 0.000); psychotic illness did not significantly impact these analyses. In 22q11.2 deletion syndrome, MDS-UPDRS-defined bradykinesia was present in 18.3%, rigidity in 14.6%, and rest tremor in 12.2%. CONCLUSIONS: Parkinsonian motor signs appear to be common and age related in 22q11.2 deletion syndrome. Longitudinal studies are needed to investigate possible symptom progression to PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Proxy WHO Disability Assessment Schedule 2.0 Is Clinically Useful for Assessing Psychosocial Functioning in Severe Mental Illness.

AIMS: This study explores how well the World Health Organization Disability Assessment Schedule (WHODAS 2.0) assesses problems with psychosocial functioning in patients with severe mental illness (SMI). Further, we assessed the relationships between psychosocial functioning and psychopathology, medication side effects, treatment setting, and quality of life. METHODS: We performed an observational, cross-sectional study on the island of Curaçao to assess psychosocial functioning in 77 patients with SMI; they mainly had psychotic disorders. We interviewed their healthcare providers using the proxy version of the WHODAS 2.0. In addition, patients were examined for psychiatric symptoms, medication side effects (including drug-induced movement disorders), and quality of life. Associations were examined with Spearman's rank correlation (ρ). RESULTS: Difficulties in psychosocial functioning were reported by patients with SMI in the WHODAS 2.0 domains of understanding and communicating [mean (M)=34.5, standard deviation (SD)=18.6), participation in society (M=25.5, SD=15.6), and getting along with people (M=24.1, SD=16.1)]. Notably, outpatients had more problems participating in society than inpatients (M=33.6, SD=18.5 versus M=23.2, SD=14.1, p=0.03). A positive correlation was observed between drug-induced parkinsonism and the WHODAS 2.0 total score (ρ =0.30; p=0.02), as well as with various subscales, getting around, and household activities. CONCLUSION: The proxy version of the WHODAS 2.0 is clinically useful for patients with severe mental illness. The highest scores on the WHODAS 2.0 were found in domains related to interactions with other people and to participation in society. Inpatient status appeared to aid participation in society; this might be due to living in the sheltered clinic environment and its associated daily activities. We further found that drug-induced parkinsonism was associated with a broad spectrum of psychosocial disabilities. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02713672; retrospectively registered in February 2016.

Dopaminergic and noradrenergic manipulation of anticipatory reward and probability event-related potentials.

Predicting what will happen in the future in terms of potential reward is essential in daily life. The aim of the current study was to investigate the neurotransmitter systems involved in the anticipation of reward value and probability. We hypothesized that dopaminergic and noradrenergic antagonism would affect anticipation of reward value and probability, respectively. Twenty-three healthy participants were included in a haloperidol (2 mg) × clonidine (0.150 mg) × placebo cross-over design and subjected to a Go/NoGo experimental task during which cues signaled the probability of subsequent target appearance. Reward value (amount of money that could be won for correct and fast responding to the target) as well as probability of target appearance was orthogonally manipulated across four task blocks. Cue-elicited EEG event-related potentials were recorded to assess anticipation of value and probability, respectively. The processing of reward value was affected by dopaminergic antagonism (haloperidol), as evidenced by reduction of the reward-related positivity and P300 to reward cues. This reduction was specifically significant for subjects with high baseline dopamine levels for the P300 and most pronounced for these subjects for the reward-related positivity. In contrast, the processing of reward probability was affected by noradrenergic antagonism (clonidine). In addition, both drugs reduced overall performance (omission rate, response speed variability). We conclude that at least anticipation of reward value and probability, respectively, is specifically affected by dopaminergic versus noradrenergic antagonism.

The genetics of drug-related movement disorders, an umbrella review of meta-analyses.

