Generation Antipsychotic Medications Research Articles

Atypical NMS and Third Generation Antipsychotic Medications: A Systematic Literature Review and Comparison with International Expert Consensus NMS Diagnostic Criteria

Atypical NMS and Third Generation Antipsychotic Medications: A Systematic Literature Review and Comparison with International Expert Consensus NMS Diagnostic Criteria

A Systematic Review on the Duration of Antipsychotic Exposure and the Risk of Cerebrovascular Events in Elderly Patients (P11-5.020)

<h3>Objective:</h3> To evaluate the impact of duration of exposure to antipsychotic medications on the risk of cerebrovascular events (CVE) in elderly patients. <h3>Background:</h3> The FDA issued black box warnings for typical (1st generation) and atypical (2nd generation) antipsychotic medications (APM) regarding an increased risk of stroke and death in elderly patients with dementia. Several studies have compared the cerebrovascular risk profiles of typical and atypical antipsychotic agents in elderly patients, but the influence of duration of antipsychotic exposure on this risk remains unclear. <h3>Design/Methods:</h3> A comprehensive literature search was performed on PubMed in June 2022, the results of which were systematically screened using predefined inclusion and exclusion criteria. Included articles adequately controlled for confounding variables and reported on the duration of continuous exposure to APM and the risk of CVE in patients over 65. Quality assessment of the included studies was performed using the Newcastle-Ottawa scoring system. <h3>Results:</h3> From the 7,515 articles generated by the search, five observational studies reporting on APM duration and CVE in elderly patients were selected based on quality as they satisfied the inclusion criteria. Four studies found that long-term (&gt; 90 days), but not short-term, use of typical APM conferred a greater CVE risk than atypical APM used for the same duration. One study including only patients with dementia did not identify a difference with short or long-term use of typical versus atypical APM. <h3>Conclusions:</h3> The duration of therapy with APM may influence the risk of CVE in elderly patients. Although atypical agents are associated with the development of metabolic syndrome, long-term use of typical APM may confer a greater risk of CVE than atypical APM. Differences in the risk of CVE are less salient in short-term use of APM. <b>Disclosure:</b> Mr. Devine has nothing to disclose. Dr. Memon has nothing to disclose.

Prevalence and factors associated with overweight, obesity, and hypertension in a large clinical sample of adults with autism spectrum disorder

Adults with autism spectrum disorder (ASD) are at risk for excess bodyweight and hypertension, yet the prevalence of and clinical predictors for these health conditions remain unknown. The objective of this study was to assess the prevalence of overweight, obesity, and hypertension in a large clinical sample of adults with a confirmed diagnosis of ASD and to examine potential clinical predictors. This retrospective chart review study included adult subjects (≥ 20 years) with ASD who had been seen within the past 5 years at a multidisciplinary developmental disorders clinic. Data collected from the electronic health record included age, sex, race and ethnicity, cognitive ability, language ability, body mass index (BMI), hypertension, and use of second generation antipsychotic medications (SGAs). Of 622 adults with a confirmed diagnosis of ASD potentially eligible for the study, 483 (78%) had one or more notes in their records from the past 5 years. Those with recent notes were 23% female, 89% White, and had a mean (SD) age of 28.1 (7.1) years. Overall prevalence estimates for adults represented by this predominantly male, White, and young clinical sample were 28% (95% CI 24%, 32%) for overweight (BMI 25–29.9 kg/m2), 35% (95% CI 31%, 40%) for obesity (≥ 30 kg/m2), and 11% (95% CI 9%, 15%) for hypertension. Controlling for age and sex, intellectual disability (ID) was significantly associated with BMI (p = 0.003) but not hypertension (p = 0.69); those with moderate or more severe ID had a mean BMI that was 2.26 kg/m2 (95% CI 0.96, 3.57) lower than those with no ID. Controlling for age and sex, neither language ability, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) subtype of autism, nor past or current use of SGAs were significantly associated with BMI or hypertension. The study identified a high prevalence of overweight and obesity in adults with ASD consistent with the prevalence of these medical comorbidities in the U.S. population.

