Julio Bobes

Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care

The lifespan of people with severe mental illness (SMI) is shorter compared to the general population. This excess mortality is mainly due to physical illness. We report prevalence rates of different physical illnesses as well as important individual lifestyle choices, side effects of psychotropic treatment and disparities in health care access, utilization and provision that contribute to these poor physical health outcomes. We searched MEDLINE (1966 - August 2010) combining the MeSH terms of schizophrenia, bipolar disorder and major depressive disorder with the different MeSH terms of general physical disease categories to select pertinent reviews and additional relevant studies through cross-referencing to identify prevalence figures and factors contributing to the excess morbidity and mortality rates. Nutritional and metabolic diseases, cardiovascular diseases, viral diseases, respiratory tract diseases, musculoskeletal diseases, sexual dysfunction, pregnancy complications, stomatognathic diseases, and possibly obesity-related cancers are, compared to the general population, more prevalent among people with SMI. It seems that lifestyle as well as treatment specific factors account for much of the increased risk for most of these physical diseases. Moreover, there is sufficient evidence that people with SMI are less likely to receive standard levels of care for most of these diseases. Lifestyle factors, relatively easy to measure, are barely considered for screening; baseline testing of numerous important physical parameters is insufficiently performed. Besides modifiable lifestyle factors and side effects of psychotropic medications, access to and quality of health care remains to be improved for individuals with SMI.

Physical illness in patients with severe mental disorders. II. Barriers to care, monitoring and treatment guidelines, plus recommendations at the system and individual level

Physical disorders are, compared to the general population, more prevalent in people with severe mental illness (SMI). Although this excess morbidity and mortality is largely due to modifiable lifestyle risk factors, the screening and assessment of physical health aspects remains poor, even in developed countries. Moreover, specific patient, provider, treatment and system factors act as barriers to the recognition and to the management of physical diseases in people with SMI. Psychiatrists can play a pivotal role in the improvement of the physical health of these patients by expanding their task from clinical psychiatric care to the monitoring and treatment of crucial physical parameters. At a system level, actions are not easy to realize, especially for developing countries. However, at an individual level, even simple and very basic monitoring and treatment actions, undertaken by the treating clinician, can already improve the problem of suboptimal medical care in this population. Adhering to monitoring and treatment guidelines will result in a substantial enhancement of physical health outcomes. Furthermore, psychiatrists can help educate and motivate people with SMI to address their suboptimal lifestyle, including smoking, unhealthy diet and lack of exercise. The adoption of the recommendations presented in this paper across health care systems throughout the world will contribute to a significant improvement in the medical and related psychiatric health outcomes of patients with SMI.

Cardiovascular and metabolic risk in outpatients with schizophrenia treated with antipsychotics: Results of the CLAMORS Study

AIM To assess the prevalence of Coronary Heart Disease (CHD) and Metabolic Syndrome (MS) in patients treated with antipsychotics. METHODS Retrospective, cross-sectional, multicenter study in which 117 Spanish psychiatrists (the CLAMORS Study Collaborative Group) recruited consecutive outpatients meeting DSM-IV criteria for Schizophrenia, Schizophreniform or Schizoaffective Disorder, receiving antipsychotic treatment for at least 12 weeks. CHD risk was assessed by SCORE (10-year CV death) and Framingham (10-year all CHD events) function. MS was defined by at least 3 of the following components: waist circumference >102 (men)/>88 (women) cm; triglycerides > or =150 mg/dl; HDL-cholesterol <40 mg/dl (men)/<50 mg/dl (women); blood pressure > or =130/85; fasting glucose > or =110 mg/dl. RESULTS 1452 evaluable patients (863 men, 60.9%), aged 40.7+/-12.2 years (mean+/-SD) were included. MS was present in 24.6% [23.6% (men), 27.2% (women); p=0.130)]. The overall 10-year risks were 0.9+/-1.9 (SCORE) and 7.2+/-7.6 (Framingham). 8% (95%CI: 6.5-9.5) and 22.1% (95%CI: 20.0-24.3) of patients showed a high/very high risk according to SCORE (> or =3%) and Framingham (> or =10%) function. Abdominal obesity and low HDL-cholesterol were more prevalent in women: 54.5% (95%CI: 50.2-58.9) versus 34.3% (95%CI: 31.0-37.7), and 46.1% (95%CI: 41.4) versus 28.5 (95%CI: 50.8), p<0.001 in both cases. Hypertension and hypertriglyceridemia were more prevalent in men: 59.0% (95%CI: 55.7-62.3) versus 46.0% (95%CI: 41.8-50.2), and 40.7% (95%CI: 37.2-44.2) versus 32.4 (95%CI: 28.3-36.5), p<0.01 in both cases. CONCLUSIONS CHD risk and MS prevalences among patients with schizophrenia treated with antipsychotics were in the same range as the Spanish general population 10 to 15 years older.

