Refractory hypotension secondary to chronic treatment with high doses of quetiapine.

Quetiapine is an atypical antipsychotic used in the treatment of depressive, schizophrenic, or bipolar disorders. It acts on dopamine D1 and D2, histamine, and 5HT1A and 5HT2 receptors. However, it also acts as an antagonist for α1 receptors causing cardiovascular side effects, including hypotension. We present the case of a patient chronically medicated with Quetiapine who developed hypotension refractory to vasoconstrictors and intraoperative fluid therapy. Noradrenalin has a strong α1 effect with lower affinity for ß2 receptors unlike adrenalin. This translates into peripheral vasoconstriction and an improved clinical picture. Therefore, it should be considered the vasoactive drug of choice in patients on high doses of Quetiapine.

Post-therapy plasma concentrations of quetiapine in Taiwanese patients.

AIMS: Quetiapine is widely used to treat psychiatric disorders such as major depression, generalized anxiety disorder, dysthymic disorder, and insomnia other than schizophrenia and bipolar disorder. This study investigated the diagnostic distribution of quetiapine use in patients in a psychiatric hospital, the doses of quetiapine prescribed, and the plasma concentrations (Cps) of quetiapine and active metabolites. METHODS: We enrolled 107 patients who had been prescribed quetiapine for at least 4 weeks. Diagnoses, demographics, and concomitant medications were recorded. Blood sampling was performed in the morning, approximately 12 h after the before-bed dose of quetiapine. RESULTS: Diagnoses comprised schizophrenia (n = 25), bipolar disorder (n = 51), major depression (n = 15), dysthymic disorder (n = 9), and others (n = 7). The daily dose (DD) of quetiapine ranged from 25 to 800 (175.9 ± 184.4) mg, with the mean Cp being 105.6 ± 215.3 ng/ml, with a mean Cps/DD ratio of 0.58 ± 0.55 ng/ml/mg. There was a moderate positive linear correlation between the dose and Cps of quetiapine (r = 0.60), and the interpatient variation in Cps/DD ratio was up to 26-fold. CONCLUSION: Quetiapine is used in various doses to treat many psychiatric disorders other than psychosis, and it is usually prescribed as a secondary antipsychotic for symptoms such as insomnia or agitation. A wide interpatient variation of the Cps/DD ratio was noticed. Patients of East Asian descent may exhibit a 50% to 100% increase in the Cps/DD ratio for quetiapine compared with patients of Western descent.

Efficacy and safety/tolerability of antipsychotics in the treatment of adult patients with major depressive disorder: a systematic review and meta-analysis.

BACKGROUND: Antipsychotics are widely used in the treatment of major depressive disorder (MDD), but there has been no comprehensive meta-analytic assessment that examined their use as monotherapy and adjunctive therapy. METHODS: A systematic review and a meta-analysis were conducted on randomized placebo-controlled trials (RCTs) that reported on the efficacy and safety/tolerability of antipsychotics for the treatment of adults with MDD. Data of both monotherapy and adjunctive antipsychotic use were extracted, but analyzed separately using a random-effects model. Co-primary outcomes were study-defined-treatment response and intolerability-related discontinuation. We also illustrated the risk/benefit balance of antipsychotics for MDD, using two-dimensional graphs representing the primary efficacy and safety/tolerability outcome. Secondary outcomes included psychopathology, remission, all-cause-discontinuation, inefficacy-related discontinuation, and adverse events. RESULTS: Forty-five RCTs with 12 724 patients were included in the analysis. In monotherapy (studies = 13, n = 4375), amisulpride [1.99 (1.55-2.55)], sulpiride [1.50 (1.03-2.17)], and quetiapine [1.48 (1.23-1.78)] were significantly superior to placebo regarding treatment response. However, intolerability-related discontinuations were significantly higher compared to placebo with amisulpride and quetiapine. In adjunctive therapy (studies = 32, n = 8349), ziprasidone [1.80 (1.07-3.04)], risperidone [1.59 (1.19-2.14)], aripiprazole [1.54 (1.35-1.76)], brexpiprazole [1.41 (1.21-1.66)], cariprazine [1.27 (1.07-1.52)], and quetiapine [1.23 (1.08-1.41)] were significantly superior to placebo regarding treatment response. However, of these antipsychotics that were superior to placebo, only risperidone was equivalent to placebo regarding discontinuation due to intolerability, while the other antipsychotics were inferior. CONCLUSION: Results suggest that there are significant differences regarding the risk/benefit ratio among antipsychotics for MDD, which should inform clinical care.

