Antipsychotic Group Research Articles

Clozapine as a first‐ or second‐line treatment in schizophrenia: a systematic review and meta‐analysis

ObjectiveNo consensus exists on whether clozapine should be prescribed in early stages of psychosis. This systematic review and meta‐analysis therefore focus on the use of clozapine as first‐line or second‐line treatment in non‐treatment‐resistant patients.MethodsArticles were eligible if they investigated clozapine compared to another antipsychotic as a first‐ or second‐line treatment in non‐treatment‐resistant schizophrenia spectrum disorders (SCZ) patients and provided data on treatment response. We performed random‐effects meta‐analyses.ResultsFifteen articles were eligible for the systematic review (N = 314 subjects on clozapine and N = 800 on other antipsychotics). Our meta‐analysis comparing clozapine to a miscellaneous group of antipsychotics revealed a significant benefit of clozapine (Hedges’ g = 0.220, P = 0.026, 95% CI = 0.026–0.414), with no evidence of heterogeneity. In addition, a sensitivity analysis revealed a significant benefit of clozapine over risperidone (Hedges’ g = 0.274, P = 0.030, 95% CI = 0.027–0.521).ConclusionThe few eligible trials on this topic suggest that clozapine may be more effective than other antipsychotics when used as first‐ or second‐line treatment. Only large clinical trials may comprehensively probe disease stage‐dependent superiority of clozapine and investigate overall tolerability.

High-density lipoprotein-cholesterol and antipsychotic medication in overweight inpatients with schizophrenia: post-hoc analysis of a Japanese nationwide survey

BackgroundPatients with schizophrenia have an increased prevalence of metabolic disturbances compared with the general population. However, the mechanisms underlying the metabolic side effects of antipsychotics are unknown. The aim of the present study was to compare the levels of high-density lipoprotein (HDL)-cholesterol in Japanese schizophrenia patients medicated with olanzapine, risperidone, or aripiprazole monotherapy.MethodsThis study was a post-hoc analysis of a nationwide survey, which included 433 Japanese outpatients with schizophrenia and 674 inpatients. A brief questionnaire was compiled that covered demographic data, systolic blood pressure, diastolic blood pressure, and HDL-cholesterol after reviewing the relevant literature and guidelines. To compare demographic and clinical characteristics, analysis of variance was performed for continuous variables and the chi-square test was performed for categorical variables. For comparisons of HDL-cholesterol levels among the three antipsychotic groups, analysis of covariance was carried out with age, diastolic blood pressure, chlorpromazine-equivalent dosage, and waist circumference as confounding variables after stratification by body mass index (BMI) for each outpatient group and inpatient group.ResultsThe mean age was 57.9 ± 14.0 years and the mean BMI was 23.4 ± 4.5 kg/m2. HDL-cholesterol levels when stratified by BMI differed significantly (p = 0.019) between the three antipsychotic groups after age, diastolic blood pressure, chlorpromazine-equivalent dosage, and waist circumference in inpatients. A significant difference in HDL-cholesterol levels was only found in the overweight inpatient group, and no significant differences in HDL-cholesterol levels were found among the three antipsychotics for outpatients of all BMI stratifications or inpatients that were underweight or of normal weight. For post-hoc analysis of HDL-cholesterol levels in overweight inpatients, HDL-cholesterol was significantly lower in the olanzapine group than in the aripiprazole group (p = 0.023).ConclusionsThis study reveals a difference in HDL-cholesterol levels in overweight Japanese inpatients with schizophrenia resulting from the use of different antipsychotics. In the post-hoc analysis of HDL-cholesterol levels in overweight inpatients, HDL-cholesterol was significantly lower in the olanzapine group than in the aripiprazole group. Further studies incorporating more detailed evaluations, including diet and physical activity, are needed to clarify the differences in HDL-cholesterol according to antipsychotic use.

