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Review of Standard Laboratory Blood Parameters in Patients with Schizophrenia and Bipolar Disorder.
Memic-Serdarevic, A, Burnazovic-Ristic, L, Sulejmanpasic, G, Tahirovic, A, Valjevac, A, Lazovic, E
Medical archives (Sarajevo, Bosnia and Herzegovina). 2020;(5):374-380
Abstract
INTRODUCTION Symptomatic and etiopathologic heterogeneity of schizophrenia (SCH) and bipolar disorder (BD) can be adequately addressed using a dimensional approach to psychopathology, as well as interpreting physiological properties and markers as predictors of disease onset and relapse. Risk factors, genetic and environmental, are likely to modify the neurobiological processes characteristic of certain physiological processes that manifest to a greater degree of overlapping symptoms. One of the most common laboratory tests in psychiatric patients is a standard laboratory blood test. It gives us an insight into the general somatic condition of the patient. It assesses the ability to transport oxygen to tissues and carbon dioxide back to the lungs via erythrocytes (RBC) and hemoglobin (HGB) as their most important constituents, and is also an indicator of iron status and blood oxygenation. AIM: Schizophrenia (SCH) and bipolar disorder (BD) are psychiatric disorders whose complex etiology and pathogenesis are still far from known. A correlation between red blood cell abnormalities and these diseases has been recognized in some studies. One of the most common laboratory tests in psychiatric patients is a standard laboratory blood test. However, so far there is a small number of published papers that relate to the relationship between laboratory parameters of blood and the aim of this paper is to reveal more light in this subject. METHODS The research was done as an observational prospective clinical study that has evaluated different physiological and pathological parameters in patients with BD and SCH over a two-year period. A total of 159 patients with schizophrenia, 61 patients diagnosed with bipolar disorder and 82 healthy subjects participated in this study. RESULTS At baseline, BD compared to SCH patients had higher mean lymphocyte count (2,6±0,7 vs. 2,0±0,6x109; p=0,006) and haemoglobin concentration (146,8±12,2 vs. 140,2±14,7 g/L; p=0,03), and significantly lower red cell distribution width (13,6±2,2 vs. 14,7±1,8%; p=0,008). In both BD and SCH patients there was a significant number of patients with low red blood cells count and low haemoglobin concentration, and high MCH and MCHC at baseline and at 3 and 6 months of follow up. CONCLUSIONS The finding that SCH as well as BD differed from controls with respect to red blood cells, hemoglobin, lymphocytes, and average platelet count was consistent with previous findings and could be understood as a qualitative measure in the evaluation of this sample. The fact that no association with other parameters was found, as well as an association with the diagnosis, does not exclude that these associations can be found in larger samples.
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Painful Life Events in Psychiatric Disorders: A Quantitative and Qualitative Analysis.
Paquet, A, Plansont, B, Girard, M
Issues in mental health nursing. 2019;(9):781-789
Abstract
We reported in a previous study the painful events experienced in the past in subjects with schizophrenia or major depression, in comparison to controls, and related them to the experimental pain sensitivity, anxiety, and the diagnosis. We present here the detailed analysis of these past painful events, with the aim of determining whether schizophrenic, depressive and control groups are qualitatively (type of painful events experienced, emotional or sensory components associated with pain) and quantitatively (duration, severity, and intensity) comparable concerning their past painful experiences. The questionnaire used relies on memory and feelings and will provide an indication about the way pain is experienced and memorized in daily life. The reported history of pain was not the same in the three groups. Depressed subjects differed from the others by the number of reported painful events. Painful events of everyday life, such as trauma without fracture and wounds, were the most highly reported painful events for all groups. Surprisingly, the daily pain events are associated to affective component of pain perception. Other kinds of event were differently reported between the groups. Experience of pain appears to be memorized and reported differently depending on the psychiatric disorder and type of event. The characteristics of each individual, their previous experience, contribute to the expression of psychiatric disorders, including in the field of pain. Past pain experience should be taken into account when attending someone for pain.
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Psychopharmacological Treatment in the RAISE-ETP Study: Outcomes of a Manual and Computer Decision Support System Based Intervention.