Association Between Sexual Dysfunction and Dose of Atypical Antipsychotics: Essential to Learn the Basics.

There is paucity of data on sexual dysfunction associated with atypical antipsychotics in Indian population. We estimated the prevalence of sexual dysfunction and assessed dose dependency, if any, in patients on monotherapy of atypical antipsychotics. This cross-sectional study analyzed the data from patients with F20 to F29 (International Classification of Diseases 10th Revision, ICD-10) receiving monotherapy of risperidone (group 1), olanzapine (group 2), or quetiapine (group 3) for at least 4 weeks. The sexual function of participants was assessed using Arizona sexual experiences (ASEX) scale. Chlorpromazine (CPZ) equivalent dose and doses in terms of dose years were calculated. Kruskal-Wallis test, Mann-Whitney U-test, and Pearson correlation were used for analysis. Of the 154 subjects, 65.58% were males, with 44%, 48%, and 8% receiving risperidone, olanzapine, and quetiapine, respectively. The mean duration of treatment was 20.9 weeks. Lower ASEX scores were reported with quetiapine. The differences in mean ASEX scores between groups 1 and 2 were statistically significant for sex drive (P = .016), sexual arousal (P = .025), and overall score (P = .037). Sexual dysfunction was more frequent with risperidone (48.5%) than with olanzapine (28.4%) and quetiapine (0%). In group 1, the duration of therapy positively correlated with the mean scores of sexual desire (P = .003) and arousal (P = .033), but this was not the case for group 2 (receiving olanzapine). The mean CPZ equivalent doses were comparable between the groups (P = .064); those receiving <200 mg CPZ dose equivalents showed greater sexual impairment. We conclude that the occurrence of atypical antipsychotic-induced sexual dysfunction is not dose dependent. Olanzapine has a better safety profile in terms of sexual dysfunction, whereas the data reflecting the experience with quetiapine are insufficient.

Randomized, Placebo-Controlled Effectiveness Study of Quetiapine XR in Comorbid Depressive and Anxiety Disorders.

Objective: Quetiapine is approved as an adjunctive treatment for major depressive disorder (MDD) and as monotherapy for bipolar depression. It is often used off-label for treating anxiety conditions and as an augmentation agent for treatment-resistant depression. However, its benefit in depression with comorbid anxiety disorders has not been systematically evaluated. The current study evaluated the benefit and tolerability of quetiapine as augmentation to first-line antidepressants for MDD comorbid with anxiety disorders.Methods: In this multicenter trial (June 2008-June 2013), 76 adults (aged 18-65 years) with a primary diagnosis of unipolar depression comorbid with at least 1 anxiety disorder (per DSM-IV-TR criteria) received flexible-dose quetiapine extended-release (XR) 50-300 mg/d or placebo as add-on for 12 weeks in a 2:1 ratio. Depression, anxiety, life satisfaction, and adverse events were assessed.Results: Depression, anxiety, and function improved significantly in both groups. On primary outcome measures, quetiapine was superior to placebo in improving depression (17-item Hamilton Depression Rating Scale score: mean difference = -3.64; 95% CI, -7.01 to -0.27) and anxiety symptoms (Hamilton Anxiety Rating Scale score: mean difference = -4.02; 95% CI, -7.41 to -0.64), as well as Clinical Global Impressions-Severity of Illness scale score (mean difference = -0.64; 95% CI, -1.13 to -0.15). On secondary measures including the Montgomery-Asberg Depression Rating Scale, Beck Depression Inventory, Penn State Worry Questionnaire, and Quality of Life Satisfaction and Enjoyment Questionnaire, quetiapine produced a greater degree of improvement compared to placebo, but group differences were not statistically significant. Quetiapine was well tolerated, with mostly minor and no serious adverse effects.Conclusions: Quetiapine augmentation may be a useful intervention for MDD with comorbid anxiety.Trial Registration: ClinicalTrials.gov Identifier: NCT00688818.