Effect of postoperative systemic antipsychotic therapy on psychiatric recurrence in patients with meningiomas

A number of patients with meningiomas and psychiatric disorders will suffer psychiatric symptom recurrence following tumorectomies. The present study reported a retrospective analysis regarding 42 cases of patients with meningiomas using complete clinical follow-up data from June 2005 to June 2013. The patients were divided into the systemic antipsychotic (SP) group (n=20) following 6months of postoperative SP therapy and the none-SP (NSP) group (n=22), who did not receive postoperative antipsychotic treatment. Patients were assessed using the Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) at the time points of prior to surgery, immediately following surgery, and 6 months, 12 months and 3 years following surgery. The effective rate, recurrence rate, rehospitalization rate and survival analysis were calculated. The BPRS score and PANSS scores (including PANSS positive, PANSS negative, PANSS general psychopathology and PANSS overall) in the SP group at 6 months, 12 months and 3 years following surgery were significantly decreased compared with the NSP group (P<0.05). The effective rate was 95, 90 and 90% at 6 months, 12 months and 3 years, respectively, in the SP group, whilst it was 68.2, 63.6 and 59%, respectively, in the NSP group, which was statistically significant (χ2=4.89, χ2=4.01 and χ2=5.12; P<0.05). The recurrence rate of the SP group was 0, 5 and 10% at 6 months, 12 months and 3 years, respectively, whilst in the NSP group it was 22.7, 31.8 and 54.5%, respectively, which was statistically significant (χ2=5.16, χ2=4.89 and χ2=9.34; P<0.05). The rehospitalization rate of the SP group was 0, 0 and 5% at 6 months, 12 months and 3 years, respectively, whilst in the NSP group it was 13.6, 22.7 and 36.4%, respectively, and the data at 12 months and 3 years was statistically significant (χ2=5.16 and χ2=6.12; P<0.05). Kaplan-Meier survival analysis indicated that the accumulative survival rates of recurrence and rehospitalization in the SP group were improved compared with the NSP group. The log-rank of recurrence was χ2=9.369 (P=0.002) and the log-rank of rehospitalization was χ2=6.330 (P=0.012). In conclusion, postoperative SP therapy is of great importance to the consolidation of mental symptoms in patients with meningiomas and psychiatric symptoms, and it may significantly reduce the recurrence and rehospitalization rates.

Long Term Efficacy of the Treatment with Olanzapine Pamoate, Risperidone and Aripiprazole Monohydrate

The use of long-acting injectable antipsychotics (LAIs) is considered to be an important treatment option, especially in early stages of schizophrenia. The aim of this study was to evaluate the efficacy, safety and sustained remission in schizophrenia patients treated with three of the available LAIs substances: olanzapine pamoate, risperidone microspheres and aripiprazole monohydrate. A retrospective chart review study evaluating the efficacy of LAIs compared to oral antispychotics during a five years period was performed. Of the 102 patients included in the study, 52 (50.9%) continued LAIs: olanzapine pamoate (n = 20, 38.4%), risperidone microsphere (n = 22, 42.3%), aripiprazole monohydrate (n = 10, 19.3%). In the LAIs group the number of relapses was smaller than in the oral antipsychotics group (12 vs. 23, P [ 0.05) as well as the number of admissions (15 vs. 30, P [ 0.05). In conclusion, relapse in schizophrenia is strongly related to nonadherence. LAIs prescription overall was underutilized despite their efficacy. Future randomized studies are needed to evaluate the long term efficacy of LAIs compared to oral treatment.

Antipsychotic drugs versus cognitive behavioural therapy versus a combination of both in people with psychosis: a randomised controlled pilot and feasibility study.

