Pharmacological treatment of hospitalised schizophrenic patients in Belgium

Objective. The aim of the present study is two-fold: (1) evaluate to what degree antipsychotic prescribing patterns are in accordance with published treatment recommendations; (2) gain insight in factors determining guideline adherence or non-adherence. Method. The medication use at first assessment of 1215 psychotic in-patients, participating in a naturalistic prospective follow-up study, was registered. Results. In Belgium, use of novel antipsychotics is frequent (69.4%) in hospitalised schizophrenic patients. In the total sample 57.8% receive only one antipsychotic drug. The majority of patients are treated with drugs of only one antipsychotic drug group, either first-generation antipsychotics (FGA) (27.8%) or second-generation antipsychotics (SGA) (42.3%). Roughly one-quarter of patients combine different types of antipsychotic. Antipsychotic dosing is adequate for the majority of patients, but one-third receive a higher than recommended dose. The use of SGA is influenced by the patients’ age and duration of illness. Polypharmacy and the administration of high doses FGA are influenced by symptom severity and illness duration. No clear determinants of SGA overdosing were found. Conclusions. SGA are most frequently used for the treatment for schizophrenic psychosis. Polypharmacy and excessive dosing are still frequently observed and appear influenced by the patient's clinical condition and illness duration. Evidence-based guidelines have not been sufficiently implemented in daily clinical practice yet.     

Drug treatments for schizophrenia: pragmatism in trial design shows lack of progress in drug design

Aims.The introduction of second generation antipsychotic (SGA) medication over a decade ago led to changes in prescribing practices; these drugs have eclipsed their predecessors as treatments for schizophrenia. However, the metabolic side effects of these newer antipsychotics have been marked and there are increasing concerns as to whether these novel drugs really are superior to their predecessors in terms of the balance between risks and benefits. In this article, we review the literature regarding comparisons between first generation antipsychotic (FGA) and SGA in terms of clinical effectiveness.Methods.Large (n > 150) randomized-controlled trials (RCTs) comparing the effectiveness (efficacy and side effects) of FGA and SGA medications other than clozapine were reviewed, as were meta-analyses that included smaller studies.Results.The superiority in efficacy and reduced extrapyramidal side effects (EPSE) of SGAs is modest, especially when compared with low-dose FGAs. However, the high risk of weight gain and other metabolic disturbances associated with certain SGAs such as olanzapine is markedly higher than the risk with FGAs at the doses used in the trials.Conclusions.The efficacy profiles of various FGAs and SGAs are relatively similar, but their side effects vary between and within classes. Overall, large pragmatic trials of clinical effectiveness indicate that the care used in prescribing and managing drug treatments to ensure tolerability may be more important than the class of drug used.Key words: antipsychotic drugs, clinical effectiveness, schizophrenia, randomized controlled trials     

The overweight: obesity and plasma lipids in adults with intellectual disability and mental illness

Background Previous studies in adults with intellectual disabilities (ID) have reported a higher prevalence of obesity than in the general population, and a trend to an increase in the prevalence of excess weight. However, little information is available on body weight status and lipids levels of adults with ID and co‐existing mental illness. The aim of this study was to address this information gap, by conducting a stepwise multiple regression analysis to predict BMI, thereby allowing the investigation of (semi‐)partial correlations, which assess the extent to which a particular predictor variable is associated with BMI over and above the other predictors. Methods A study of the patients with ID and psychiatric illness registered in the service. Collected data included body mass index (BMI), age, gender, the presence of additional physical conditions, residential status, mental illness and use the psychotropic medication. We analysed the lipid profile including serum cholesterol together with low‐density lipoprotein, high‐density lipoprotein (HDL), triglycerides and the serum cholesterol/HDL ratio. Data for these variables were entered into a stepwise multiple linear regression to predict BMI. Results 28% of the participants were overweight and 41% obese. Most of the obese patients were men with mild ID (P = 0.039). Level of ID (P = 0.003), gender (P = 0.001) and serum triglycerides (P = 0.026) had significant predictive value in the regression model. There were no significant differences in either the mean serum cholesterol levels or the mean triglyceride levels between those taking and those not taking first‐generation antipsychotics, second‐generation antipsychotics or anti‐epileptic medication. Conclusions The rate of obesity in our sample was higher than in previous studies. The most predictive combination of predictors to predict BMI was ID level, gender and serum triglyceride levels. Serum triglyceride and cholesterol levels did not appear to be unduly affected by first‐ or second‐generation antipsychotic medication or by antiepileptic medication.     