Impaired central set point of thyroid homeostasis during quetiapine treatment in the acute phase of schizophrenia.

AIM: To evaluate the impact of quetiapine treatment on central set point of thyroid homeostasis in patients with acute phase schizophrenia. METHODS: During Jan. 2016 to Dec. 2018, we conducted a retrospective cohort study in "the Second Affiliated Hospital of Xinxiang Medical University". All patients admitted for treatment of schizophrenia being euthyroid at admission and reevaluated for thyroid function during hospitalization were recruited and followed until discharge. Patients treated with mood stabilizers during hospitalization were excluded. Quetiapine use was the exposure measure. The primary outcomes were the parameters of central set point of thyroid homeostasis measured by "thyroid-stimulating hormone (TSH) index" and "thyroid feedback quantile-based index (TFQI)". Multiple regression models were used to estimate the association between quetiapine exposure and outcomes. RESULTS: A total of 1302 patients were enrolled in this study. Quetiapine exposure was associated with a more significant decline in the TSH index and TFQI, and the adjusted ß and 95% confidence interval (CI) were -0.12 (-0.22, -0.01) and -0.10 (-0.15, -0.05), respectively. A dose-response association between quetiapine exposure and decline in TSH index and TFQI was observed (P < 0.05). Sensitivity analyses restricting to patients under mono-atypical antipsychotic therapy, or selecting patients in the non-quetiapine group matched to quetiapine group yielded similar results. CONCLUSION: Quetiapine was associated with TSH index and TFQI reduction in a dose-response pattern, suggesting that impaired central set point may be involved in the mechanism by which quetiapine affects hypothalamus-pituitary-thyroid axis in acute phase schizophrenia patients.

Levetiracetam adjunct to quetiapine for the acute manic phase of bipolar disorder: a randomized, double-blind and placebo-controlled clinical trial of efficacy, safety and tolerability.

Unsatisfactory responses to bipolar disorder treatments have necessitated novel therapeutic approaches. Evidence of levetiracetam's effectiveness in mania was reported in previous studies. This study evaluated its efficacy, safety and tolerability as an adjunct to quetiapine in mania. Forty-four patients with Young Mania Rating Scale (YMRS) score ≥20 entered and were randomized to receive levetiracetam plus quetiapine or placebo plus quetiapine for 6 weeks. Patients were assessed using the YMRS and Beck Scale for Suicidal Ideations (BSSI) at baseline and weeks 2, 4 and 6. Changes in the scores, remission rates and response to treatment were compared between the groups. Forty patients completed the trial. The general linear model (GLM) repeated measures demonstrated a significant effect for time × treatment interaction on the YMRS score during the trial (P = 0.04). A greater reduction in YMRS scores was seen in the levetiracetam group compared with the placebo group from baseline to week 4 (P = 0.045). Response to treatment was significantly better in the levetiracetam group (P = 0.046). No significant effect for time × treatment interaction on BSSI score was seen in GLM repeated measures. Finally, there was no significant difference in the frequency of adverse events. Adjunctive levetiracetam is effective, safe and well-tolerated in patients with mania. Further high-quality, large-scale trials are recommended.

Associations between off-label low-dose olanzapine or quetiapine and cardiometabolic mortality.