This umbrella review investigates which genetic factors are associated with drug-related movement disorders (DRMD), in an attempt to provide a synthesis of published evidence of candidate-gene studies. To identify all relevant meta-analyses, a literature search was performed. Titles and abstracts were screened by two authors and the methodological quality of included meta-analyses was assessed using 'the assessment of multiple systematic reviews' (AMSTAR) critical appraisal checklist. The search yielded 15 meta-analytic studies reporting on genetic variations in 10 genes. DRD3, DRD2, CYP2D6, HTR2A, COMT, HSPG2 and SOD2 genes have variants that may increase the odds of TD. However, these findings do not concur with early genome-wide association studies. Low-power samples are susceptible to 'winner's curse', which was supported by diminishing meta-analytic effects of several genetic variants over time. Furthermore, analyses pertaining to the same genetic variant were difficult to compare due to differences in patient populations, methods used and the choice of studies included in meta-analyses. In conclusion, DRMD is a complex phenotype with multiple genes that impact the probability of onset. More studies with larger samples using other methods than by candidate genes, are essential to developing methods that may predict the probability of DRMD. To achieve this, multiple research groups need to collaborate and a DRMD genetic database needs to be established in order to overcome winner's curse and publication bias, and to allow for stratification by patient characteristics. These endeavours may help the development of a test with clinical value in the prevention and treatment of DRMD.

From impact factors to real impact: translating evidence on lifestyle interventions into routine mental health care.

The scandal of premature mortality in people with serious mental illness is well established. Despite an increase in studies evaluating the efficacy of lifestyle interventions, translating this evidence into routine clinical care and policies is challenging, in part due to limited effectiveness or implementation research. We highlight the challenge of implementation that is increasingly recognized in clinical practice, advocate for adopting implementation science to study the implementation and systematic update of effective interventions in practice and policy, and provide directions for future research.

Implementation barriers and facilitators of an integrated multidisciplinary lifestyle enhancing treatment for inpatients with severe mental illness: the MULTI study IV.

BACKGROUND: Despite an increase in studies showing the efficacy of lifestyle interventions in improving the poor health outcomes for people with severe mental illness (SMI), routine implementation remains ad hoc. Recently, a multidisciplinary lifestyle enhancing treatment for inpatients with SMI (MULTI) was implemented as part of routine care at a long-term inpatient facility in the Netherlands, resulting in significant health improvements after 18 months. The current study aimed to identify barriers and facilitators of its implementation. METHODS: Determinants associated with the implementation of MULTI, related to the innovation, the users (patients, the healthcare professionals (HCPs)), and the organisational context, were assessed at the three wards that delivered MULTI. The evidence-based Measurement Instrument for Determinants of Innovations was used to assess determinants (29 items), each measured through a 5-point Likert scale and additional open-ended questions. We considered determinants to which ≥20% of the HCPs or patients responded negatively ("totally disagree/disagree", score < 3) as barriers and to which ≥80% of HCPs or patients responded positively ("agree/totally agree", score > 3) as facilitators. We included responses to open-ended questions if the topic was mentioned by ≥2 HCPs or patients. In total 50 HCPs (online questionnaire) and 46 patients (semi-structured interview) were invited to participate in the study. RESULTS: Participating HCPs (n = 42) mentioned organisational factors as the strongest barriers (e.g. organisational changes and financial resources). Patients (n = 33) mentioned the complexity of participating in MULTI as the main barrier, which could partly be due to organisational factors (e.g. lack of time for nurses to improve tailoring). The implementation was facilitated by positive attitudes of HCPs and patients towards MULTI, including their own role in it. Open responses of HCPs and patients showed strong commitment, collaboration and ownership towards MULTI. CONCLUSIONS: This is the first study analysing the implementation of a pragmatic lifestyle intervention targeting SMI inpatients in routine clinical care. Positive attitudes of both HCPs and patients towards such an approach facilitated the implementation of MULTI. We suggest that strategies addressing organisational implementation barriers are needed to further improve and maintain MULTI, to succeed in achieving positive health-related outcomes in inpatients with SMI.

Changes in physical and psychiatric health after a multidisciplinary lifestyle enhancing treatment for inpatients with severe mental illness: The MULTI study I.

Patients hospitalized with severe mental illness (SMI) often have an unhealthy lifestyle. Changing their sedentary behavior and deficiency in physical activity is challenging and effective interventions are lacking. We evaluated changes in sedentary behavior, physical activity, metabolic health and psychotic symptoms after 18 months of Multidisciplinary Lifestyle enhancing Treatment for Inpatients with SMI (MULTI) compared to treatment as usual (TAU) and explored mediation by change in total activity. We measured sedentary behavior and physical activity using accelerometry (ActiGraph GT3X+), reflected in total activity counts. Data on metabolic health and psychotic symptoms were retrieved from routine screening data within our cohort of inpatients with SMI. Of 65 patients receiving MULTI versus 43 receiving TAU, data were analyzed using linear and logistic multilevel regression, adjusting for baseline values of outcome and differences between groups. Compared to TAU, in which no improvements were observed, we found significantly (p < 0.05) improved total activity (B = 0.5 standardized total activity counts per hour), moderate-to-vigorous physical activity (B = 1.8%), weight (B = -4.2 kg), abdominal girth (B = -3.5 cm), systolic blood pressure (B = -8.0 mmHg) and HDL cholesterol (B = 0.1 mmol/l). No changes in psychotic symptoms were observed. Changes in total activity did not mediate metabolic improvements, suggesting that multiple components of MULTI contribute to these improvements. In contrast to previously unsuccessful attempts to change lifestyle behavior in inpatients with SMI in the longer term, MULTI showed to be a feasible treatment to sustainably improve PA and metabolic health.

