M. De Hert

Cardiovascular disease and diabetes in people with severe mental illness position statement from the European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC)

People with severe mental illnesses, such as schizophrenia, depression or bipolar disorder, have worse physical health and reduced life expectancy compared to the general population. The excess cardiovascular mortality associated with schizophrenia and bipolar disorder is attributed in part to an increased risk of the modifiable coronary heart disease risk factors; obesity, smoking, diabetes, hypertension and dyslipidaemia. Antipsychotic medication and possibly other psychotropic medication like antidepressants can induce weight gain or worsen other metabolic cardiovascular risk factors. Patients may have limited access to general healthcare with less opportunity for cardiovascular risk screening and prevention than would be expected in a non-psychiatric population. The European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC) published this statement with the aim of improving the care of patients suffering from severe mental illness. The intention is to initiate cooperation and shared care between the different healthcare professionals and to increase the awareness of psychiatrists and primary care physicians caring for patients with severe mental illness to screen and treat cardiovascular risk factors and diabetes.

Metabolic and endocrine adverse effects of second-generation antipsychotics in children and adolescents: A systematic review of randomized, placebo controlled trials and guidelines for clinical practice

Second-generation antipsychotics (SGA) are being used more often than ever before in children and adolescents with psychotic and a wide range of non-psychotic disorders. Several SGA have received regulatory approval for some paediatric indications in various countries, but off-label use is still frequent. The aim of this paper was to perform a systematic review and critically evaluate the literature on cardiometabolic and endocrine side-effects of SGA in children and adolescents through a Medline/Pubmed/Google Scholar search of randomized, placebo controlled trials of antipsychotics in children and adolescents (<18 years old) until February 2010. In total, 31 randomized, controlled studies including 3595 paediatric patients were identified. A review of these data confirmed that SGA are associated with relevant cardiometabolic and endocrine side-effects, and that children and adolescents have a high liability to experience antipsychotic induced hyperprolactinaemia, weight gain and associated metabolic disturbances. Only weight change data were sufficiently reported to conduct a formal meta-analysis. In 24 trials of 3048 paediatric patients with varying ages and diagnoses, ziprasidone was associated with the lowest weight gain (-0.04kg, 95% confidence interval [CI]: -0.38 to +0.30), followed by aripiprazole (0.79kg, 95% CI: 0.54 to 1.04], quetiapine (1.43kg, 95% CI: 1.17 to 1.69) and risperidone (1.76kg, 95% CI: 1.27 to 2.25) were intermediate, and olanzapine was associated with weight gain the most (3.45kg, 95% CI: 2.93 to 3.97). Significant weight gain appeared to be more prevalent in patients with autistic disorder who were also younger and likely less exposed to antipsychotics previously. These data clearly suggest that close screening and monitoring of metabolic side effects is warranted and that the least cardiometabolically problematic agents should be used first whenever possible. A good collaboration between child- and adolescent psychiatrists, general practitioners and paediatricians is essential to maximize overall outcomes and to reduce the likelihood of premature cardiovascular morbidity and mortality.

A systematic review of correlates of physical activity in patients with schizophrenia

Vancampfort D, Knapen J, Probst M, Scheewe T, Remans S, De Hert M. A systematic review of correlates of physical activity (PA) in patients with schizophrenia.

The Effects of Novel and Newly Approved Antipsychotics on Serum Prolactin Levels: A Comprehensive Review

Since the 1970s, clinicians have increasingly become more familiar with hyperprolactinemia (HPRL) as a common adverse effect of antipsychotic medication, which remains the cornerstone of pharmacological treatment for patients with schizophrenia. Although treatment with second-generation antipsychotics (SGAs) as a group is, compared with use of the first-generation antipsychotics, associated with lower prolactin (PRL) plasma levels, the detailed effects on plasma PRL levels for each of these compounds in reports often remain incomplete or inaccurate. Moreover, at this moment, no review has been published about the effect of the newly approved antipsychotics asenapine, iloperidone and lurasidone on PRL levels. The objective of this review is to describe PRL physiology; PRL measurement; diagnosis, causes, consequences and mechanisms of HPRL; incidence figures of (new-onset) HPRL with SGAs and newly approved antipsychotics in adolescent and adult patients; and revisit lingering questions regarding this hormone. A literature search, using the MEDLINE database (1966–December 2013), was conducted to identify relevant publications to report on the state of the art of HPRL and to summarize the available evidence with respect to the propensity of the SGAs and the newly approved antipsychotics to elevate PRL levels. Our review shows that although HPRL usually is defined as a sustained level of PRL above the laboratory upper limit of normal, limit values show some degree of variability in clinical reports, making the interpretation and comparison of data across studies difficult. Moreover, many reports do not provide much or any data detailing the measurement of PRL. Although the highest rates of HPRL are consistently reported in association with amisulpride, risperidone and paliperidone, while aripiprazole and quetiapine have the most favorable profile with respect to this outcome, all SGAs can induce PRL elevations, especially at the beginning of treatment, and have the potential to cause new-onset HPRL. Considering the PRL-elevating propensity of the newly approved antipsychotics, evidence seems to indicate these agents have a PRL profile comparable to that of clozapine (asenapine and iloperidone), ziprasidone and olanzapine (lurasidone). PRL elevations with antipsychotic medication generally are dose dependant. However, antipsychotics having a high potential for PRL elevation (amisulpride, risperidone and paliperidone) can have a profound impact on PRL levels even at relatively low doses, while PRL levels with antipsychotics having a minimal effect on PRL, in most cases, can remain unchanged (quetiapine) or reduce (aripiprazole) over all dosages. Although tolerance and decreases in PRL values after long-term administration of PRL-elevating antipsychotics can occur, the elevations, in most cases, remain above the upper limit of normal. PRL profiles of antipsychotics in children and adolescents seem to be the same as in adults. The hyperprolactinemic effects of antipsychotic medication are mostly correlated with their affinity for dopamine D2 receptors at the level of the anterior pituitary lactotrophs (and probably other neurotransmitter mechanisms) and their blood–brain barrier penetrating capability. Even though antipsychotics are the most common cause of pharmacologically induced HPRL, recent research has shown that HPRL can be pre-existing in a substantial portion of antipsychotic-naïve patients with first-episode psychosis or at-risk mental state.