SummaryBackgroundLittle evidence is available for head-to-head comparisons of psychosocial interventions and pharmacological interventions in psychosis. We aimed to establish whether a randomised controlled trial of cognitive behavioural therapy (CBT) versus antipsychotic drugs versus a combination of both would be feasible in people with psychosis.MethodsWe did a single-site, single-blind pilot randomised controlled trial in people with psychosis who used services in National Health Service trusts across Greater Manchester, UK. Eligible participants were aged 16 years or older; met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service; were in contact with mental health services, under the care of a consultant psychiatrist; scored at least 4 on delusions or hallucinations items, or at least 5 on suspiciousness, persecution, or grandiosity items on the Positive and Negative Syndrome Scale (PANSS); had capacity to consent; and were help-seeking. Participants were assigned (1:1:1) to antipsychotics, CBT, or antipsychotics plus CBT. Randomisation was done via a secure web-based randomisation system (Sealed Envelope), with randomised permuted blocks of 4 and 6, stratified by gender and first episode status. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions. Choice and dose of antipsychotic were at the discretion of the treating consultant. Participants were followed up for 1 year. The primary outcome was feasibility (ie, data about recruitment, retention, and acceptability), and the primary efficacy outcome was the PANSS total score (assessed at baseline, 6, 12, 24, and 52 weeks). Non-neurological side-effects were assessed systemically with the Antipsychotic Non-neurological Side Effects Rating Scale. Primary analyses were done by intention to treat; safety analyses were done on an as-treated basis. The study was prospectively registered with ISRCTN, number ISRCTN06022197.FindingsOf 138 patients referred to the study, 75 were recruited and randomly assigned—26 to CBT, 24 to antipsychotics, and 25 to antipsychotics plus CBT. Attrition was low, and retention high, with only four withdrawals across all groups. 40 (78%) of 51 participants allocated to CBT attended six or more sessions. Of the 49 participants randomised to antipsychotics, 11 (22%) were not prescribed a regular antipsychotic. Median duration of total antipsychotic treatment was 44·5 weeks (IQR 26–51). PANSS total score was significantly reduced in the combined intervention group compared with the CBT group (–5·65 [95% CI −10·37 to −0·93]; p=0·019). PANSS total scores did not differ significantly between the combined group and the antipsychotics group (–4·52 [95% CI −9·30 to 0·26]; p=0·064) or between the antipsychotics and CBT groups (–1·13 [95% CI −5·81 to 3·55]; p=0·637). Significantly fewer side-effects, as measured with the Antipsychotic Non-neurological Side Effects Rating Scale, were noted in the CBT group than in the antipsychotics (3·22 [95% CI 0·58 to 5·87]; p=0·017) or antipsychotics plus CBT (3·99 [95% CI 1·36 to 6·64]; p=0·003) groups. Only one serious adverse event was thought to be related to the trial (an overdose of three paracetamol tablets in the CBT group).InterpretationA head-to-head clinical trial of CBT versus antipsychotics versus the combination of the two is feasible and safe in people with first-episode psychosis.FundingNational Institute for Health Research.

The prevalence of metabolic syndrome in patients receiving antipsychotics in Qatar: a cross sectional comparative study

BackgroundMetabolic abnormalities are common in patients maintained on antipsychotics. These abnormalities increase the risk of cardiovascular diseases and mortality in this population. The aim of this study is to assess the prevalence of metabolic syndrome (MetS) in subjects maintained on antipsychotics relative to controls in Qatar, and to assess the factors contributing to the development of MetS.MethodsA cross sectional design was used to collect data and fasting blood samples from subjects maintained on antipsychotics for at least six months (n = 112) and from a control group (n = 114). The groups were compared in regard to prevalence of MetS, and multiple regression analysis was used to determine the risk factors in each group.ResultsThe two groups (antipsychotics vs. control) were similar in regard to age (35.73 ± 10.28 vs. 35.73 ± 8.16 years) and gender ratio. The MetS was higher among the subjects on antipsychotics, but this difference did not reach statistical significance. Blood pressure (BP) was significantly higher in the antipsychotics group and BMI was the major risk factor to develop MetS in this group.ConclusionsThe prevalence of MetS in both groups is high and mostly attributed to obesity and high BP. Public health interventions are needed to address this major health problem overall. Larger studies are needed to further assess the impact of antipsychotics and mental illness on the development of MetS.

The utility of novel outcome measures in a naturalistic evaluation of schizophrenia treatment.

BackgroundA number of naturalistic studies have investigated paliperidone palmitate (PP) using proxy measures of effectiveness. An unexplored option is to examine the utility of the mental health clustering tool (MHCT), which is used in UK clinical practice to measure patient well-being and is linked to allocation of resources. This study evaluated the effectiveness of PP using the MHCT, the Health of the Nation Outcome Scales (HoNOS), and, for comparison, more conventional outcome measures.MethodsThis was a naturalistic, 1-year evaluation of PP (n=50) in schizophrenia as well as a comparator antipsychotic drugs group. Changes in the MHCT cluster-score cost ranking and four HoNOS-derived factors were analyzed using a mixed-model statistical analysis to explore the utility of these measures.ResultsAt 1 year, 30 patients (60%) continued PP treatment. The mean “cluster-score cost ranking” (−1.5) and Severe Disturbance factor scores (−1.1) were significantly lower (p-value [adjusted] =0.0003, p-value [adjusted] =0.002, respectively) after 1 year of antipsychotic treatment but no differences were found between PP and the comparator antipsychotic drugs group. Patients prescribed PP were 1.8 times (95% CI 1.1−3.1) more likely to be discharged from hospital than those in the comparator antipsychotic drugs group.ConclusionPP’s continuation rate after 1 year made the study similar to the existing evaluations, and it was possible to prospectively evaluate antipsychotic effectiveness using the novel measures although these did not discriminate between PP and the comparator group. The investigation illustrates that in principle these novel measures are meaningful in naturalistic study designs.