Metabolic side effects of second generation antipsychotic agents in antipsychotic-naïve patients: one-month prospective evaluation

The present study investigated the effects of second generation antipsychotics (SGA) on the metabolism of 15 antipsychotic-na?ve outpatients. Evaluations were performed at baseline and after 1 month of treatment. A significant increase in mean body mass index (BMI) and mean waist circumference was observed. These results suggest the importance of monitoring patients from the first few weeks of antipsychotic treatment.     

Anticholinergic use in hospitalised schizophrenic patients in Belgium

This naturalistic study aims to evaluate the influence of antipsychotic treatment on the use of anticholinergics. The observed use of anticholinergics will give an indication of the occurrence of extrapyramidal side effects (EPS) in the different antipsychotic treatment conditions. The medication use of 1215 hospitalised patients with DSM-IV 295.xx diagnosis is recorded. Four antipsychotic treatment conditions are distinguished: 1) only first generation antipsychotics (FGA): patients receive one or a combination of first generation antipsychotics, 2) a combination of high potency FGA and second generation antipsychotics (SGA), 3) a combination of low potency FGA and SGA, and 4) only SGA: patients receive one or a combination of SGA. Antipsychotic treatment significantly influences the use of anticholinergics. Anticholinergic use is highest in patients treated with high potency FGA (whether or not in combination with SGA) as compared with patients only treated with SGA and patients combining SGA with low potency FGA. The two latter groups do not significantly differ. However, there were no significant differences in the prevalence of EPS with the exception of akathisia between FGA and SGA. Thus, through the use of anticholinergics, EPS induced by FGA can be effectively reduced.     

Experience of child and adolescent mental health clinicians working within an at-risk mental state for psychosis service: a qualitative study

Aim: To qualitatively examine the common experiences of child and adolescent mental health clinicians working with adolescents suspected of having an ‘at‐risk mental state’ (ARMS) for psychosis. Methods: A semistructured interview was conducted with six experienced child and adolescent mental health clinicians working in North East England. Results: A thematic analysis of clinicians' experiences indicated that the identification and management of an ARMS within this patient group is particularly complex. In terms of treatment options, approaches that promoted social inclusion were favoured, but the use of antipsychotic medication was perceived as a ‘last resort’, requiring serious consideration. Clear guidelines and an overall consensus were judged to be lacking in terms of coordinating care and multi‐agency working practices. Conclusions: Establishing a formalized care pathway that also incorporates regular training and supervision may be required by this and other clinical services working with adolescents suspected of having an ARMS. Improved identification, a firmer evidence base regarding treatment practices and clear guidelines are required for this age group. This need will become more urgent should a psychosis risk syndrome be included as a diagnostic category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM‐V).     

Evaluating the CANSAS self-report (CANSAS-P) as a screening instrument for care needs in people with psychotic and affective disorders

The metabolic profiles of Chinese patients treated with second-generation antipsychotic (SGA) medication and first-generation antipsychotic (FGA) medication were compared. The sample comprised 99 patients treated with SGA (risperidone, olanzapine and ziprasidone) and 99 with FGA (chlorpromazine, haloperidol and trifluoperazine) from the outpatient clinic of a teaching hospital in Hong Kong. The most frequent psychiatric diagnosis was schizophrenia, followed by affective disorder and other psychiatric diagnoses. Subjects were measured for body weight, body height, fasting lipid and glucose levels. SGA was associated with higher LDL-cholesterol level than FGA. Individual comparison of different antipsychotics showed that patients on olanzapine had the greatest increases in cholesterol and triglycerides among all antipsychotics. The finding suggested SGA, particularly olanzapine, were associated with more metabolic risk factors than first-generation antipsychotics.     