Long Term Metabolic and Inflammatory Effects of Second-Generation Antipsychotics: A Study in Mentally Disordered Offenders.

Mentally disordered offenders provided with forensic psychiatric care are often treated with second generation antipsychotic (SGA) medication and experience metabolic and inflammatory side effects. Aim: In this paper, we monitored the three-year fluctuation of selected anthropometric, biochemical, and inflammatory indices in forensic psychiatric patients receiving antipsychotic (AP) medication for more than five years, according to the type of AP. Methods: Thirty-five patients with psychotic disorders were classified into two groups based on the type of AP. Specifically: AP1, related to a lower risk, and AP2, related to an increased risk of weight gain (WG) and metabolic complications. Biochemical, hematological, anthropometric, blood pressure (BP), and medication data were retrieved from the individual medical files. Statistical analysis was performed with SPSS 23. Results: No significant differences in weight and glucose and cholesterol levels were observed, but patients taking AP2 more often needed drugs to control diabetes mellitus (DM), lipidemia, and cardiovascular disease (CVD). In those taking AP1, the mean HDL level decreased significantly over time (p < 0.05) and a higher proportion developed higher BP (52.9% of AP1 vs. 16.7% AP2). In the AP2 group the median level of C-reactive protein (CRP) (p < 0.001) and the white blood cell count (WBC) increased over the three years (p < 0.001). Conclusions: The proposed sub-classification of SGAs into AP1 and AP2, depending on their potential for metabolic and inflammatory effects, might facilitate study of their long-term side-effects but also help in personalized prevention or treatment measures to counteract these side-effects.

Low Rates of Clinician Monitoring for Second Generation Antipsychotic Medications in Community Pediatric Practice.

Second generation antipsychotic (SGA) medications are frequently prescribed to pediatric patients in the United States. This retrospective observational study sought to ascertain the extent of adherence to established pediatric SGA monitoring guidelines in community practice. The team used the electronic health record to determine clinician adherence to SGA monitoring guidelines at baseline, 12-week, and annual times relative to prescribing an SGA. At the time of their SGA prescription, 5.5% of pediatric patients had received all of the orders according to the monitoring guidelines. Annually, 2.5% of patients had received the necessary orders to completely adhere to monitoring guidelines; 42% of patients received no monitoring orders. Monitoring was more likely for children who had multiple types of providers and interacted with the healthcare system beyond a traditional office visit. This research informs healthcare providers about the gap between prescribing and monitoring for SGA medications in community practice for pediatric populations.

Association of antipsychotic use with raised eosinophil count.

The current study aimed to assess the possibility of an association between first and second generation antipsychotic medication and raised eosinophil count. A total of 22 in-patients at the psychiatric unit of the University General Hospital ‘Attikon’, a tertiary hospital, were included in the present study. Patients had received antipsychotic monotherapy and did not have any co-morbidities or require additional treatments. Patients were monitored weekly and their eosinophil count was assessed. One-way ANOVA and summary measures analysis were applied to study the effect of time and medication type on the absolute eosinophil concentration (or relative percentage) for each patient. The differences in mean eosinophil concentrations or relative percentage by patient and time were also assessed. An increase in the absolute concentration and the relative percentage of eosinophils over time was observed in patients receiving Olanzapine, Haloperidol and Aripiprazole. However, there was no difference between individual medications. In conclusion, antipsychotics may be associated with increased eosinophil count over time; however, larger studies involving more patients and a longer follow-up are required to reach a definitive conclusion.