Assessment of inpatient psychiatric readmission risk among patients discharged on an antipsychotic polypharmacy regimen: A retrospective cohort study.

Patients are frequently prescribed multiple antipsychotic medications, leading to higher healthcare costs and increased risk for side effects. The efficacy of multiple versus single antipsychotics to prevent acute relapse, measured by incidence of inpatient readmission, is investigated in Arizona, USA. A retrospective chart review compared socio-demographic and clinical data from 1,010 patients discharged on a single and 377 discharged on multiple antipsychotic medications. Case management records were reviewed for readmission within one year of discharge. Younger age, diagnosis of Schizophrenia or Schizoaffective Disorder, prescription of mood stabilizer, shorter length of stay, and discharge to residential treatment or crisis recovery unit were associated with multiple antipsychotics at discharge. Readmission rates of the single (13.7%) versus multiple (15.9%) antipsychotic groups were not statistically different (p=0.286). Logistic regression analysis established that only age (younger) and the prescription of a mood stabilizer at discharge were significant predictors for increased risk for readmission (p=0.010 and p=0.049, respectively). A Cox survival analysis supported these findings. Concomitant antipsychotic polypharmacy at discharge did not reduce readmission risk over a one-year period. Given the increased risk of side effects and financial costs of polypharmacy, this study did not provide evidence to support this practice. Strikingly, only two variables predicted readmission risk, younger age and prescription of mood stabilizer. Although practitioners should follow practice guidelines more closely to prevent unnecessary exposure to potentially lethal side effects of antipsychotic polypharmacy, further studies are needed to better identify patients at high risk for readmission.

Association of antipsychotic and antidepressant treatment with metabolic syndrome and 10 years' coronary heart disease risk

Background: Cardiovascular risk is becoming a growing concern in patients receiving psychotropic medications. An increased Framingham risk score (FRS) and 10-year coronary artery disease risk has been reported in patients suffering from mental diseases. Aim: This study aims to evaluate the cardiometabolic risk profile in patients suffering from psychiatric disorders being treated with antipsychotics and antidepressants. Materials and Methods: This cross-sectional study was conducted on 68 patients diagnosed with psychiatric disorders according to International Statistical Classification of Diseases-10 at a tertiary health-care center. Patient's demographic details, family history, level of education, duration of disease, use of alcohol and or nicotine, use of concomitant medications, psychotropic drug history, history of treatment of diabetes, dyslipidemia, hypertension, or any other medical conditions were also recorded. Waist circumference, blood pressure, fasting blood sugar, triglyceride, and high-density lipoprotein values were estimated by taking fasting venous samples under aseptic measures. Metabolic syndrome was diagnosed using the International Diabetes Federation Criteria. Ten-year cardiovascular risk was assessed using the FRS. Statistical evaluation was done using appropriate parametric and nonparametric statistical methods. Results: A total of 49 patients were being treated with antipsychotic drugs and 19 were receiving antidepressants. The mean age of patient receiving antipsychotics were 37.51, and those receiving antidepressant were 34.15. The metabolic syndrome was 36.76% in patients taking antipsychotics as compared to 11.76% in patients on antidepressant. The mean FRS score in antipsychotic group was 7.48, and those receiving antidepressants were 4.7. The 10-year coronary heart disease (CHD) risk score was significantly higher in patients receiving antipsychotics as compared to patients on antidepressants. Conclusion: Treatment with antipsychotics is associated with significantly higher 10-year CHD risk scores as compared to treatment with antidepressants.

DNA methylation of membrane-bound catechol-O-methyltransferase in Malaysian schizophrenia patients.