Obesity as a risk factor for antipsychotic noncompliance

OBJECTIVE: Weight gain is a common side effect of antipsychotic medications and is of particular concern with most of the newer "atypical" antipsychotics. It is, therefore, increasingly important to understand the impact of obesity and perceived weight problems on compliance with these medications. METHODS: A survey of treatment and health issues was mailed to local chapters of the National Alliance for the Mentally Ill (NAMI) and National Mental Health Association (NMHA), who distributed them to people with schizophrenia. Noncompliance was defined as a self-report of missing any antipsychotic medication in the previous month. The primary independent variables were (1) body mass index (BMI; weight [kg]/height [m2])-categorized as normal (< 25, n = 73), overweight (25-30, n = 104), or obese (> 30, n = 100)-and (2) subjective distress over weight gain. Other independent variables included demographics, medication attitudes, and treatment satisfaction. RESULT: BMI status and subjective distress from weight gain were predictors of noncompliance. Obese individuals were more than twice as likely as those with a normal BMI to report missing their medication (OR = 2.5; CI 1.1-5.5). A comprehensive model suggested that the primary mediator of noncompliance was distress over weight gain. CONCLUSIONS: There appears to be a significant, positive association between obesity and subjective distress from weight gain and medication noncompliance, even when accounting for other possible confounding factors.     

Valproic acid-associated weight gain in older children and teens with epilepsy

This research was undertaken to determine the incidence and predictors of weight gain in older children and teens treated with valproate for epilepsy. Subjects who were 10 to 17 years of age, who began valproate treatment between January 1, 1996, and December 31, 2000, and who had documented weight and height measurements at medication initiation and at least one follow-up visit were retrospectively identified. Exclusion criteria were follow-up <2 months, discontinuation of valproate within 2 months, concurrent therapy with medication known to affect weight, or gastrostomy feeding. Body mass index was calculated at initiation and either discontinuation of valproate or last follow-up and stratified into four categories: underweight, (/=eighty-fifth to ninety-fifth percentile) and overweight (ninety-fifth percentile or higher). Potential predictors of change in body mass index were examined. Mild-to-moderate weight gain was observed in 58% of the 43 subjects treated with valproate (median increase, 2; twenty-fifth to seventy-fifth percentile, 1-6.4). Seventy-nine percent remained in the same body mass index category, and 14% moved up to a potentially overweight or overweight category. The only predictor of an overweight category at follow-up was a potentially overweight or overweight category at initiation (P <0.0002). Two factors tended to predict an increase in body mass index: normal neurocognitive status (P = 0.06) and primary generalized seizure type (P = 0.07).     

Managing weight gain and metabolic issues in patients treated with atypical antipsychotics

The proven efficacy of second-generation antipsychotics (SGA) has led many clinicians to switch patients from a conventional antipsychotic to an SGA. However, SGAs may be associated with weight gain, dyslipidemia, high blood pressure, and ultimately with cardiovascular disease, diabetes, and metabolic syndrome. Clinicians should be aware of patients' individual risk factors for developing these illnesses and should carefully screen for changes in weight, body mass index, waist size, or lipid levels that could be potentially harmful and increase the risk for a more serious illness.     

Body mass index and prevalence of obesity in a French cohort of patients with schizophrenia

Objective: To evaluate the distributions of body mass index in a large sample of patients with schizophrenia, and to examine the association between body weight and antipsychotic drugs. Method: The data source was baseline data from a national survey conducted in 2005–2006 in 5756 patients. Results: The mean age of the patients was 37.1 ± 11.8 years, and the mean BMI was 25.5 ± 5.2 kg/m². In the final logistic regression model, the prevalence of obesity was significantly higher in female patients, age 40–59 vs. 18–29 years, patients in sheltered employment (vs. no income), out‐patients (vs. full‐time in‐patients) and patients treated with concomitant antidepressant. There was a higher rate of obesity, relative to an absence of antipsychotics at entry, for patients receiving the following individual drugs: clozapine, olanzapine, risperidone and amisulpride. Conclusion: In patients treated with atypical antipsychotics, we found a significantly higher prevalence of obesity than in those not treated with any antipsychotic medication.     