Tratamento com aripiprazol para esquizofrenia no contexto do Sistema Único de Saúde em Goiás: análise de impacto orçamentário e revisão de estudos de análise de custoutilidade

Technology: Aripiprazole, second generation antipsychotic medication. Indication: treatment of schizophrenia. Objectives: To show evidence of health economic analysis in the scenario of Brazilian Public Health System (BPHS) and international contexts, for schizophrenia treatment with Aripiprazole, compared to other oral antipsychotics used in BPHS. To make a budget impact analysis for the Goias Public Health System perspective and estimate direct expenditures for the acquisition of Aripiprazole by State Department of Health of Goias, in a scenario of technology incorporation of Aripiprazole for the treatment of schizophrenia, in the period from 2021 to 2025. Materials and Methods: Bibliographical searches were done in the PUBMED and Virtual Health Library databases, in 2020 June. An evaluation of the methodological quality of systematic reviews and economic studies was done using the tools AMSTAR (Assessing the Methodological Quality of Systematic Reviews), and QHES (Quality of Health Economic Studies) checklist, respectively. Calculation of budget impact, following guidelines of the Brazilian Health Ministry, and projection of expenditures for the State Department of Health of Goias. Results: 1 systematic review and 1 Brazilian economic study were selected and included in the study of rapid evidence review. Conclusion: In the Brazilian context, Aripiprazole is cost-effective when compared to Chlorpromazine, Haloperidol, Quetiapine and Ziprasidone. However, it is less cost-effective than Risperidone and Olanzapine. If it is standardized by State Department of Health of Goias, it will promote annual savings for BPHS from R$ 250,042.05 to R$ 407,418.41, in its maximum dissemination. The direct expenses are estimated at R$ 1,582,115.24 to R $ 27,960,108.08.

Association between cortical volume and gray-white matter contrast with second generation antipsychotic medication exposure in first episode male schizophrenia patients

This cross-sectional study examines the differences in cortical volume and gray-to-white matter contrast (GWC) in first episode schizophrenia patients (SCZ) compared to healthy control participants (HC) and in SCZ patients as a function of exposure to second generation antipsychotic medication. We hypothesize 1) SCZ exhibit regionally lower cortical volumes relative to HCs, 2) cortical volume will be greater with longer exposure to second generation antipsychotics prior to the MRI scan, and 3) lower GWC with longer exposure to second generation antipsychotics prior to the MRI scan, suggesting more blurring from greater intracortical myelin. To accomplish this, MRI scans from 71 male SCZ patients treated with second generation oral risperidone and 42 male HCs were examined. 3D T1-weighted MPRAGE images collected at 1.5T were used to estimate cortical volume and GWC by sampling signal intensity at 30% within the cortical ribbon. Average cortical volume and GWC were calculated and compared between SCZ and HC. Cortical volume and GWC in SCZ patients were correlated with duration of medication exposure for the time period prior to the scan. First-episode SCZ patients had significantly lower cortical volume compared to HCs in bilateral temporal, superior and rostral frontal, postcentral gyral, and parahippocampal regions. In SCZ patients, greater cortical volume was associated with (log-transformed) duration of second-generation antipsychotic medication exposure in bilateral precuneus, right lingual, and right superior parietal regions. Lower GWC was correlated with longer duration of medication exposure bilaterally in the superior frontal lobes. In summary, second generation antipsychotics may increase cortical volume and decrease GWC in first episode SCZ patients.

T65. EFFECTS OF AN INTEGRATED COGNITIVE BEHAVIORAL SOCIAL SKILLS TRAINING AND COMPENSATORY COGNITIVE TRAINING INTERVENTION ON NEGATIVE SYMPTOM SEVERITY AND NEUROCOGNITION

