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.

Movement Disorders in Adults With Intellectual Disability and Behavioral Problems Associated With Use of Antipsychotics.

BACKGROUND: Antipsychotic drugs are prescribed to approximately 30% to 40% of adults with intellectual disability (ID) and behavioral problems despite lack of evidence of effectiveness and potential adverse effects, including movement disorders. AIMS: The aim of this study was to examine the prevalence of movement disorders (dyskinesia, akathisia, dystonia, and parkinsonism) in in-patient adults with mild to borderline ID and behavioral problems associated with use of antipsychotics. METHODS: Prevalence of movement disorders was measured with a standardized protocol. The strength of the association between antipsychotic drug use and movement disorders was assessed using logistic regression analysis. RESULTS: Almost half (44.0%) of 134 in-patient adults with ID and behavioral problems had any movement disorder. Parkinsonism, dyskinesia, akathisia, and dystonia were present in, respectively, 36.6%, 11.2%, 9.0%, and 0.7% of patients with ID. It appeared that current use of any antipsychotic drug (odds ratio, 3.0; 95% confidence interval, 1.0-8.4) and a dose in target range (odds ratio, 5.5; 95% confidence interval, 1.5-20.4) were significantly associated with the risk of having movement disorders. CONCLUSIONS: The prevalence of movement disorders in people with ID and behavioral problems is high, especially in ID patients using antipsychotics. More attention is needed for these movement disorders and their potential impact.

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.

Evaluating the implementation of a multidisciplinary lifestyle intervention for people with severe mental illness in sheltered housing: effectiveness-implementation hybrid randomised controlled trial.

BACKGROUND: Lifestyle interventions can improve health-related outcomes for people with severe mental illness (SMI), but few studies evaluate this potential in everyday settings. After a successful approach in routine inpatient mental healthcare (MULTI), we sought to replicate this multidisciplinary lifestyle-enhancing support in people with SMI living in sheltered housing (MULTI_sh). AIMS: To evaluate the effectiveness and implementation of MULTI_sh (trial registration: NCT03157557). METHOD: In an effectiveness-implementation hybrid cluster-randomised controlled trial, six municipalities with sheltered housing facilities in The Netherlands were randomly assigned to MULTI_sh (n = 3) or treatment as usual (TAU, n = 3). After 12 months, we evaluated effects on metabolic health, sedentary behaviour/physical activity (ActiGraph GT3X+), quality of life (EuroQol 5D, WHOQoL-Bref) and psychopathology (Brief Psychiatric Rating Scale Expanded Version) using multiple regression, adjusting for baseline values and municipalities (intention to treat and per protocol). In addition, implementation fidelity and barriers/facilitators were evaluated (Measurement Instrument for Determinants of Innovation). RESULTS: Of 177 eligible patients, 74 (42%) could be included in the analyses. Health outcomes did not substantially improve with MULTI_sh (n = 45) compared with TAU (n = 29). MULTI_sh was not implemented as intended. Most patients and all healthcare professionals believed that patients' lifestyle should be part of treatment, but implementation was primarily (in)directly hindered by organisational factors (e.g. staff shortages, complexity of participation, lack of time and difficulty getting patients involved). CONCLUSIONS: MULTI_sh was not implemented as intended and no clinical health improvements were found. Organisations are decisive in the success or failure of the implementation of lifestyle interventions for people with SMI. More intensive implementation strategies on this level are warranted in sheltered housing.

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.

Movement disorders in nonpsychotic siblings of patients with nonaffective psychosis.

Movement disorders such as dyskinesia and Parkinsonism have frequently been reported in (drug-naïve) patients with nonaffective psychosis. Therefore movement disorders may be related to schizophrenia. Siblings of patients with nonaffective psychosis also appear to have subtle forms of movement disorders. This suggests that motor abnormalities may also be related to the risk of developing the disease. Subtle forms are not always detected with the use of the standard observation-based clinical rating scales, which are less sensitive than mechanical instrument measurement. This study compared the presence and severity of dyskinesia and Parkinsonism in 42 non-psychotic siblings of patients with nonaffective psychosis and in 38 controls as measured by mechanical instruments and clinical rating scales. There were no significant differences in movement disorders between siblings and controls on the basis of clinical assessments. However, mechanical measurements indicated that siblings compared to controls displayed significantly more dyskinesia and Parkinsonism signs. These results suggest that motor signs could be markers of vulnerability for psychosis or schizophrenia. In addition this study shows that mechanical instrument measurement of movement disorders is more sensitive than assessment with clinical rating scales. Therefore, it may be used in screening programs for populations at risk for 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.