Weight gain with clozapine compared to first generation antipsychotic medications

Few studies have examined gender differences in the propensity to gain weight on clozapine. Weight gain increases risk for many medical illnesses and is of particular concern for people with schizophrenia who are more overweight than the general population. Long-stay patients in Connecticut state hospitals were randomly assigned to switch to open-label treatment with clozapine (n = 138) or to continue receiving first generation (conventional) antipsychotic medications (n = 89). Using survival and random regression models, we examined percentage of body weight gained during 2 years for patients assigned to clozapine versus those who continued taking first generation antipsychotic medications. We also examined the impact of gender on weight gain. Patients who switched to clozapine gained a greater percentage of weight (13 pounds, 7%) than did patients remaining on first generation medications (5 pounds, 4%) at the end of 2 years. Normal-weight patients on clozapine were more likely to become obese (body mass index [BMI] > or = 30). Patients gained weight whether they switched to clozapine or remained on first generation antipsychotic medications, but weight gain was significantly greater (1 BMI unit) in the clozapine-treated group, particularly among women.     

Newer antipsychotic drugs and obesity in children and adolescents. How should we assess drug‐associated weight gain?

OBJECTIVE: Antipsychotic drugs may contribute to weight gain in children and adolescents. METHOD: We used Medline's PubMed in the pediatric age using key words 'weight gain' and 'obesity', for each newer antipsychotic drug. RESULTS: We found 21 articles linking weight gain and obesity with newer antipsychotic drugs among youths. Risperidone was the most commonly cited agent. Weight gain from olanzapine was the largest among the more commonly prescribed newer agents. All studies reported absolute weight gain. Only a few studies used the better measure of body mass index (BMI). None incorporated growth charts to allow for changes in weight and height over time because of growth. CONCLUSION: Weight gain may be a major problem when prescribing newer antipsychotic drugs in the pediatric population. Risperidone is associated with less weight gain than olanzapine. Published reports and studies have not utilized state-of-the-art techniques using BMI with readily available growth charts.     

Weight gain and increase of body mass index among children and adolescents treated with antipsychotics: a critical review

We performed an updated review of the available literature on weight gain and increase of body mass index (BMI) among children and adolescents treated with antipsychotic medications. A PubMed search was conducted specifying the following MeSH terms: (antipsychotic agents) hedged with (weight gain) or (body mass index). We selected 127 reports, including 71 intervention trials, 42 observational studies and 14 literature reviews. Second-generation antipsychotics (SGAs), in comparison with first-generation antipsychotics, are associated with a greater risk for antipsychotic-induced weight gain although this oversimplification should be clarified by distinguishing across different antipsychotic drugs. Among SGAs, olanzapine appears to cause the most significant weight gain, while ziprasidone seems to cause the least. Antipsychotic-induced BMI increase appears to remain regardless of the specific psychotropic co-treatment. Children and adolescents seem to be at a greater risk than adults for antipsychotic-induced weight gain; and the younger the child, the higher the risk. Genetic or environmental factors related to antipsychotic-induced weight gain among children and adolescents are mostly unknown, although certain genetic factors related to serotonin receptors or hormones such as leptin, adiponectin or melanocortin may be involved. Strategies to reduce this antipsychotic side effect include switching to another antipsychotic drug, lowering the dosage or initiating treatment with metformin or topiramate, as well as non-pharmacological interventions. Future research should avoid some methodological limitations such as not accounting for age- and sex-adjusted BMI (zBMI), small sample size, short period of treatment, great heterogeneity of diagnoses and confounding by indication.     

Attitudes and knowledge of child and adolescent mental health clinicians in relation to the psychosis risk syndrome

Aim: To evaluate the knowledge and attitudes of clinicians in a Child and Adolescent Mental Health Service in relation to the ‘At‐Risk Mental State’ concept in psychosis. Methods: A questionnaire was constructed and administered to child and adolescent mental health clinicians working in North East England. Results: Sixty‐seven per cent (n = 121) of eligible clinicians responded. Almost all the participants believed that young people ‘At‐Risk’ needed support. However, only around half felt confident in identifying this patient group. Approximately a third felt that antipsychotic medication may be useful. Some interprofessional differences were noted in relation to both knowledge and attitudes. Conclusions: Further training would be required for most health workers in this sample to feel confident in identifying the syndrome. These findings require replication in other service settings and may have implications for the implementation of a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnostic category relating to the At‐Risk Mental State.     