BackgroundNegative symptoms in schizophrenia (SZ) remain an unmet treatment need as they are highly prevalent, associated with poor functional outcomes, and resistant to pharmacologic treatment. Similarly, cognitive impairment is common in schizophrenia and is closely tied to negative symptoms and functional deficits. Two psychosocial interventions, Cognitive-Behavioral Social Skills Training (CBSST) and Compensatory Cognitive Training (CCT), have independently been linked to improved cognitive functioning, and have demonstrated clinically significant effect sizes in reducing negative symptoms; however, neither has been used to specifically target negative symptoms as the primary outcome and they have not yet been integrated. The two intervention strategies are likely to have different mechanisms of action, and bundling of these interventions may contribute to stronger, synergistic treatment effects. As such, the current pilot randomized controlled trial examined the efficacy of an integrated CBSST-CCT intervention compared to Goal-focused Supportive Contact (SC) on negative symptoms and objective cognitive performance.MethodsSixty-two adults with SZ or schizoaffective disorder with moderate-to-severe negative symptoms were randomized to receive 25 twice-weekly, 1-hour manualized group sessions (12.5 weeks total duration) of either CBSST-CCT or SC delivered by master’s level clinicians in five community settings. CBSST was modified to strengthen its impact on negative symptoms. CCT was included to bolster impaired functions in prospective memory, attention, learning, and memory, thereby enhancing attention to CBSST content, learning of content, and memory for content. SC was used as a robust control condition, supporting systematic recovery goal setting by teaching participants to break down goals into short-term goals and SMART goal steps. SC provided the same frequency and amount of therapist and group member contact as CBSST-CCT. Analyses of covariance (ANCOVAs) examined treatment-related improvements in negative symptom severity (Clinical Assessment Interview for Negative Symptoms and Scale for the Assessment of Negative Symptoms [SANS]) and neuropsychological performance (MATRICS Consensus Cognitive Battery) at post-treatment.ResultsThe sample consisted of mostly male (63%), White (65%) participants, aged 22–65 (M=49.5, SD=10.7), with a mean of 11.8 years of education (SD=2.6). Most participants were never married (61%), living independently (65%), and prescribed second generation antipsychotic medication (66%). Participants in the SC group were significantly older than those in the CBSST-CCT group (mean age=54 vs. 46; p=.004); thus, age was included as a covariate in analyses, along with baseline score on the outcome measure. ANCOVAs demonstrated that compared to the SC group, the CBSST-CCT group had more negative symptom improvement on the SANS (p=.036, η_p^2=.135), with improvements in diminished motivation/pleasure driving this effect (p=.004, η_p^2=.235). Moreover, CBSST-CCT participants demonstrated improved verbal learning at post-treatment compared to SC participants (p=.014, η_p^2=.174). No other significant group differences were found.DiscussionCBSST-CCT has the potential to improve negative symptom severity and cognitive functioning in high-negative-symptom patients. CBSST-CCT warrants larger investigations to examine its efficacy in treating negative symptoms, along with other symptoms, cognition, and functioning.

S170. PROGRESSIVE SUBCORTICAL VOLUME LOSS IN TREATMENT-RESISTANT SCHIZOPHRENIA PATIENTS AFTER COMMENCING CLOZAPINE TREATMENT

BackgroundThe association of antipsychotic medication with abnormal brain morphometry in schizophrenia remains uncertain. Early studies investigating a switch from first generation antipsychotic to clozapine have steadily shown a decrease of caudate volume over time; however nowadays most patients are already on second generation antipsychotic medications prior to clozapine commencement and it remains unclear whether switching to clozapine in such circumstances would have any such effect on the basal ganglia. In this study we aimed to comprehensively investigate whether after 6 months of switching to clozapine, subcortical structures demonstrate any progressively neuroanatomical changes in patients with treatment-resistant schizophrenia compared to healthy controls, and whether any such changes are related to clinical variables including treatment response and amount of clozapine taken.MethodsMRI images were acquired for all participants at baseline and after 6 months at University Hospital Galway in a 1.5 T scanner. The longitudinal pipeline of Freesurfer v.5.3.0, based on an unbiased within-subject anatomical template, was employed to segment eight subcortical regions-of-interest: lateral ventricle, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala and nucleus accumbens. Subcortical volumes were bilaterally extracted following quality check of raw data and segmentation. Clinical assessments included the Positive and Negative Syndrome Scale (PANSS), The Scale for the Assessment of Positive Symptoms (SAPS), The Scale for the Assessment of Negative Symptoms (SANS) and Global Assessment Functioning Score (GAF). Two-way repeated ANCOVA was used to assess group differences in subcortical volumes over time and partial correlations to determine association with clinical variables. Change in volume was expressed using the following formula: (Follow Up -Baseline)/Baseline x 100.Results33 patients with treatment-resistant schizophrenia (TRS) and 31 healthy volunteers (HC) matched for sex and age were successfully recruited at both baseline prior to clozapine treatment and after 6 months. There was a significant effect of time on subcortical brain volumes between TRS and controls (F(7,143)= 52.54, p<0.001). Corrected post-hoc analyses demonstrated that patients had significant enlargement of lateral ventricles (F(1,59)= 48.89; p<0.001) and reduction of thalamus (F(1,59)= 34.85; p<0.001), caudate (F(1,59)= 59.35; p<0.001), putamen (F(1,59)= 87.20; p<0.001) and hippocampus (F(1,59)= 14.49; p<0.001) volumes. Thalamus and putamen volume reduction was associated with improvement in PANSS (r=0.42; p=0.021, r=0.39; p=0.033), SANS (r=0.36; p=0.049, r=0.40; p=0.027) and GAF (r=-0.39; p=0.038, r=-0.42; p=0.024). Reduced thalamic volume over time was associated with increased serum level at follow-up (r=-0.44; p=0.010). There was no significant overall effect of time on subcortical brain structures between patients responding to clozapine compared to patients non-responding to clozapine (F(7,20)=0.50; p=0.834).DiscussionThis study demonstrates that, despite the clinical and functional improvement of most patients with schizophrenia who are switched to clozapine, there is a counterintuitive progressive volume reduction in several subcortical structures over time. Furthermore, patients who have the greatest symptomatic improvement display the largest thalamo-putaminal reductions, indicating that volume reduction reflects an adaptive response associated with symptom improvement rather than a harmful or neurotoxic process in these patients.