Olanzapine and quetiapine are routinely used off-label at lower doses, though it remains unclear whether treatment is associated with mortality. Here, we examined the associations between low-dose olanzapine/quetiapine, defined as 5 mg/day of olanzapine equivalents (OE) with cardiometabolic mortality in a population-based, longitudinal cohort of individuals who sought specialized psychiatric services. Through cross-linked Swedish registries, 428,525 individuals without psychotic, bipolar, or cardiometabolic disorders, or previous treatment with antipsychotics or cardiometabolic-related drugs were followed for up to 10.5 years. Extended stratified Cox proportional hazards regressions were employed to estimate the hazard ratios (HR) of cardiometabolic mortality as a function of cumulative OE exposures, adjusted for age, sex, inpatient care, and time-dependent psychiatric diagnoses and treatments. Individuals were followed for a total of 2.1 million person-years. Treatment with olanzapine/quetiapine occurred in 18,317 of the cohort. In total, 2606 cardiometabolic-related deaths occurred. Treatment status (treated vs. untreated) was not significantly associated with cardiometabolic mortality (adjusted HR 0.86, 95% CI 0.64-1.15, P = 0.307). However, compared to no treatment, treatment for <6 months was significantly associated with a reduced risk (adjusted HR 0.56, 95% CI 0.37-0.87, P = 0.010) whereas treatment for 6-12 months was significantly associated with an increased risk (adjusted HR 1.89, 95% CI 1.22-2.92, P = 0.004), but not significantly beyond 12 months. Among those treated, each year exposed to an average 5 mg/day was significantly associated with increased cardiometabolic mortality (adjusted HR 1.45, 95% CI 1.06-1.99, P = 0.019). Overall, low-dose olanzapine/quetiapine treatment was weakly associated with cardiometabolic mortality. Clinicians should consider potential cardiometabolic sequelae at lower doses.

Quetiapine for Bipolar Depressive Episode in Obsessive-Compulsive Disorder Patients Maintained on Selective Serotonin Reuptake Inhibitor Treatment.

OBJECTIVES: A meaningful proportion of patients with obsessive-compulsive disorder (OCD) develop symptoms of bipolar depression (BP-D). In the present investigation, we aimed to determine whether quetiapine is efficacious in OCD patients who despite continuous treatment with a selective serotonin reuptake inhibitor developed an acute episode of BP-D. METHODS: We analyzed 68 charts of Diagnostic and Statistical Manual of Mental Disorders Fifth Edition OCD patients from our outpatient clinic and identified 15 patients who in addition met Diagnostic and Statistical Manual of Mental Disorders Fifth Edition criteria for bipolar II disorder, depressive episode. Eleven (7 men and 4 women, aged 24-54 years) patients for whom quetiapine was added to treat the index episode of BP-D were included. Treatment response was assessed retrospectively and defined as a score of "much improved" or "very much improved" on the Clinical Global Impression-Improvement scale. RESULTS: Quetiapine was added for treatment of BP-D in a dose range of 150 to 400 mg (mean, 273 mg). Eight (73%) of the 11 study patients fulfilled the criterion of response, that is a score of "much improve" (4 patients) and "very much improved" (4 patients) on the Clinical Global Impression-Improvement scale. Notably, quetiapine was associated with additional improvement of OCD symptoms in 6 of 8 study responders. Quetiapine was well tolerated. The most frequently detected side effects were drowsiness (5 patients), constipation (4 patients), and orthostatic hypotension (2 patients). CONCLUSIONS: The revealed beneficial effect of quetiapine addition for acute episode of BP-D in OCD patients maintained on selective serotonin reuptake inhibitor treatment merits further controlled investigation.

Neuroleptic malignant syndrome in a patient treated with clotiapine.

BACKGROUND: Neuroleptic malignant syndrome (NMS), which is linked to the use of antipsychotic medication, is a potentially lethal neurological emergency. The interest of our study is that NMS induced by the use of clotiapine has never previously been described. SUBJECTS AND METHODS: We present the case of a 61-year old man whose sleep disorders were treated with clotiapine 40 mg/day. After 7 days of taking 40 mg clotiapine, the patient presented with a deterioration of his general health which had gradually taken hold, with altered consciousness accompanied by generalised muscle rigidity and hypersalivation. Laboratory blood tests revealed elevated levels of Creatine Phosphokinase (CPK) at 812 U/l. The patient was diagnosed with NMS and treated accordingly. RESULTS: The mechanism that underlies the appearance of NMS remains largely unknown. Clotiapine is a second-generation antipsychotic, first released onto the market in the 1970s, and is available in a few countries, including Belgium. NMS is treated as a medical emergency due to the possibility of morbidity and death. The first step in the treatment of NMS consists in withholding the agent suspected of provoking the symptoms. CONCLUSIONS: NMS is difficult to diagnose due to a great variability in clinical presentations and the absence of specific tests and laboratory results. The use of clotiapine in treating sleep disorders can provoke NMS as a life-threatening side-effect. To our knowledge, this is the first time a case of clotiapine-induced NMS has been published.