Body weight gain induced by a newer antipsychotic agent reversed as negative symptoms improved

OBJECTIVE: We describe a patient in whom improvement in negative symptoms contributed to early weight loss and subsequent long-term improvement in weight management. METHOD: Case report. RESULTS: A 26-year-old woman with schizophrenia gained 7 kg over the course of 1 year after starting treatment with olanzapine. However, as negative symptoms gradually improved with treatment, she became motivated to diet and exercise regularly. She quickly lost 9 kg and subsequently maintained optimal weight (55 kg; body mass index, 24.1 kg/m(2) ). CONCLUSION: Important strategies for minimizing weight gain in patients taking antipsychotic agents include improving negative symptoms of avolition and apathy, regular monitoring of body weight and potential medical consequences of overweight and obesity, and educating the patient about the importance of diet and regular exercise.     

Impact of biopsychosocial factors on psychiatric training in Japan and overseas: Are psychiatrists oriented to mind,brain, or sociocultural issues?

Aim: To clarify the impact of biopsychosocial factors on psychiatric training under the new and traditional postgraduate medical education system in Japan and to compare them with young psychiatrists from other countries. Methods: Psychiatric residents and early‐career psychiatrists were recruited in Japan and other countries. Using mail‐based and web‐based self‐administered questionnaires, we evaluated participants' demographic information, motivation to become psychiatrists, interest and commitment to various aspects of psychiatry, and reactions to a case vignette, focusing on biopsychosocial factors. Results: A total of 137 responses, 81 from Japan and 56 from other countries, were collected. Before starting psychiatric training, Japanese participants showed a strong interest in ‘mind’ and less interest in ‘brain’ and ‘environmental factors’, while the interest in ‘brain’ and ‘environmental factors’ is presently as high as that in ‘mind.’ Japanese participants reported less commitment to their training toward ICD/DSM‐based diagnosis, interview, pharmacotherapy, psychosocial treatment and epidemiology, compared with participants from other countries. In particular, Japanese participants showed less commitment to their training in suicide prevention, despite their perception of its high importance due to a high suicide rate in Japan. Suicide risk of a case vignette proved to be differently assessed according to participants' commitment levels to each aspect of psychiatry. Conclusion: Our results suggest that young psychiatrists' attitudes concerning the biopsychosocial model generally become well‐balanced with psychiatric training, however sociocultural factors do not seem to be well represented in the Japanese psychiatric training system. Additional training on sociocultural issues, such as suicide in Japan, should be considered.     

Brain reward system's alterations in response to food and monetary stimuli in overweight and obese individuals

The brain's reward system is crucial to understand obesity in modern society, as increased neural responsivity to reward can fuel the unhealthy food choices that are driving the growing obesity epidemic. Brain's reward system responsivity to food and monetary rewards in individuals with excessive weight (overweight and obese) versus normal weight controls, along with the relationship between this responsivity and body mass index (BMI) were tested. The sample comprised 21 adults with obesity (BMI > 30), 21 with overweight (BMI between 25 and 30), and 39 with normal weight (BMI < 25). Participants underwent a functional magnetic resonance imaging (fMRI) session while performing two tasks that involve the processing of food (Willing to Pay) and monetary rewards (Monetary Incentive Delay). Neural activations within the brain reward system were compared across the three groups. Curve fit analyses were conducted to establish the association between BMI and brain reward system's response. Individuals with obesity had greater food‐evoked responsivity in the dorsal and ventral striatum compared with overweight and normal weight groups. There was an inverted U‐shape association between BMI and monetary‐evoked responsivity in the ventral striatum, medial frontal cortex, and amygdala; that is, individuals with BMIs between 27 and 32 had greater responsivity to monetary stimuli. Obesity is associated with greater food‐evoked responsivity in the ventral and dorsal striatum, and overweight is associated with greater monetary‐evoked responsivity in the ventral striatum, the amygdala, and the medial frontal cortex. Findings suggest differential reactivity of the brain's reward system to food versus monetary rewards in obesity and overweight. Hum Brain Mapp 38:666–677, 2017. © 2016 Wiley Periodicals, Inc.