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.

Non-therapeutic risk factors for onset of tardive dyskinesia in schizophrenia: a meta-analysis.

A meta-analysis of prospective studies with schizophrenia patients was conducted to examine whether the evidence exists for risk factors for the emergence of Tardive Dyskinesia (TD) in schizophrenia. A computer assisted Medline/PubMed and Embase search was conducted in January 2008 for the years 1985-2007. Selected were truly prospective studies of incident cases of TD in a population with at least 80% patients with schizophrenia. Measures of relative risk were collected from the individual studies, either directly or by calculating the relative risk from the cox- or logistic regression coefficient provided in the article. Hazard Ratio's and Odds Ratio's were pooled using fixed and random effect models in case of multiple studies using the same measure of risk and outcome. Only eight studies satisfied the inclusion criteria reporting on 25 different single estimate risk factors. Of 25 risk factors, six concerned replicated estimates suitable for meta-analysis. Of these, non-white ethnic group and early extrapyramidal symptoms qualified as risk factors for the emergence of TD in schizophrenia. The association with older age was suggestive but inconclusive. Despite many reported risk factors for TD in schizophrenia, little conclusive evidence exists to corroborate this. However, the fact that early EPS predicts onset of TD has important clinical and research implications.

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.

Less Medication Use in Inpatients With Severe Mental Illness Receiving a Multidisciplinary Lifestyle Enhancing Treatment. The MULTI Study III.

Besides having an unhealthy lifestyle contributing to premature mortality, inpatients with severe mental illness (SMI) use high dosages of medication. Previous research has shown improved health after lifestyle improvements in SMI. In addition, we aimed to retrospectively study whether a multidisciplinary lifestyle enhancing treatment (MULTI) was associated with changes in medication use after 18 months, as compared with patients that continued treatment as usual (TAU) and explored mediation by a change in physical activity. We conducted an observational study within a cohort of inpatients with SMI, who received MULTI (N = 65) or continued TAU (N = 49). Data on their somatic and psychotropic medications were collected, converted into defined daily dose (DDD), and analyzed using linear multilevel regression, correcting for baseline value and differences between groups in age, diagnosis, and illness severity. Compared with TAU, the DDD for psychotropic medication significantly decreased with MULTI (B = -0.55, P = 0.02). Changes in total activity did not mediate this association, suggesting that multiple components of MULTI contributed. Corrected between-group analyses for subgroups of medication were not possible due to lack of power and skewed distributions. Within-group data showed a decreased proportion of users as well as median DDD in both groups for almost all medications. In addition to previously reported health improvements after 18 months of MULTI, we observed a significant decrease in dose of psychotropic medication in MULTI compared to TAU. This first study evaluating a wide range of medications indicates a possible effect of lifestyle improvements on medication use in inpatients with SMI. Findings need to be confirmed in future controlled studies, however.

Evidence that early extrapyramidal symptoms predict later tardive dyskinesia: a prospective analysis of 10,000 patients in the European Schizophrenia Outpatient Health Outcomes (SOHO) study.

OBJECTIVE: This study examined whether extrapyramidal symptoms predict incidence of tardive dyskinesia 1 year later. METHOD: Simple, global measures were used to rate extrapyramidal symptoms and tardive dyskinesia in a prospective, observational health outcomes study. Baseline and 3-, 6-, and 12-month data on 9,298 patients were analyzed by using a Cox proportional-hazard model. Onset of tardive dyskinesia was examined in two groups: 1) no tardive dyskinesia at baseline (broad risk set) and 2) no tardive dyskinesia at baseline and 3 months (narrow risk set). RESULTS: Baseline extrapyramidal symptoms predicted later onset of tardive dyskinesia (broad risk set: hazard ratio=2.0, narrow risk set: hazard ratio=1.6). In analyses adjusted for age, gender, and medication exposure, this effect size was not reduced. About half of patients who developed tardive dyskinesia had earlier extrapyramidal symptoms. CONCLUSIONS: Although the association of tardive dyskinesia and extrapyramidal symptoms is significant, extrapyramidal symptoms do not robustly identify individuals at high risk for tardive dyskinesia. However, drug regimens and disease processes that increase extrapyramidal symptoms are likely to result in increased risk of tardive dyskinesia.

Tardive dyskinesia in schizophrenia is associated with prolactin-related sexual disturbances.