BRAIN GLUCOSE METABOLISM IN BORDERLINE PERSONALITY DISORDER

We searched for regional cerebral metabolic disturbances in patients with borderline personality disorder (BPD). Ten inpatients with BPD, no current DSM-IIIR Axis I diagnosis and free of any psychotropic substances, were compared with 15 age-matched control subjects using positron emission tomography with 2-deoxy-2-[18F]fluoro-D-glucose and semiquantitative analysis of regional glucose metabolic activity. We found relative hypometabolism in patients with borderline personality disorder at the level of the premotor and prefrontal cortical areas, the anterior part of the cingulate cortex and the thalamic, caudate and lenticular nuclei. This study shows significant cerebral metabolic disturbances in patients with borderline personality disorder. These metabolic disturbances, which are similar to some of those described in other psychiatric entities, may help to understand the characteristic clinical aspects of this disorder.

Suicide prevention strategies revisited: 10-year systematic review.

BACKGROUND Many countries are developing suicide prevention strategies for which up-to-date, high-quality evidence is required. We present updated evidence for the effectiveness of suicide prevention interventions since 2005. METHODS We searched PubMed and the Cochrane Library using multiple terms related to suicide prevention for studies published between Jan 1, 2005, and Dec 31, 2014. We assessed seven interventions: public and physician education, media strategies, screening, restricting access to suicide means, treatments, and internet or hotline support. Data were extracted on primary outcomes of interest, namely suicidal behaviour (suicide, attempt, or ideation), and intermediate or secondary outcomes (treatment-seeking, identification of at-risk individuals, antidepressant prescription or use rates, or referrals). 18 suicide prevention experts from 13 European countries reviewed all articles and rated the strength of evidence using the Oxford criteria. Because the heterogeneity of populations and methodology did not permit formal meta-analysis, we present a narrative analysis. FINDINGS We identified 1797 studies, including 23 systematic reviews, 12 meta-analyses, 40 randomised controlled trials (RCTs), 67 cohort trials, and 22 ecological or population-based investigations. Evidence for restricting access to lethal means in prevention of suicide has strengthened since 2005, especially with regard to control of analgesics (overall decrease of 43% since 2005) and hot-spots for suicide by jumping (reduction of 86% since 2005, 79% to 91%). School-based awareness programmes have been shown to reduce suicide attempts (odds ratio [OR] 0·45, 95% CI 0·24-0·85; p=0·014) and suicidal ideation (0·5, 0·27-0·92; p=0·025). The anti-suicidal effects of clozapine and lithium have been substantiated, but might be less specific than previously thought. Effective pharmacological and psychological treatments of depression are important in prevention. Insufficient evidence exists to assess the possible benefits for suicide prevention of screening in primary care, in general public education and media guidelines. Other approaches that need further investigation include gatekeeper training, education of physicians, and internet and helpline support. The paucity of RCTs is a major limitation in the evaluation of preventive interventions. INTERPRETATION In the quest for effective suicide prevention initiatives, no single strategy clearly stands above the others. Combinations of evidence-based strategies at the individual level and the population level should be assessed with robust research designs. FUNDING The Expert Platform on Mental Health, Focus on Depression, and the European College of Neuropsychopharmacology.

Frequency of Sexual Dysfunction and Other Reproductive Side-effects in Patients with Schizophrenia Treated with Risperidone, Olanzapine, Quetiapine, or Haloperidol: The Results of the EIRE Study

Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%). Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment ( 12 weeks) are lacking. Our results suggest that none of the atypical antipsychotics that we studied significantly improved sexual dysfunction and other reproductive side-effects of the conventional antipsychotic, haloperidol, in stabilized patients during long-term treatment. Quetiapine appears to improve this profile during short-term treatment; however, longterm data, with larger samples, are required with this latter drug.

Efficacy of Functional Remediation in Bipolar Disorder: A Multicenter Randomized Controlled Study

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukeys post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.

Adolescent subthreshold-depression and anxiety: psychopathology, functional impairment and increased suicide risk

BACKGROUND  Subthreshold-depression and anxiety have been associated with significant impairments in adults. This study investigates the characteristics of adolescent subthreshold-depression and anxiety with a focus on suicidality, using both categorical and dimensional diagnostic models. METHODS  Data were drawn from the Saving and Empowering Young Lives in Europe (SEYLE) study, comprising 12,395 adolescents from 11 countries. Based on self-report, including Beck Depression Inventory-II (BDI-II), Zung Self-Rating Anxiety Scale (SAS), Strengths and Difficulties Questionnaire (SDQ) and Paykel Suicide Scale (PSS) were administered to students. Based on BDI-II, adolescents were divided into three groups: nondepressed, subthreshold-depressed and depressed; based on the SAS, they were divided into nonanxiety, subthreshold-anxiety and anxiety groups. Analyses of Covariance were conducted on SDQ scores to explore psychopathology of the defined groups. Logistic regression analyses were conducted to explore the relationships between functional impairments, suicidality and subthreshold and full syndromes. RESULTS  Thirty-two percent of the adolescents were subthreshold-anxious and 5.8% anxious, 29.2% subthreshold-depressed and 10.5% depressed, with high comorbidity. Mean scores of SDQ of subthreshold-depressed/anxious were significantly higher than the mean scores of the nondepressed/nonanxious groups and significantly lower than those of the depressed/anxious groups. Both subthreshold and threshold-anxiety and depression were related to functional impairment and suicidality. CONCLUSIONS Subthreshold-depression and subthreshold-anxiety are associated with an increased burden of disease and suicide risk. These results highlight the importance of early identification of adolescent subthreshold-depression and anxiety to minimize suicide. Incorporating these subthreshold disorders into a diagnosis could provide a bridge between categorical and dimensional diagnostic models.