The Deletion of AMPK β1 Worsens Glucose Tolerance and Liver Lipid Accumulation, but Doesn’t Impact the Metabolic Effects of Olanzapine in Male Mice

Second generation antipsychotic (SGA) medications, like olanzapine (OLZ), are an important component in the pharmacological management of many conditions including schizophrenia. These drugs, have been linked with a neuroendocrine signaling axis that, leads to weight gain, however, peripheral mechanisms and predictors are currently poorly understood. 5’AMP activated protein kinase (AMPK) is a ubiquitously expressed, energy‐sensing enzyme and significant associations between polymorphisms in AMPK subunit genes and OLZ‐induced weight gain have been demonstrated. Conversely, others have suggested that the central activation of AMPK mediates the deleterious metabolic effects of SGAs. The purpose of this study was to determine if reductions in AMPK activity, primarily in the liver, would impact the chronic effects of OLZ treatment. We hypothesized that the absence of AMPK β1, a subunit which is primarily found in the liver, at least in mice, would worsen the metabolic side effects of OLZ. To address this question, we housed male AMPK β1 knockout (KO) and wildtype (WT) mice at thermoneutrality (29°C) and fed them either a control diet (HFD, 45% kcal from fat) or a diet supplemented with OLZ (HFD+OLZ, 50mg/kg diet) for 10 weeks. OLZ treatment did not increase food intake or weight gain to a greater extent than the control diet in either genotype. There was a main effect of the OLZ containing diet to increase heat production, TEE and fat oxidation during the light and dark cycles. The OLZ‐fed mice also demonstrated suppressed RER during the dark cycle. Interestingly, the OLZ‐fed KO mice were more physically active during the light cycle than the OLZ‐fed WT mice. The AMPK β1 KO mice were more glucose intolerant than the WT control mice. On the other hand, the AMPK β1 KO male mice on both diets demonstrated lower circulating serum glycerol and NEFA levels but increased liver TAG accumulation. In conclusion, our findings provide evidence that the absence of AMPK β1 does not potentiate the effects of OLZ on weight gain, but worsens liver lipid accumulation and glucose tolerance.Support or Funding InformationThis study was supported by Canadian Institutes of Health Research

Trihexyphenidyl abuse in psychiatric outpatient clinic of a general hospital in Northern Nigeria

Background: Concomitant prescription of anticholinergics with first generation antipsychotic medications is widely practiced in psychiatry to avert or abort extrapyramidal side effect resulting from the latter. Trihexyphenidyl (Benzhexol) is the most commonly prescribed and the most likely to be abused amidst the anticholinergics in Nigeria. Objectives: To explore the prevalence and the associated factors for Trihexyphenidyl abuse among psychiatric outpatients in Nigeria. Methodology: 64 stable outpatients who met the inclusion criteria were interviewed with a sociodemographic questionnaire and a ten items Drug Abuse Screening Test (DAST-10), other relevant data were obtained from their case notes at the psychiatric clinic of Sarkin Maska Shehu (SMASH) Hospital, Funtua, Katsina State. Data were tabulated and analysed with Microsoft Excel and version 11.65 of Window Program for Epidemiologist (WINPEPI).