This study examined catechol-O-methyltransferase (COMT) DNA methylation in the peripheral blood of schizophrenia patients and also in healthy controls to investigate its potential use as a peripheral biomarker of schizophrenia and its relations with the clinical variables of schizophrenia patients. We examined the DNA methylation levels of COMT using genomic DNA from the peripheral blood of schizophrenia patients (n = 138) and healthy control participants (n = 132); all were Malaysian Malays. The extracted DNA was bisulfite converted, and the percentage methylation ratio value was calculated based on the results following a MethyLight protocol analysis. The percentage methylation ratio of COMT was lower in schizophrenia than it was in the healthy controls (P < 0.001) and was different between the body mass index (P = 0.003) and antipsychotic (P = 0.004) groups. The COMT DNA methylation rate was lower in patients receiving atypical antipsychotics (P = 0.004) and risperidone (P = 0.049) as compared to typical antipsychotics. The Excitement and Depressed subdomains of the Positive and Negative Syndrome Scale were inversely related (P < 0.001) and therefore predictors (Excitement: b = -11.396, t = -4.760, P < 0.001; Depressed: b = -7.789, t = -3.487, P = 0.001) of COMT DNA methylation. Our results suggested that the methylation level was affected by the severity of the clinical symptoms of schizophrenia and might also be influenced by pharmacological treatment. The epigenetic alteration of COMT in the peripheral blood could be a potential peripheral biomarker of schizophrenia.

The efficacy, acceptability, and safety of five atypical antipsychotics in patients with first-episode drug-na\xefve schizophrenia: a randomized comparative trial

BackgroundDifferences in effectiveness and tolerability between different atypical antipsychotics may affect schizophrenic patients’ treatment adherence or prognosis. However, which kind of antipsychotic was more effective and safe in the treatment of schizophrenia is still being debated. This study attempted to understand whether there are any differences in efficacy, acceptability, and safety between the five atypical antipsychotics in patients with first-episode schizophrenia.MethodsTwo hundred cases of inpatients with first-episode drug-naïve schizophrenia were randomly assigned to 6–8 weeks of treatment with either of aripiprazole, risperidone, quetiapine, olanzapine, or ziprasidone from October 2012 to November 2014. The efficacy, acceptability, and safety measurement after 6–8 weeks of treatment of the five kinds of antipsychotics were evaluated by the deduction rate of Brief Psychiatric Rating Scale (BPRS) total score, the proportion of treatment discontinuation, and adverse events, respectively. Whether the treatment discontinuation or combination therapy for baseline antipsychotics after titration mainly depended on ineffective or less effective on an initial-assigned antipsychotic during the study period.ResultsBPRS total scores in each antipsychotic group were significantly decreased at the end of the study (P < 0.01), and only the deduction rate of BPRS total scores in the risperidone group was markedly higher than those in the groups of aripiprazole (P < 0.01) and olanzapine (P < 0.05) after controlling the impact of the differences of age of onset. There were significant differences between quetiapine (χ2 = 5.46, P = 0.019), olanzapine (χ2 = 5.6, P = 0.018), and ziprasidone regarding the proportion of maintaining on initially allocated therapy. In addition, the difference in treatment discontinuation between male and female patients was also significant (χ2 = 9.897, P = 0.002), and odds ratio of treatment discontinuation in male and female patients was 0.37 (95% CI 0.198–0.693); however, no difference in treatment discontinuation was found between five antipsychotics. Extrapyramidal symptoms in the groups of quetiapine and olanzapine were notably less than the other three kinds of antipsychotics (P < 0.05), but there were no significant differences in other adverse events between the five antipsychotic groups.ConclusionsRisperidone was more effective than aripiprazole and olanzapine in treating first-episode schizophrenia. The present study revealed the superiority of quetiapine and olanzapine over ziprasidone with remarkably less severe extrapyramidal adverse effects, especially with lower drop-out and treatment discontinuation. There were no differences in terms of other adverse events although the risk of treatment discontinuation was higher in female patients.Trial registration 2012-3-88. Registered 20 July 2012

Long-term metabolic effects of aripiprazole, ziprasidone and quetiapine: a pragmatic clinical trial in drug-naïve patients with a first-episode of non-affective psychosis.