Relationships between obesity, functional exercise capacity, physical activity participation and physical self-perception in people with schizophrenia

Vancampfort D, Probst M, Sweers K, Maurissen K, Knapen J, De Hert M. Relationships between obesity, functional exercise capacity, physical activity participation and physical self‐perception in people with schizophrenia.

Second-generation antipsychotics and constipation: A review of the literature

Antipsychotics are the cornerstone in the management of psychotic disorders and schizophrenia. They are effective agents but also have a wide range of side effects. In the recent literature constipation as possible side effect has received little attention. A review of the literature concerning constipation associated with antipsychotics was performed. Overall constipation is a rarely studied or reported side effect of antipsychotic medication. Nevertheless constipation is a common side effect. Antipsychotic agents differ in their liability to induce constipation. Constipation can be severe and can lead to serious consequences such as paralytic ileus, bowel occlusion and death. Active screening, monitoring and treatment are recommended. Further research on incidence, prevalence, underlying mechanisms and preventive measures is required.

EPA guidance on tobacco dependence and strategies for smoking cessation in people with mental illness.

Tobacco dependence is the most common substance use disorder in adults with mental illness. The prevalence rates for tobacco dependence are two to four times higher in these patients than in the general population. Smoking has a strong, negative influence on the life expectancy and quality of life of mental health patients, and remains the leading preventable cause of death in this group. Despite these statistics, in some countries smokers with mental illness are disadvantaged in receiving intervention and support for their tobacco dependence, which is often overlooked or even tolerated. This statement from the European Psychiatric Association (EPA) systematically reviews the current evidence on tobacco dependence and withdrawal in patients with mental illness and their treatment. It provides seven recommendations for the core components of diagnostics and treatment in this patient group. These recommendations concern: (1) the recording process, (2) the timing of the intervention, (3) counselling specificities, (4) proposed treatments, (5) frequency of contact after stopping, (6) follow-up visits and (7) relapse prevention. They aim to help clinicians improve the care, health and well-being of patients suffering from mental illness.

Parsing the components of the psychomotor syndrome in schizophrenia

Docx L, Morrens M, Bervoets C, Hulstijn W, Fransen E, De Hert M, Baeken C, Audenaert K, Sabbe B. Parsing the components of the psychomotor syndrome in schizophrenia.

The functional exercise capacity is correlated with global functioning in patients with schizophrenia

Vancampfort D, Probst M, Scheewe T, Knapen J, De Herdt A, De Hert M. The functional exercise capacity is correlated with global functioning in patients with schizophrenia.

Association of the metabolic syndrome with physical activity performance in patients with schizophrenia

AIMnThe primary aim of this study was to determine whether the presence of the metabolic syndrome (MetS) limits physical activity (PA) in patients with schizophrenia. A secondary aim was to investigate cross-sectional associations of leisure-time PA, sports participation and PA performance with MetS parameters.nnnMETHODSnPatients with schizophrenia who had MetS (n=37) were compared with those without MetS (n=69). Patients were assessed for PA performance using a 6-minute walk test (6MWT) and PA participation using the Baecke PA questionnaire, as well as for antipsychotic medication dose (expressed in chlorpromazine equivalents), negative symptoms and smoking behaviour.nnnRESULTSnThe two patient groups were similar in age, gender, mean antipsychotic medication dose, negative symptomatology and smoking behaviour. Distance achieved on the 6MWT was 13.7% shorter (P<0.001) in patients with versus patients without MetS (527.6±108.9 m vs 610.0±93.7 m, respectively). Patients with MetS were also significantly less involved in sports activities (P=0.001) and less physically active during leisure time (P=0.002). Also, the distance of the 6MWT was moderately correlated with body mass index (r=-0.44, P<0.001), waist circumference (r=-0.43, P<0.001), sports participation (r=0.60, P<0.001) and leisure-time PA (r=0.42, P<0.001).nnnCONCLUSIONnMetS is associated with poorer PA performance in patients with schizophrenia. The additional burden of MetS places patients with schizophrenia at even greater risk for physical and functional limitations in daily life.