Confused Connections? Targeting White Matter to Address Treatment Resistant Schizophrenia.

Despite development of comprehensive approaches to treat schizophrenia and other psychotic disorders and improve outcomes, there remains a proportion (approximately one-third) of patients who are treatment resistant and will not have remission of psychotic symptoms despite adequate trials of pharmacotherapy. This level of treatment response is stable across all stages of the spectrum of psychotic disorders, including early phase psychosis and chronic schizophrenia. Our current pharmacotherapies are beneficial in decreasing positive symptomology in most cases, however, with little to no impact on negative or cognitive symptoms. Not all individuals with treatment resistant psychosis unfortunately, even benefit from the potential pharmacological reductions in positive symptoms. The existing pharmacotherapy for psychosis is targeted at neurotransmitter receptors. The current first and second generation antipsychotic medications all act on dopamine type 2 receptors with the second generation drugs also interacting significantly with serotonin type 1 and 2 receptors, and with varying pharmacodynamic profiles overall. This focus on developing dopaminergic/serotonergic antipsychotics, while beneficial, has not reduced the proportion of patients experiencing treatment resistance to date. Another pharmacological approach is imperative to address treatment resistance both for response overall and for negative symptoms in particular. There is research suggesting that changes in white matter integrity occur in schizophrenia and these may be more associated with cognition and even negative symptomology. Here we review the evidence that white matter abnormalities in the brain may be contributing to the symptomology of psychotic disorders. Additionally, we propose that white matter may be a viable pharmacological target for pharmacoresistant schizophrenia and discuss current treatments in development for schizophrenia that target white matter.

Comparison of therapeutic effects of monotherapy of chlorpromazine, risperidone and their combination in newly diagnosed schizophrenic patients

Background: This study evaluates and compares how negative and positive symptoms of schizophrenia were influenced with monotherapy with a first-generation anti-psychotic medication (Chlorpromazine) and a second generation anti-psychotic medication (Risperidone) and by their combination, both of which are commonly used in clinical psychiatric practice.Methods: It was randomized, double-blind, controlled clinical study performed in Indian newly diagnosed schizophrenic patients in the Department of psychiatry from Feb 2003 to March 2004. Patients 18 (eighteen) patients aged 20 to 60 years diagnosed schizophrenics according to ICD-10 Criteria who visited in outpatient department of psychiatry during study period. Three groups of 6 Patient each, group-1 - was treated with oral Chlorpromazine 100 mg 12 hly, group -2 - was treated with oral Risperidone 2mg 12 hly group 3 -was treated with combination of oral Chlorpromazine 100mg 12 hly + oral Risperidone 2 mg 12 hly. How symptomatology in schizophrenic patients affected, is measured by applying various validated psychiatric scales like Brief psychiatric Rating Score (BPRS), Scale for assessment of positive symptom(SAPS), and Scale for Assessment of Negative Symptoms (SANS).Results: the study showed that the combination therapy of oral Chlorpromazine 100 mg 12 hly + Risperidone 2mg 12 hly had reduced the overall beneficial effects which were achieved with monotherapy of both the drugs.Conclusions: In this study, the therapeutic effects of combination of oral Chlorpromazine 100 mg 12 hly + Risperidone 2 mg 12 hly found to be reduced on positive symptoms and negative symptoms of schizophrenia, assessed on SAPS and SANS scoring scales when compared with beneficial effects which were achieved with monotherapy of both the drugs.