Atypical antipsychotics for disruptive behaviour disorders in children and youths.

BACKGROUND: This is an update of the original Cochrane Review, last published in 2012 (Loy 2012). Children and youths with disruptive behaviour disorders may present to health services, where they may be treated with atypical antipsychotics. There is increasing usage of atypical antipsychotics in the treatment of disruptive behaviour disorders. OBJECTIVES: To evaluate the effect and safety of atypical antipsychotics, compared to placebo, for treating disruptive behaviour disorders in children and youths. The aim was to evaluate each drug separately rather than the class effect, on the grounds that each atypical antipsychotic has different pharmacologic binding profile (Stahl 2013) and that this is clinically more useful. SEARCH METHODS: In January 2017, we searched CENTRAL, MEDLINE, Embase, five other databases and two trials registers. SELECTION CRITERIA: Randomised controlled trials of atypical antipsychotics versus placebo in children and youths aged up to and including 18 years, with a diagnosis of disruptive behaviour disorders, including comorbid ADHD. The primary outcomes were aggression, conduct problems and adverse events (i.e. weight gain/changes and metabolic parameters). The secondary outcomes were general functioning, noncompliance, other adverse events, social functioning, family functioning, parent satisfaction and school functioning. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors (JL and KS) independently collected, evaluated and extracted data. We used the GRADE approach to assess the quality of the evidence. We performed meta-analyses for each of our primary outcomes, except for metabolic parameters, due to inadequate outcome data. MAIN RESULTS: We included 10 trials (spanning 2000 to 2014), involving a total of 896 children and youths aged five to 18 years. Bar two trials, all came from an outpatient setting. Eight trials assessed risperidone, one assessed quetiapine and one assessed ziprasidone. Nine trials assessed acute efficacy (over four to 10 weeks); one of which combined treatment with stimulant medication and parent training. One trial was a six-month maintenance trial assessing symptom recurrence.The quality of the evidence ranged from low to moderate. Nine studies had some degree of pharmaceutical support/funding. Primary outcomesUsing the mean difference (MD), we combined data from three studies (238 participants) in a meta-analysis of aggression, as assessed using the Aberrant Behaviour Checklist (ABC) ‒ Irritability subscale. We found that youths treated with risperidone show reduced aggression compared to youths treated with placebo (MD -6.49, 95% confidence interval (CI) -8.79 to -4.19; low-quality evidence). Using the standardised mean difference (SMD), we pooled data from two risperidone trials (190 participants), which used different scales: the Overt Aggression Scale ‒ Modified (OAS-M) Scale and the Antisocial Behaviour Scale (ABS); as the ABS had two subscales that could not be combined (reactive and proactive aggression), we performed two separate analyses. When we combined the ABS Reactive subscale and the OAS-M, the SMD was -1.30 in favour of risperidone (95% CI -2.21 to -0.40, moderate-quality evidence). When we combined the ABS Proactive subscale and OAS-M, the SMD was -1.12 (95% CI -2.30 to 0.06, moderate-quality evidence), suggesting uncertainty about the estimate of effect, as the confidence intervals overlapped the null value. In summary, there was some evidence that aggression could be reduced by risperidone. Data were lacking on other atypical antipsychotics, like quetiapine and ziprasidone, with regard to their effects on aggression.We pooled data from two risperidone trials (225 participants) in a meta-analysis of conduct problems, as assessed using the Nisonger Child Behaviour Rating Form ‒ Conduct Problem subscale (NCBRF-CP). This yielded a final mean score that was 8.61 points lower in the risperidone group compared to the placebo group (95% CI -11.49 to -5.74; moderate-quality evidence).We investigated the effect on weight by performing two meta-analyses. We wanted to distinguish between the effects of antipsychotic medication only and the combined effect with stimulants, since the latter can have a counteracting effect on weight gain due to appetite suppression. Pooling two trials with risperidone only (138 participants), we found that participants on risperidone gained 2.37 kilograms (kg) more (95% CI 0.26 to 4.49; moderate-quality evidence) than those on placebo. When we added a trial where all participants received a combination of risperidone and stimulants, we found that those on the combined treatment gained 2.14 kg more (95% CI 1.04 to 3.23; 3 studies; 305 participants; low-quality evidence) than those on placebo. Secondary outcomesOut of the 10 included trials, three examined general functioning, social functioning and parent satisfaction. No trials examined family or school functioning. Data on non-compliance/attrition rate and other adverse events were available from all 10 trials. AUTHORS' CONCLUSIONS: There is some evidence that in the short term risperidone may reduce aggression and conduct problems in children and youths with disruptive behaviour disorders There is also evidence that this intervention is associated with significant weight gain.For aggression, the difference in scores of 6.49 points on the ABC ‒ Irritability subscale (range 0 to 45) may be clinically significant. It is challenging to interpret the clinical significance of the differential findings on two different ABS subscales as it may be difficult to distinguish between reactive and proactive aggression in clinical practice. For conduct problems, the difference in scores of 8.61 points on the NCBRF-CP (range 0 to 48) is likely to be clinically significant. Weight gain remains a concern.Caution is required in interpreting the results due to the limitations of current evidence and the small number of high-quality trials. There is a lack of evidence to support the use of quetiapine, ziprasidone or any other atypical antipsychotic for disruptive behaviour disorders in children and youths and no evidence for children under five years of age. It is uncertain to what degree the efficacy found in clinical trials will translate into real-life clinical practice. Given the effectiveness of parent-training interventions in the management of these disorders, and the somewhat equivocal evidence on the efficacy of medication, it is important not to use medication alone. This is consistent with current clinical guidelines.