The use of second-generation antipsychotics (SGA) has been associated with metabolic changes. However, there are differences in the metabolic profile between SGAs. We have previously observed that ziprasidone had a more benign early metabolic profile compared to aripiprazole and quetiapine. However, a long-term follow-up is preferred to detect clinically relevant impairment in metabolic parameters. We aimed to compare the effect of aripiprazole, ziprasidone, and quetiapine on metabolic measures in first-episode non-affective psychosis patients after 1year of treatment. One hundred and sixty-five drug-naïve patients, suffering from a first episode of non-affective psychosis, were randomly assigned to receive quetiapine, ziprasidone, or aripiprazole. Weight and glycemic/lipid parameters were recorded at baseline and after 1year of treatment. After 1year of antipsychotic treatment, we found significant increments in weight, BMI, total cholesterol, LDL-cholesterol, triglycerides, and the triglyceride/HDL index in the sample as a whole. These changes produced a significant rise in the percentage of patients with obesity, hypercholesterolemia, and hypertriglyceridemia. However, when comparing the differential effect of each antipsychotic medication, we found no significant differences in any of the metabolic parameters between antipsychotics groups after 1year of treatment. We concluded that the antipsychotics studied present similar metabolic profiles. However, the primary exposure to SGAs during the first year of psychosis was associated with significant increases in weight and metabolic parameters, leading to increments in obesity, hypertriglyceridemia, and hypercholesterolemia.

Cognitive Functioning in Euthymic Bipolar Patients on Monotherapy with Novel Antipsychotics or Mood Stabilizers.

Bipolar disorder is associated with cognitive dysfunction in several domains. Medication effect is a potential confounder that can only be statistically controlled in many studies. The cognitive profile in bipolar disorder during remission on maintenance antipsychotics or mood stabilizers medication has not been compared before. We compared the cognitive profile of bipolar disorder patients euthymic for 2 month or more on monotherapy with novel antipsychotics (AP) (n=16), lithium carbonate (Li) (n=25) or valproic acid (VPA; n=26). Forty-two individuals were assessed as controls. The cognitive battery included Wechsler Adult Intelligence Scale-Revised (WAIS-R) subtests, the Wechsler Memory Scale (WMS), and Wisconsin Card Sorting Test (WCST). All three patient groups compared to controls performed poorly on the working memory and verbal memory tasks (F=3.59, df=3, p=0.02 for WAIS-R Arithmetic and F=123.64, df=3, p<0.01 for WMS Logical Memory). The differences remained significant after controlling for age. Across patients, the only significant difference was between the Li and AP groups in terms of working memory. The Li group performed better (F=3.59, df=2, p=0.02) and the difference survived correction for age and clinical features. The findings of this study suggest that working memory impairment in bipolar patients on monotherapy with atypical AP, whereas verbal memory impairment might be related to bipolar disorder itself. Working memory might be a state marker, whereas verbal memory could be a trait marker of bipolar disorder. Atypical AP might have an adverse effect on cognition in bipolar disorder. These findings cannot be generalized to all bipolar patients, particularly the poor responders to monotherapy.

Improved Metabolic and Psychiatric Outcomes with Discontinuation of Atypical Antipsychotics in Youth Hospitalized in a State Psychiatric Facility.

To assess the impact of antipsychotic tapering and discontinuation on measures of metabolic functioning and psychiatric symptom severity in severely impaired youth hospitalized in a psychiatric state hospital. The study examined psychiatric and metabolic measures in 67 hospitalized children and adolescents (mean age 11.9; 56 with discontinued use of antipsychotics, 10 with continued use of antipsychotics, and 1 started on an antipsychotic) from admission to discharge. Upon admission, 56 youth were tapered off of antipsychotic medications, started on other forms of pharmacotherapy (92.9% were started on medications used to treat attention-deficit/hyperactivity disorder), and received evidence-based behavioral programming and were ultimately discharged from the hospital. The mean duration of treatment was 228 days for the discontinuation group and 204 days for the continuation group. Significant decreases in body mass index [BMI; t(53) = 7.12, p = 0.0001] and BMI percentile [t(53) = 6.73, p = 0.0001] were found from admission to discharge in the antipsychotic discontinuation group. Changes in BMI, BMI percentile, or systolic blood pressure were not found in the group (n = 10) who were maintained on antipsychotics. Both groups experienced a significant increase in their Global Assessment of Functioning score [t(52) = 19.98, p = 0.0001 for discontinued; t(8) = 5.092, p = 0.001 for maintained]. Psychiatric symptom severity scores significantly improved in many subscales relevant to disruptive behaviors and mood disorders for those who were removed from the medications. For those maintained on the antipsychotics, there were fewer changes in psychiatric symptom scores. Discontinuation of atypical antipsychotic medications in conjunction with tailoring treatment to presenting diagnoses resulted in metabolic and psychiatric symptom improvement among severely impaired state hospital inpatient youth. These results serve as a feasibility demonstration that discontinuation of antipsychotics does not provoke psychiatric destabilization, particularly among disruptive behavior disordered youth.