Adjuvant role of testosterone in treatment of schizophrenia and its interaction with combination of first and second generation anti-psychotics, chlorpromazine and risperidone

Background: There is great controversy about role of male sex steroid, testosterone, in mental disorders like schizophrenia. This study assessed the effectiveness of testosterone in schizophrenic patients and probes how it modulates the action of combination of first and second generation anti-psychotic medications (Chlorpromazine + Risperidone) both of which are very commonly used anti-psychotic agents in clinical psychiatric practice.Methods: It Is randomized, double-blind, Clinical study performed in Indian schizophrenic patients (new cases) in the Department of psychiatry from Feb 2003 to March 2004. Patients twelve (12) patients aged 20 to 60 years diagnosed schizophrenics according to ICD-10 Criteria who visited in outpatient department of psychiatry during study period. 12 Patient was treated with combination of oral Chlorpromazine 200mg BD + oral Risperidone 2mg BD, half of the 12 patients also received single dose of testosterone 100mg intramuscularly with above-mentioned treatment. Measure How symptomatology in schizophrenic patients affected is measured by applying various validated psychiatric scales like Brief psychiatric Rating Score (BPRS), Scale for assessment of positive symptom(SAPS), and Scale for Assessment of Negative Symptoms (SANS).Results: Single dose of Testosterone 100mg administered initially by I.M. route potentiated the reduction level in negative symptoms of schizophrenia by 119% in patients receiving oral Chlorpromazine 200mg along with oral Risperidone 4mg/day.Conclusions: In this study, Testosterone potentiated the effects of combination of oral Chlorpromazine 100mg BD + Risperidone 2mg BD, on general psychotic manifestations, positive symptoms and negative symptoms of schizophrenia, assessed on BPRS, SAPS and SANS scoring scales, however the effect is most pronounced in negative symptomology of schizophrenia.

Aripiprazole and pregnancy: A retrospective, multicentre study

BackgroundAripiprazole is a second generation antipsychotic medication that has been a useful addition to the treatment of severe mental illness due to its low metabolic and sedation risk profile. Pregnancy is a time of high risk of metabolic complications such as gestational diabetes and the postpartum period is often a time when sedation can compromise infant care. To date there is limited data in pregnancy on the safety of aripiprazole use. While available data do not suggest an elevated malformation risk in pregnancy, there is less information available on pregnancy and neonatal complications. MethodsThis study presents preliminary data on pregnancy and neonatal complications on 26 women who took aripiprazole in pregnancy. These women attended at antenatal clinics for women with severe mental illness at two hospitals in Australia. ResultsOverall aripiprazole was not associated with an increased risk of gestational diabetes. However, use of aripiprazole in pregnancy was associated with an increased risk of pregnancy hypertension, lower birth weight, shorter gestation at birth and higher rates of admission of the neonate than the expected population rates. LimitationsThese findings need to be replicated in a larger, well-designed study to ensure they do not reflect confounding factors. ConclusionsFindings demonstrate that aripiprazole is unlikely to pose a metabolic risk in pregnancy but other pregnancy complications including hypertension, need to be examined in further studies.

Use of atypical antipsychotics in pregnancy and maternal gestational diabetes

BackgroundSecond generation antipsychotic medications (SGAs) are widely used by reproductive-age women to treat a number of psychiatric illnesses. Some SGAs have been associated with an increased risk of developing diabetes, although information regarding their diabetogenic effect in pregnant women is scarce. ObjectiveTo evaluate the risk of gestational diabetes (GDM) among women treated with SGA. MethodThe Massachusetts General Hospital (MGH) National Pregnancy Registry for Atypical Antipsychotics (NPRAA) collects data on drug use, pregnancy outcomes, and other characteristics from pregnant women, ages 18–45 years, using 3 phone interviews conducted at (1) enrollment during pregnancy, (2) 7 months' gestation, and (3) 2–3 months postpartum. Information on GDM was abstracted from obstetric and delivery medical records. The study population was restricted to women without pre-gestational diabetes. Pregnancies exposed to SGAs during the first trimester were compared with a reference group of women with psychiatric conditions but not treated with SGAs during pregnancy. Generalized linear models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for GDM. ResultsOf 303 women exposed to SGAs, 33 (10.9%) had GDM compared to 16 (10.7%) in the 149 non-exposed women. The crude OR of GDM for SGA was 1.02 (95% CI, 0.54–1.91). After adjustment for maternal age, race, marital status, employment status, level of education, smoking, and primary psychiatric diagnosis, the OR moved to 0.79 (0.40–1.56). ConclusionsFindings did not suggest an increased risk of GDM associated with exposure to SGAs during pregnancy in women who had used SGA before pregnancy without developing diabetes, compared to psychiatrically ill women who were not exposed to SGA. Trial RegistrationClinicalTrials.gov identifier: NCT01246765.