Tardive dyskinesia (TD) may occur in never-medicated patients with psychotic illness, indicating the existence of non-medication, possibly disease-related, causes. We tested the hypothesis that, independent of the antipsychotic-induced rise in prolactin, the incidence of TD would be associated with the incidence of prolactin-related sexual disturbances (PRSD), which would be suggestive of a common pathology involving multiple dopamine tracts. Simple, global measures of TD and PRSD (loss of libido, amenorrhea, gynaecomastia, impotence, and galactorrhea) were rated in a prospective, observational European Health Outcomes Study (SOHO). New onset of TD and new onset of PRSD at 3, 6, and 12 months was analyzed in a risk set of 4263 patients using a Cox proportional hazard model yielding adjusted hazard ratios (aHR). Incidence of TD was significantly and linearly comorbid with the incidence of PRSD in both men and women. Compared to those with no PRSD, the risk for TD was 2.0 (95% CI: 1.1, 3.7) with one PRSD, 2.4 (95% CI: 1.3, 4.5) with two PRSD, and 3.6 (95% CI: 1.1, 11.8) with three PRSD. Associations were stronger in those who only had received prolactin-sparing medications (aHR per unit PRSD increase=2.0, 95% CI: 1.2, 3.3) than in those who only had received prolactin-raising medications (aHR=1.3, 95% CI: 0.9, 1.9). In people with schizophrenia, TD and PRSD show comorbidities that are independent of antipsychotic-induced alterations in plasma prolactin. This may suggest a shared, pandopaminergic pathological mechanism associated with schizophrenia itself, rather than only a medication effect.

Instrumental measurements of spontaneous dyskinesia and schizotypy in subjects with auditory verbal hallucinations and healthy controls.

Spontaneous dyskinesia is associated with non-affective psychosis. Few studies investigated dyskinesia in individuals with subclinical psychotic experiences. We examined dyskinesia using instrumental measurements of force variability in 34 individuals with frequent auditory verbal hallucinations but without a clinical psychotic disorder and 31 matched healthy controls. Schizotypy was assessed using the Schizotypal Personality Questionnaire. We found a positive correlation between dyskinesia and schizotypy in the total group. In addition, when using a cut-off point based on the 95th percentile of force variability in the control group, we found a greater proportion of subjects with dyskinesia in the group with auditory verbal hallucinations than in the control subjects. Current findings are in agreement with the concept of psychosis as a continuous phenomenon and with movement disorders being an integral part of psychosis.

The Relation between Psychiatric Diagnoses and Constipation in Hospitalized Patients: A Cross-Sectional Study.

Objective. Constipation is a prevalent problem in patients with psychiatric disorders; it reduces quality of life and may lead to severe complications. The prevalence distribution of constipation across all psychiatric diagnoses in patients with severe mental illness (SMI) has hardly been studied. The aim of this study is to estimate the association between psychiatric disorders and constipation in SMI inpatients. Methods. The strength of the association between constipation (based on use of laxatives) and DSM-IV psychiatric diagnosis was studied in a cross-sectional study with "adjustment disorders" as the reference group. The association was analyzed using logistic regression. Results. Of the 4728 patients, 20.3% had constipation. In the stratum of patients older than 60 years, all psychiatric categories except for substance related disorders were significantly associated with a higher prevalence of constipation (odds ratios ranging from 3.38 to 6.52), whereas no significant associations were found in the stratum of patients between 18 and 60 years (odds ratios ranging from 1.00 to 2.03). Conclusion. In the elderly, all measured psychiatric diagnoses are strongly associated with an increased prevalence of constipation. Physicians should be extra alert for constipation in SMI patients, independent of specific psychiatric diagnoses.

Reliability and validity of an instrument for the assessment of bradykinesia.

Bradykinesia is associated with reduced quality of life and medication non-compliance, and it may be a prodrome for schizophrenia. Therefore, screening/monitoring for subtle bradykinesia is of clinical and scientific importance. This study investigated the validity and reliability of such an instrument. Included were 70 patients with psychotic disorders. Inertial sensors captured mean cycle duration, amplitude and velocity of four movement tasks: walking, elbow flexion/extension, forearm pronation/supination and leg agility. The concurrent validity with the Unified Parkinson's Disease Rating Scale (UPDRS) bradykinesia subscale was determined using regression analysis. Reliability was investigated with the intra-class correlation coefficient. The duration, amplitude and velocities of the four tasks measured by the instrument explained 67% of the variance on the UPDRS bradykinesia subscale. The instrument test-retest reliability was high. The instrument investigated in this study is a valid and reliable alternative to observer-rated scales. It is an ideal tool for monitoring bradykinesia as it requires little training and experience to achieve reliable results.