Chlorpromazine versus clotiapine for schizophrenia.

BACKGROUND: Schizophrenia is a chronic, disabling and severe mental disorder, characterised by disturbance in perception, thought, language, affect and motor behaviour. Chlorpromazine and clotiapine are among antipsychotic drugs used for the treatment of people with schizophrenia. OBJECTIVES: To determine the clinical effects, safety and cost-effectiveness of chlorpromazine compared with clotiapine for adults with schizophrenia. SEARCH METHODS: We searched Cochrane Schizophrenia's Trials Register (last update search 16/01/2016), which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO and clinical trials registries. There are no language, date, document type, or publication status limitations for inclusion of records in the Register. SELECTION CRITERIA: All randomised clinical trials focusing on chlorpromazine versus clotiapine for schizophrenia. We included trials meeting our selection criteria and reporting useable data. DATA COLLECTION AND ANALYSIS: We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. MAIN RESULTS: We have included four studies, published between 1974 and 2003, randomising 276 people with schizophrenia to receive either chlorpromazine or clotiapine. The studies were poor at concealing allocation of treatment and blinding of outcome assessment. Our main outcomes of interest were clinically important change in global and mental state, specific change in negative symptoms, incidence of movement disorder (dyskinesia), leaving the study early for any reason, and costs. All reported data were short-term (under six months' follow-up).The trials did not report data for the important outcomes of clinically important change in global or mental state, or cost of care. Improvement in mental state was reported using the Positive and Negative Syndrome Scale (PANSS). When chlorpromazine was compared with clotiapine the average improvement scores for mental state using the PANSS total was higher in the clotiapine group (1 RCT, N = 31, MD 11.50 95% CI 9.42 to 13.58, very low-quality evidence). The average change scores on the PANSS negative sub-scale were similar between treatment groups (1 RCT, N = 21, MD -0.97 95% CI -2.76 to 0.82, very low-quality evidence). There was no clear difference in incidence of dyskinesia (1 RCT, N = 68, RR 3.00 95% CI 0.13 to 71.15, very low-quality evidence). Similar numbers of participants left the study early from each treatment group (3 RCTs, N = 158, RR 0.68 95% CI 0.24 to 1.88, very low-quality evidence). AUTHORS' CONCLUSIONS: Clinically important changes in global and mental state were not reported. Only one trial reported the average change in overall mental state; results favour clotiapine but these limited data are very difficult to trust due to methodological limitations of the study. The comparative effectiveness of chlorpromazine compared to clotiapine on change in global state remains unanswered. Results in this review suggest chlorpromazine and clotiapine cause similar adverse effects, although again, the quality of evidence for this is poor, making firm conclusions difficult.