Anticholinergic Use and Misuse in Psychiatry: A Comprehensive and Critical Review

Anticholinergic medications such as Trihexyphenidyl; Biperidine are widely prescribed to prevent or to treat extrapyramidal side effects produced by neuroleptic drugs. Concomitant use of anticholinergic drugs is more common with the first generation antipsychotic medications. There is a considerable body of data suggesting that anticholinergic drugs have a potential of abuse. In this article, we review the psychiatric use, mechanism of action and the abuse of each anticholinergic drug.

Safety and Efficacy of Antipsychotics in Pregnancy and Lactation

The clinical profiles of antipsychotic medications have improved dramatically since the first generation was introduced in the 1950s. Second Generation Antipsychotic medications (SGAs), which became available in 1990, generate fewer side effects, including reduced incidence of extrapyramidal symptoms such as hyperprolactinemia. This improves the female patients’ ability to become pregnant, a process which is compromised by first generation drugs. However, use of antipsychotic medications has become increasingly prevalent. The likelihood of females with depression, bipolar disorder, psychosis to have an unplanned pregnancy, and the incidence of foetal exposure to psychotropic drugs during the first trimester of pregnancy has also increased. The paucity of exposure and outcome data leaves the safety and effects of use of antipsychotic medications during pregnancy as a subject to controversy. The evidence is insufficient to provide adequate support for clinical practices, and also to the professionals in the related fields of psychiatry, obstetrics-gynecology, and primary care. There is often contradicting information given to patients due to the lack of current studies pertaining to this area. The studies of SGA’s use during breastfeeding suggest that olanzapine, risperidone, and quetiapine may be safe at certain levels whereas medications like clozapine achieve relatively high concentrations in breast milk and may cause agranulocytosis and somnolence. Therefore, the purpose of this review is to report the most relevant and up-to-date findings of antipsychotic medication use during pregnancy and lactation in detail, so that physicians may have more insight regarding medications and provide female patients of childbearing potential with knowledge of the benefits and risks of antipsychotic drugs.

Therapeutic effectiveness and tolerability of aripiprazole as initial choice of treatment in first episode psychosis in an early intervention service: A one-year outcome study

IntroductionAripiprazole has been associated with a low prevalence of metabolic side effects as compared to other second generation antipsychotic (SGA) medications mostly in patients with long standing illness. The purpose of the present study was to assess specifically the effectiveness and safety of aripiprazole as a first choice for antipsychotic therapy for young patients presenting with a previously untreated first episode of a psychotic disorder (FEP). MethodsSeventy-three patients presenting with a FEP and with minimal prior exposure to antipsychotic medications were recruited to be part of an open label naturalistic outcome study using aripiprazole as the first choice of antipsychotic medication. Data on positive, negative and total symptom severity including general psychopathological symptoms, level of functioning and metabolic indices were collected prospectively over a one-year period. ResultsAs compared to baseline, patients treated with aripiprazole (mean dose 9.6mg) improved significantly on measures of positive (p<0.001), negative (p<0.001) and total severity-general psychopathology symptoms (p<0.001) and level of functioning (p<0.001). Seventy two percent of the participants achieved positive symptom remission and 50% achieved total remission (positive and negative) at one year of follow up. Unlike reports on patients with longer standing illness, significant weight gain (p<0.001) was observed, with 44% of participants experiencing >7% increase in body weight. ConclusionFEP patients starting treatment with aripiprazole improved on symptoms and social and occupational functioning. Aripiprazole was well tolerated except for a significant weight gain.