An Investigation of Cardiovascular Risks in a Group of Children and Adolescents Who Use Atypical Antipsychotics

ABSTRACTThis study was conducted to identify the metabolic parameters and body measurements associated with cardiovascular risks in a group of children and adolescents who as part of inpatient treatment received atypical antipsychotics at a psychiatric hospital in Turkey. Body mass indexes (BMIs), waist circumferences (WCs), diastolic blood pressures (DBPs), systolic blood pressures (SBPs) and heart rates (HRs) of the patients were evaluated during hospitalization and at discharge. A statistically significant difference was found among the mean BMIs, WCs, DBPs and HRs of the patients at the stages of their hospitalization and discharge (p < 0.05). On the basis of the study findings, it is recommended that mental health nurses evaluate these risk factors in children and adolescents and provide education on this subject to the patients and their families.

Sociodemographic and Clinical Predictors of Response in Manic Episodes: A Naturalistic, Prospective, Cohort Study.

Background:Response to treatment of a manic episode is dependent on several sociodemographic and clinical factors as reported by researchers from other countries. The prescription of mood stabilizers and/or antipsychotics for manic episode depends on these factors. There is a lack of availability of data from India on this topic. Hence, this study was planned to identify the predictors of pharmacological response.Materials and Methods:Forty-two patients with a diagnosis of bipolar affective disorder current episode manic were enrolled and assessed for sociodemographic variables and clinical variables such as age of onset, family history, comorbidities, index episode, and number of past episodes. They were divided into four groups depending on the treatment they were receiving, namely, lithium with an antipsychotic (n = 25), lithium with divalproex and an antipsychotic (n = 8), divalproex with an antipsychotic (n = 5), and the miscellaneous group (n = 4). The primary outcome measure was improvement in the Young Mania Rating Scale score and secondary outcome measure was duration of ward stay.Results:There was a significant improvement in all the treatment modalities and it was comparable. There was no significant impact of any sociodemographic or clinical variable on treatment outcome except that females had significantly better response than males. There was nearly significant shorter duration of hospitalization in the lithium and antipsychotics groups compared to divalproex group.Conclusion:All treatment modalities are equally efficacious in the management of manic episode in short term. However, lithium and antipsychotics tend to produce early response than divalproex. Other sociodemographic and clinical predictors were not significantly associated with response.

Economic evaluation of antipsychotics for the treatment of schizophrenia: a systematic review

Objective: The aim of this study is to conduct a systematic review on cost-effectiveness analysis of oral antipsychotic agents to identify the trend of cost-effectiveness of drugs available for the treatment of schizophrenia. Methods: A search was conducted in three databases (MEDLINE, LILACS and PsycINFO) for head-to-head economic comparisons of antipsychotic agents. A manual search in journals, dissertations and theses databases, congresses abstracts and the Cochrane Library was also conducted to ensure comprehensiveness. After evaluation by independent reviewers, complete economic evaluations of oral antipsychotic medications were included in the final analysis. Results: Twenty four studies were included in the final analysis. The trend observed in the pooled studies showed that risperidone, olanzapine and clozapine were the most cost-effective drugs included to treat schizophrenia. Aripiprazole and haloperidol were considered comparable to quetiapine or ziprasidone and less cost-effective than olanzapine and risperidone in the pooled analysis. After removal of comparisons that had sponsored drugs included, risperidone, olanzapine and clozapine were still considered the most cost-effective strategies to treat schizophrenia. The analysis of only cost-utility studies shows approximately the same results of the other analysis. Conclusions: An analysis that consider first- vs. second-generation antipsychotics polled together might be biased by the different profiles of the specific drugs, not considering the heterogeneity of the group of second-generation antipsychotics. There seems to be a difference in the cost-effectiveness profiles between specific antipsychotic drugs. Risperidone, olanzapine and clozapine seem to be the drugs most considered cost-effective to treat schizophrenia. This result was robust to changes in funding.