Chlorpromazine versus metiapine for schizophrenia.

BACKGROUND: Chlorpromazine, a widely available and inexpensive antipsychotic drug, is considered the benchmark treatment for schizophrenia worldwide. Metiapine, a dibenzothiazepine derivative, has been reported to have potent antipsychotic characteristics. However, no evidence currently exists on the effectiveness of chlorpromazine in treatment of people with schizophrenia compared to metiapine, a newer antipsychotic. OBJECTIVES: To compare the effect of chlorpromazine versus metiapine for the treatment of people with schizophrenia SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials in November 2015 and 2016. SELECTION CRITERIA: All randomised controlled trials (RCTs) focusing on chlorpromazine versus metiapine for adults with schizophrenia. We included trials meeting our selection criteria and reporting useable data. DATA COLLECTION AND ANALYSIS: We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. MAIN RESULTS: We included three studies randomising 161 people with schizophrenia. Data were available for only two of our seven prestated main outcomes. Clinically important improvement in global state was measured using the Clinical Global Impression (CGI). There was no clear difference between chlorpromazine and metiapine groups (2 RCTs, n = 120, RR 1.11, 95% CI 0.84 to 1.47, very low quality evidence) and numbers of participants with parkinsonism at eight weeks were similar (2 RCTs, n = 70, RR 0.97, 95% CI 0.46 to 2.03, very low quality evidence). There were no useable data available for the other key outcomes of clinically important improvement in mental state, readmission due to relapse, satisfaction with treatment, aggressive or violent behaviour, or cost of care. AUTHORS' CONCLUSIONS: Chlorpromazine has been the mainstay treatment for schizophrenia for decades, yet available evidence comparing this drug to metiapine fails to provide high-quality trial based data. However, the need to determine whether metiapine is more or less effective than chlorpromazine seems to be lacking in clinical relevance and future research on this comparison seems unlikely.

A Very Unusual Accidental Mechanical Asphyxia of Choking with a Whole Solea Solea.

The case here reported involves a schizophrenic 19-year-old girl under treatment with clotiapine, which was well tolerated except for a moderate dry mouth. The woman ingested a whole sole (Solea solea), which caused a very rapid death by choking. A complete autopsy was performed 24 h later, as well as histological and toxicological analysis. At autopsy, the sole was wedged in the esophagus causing a choking ab extrinseco. The fish had a length of 18 cm and a maximum width of 6 cm, weighing 188.7 g. Toxicological analysis detected 0.57 mg/L of clotiapine in blood, which falls within the therapeutic range. The peculiarity of this case is represented by two factors: one is the choking by fish and the second was the adverse affect caused by clotiapine, which induced a condition of dry mouth making the act of swallowing even more difficult, thereby contributing to a very rapid mechanical asphyxia and the death of the young woman.

[Eating disorders in psychiatric patients during treatment with second generation antipsychotics].

AIM: To identify the frequency and characteristics of eating disorders in patients with schizophrenia treated with second generation antipsychotics. MATERIAL AND METHODS: A sample included 56 patients (48 women and 8 men, mean age 28 ± 4.5 years) with schizophrenia and schizoaffective disorder. Patients received risperidone, quetiapine and olanzapine. The study employed clinical-anamnestic, endocrinological methods and assessment of eating behavior with DEBQ (The Dutch Eating Behavior Questionnaire). All of the patients had extra Body mass or obesity: extra Body mass of the 1st grade was found in 18 patients (BMI<30 kg/m²) and obesity grade 2-3 in 38 patients (BMI>30 kg/m²). RESULTS AND CONCLUSION: Authors identified different types of eating disorders: external, restrictive and emotiogenic as well as the relationship of their prevalence and severity with sex, drug, presence and grade of obesity. Based on these RESULTS: we developed recommendations for management of patients treated with second generation antipsychotics.

Randomized Trial of the Effect of Four Second-Generation Antipsychotics and One First-Generation Antipsychotic on Cigarette Smoking, Alcohol, and Drug Use in Chronic Schizophrenia.