School-based suicide prevention programmes: the SEYLE cluster-randomised, controlled trial

BACKGROUND Suicidal behaviours in adolescents are a major public health problem and evidence-based prevention programmes are greatly needed. We aimed to investigate the efficacy of school-based preventive interventions of suicidal behaviours. METHODS The Saving and Empowering Young Lives in Europe (SEYLE) study is a multicentre, cluster-randomised controlled trial. The SEYLE sample consisted of 11,110 adolescent pupils, median age 15 years (IQR 14-15), recruited from 168 schools in ten European Union countries. We randomly assigned the schools to one of three interventions or a control group. The interventions were: (1) Question, Persuade, and Refer (QPR), a gatekeeper training module targeting teachers and other school personnel, (2) the Youth Aware of Mental Health Programme (YAM) targeting pupils, and (3) screening by professionals (ProfScreen) with referral of at-risk pupils. Each school was randomly assigned by random number generator to participate in one intervention (or control) group only and was unaware of the interventions undertaken in the other three trial groups. The primary outcome measure was the number of suicide attempt(s) made by 3 month and 12 month follow-up. Analysis included all pupils with data available at each timepoint, excluding those who had ever attempted suicide or who had shown severe suicidal ideation during the 2 weeks before baseline. This study is registered with the German Clinical Trials Registry, number DRKS00000214. FINDINGS Between Nov 1, 2009, and Dec 14, 2010, 168 schools (11,110 pupils) were randomly assigned to interventions (40 schools [2692 pupils] to QPR, 45 [2721] YAM, 43 [2764] ProfScreen, and 40 [2933] control). No significant differences between intervention groups and the control group were recorded at the 3 month follow-up. At the 12 month follow-up, YAM was associated with a significant reduction of incident suicide attempts (odds ratios [OR] 0·45, 95% CI 0·24-0·85; p=0·014) and severe suicidal ideation (0·50, 0·27-0·92; p=0·025), compared with the control group. 14 pupils (0·70%) reported incident suicide attempts at the 12 month follow-up in the YAM versus 34 (1·51%) in the control group, and 15 pupils (0·75%) reported incident severe suicidal ideation in the YAM group versus 31 (1·37%) in the control group. No participants completed suicide during the study period. INTERPRETATION YAM was effective in reducing the number of suicide attempts and severe suicidal ideation in school-based adolescents. These findings underline the benefit of this universal suicide preventive intervention in schools. FUNDING Coordination Theme 1 (Health) of the European Union Seventh Framework Programme.

Healthy lifestyle habits and 10-year cardiovascular risk in schizophrenia spectrum disorders: an analysis of the impact of smoking tobacco in the CLAMORS schizophrenia cohort.

AIM We analysed the impact of tobacco smoking over several healthy lifestyle habits along with the impact on 10-years cardiovascular event (CVE) risk in the CLAMORS schizophrenia cohort. METHODS This analysis was performed within the scope of the CLAMORS study which included consecutive outpatients meeting DSM-IV criteria for schizophrenia spectrum disorder. Beside smoking history, data on usual healthy lifestyle habits included current exercise, saturated fat sparing diet, low-caloric diet, and daily dietary fibre, salt, caffeine and alcohol consumption were recorded. The 10-year CVE risk was calculated with Framingham function. RESULTS 1704 patients (61.1% male), 18 to 74 years were examined. Prevalence of smoking was 54.54% (95% CI: 52.16%-56.90%) significantly higher than in age and sex matched general population subjects, 31.51% (31.49%-31.52%); OR=2.61 (2.37-2.87, p<0.0001). After controlling by confounders smokers showed a 10-year CVE risk excess versus non-smokers of 2.63 (2.16-3.09), p<0.001. Smoking cessation would reduce the likely of high/very high 10-year CVE risk (above 10%) by near 90% [OR=0.10 (0.06-0.18), p<0.0001]. Also, smokers were more likely to consume alcohol daily [4.13 (3.07-5.54), p<0.0001] and caffeine [3.39 (2.72-4.23), p<0.0001] than non-smoker patients with schizophrenia, and less likely to avoid daily consumption of salt [0.58 (0.43-0.78), p<0.0001], saturated fat [0.71 (0.56-0.91), p=0.006], high fibre diet [0.67 (0.53-0.84), p=0.001], or to follow a low-caloric diet [0.63 (0.48-0.81), p<0.0001]. Smokers also were less likely to do exercise habitually [0.62 (0.48-0.82, p=0.001]. CONCLUSION Compared with the general population, patients with schizophrenia showed significant higher prevalence of smoking. Smokers who stop smoking would benefit by a near 90% reduction in the likely of 10-year cardiovascular event risk above 10%.