Antipsychotics are frequently prescribed agents in individuals with intellectual disability, often for behavioral symptoms. Efficacy of antipsychotics for this is ambiguous, so discontinuation should be considered. Weight gain and metabolic dysregulation are well-known adverse effects of antipsychotics which increase the risk of the metabolic syndrome.We performed a discontinuation study in 99 adults with intellectual disability, living in residential facilities who used antipsychotics for behavioral symptoms for more than 1 year. The aim of the present study was to investigate the effects of discontinuation of long-term used antipsychotics on weight, body mass index (BMI), and parameters of the metabolic syndrome and to investigate the influence of genetic polymorphisms and medication factors on these outcomes.Discontinuation of antipsychotics led to a mean decrease of 4 cm waist circumference, of 3.5 kg weight, 1.4 kg/m BMI, and 7.1 mm Hg systolic blood pressure. In those participants who had not completely discontinued use of antipsychotics we found a decrease in weight and BMI and an increase in fasting glucose. The presence of the C-allele of serotonin 5-hydroxytryptamine receptor polymorphism rs141334 was associated with higher waist circumference and higher plasma levels of triglycerides and lower levels of high-density lipoprotein. Achievement of complete discontinuation predicted a larger decrease in waist circumference and BMI.In conclusion, results of the study show the beneficial effects of discontinuation of long-term used antipsychotics on metabolic outcomes.

Amitriptyline (AMI) and valproic acid (VPA) are common psychotropic drugs which are frequently used in psychiatry and also administered in neurology or anesthesia in the absence of a psychiatric indication. On the basis of the case of a 73-year-old man with therapy-resistant major depressive episode who experienced anticholinergic delirium after adding VPA to AMI, we retrospectively analyzed therapeutic drug monitoring data of the years 2008 to 2010. We assessed cases receiving a combination of AMI and VPA, and obtained a control sample of AMI patients without VPA which were matched for sex, age, daily dose, and comedication. Both samples were compared regarding the serum levels of AMI and nortriptyline (NOR) as well as the ratio of NOR and AMI with the Mann-Whitney U test. The combination of AMI and VPA led to a remarkable increase of AMI and NOR serum levels. When comparing 33 patients who received comedication with VPA versus 33 matched controls, the total concentration by combining mean AMI and NOR serum levels (237.1 [119.9] vs 126.4 [52.8] ng/mL) and NOR/AMI ratio (1.300 [0.905] vs 0.865 [0.455]) was significantly higher.Both AMI and VPA are widely prescribed drugs. A combination of both is common for psychiatric or neurologic patients. A cautious dosing of AMI with VPA comedication is advisable, and therapeutic drug monitoring should be performed because this combination may lead to a remarkable increase of AMI and NOR serum levels.

BACKGROUND:

The prevalence of diabetes in patients with schizophrenia is 2- to 3-fold higher than in the general population. Glucose abnormalities were detected in 11.9% of Japanese schizophrenic patients in a recent cross-sectional study that included fasting glucose monitoring. However, detailed studies of glucose intolerance using the glucose tolerance test have been limited in Japanese patients with schizophrenia. We investigated the prevalence of abnormal glucose tolerance after glucose loading among Japanese inpatients with schizophrenia, with normal fasting glucose levels.

METHOD:

A total of 258 inpatients with schizophrenia participated in this study after giving their written informed consent. A 75-g oral glucose tolerance test was conducted in the morning after a 12-hour overnight fast.

RESULTS:

Among patients with normal fasting glucose, 81.3% had normal glucose tolerance, 17.3% had impaired glucose tolerance, and 1.3% were diagnosed with diabetes.

CONCLUSIONS:

This study showed that the frequency of impaired glucose tolerance in patients with schizophrenia with normal fasting glucose levels might be higher than in the general population. Careful monitoring and screening of patients with schizophrenia for abnormal glucose metabolism might therefore be necessary.