Risk of underdiagnosis of hypertension in schizophrenia patients

ABSTRACTAim: Arterial hypertension requires proper screening and management, and its underdiagnosis in patients with schizophrenia (SZ) and/or antipsychotic treatment has been postulated. The objective of the study is to assess whether there are differences in the proportion of screened patients with a blood pressure >140/90 mmHg that are undiagnosed or not confirmed later (risk of underdiagnosis). Methods: Cross-sectional study of clinical records from SIDIAPQ (Spain) during the 2006–2011 period. Three groups were studied: SZ, no SZ but under antipsychotic treatment, and control groups. Patients with established hypertension, cardiovascular disease, dementia, or diagnosis of SZ or starting with antipsychotic treatment during this period were excluded. Results: The SZ group had a lower risk of underdiagnosis than the control group (OR 0.91; 95% CI: 0.83–0.99; p < 0.05), at the expense of men (OR 0.8; 95% CI: 0.71–0.9; p < 0.001) and patients younger than 50 years of age (OR: 0.84; 95% CI: 0.74–0.93; p < 0.003). In the no SZ but under antipsychotic treatment group there were some differences, but not in the overall results. Conclusion: Preventive management of hypertension seemed to be sufficient for SZ and antipsychotic treatment patients. The lower prevalence of hypertension found in these groups may be due to other factors (blood pressure-lowering effect of psychoactive drugs or smoking) but these hypotheses must be evaluated with specific studies.

Comparison of long-acting and oral antipsychotic treatment effects in patients with schizophrenia, comorbid substance abuse, and a history of recent incarceration: An exploratory analysis of the PRIDE study

IntroductionComorbid substance abuse is known to blunt response to treatment for underlying psychiatric disorders, but it has not been investigated in schizophrenia when comparing the effects of long-acting injectable antipsychotics with those of oral antipsychotics. MethodsThis exploratory analysis compared once-monthly paliperidone palmitate (PP1M) with daily oral antipsychotics on time to treatment failure in patients with schizophrenia and a history of incarceration. Subjects were stratified into substance abuse (reported substance or alcohol misuse in the past 30days on the baseline Addiction Severity Index–Lite Version and/or met criteria for a current MINI diagnosis of a substance abuse disorder) and nonabuse cohorts. ResultsIn the substance abuse cohort, treatment failure was observed in 56.2% (73/130) and 64.2% (86/134) of subjects in the PP1M and oral antipsychotic groups, respectively. For the nonabuse cohort, treatment failure was observed in 36.5% (35/96) and 53.6% (45/84) of subjects in the PP1M and oral antipsychotic groups, respectively. Median (95% confidence interval [CI]) time to first treatment failure was 291 (179–428) days and 186 (94–296) days in the PP1M and oral antipsychotic groups, respectively. Median (95% CI) time to first treatment failure was >450 and 284 (147 to >450) days in the respective treatment groups. ConclusionGreater treatment effects were evident with PP1M compared with oral antipsychotics in both cohorts. The observed beneficial effect of PP1M was attenuated in the substance-abuse cohort, further reinforcing both the need for and value of continued research to optimize patient care in these complex patient populations.

A retrospective analysis of the effectiveness of antipsychotics in the treatment of ICU delirium

PurposeConflicting data exists on the efficacy of antipsychotics for treatment of intensive care unit (ICU) delirium. The purpose of this study was to compare time to delirium resolution for ICU patients who were managed with and without antipsychotics. Materials and methodsThis retrospective cohort evaluation included patients admitted to 12 ICUs at 5 sites over 5 weeks diagnosed with delirium. The primary outcome was time to delirium resolution. Secondary outcomes included ICU length of stay (LOS), mortality, discharge disposition and delirium redevelopment. A Cox proportional hazards model explored the relationship between covariates including antipsychotics and time to delirium resolution. ResultsA total of 255 patients met inclusion criteria; 69 (27%) received antipsychotics. In the antipsychotic group, time to resolution of delirium was longer (Median: 36hours vs. 13hours, p<0.001) and ICU LOS was longer (Median: 5.9days vs. 3.8days, p=0.005), but there were no differences in mortality or discharge disposition. Patients who used antipsychotics (HR=0.512; 95% CI: 0.276–0.952) and received mechanical ventilation (HR=0.381; 95% CI: 0.217–0.669) had slower rate for time to delirium resolution. ConclusionsWhile the treatment of delirium with antipsychotics remains common, antipsychotics were not associated with a shorter time to resolution of delirium.