No large-scale randomized trial has compared the effect of different second-generation antipsychotic drugs and any first-generation drug on alcohol, drug and nicotine use in patients with schizophrenia. The Clinical Antipsychotic Trial of Intervention Effectiveness study randomly assigned 1432 patients formally diagnosed with schizophrenia to four second-generation antipsychotic drugs (olanzapine, risperidone quetiapine, and ziprasidone) and one first-generation antipsychotic (perphenazine) and followed them for up to 18 months. Secondary outcome data documented cigarettes smoked in the past week and alcohol and drug use severity ratings. At baseline, 61% of patients smoked, 35% used alcohol, and 23% used illicit drugs. Although there were significant effects of time showing reduction in substance use over the 18 months (all p < 0.0001), this study found no evidence that any antipsychotic was robustly superior to any other in a secondary analysis of data on substance use outcomes from a large 18-month randomized schizophrenia trial.

[Lipid spectrum changes and ECG in patients with paranoid schizophrenia in the course of therapy with atypical antipsychotics].

OBJECTIVE: To study correlations between parameters of lipid metabolism and ECG in patients with schizophrenia in light of therapy with atypical antipsychotics. MATERIAL AND METHODS: We examined 42 patients with paranoid schizophrenia. All patients received atypical neuroleptics - seroquel, zyprexa, and rispolept. A group of controls included 25 healthy people. RESULTS: There was a significant increase (p=0.0002) in body mass (in average by 1.5 kg) in 88% patients. A significant increase in the concentration of serum triglycerides was identified as well. The concentration of VLDL in the patients with schizophrenia was 2 times higher compared to controls. After treatment, VLDL concentration increased even more considerably An increase in atherogenic index (AI) was up to 3.1 in patients with schizophrenia compared to 2.2 in controls. After treatment, Al increased up to 4 that demonstrated the high risk of development of atherosclerosis. A significant increase in QT interval in the ECG and heart rate (p=0.03) was revealed only in patients receiving rispolept. In patients receiving zyprexa and seroquel only heart rate was increased. CONCLUSION: The antipsychotics studied increase the risk of development of cardiovascular pathology.

Quetiapine-associated leucopenia and thrombocytopenia: a case report.

BACKGROUND: There have been few reports regarding quetiapine-associated hematological effects other than white-blood-cell alteration. We present the first reported Han-Chinese case that developed leucopenia and thrombocytopenia after taking quetiapine. CASE PRESENTATION: We present a case of a person with a bipolar I disorder who experienced leucopenia and thrombocytopenia after taking 400 mg/day of quetiapine and 1000 mg/day of valproic acid for three and one-half months. The hematological toxicity abated upon the discontinuation of both drugs. However, due to the intolerable side effects of the replaced antipsychotic (haloperidol), and according to the patient's preference, we prescribed quetiapine and valproic acid again. There was a recurrence of leucopenia and a decreased platelet count by the sixth day. The adverse effects disappeared soon after we discontinued quetiapine, while keeping valproic acid treatment. CONCLUSION: Quetiapine-associated leucopenia and thrombocytopenia seems reversible but possibly fatal. Therefore, clinical practitioners should be aware of this adverse reaction.

Antipsychotic use in pregnancy.

INTRODUCTION: Antipsychotic medications are being prescribed for a growing number of women with mental illnesses. However, evidence regarding their safety in pregnancy is still insufficient to provide adequate support for clinical practice, creating increasing concern among pregnant women and clinicians. AREAS COVERED: The aim of this article is to review published data regarding the safety of antipsychotic medications in pregnancy with a focus on the most commonly used atypical antipsychotics. EXPERT OPINION: Given the potential harm of not treating severe psychiatric illnesses during pregnancy, careful administration of antipsychotics is recommended for pregnant women who suffer from severe mental disorders. The most frequently used antipsychotics in pregnancy are olanzapine, risperidone and quetiapine, and do not appear to cause consistent, congenital harm to the fetus. No specific patterns of fetal limb or organ malformation related to these drugs have been reported. There is some evidence suggesting an association between antipsychotic use in pregnancy and the development of gestational diabetes. Also there appears to be an association between antipsychotic medication use in pregnancy and increased neonatal respiratory distress and withdrawal symptoms. Further studies are needed for clinicians to balance good maternal mental health, healthy pregnancies and good infant health outcomes.