Clozapine Monotherapy as a Treatment for Antipsychotic-Induced Tardive Dyskinesia: A Meta-Analysis.

OBJECTIVE: Tardive dyskinesia (TD) is an antipsychotic-induced movement disorder that typically occurs after long-term exposure to antipsychotic drugs. There is evidence that switching to clozapine reduces TD. This meta-analysis reviews the effect of switching to clozapine on the severity of TD. DATA SOURCES: The PubMed, PsycINFO, and Embase databases were searched for clozapine, tardive dyskinesia, and related keywords. The search was restricted to articles written in English and Dutch, and it was last updated on October 13, 2015. STUDY SELECTION: Sixteen studies were included in the meta-analysis. Inclusion criteria were a diagnosis of schizophrenia or a related disorder, a switch to clozapine monotherapy, and reports of scores on a TD rating scale before and after the switch to clozapine. DATA EXTRACTION: Two independent investigators extracted the data. Data were converted to standardized mean change scores and analyzed in a random-effects model. RESULTS: A random-effects model showed that the overall effect of switching to clozapine was a significant reduction in TD (npatients = 1,060, d = -0.40, P < .01), especially in the 4 studies that investigated the severity of TD as a primary outcome (npatients = 48, d = -2.56, P = .02). CONCLUSIONS: The overall results show that clozapine treatment can yield a slight reduction in TD. The severity of TD was reduced greatly in patients with moderate to severe TD. In patients with minimal to mild TD, switching to clozapine seldom worsens TD and a trend toward reduction is seen. These results support that a switch to clozapine should be considered for patients with moderate to severe TD and/or patients who experience substantial discomfort due to TD.

No Effect of Dose Adjustment to the CYP2D6 Genotype in Patients With Severe Mental Illness.

Background: The CYP2D6 enzyme is involved in the metabolism of numerous psychopharmacological drugs. Guidelines recommend how to adjust the dose of medication based on the CYP2D6 genotype. Aims: To evaluate the effect of dose adjustment to the CYP2D6 genotype and phenotype, in patients with severe mental illness (SMI) already receiving psychopharmacological treatment. Methods: A total of 269 psychiatric patients (on the island Curaçao) receiving antipsychotic treatment were genotyped for CYP2D6. Of these, 45 patients were included for dose adjustment according to the clinical guideline of the Royal Dutch Association for the Advancement of Pharmacy, i.e., 17 CYP2D6 poor metabolizers, 26 intermediate metabolizers, and 2 ultrarapid metabolizers. These 45 patients were matched for age, gender, and type of medication with a control group of 41 patients who were CYP2D6 extensive metabolizers (i.e., with a normal CYP2D6 function). At baseline and at 4 months after dose adjustment, subjective experience, psychopathology, extrapyramidal side-effects, quality of life, and global functioning were assessed in these two groups. Results: At baseline, there were no differences between the groups regarding the prescribed dosage of antipsychotics, the number of side-effects, psychiatric symptoms, global functioning, or quality of life. After dose adjustment, no significant improvement in these parameters was reported. Conclusion: In psychiatric patients with SMI already receiving antipsychotic treatment, dose adjustment to the CYP2D6 genotype or phenotype according to the guidelines showed no beneficial effect. This suggests that dose adjustment guidelines are currently not applicable for patients already using antipsychotics. ClinicalTrials.gov: Cost-effectiveness of CYP2D6 and CYP2C19 Genotyping in Psychiatric Patients in Curacao; Identifier: NCT02713672; https://clinicaltrials.gov/ct2/show/NCT02713672?term=CYP2D6&rank=5.