Effects of antipsychotic treatment on tardive dyskinesia: a 6-month evaluation of patients from the European Schizophrenia Outpatient Health Outcomes (SOHO) Study.

OBJECTIVE: To compare the incidence and persistence of tardive dyskinesia between patients diagnosed with schizophrenia (ICD-10 and/or DSM-IV) who were treated with second-generation antipsychotics and first-generation antipsychotics in routine clinical practice. METHOD: The European Schizophrenia Outpatient Health Outcomes (SOHO) study is a 3-year, prospective, observational study. Each country had a start date for patient enrollment before October 2000. All enrollment was completed by June 30, 2001. A simple, global measure of tardive dyskinesia was rated by participating clinicians. For the current analysis, data at baseline, 3 months, and 6 months were analyzed using a generalized estimating equation model. RESULTS: Second-generation antipsychotics conferred a lower risk for tardive dyskinesia at 6 months than first-generation antipsychotics (0.9% vs. 3.8%, odds ratio [OR] = 0.29, 95% confidence interval [CI] = 0.18 to 0.46). In addition, patients with tardive dyskinesia at baseline who were receiving second-generation antipsychotics were less likely than patients receiving first-generation antipsychotics to have tardive dyskinesia symptoms at 6 months (43.6% vs. 60.8%, OR = 0.50, 95% CI = 0.30 to 0.85). A sensitivity analysis suggested no bias related to pharmaceutical industry financial support. CONCLUSION: The results suggest that the relative advantage of second-generation antipsychotics in terms of lower rates of incidence and persistence of tardive dyskinesia, observed in technical randomized controlled trials, generalizes to routine clinical care.

Efficacy and safety of deep brain stimulation in patients with medication-induced tardive dyskinesia and/or dystonia: a systematic review.

BACKGROUND: Tardive dyskinesia and dystonia (TDD) are severe side effects of dopamine-blocking agents, particularly antipsychotics. While deep brain stimulation (DBS) has proven effective in the treatment of TDD, little is known about the possible psychiatric complications of DBS in psychiatric patients. OBJECTIVE: To assess the efficacy and safety, specifically the psychiatric side effects, of DBS in patients with medication-induced TDD. DATA SOURCES: PubMed and EMBASE databases were searched systematically on May 25, 2011, for articles written in English, using the search terms deep brain stimulation AND tardive. STUDY SELECTION: Of the 88 original articles retrieved, 17 studies involving 50 patients with TDD who underwent DBS were included in the review. DATA EXTRACTION: Data on the severity of the movement disorders before and after DBS, as rated on the Burke-Fahn-Marsden Dystonia Rating Scale or similar scales, were extracted. Data on psychiatric symptoms before and after DBS were used to calculate the percent improvement per patient per rating scale. Overall improvement and confidence intervals were calculated using a 1-sample, 2-sided Student t test. RESULTS: The mean improvement of TDD of the combined patients 3 to 76 months after implantation was 77.5% (95% CI, 71.4%-83.3%; P < .000) on the Burke-Fahn-Marsden Dystonia Rating Scale. Of the 50 patients, 1 experienced an exacerbation of depression, and 1 experienced an exacerbation of psychosis. CONCLUSIONS: DBS seems to be effective and relatively safe for patients with treatment-resistant TDD; however, the results should be interpreted with caution, as most of the data are from case reports and small trials.

Antipsychotic-induced hyperprolactinemia and testosterone levels in boys.

AIMS: This cross-sectional study investigates the effect of antipsychotic (AP)-induced hyperprolactinemia on testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), inhibin B, and puberty in boys with mainly autism spectrum disorders (ASD). METHOD: One hundred and four physically healthy 10- to 19-year-old boys with ASD or disruptive behavior disorder (DBD) were recruited between October 2006 and November 2009. Fifty-six adolescents had been treated with AP for >16 months; 48 had never been exposed to AP. Morning non-fasting levels of serum prolactin, testosterone, LH, FSH and inhibin B were obtained and Tanner pubertal stage was determined. Patients with hyperprolactinemia (n = 28) were compared to those without hyperprolactinemia (n = 76) using non-parametric or parametric tests, as appropriate. RESULTS: Patients with AP-induced hyperprolactinemia had significantly lower testosterone levels with adjustment for age (p = 0.035) compared to patients without hyperprolactinemia and without AP treatment. The difference was not significant within the AP-treated group, and the level of testosterone was within the reference range compared to age- and gender-matched normative data. There was no between-group difference for LH, FSH, inhibin B or Tanner stages. CONCLUSION: AP-induced hyperprolactinemia is related to significantly lower testosterone levels in pubertal boys with ASD and DBD.