Meta-analyses have found conflicting evidence on the link between antipsychotics and cerebrovascular events (CVEs). The primary aim of this study was to evaluate the association between any antipsychotic prescription and CVEs in Italian elderly; second, to compare the effect of typical and atypical antipsychotics on CVEs; and third, to investigate the effect of antipsychotics on CVEs in the subgroup of persons coprescribed with acetylcholinesterase inhibitors (AChEIs). Administrative claims from community-dwelling people aged 65 to 94 years living in Northern Italy were analyzed using a retrospective case-control design, from 2003 to 2005. The primary outcome measure was a hospital discharge diagnosis of CVEs during 2005. Four age-, sex-, and local health unit-matched control subjects were identified for each case. Antihypertensive drugs, anticoagulants, platelet inhibitors, antidiabetic drugs, lipid-lowering drugs, and AChEI were used as covariates in conditional logistic regression models testing the odds ratio (OR) for CVEs due to antipsychotics use. Three thousand eight hundred fifty-five cases of CVEs were identified and matched with 15,420 control subjects. In multiadjusted models, the association of any antipsychotics, typical or atypical with CVEs, was not significant. When antipsychotics were categorized according to the number of boxes prescribed during the observational period, being prescribed with at least 19 boxes of typical antipsychotics was significantly associated with CVEs (OR, 2.4; 95% confidence interval, 1.08-5.5). An interaction was found between any antipsychotic and AChEI coprescription on CVEs (OR, 0.46; 95% confidence interval, 0.23-0.92). In conclusion, only typical antipsychotics were associated with an increased odd of CVEs, but the association was duration dependent. Persons prescribed simultaneously with AChEI and antipsychotics may be at a lower risk of CVEs.

Posttraumatic stress disorder (PTSD) is associated with increased smoking initiation, maintenance, and relapse. Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are neurosteroids that have been associated with mood measures as well as smoking status, and nicotine is associated with increased DHEA and DHEAS levels. Given the difficulties with mood experienced by smokers with PTSD, the purpose of the current study was to evaluate the association between negative affect and anxiety sensitivity with DHEA and DHEAS levels. Ninety-six smokers with and without PTSD provided blood samples for neurosteroid analyses and completed self-report measures of anxiety sensitivity and electronic diary ratings of negative affect. As expected, PTSD smokers reported higher levels of anxiety sensitivity (F1,94 = 20.67, partial η = 0.18, P < 0.0001) and negative affect (F1,91 = 7.98, partial η = 0.08, P = 0.006). After accounting for age and sex, DHEAS was significantly inversely associated with both anxiety sensitivity (F3,92 = 6.97, partial η = 0.07, P = 0.01) and negative affect (F3,87 = 10.52, partial η = 0.11, P = 0.002) across groups. Effect sizes indicated that these effects are moderate to high. No significant interactions of diagnosis and DHEA(S) levels with mood measures were detected. Given that nicotine is known to elevate DHEA(S) levels, these results suggest that DHEAS may serve as a biomarker of the association between mood and nicotine among smokers. Implications for the results include (1) the use of DHEAS measurement across time and across quit attempts and (2) the potential for careful use of DHEA supplementation to facilitate abstinence during smoking cessation.

OBJECTIVE:

The Child and Adolescent First-Episode Psychosis Study is a longitudinal study of early-onset first psychotic episodes. This report describes the naturalistic psychopharmacological treatment administered during a 24-month follow-up period, as well as discontinuation rates, reasons for discontinuation, and adverse effects.

METHODS:

The sample comprised 110 patients, aged 9 to 17 years, with a first psychotic episode. Pharmacological treatment, changes, reasons for discontinuation, and the UKU (Udvalg for Kliniske Undersogelser) Side Effect Rating Scale were registered at 6, 12, and 24 months of follow-up.

RESULTS:

Second-generation antipsychotics, especially risperidone, quetiapine, and olanzapine, were the most commonly used. The discontinuation rate was 44.5% at 6 months, 59.1% at 12 months, and 70.9% at 24 months. Discontinuation rates or reasons for discontinuation (adverse reaction, insufficient response, and other) did not differ significantly between antipsychotics. At 6 months, significant differences were found in body mass index increase and body mass index z score increase, which were higher with olanzapine, and in neurological effects, which were higher with risperidone; at 12 and 24 months, these differences were no longer significant. High maintenance rates were found in the clozapine group, although they had higher scores on the autonomic subscale of the UKU.

CONCLUSIONS:

A long follow-up period reveals high discontinuation rates similar to those observed in adults, particularly during the first year. No differences were found between antipsychotics. Differences in adverse effects were found at 6 months but not subsequently after changes in treatment. Clozapine had a high maintenance rate, and its tolerability was comparable to that of other antipsychotics.