Robinson, DG, Schooler, NR, Correll, CU, John, M, Kurian, BT, Marcy, P, Miller, AL, Pipes, R, Trivedi, MH, Kane, JM
The American journal of psychiatry. 2018;(2):169-179
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Abstract
OBJECTIVE The Recovery After an Initial Schizophrenia Episode-Early Treatment Program compared NAVIGATE, a comprehensive program for first-episode psychosis, to clinician-choice community care over 2 years. Quality of life and psychotic and depressive symptom outcomes were found to be better with NAVIGATE. Compared with previous comprehensive first-episode psychosis interventions, NAVIGATE medication treatment included unique elements of detailed first-episode-specific psychotropic medication guidelines and a computerized decision support system to facilitate shared decision making regarding prescriptions. In the present study, the authors compared NAVIGATE and community care on the psychotropic medications prescribed, side effects experienced, metabolic outcomes, and scores on the Adherence Estimator scale, which assesses beliefs related to nonadherence. METHOD Prescription data were obtained monthly. At baseline and at 3, 6, 12, 18, and 24 months, participants reported whether they were experiencing any of 21 common antipsychotic side effects, vital signs were obtained, fasting blood samples were collected, and the Adherence Estimator scale was completed. RESULTS Over the 2-year study period, compared with the 181 community care participants, the 223 NAVIGATE participants had more medication visits, were more likely to receive a prescription for an antipsychotic and more likely to receive one conforming to NAVIGATE prescribing principles, and were less likely to receive a prescription for an antidepressant. NAVIGATE participants experienced fewer side effects and gained less weight; other vital signs and cardiometabolic laboratory findings did not differ between groups. Adherence Estimator scores improved in the NAVIGATE group but not in the community care group. CONCLUSIONS As part of comprehensive care services, medication prescription can be optimized for first-episode psychosis, contributing to better outcomes with a lower side effect burden than standard care.
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Safety and tolerability of antipsychotic co-treatment in patients with schizophrenia: results from a systematic review and meta-analysis of randomized controlled trials.
Galling, B, Roldán, A, Rietschel, L, Hagi, K, Walyzada, F, Zheng, W, Cao, XL, Xiang, YT, Kane, JM, Correll, CU
Expert opinion on drug safety. 2016;(5):591-612
Abstract
INTRODUCTION Antipsychotic co-treatment is common in schizophrenia, despite lacking evidence for its efficacy and safety. Areas: We conducted a systematic search of PubMed/PsycInfo/CJN/WangFan/CBM without language restrictions from database inception until 05/25/2015 for randomized trials comparing antipsychotic monotherapy with antipsychotic co-treatment in ≥20 adults with schizophrenia reporting meta-analyzable adverse events (AEs) data. Meta-analyzing 67 studies (n=4,861, duration=10.3±5.2 weeks), antipsychotic co-treatment was similar to monotherapy regarding intolerability-related discontinuation (risk ratio (RR)=0.84, 95% confidence interval (CI)=0.53-1.33, p=0.455). While incidence of ≥1 AE was lower with antipsychotic co-treatment (RR=0.77, 95%CI=0.66-0.90, p=0.001), these results were solely driven by open-label and efficacy-focused studies. Adjunctive D2-antagonists lead to less nausea (RR=0.220, 95%CI=0.06-0.87, p=0.030) and insomnia (RR=0.26, 95%CI=0.08-0.86, p=0.028), but higher prolactin (SMD=2.20, 95%CI=0.43-3.96, p=0.015). Conversely, adjunctive partial D2-agonists (aripiprazole=100%) resulted in lower electrocardiogram abnormalities (RR=0.43, 95%CI=0.25-0.73, p=0.002), constipation (RR=0.45, 95%CI=0.25-0.79, p=0.006), drooling/hypersalivation (RR=0.14, 95%CI=0.07-0.29, p<0.001), prolactin (SMD=-1.77, 95%CI=-2.38, -1.15, p<0.001), total and LDL-cholesterol (SMD=-0.33, 95%CI=-0.55, -0.11, p=0.003; SMD=-0.33, 95%CI=-0.54, -0.10, p=0.004). EXPERT OPINION No double-blind evidence for altered AE burden associated with antipsychotic co-treatment was found. However, AEs were insufficiently and incompletely reported and follow-up duration was modest. Adjunctive partial D2-agonists might be beneficial for counteracting several AEs. High-quality, long-term studies that comprehensively assess AEs are needed.
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Glycopyrrolate in comparison to hyoscine hydrobromide and placebo in the treatment of hypersalivation induced by clozapine (GOTHIC1): study protocol for a randomised controlled feasibility study.
Qurashi, I, Chu, S, Husain, N, Drake, RJ, Chaudhry, I, Deakin, JF
Trials. 2016;(1):553
Abstract
BACKGROUND Clozapine is the only medication licensed for the treatment of resistant schizophrenia in the UK. Although efficacious, a common and unpopular side effect of clozapine treatment is clozapine-induced hypersalivation (CIH), which can contribute to non-adherence. The standard treatment for CIH in the UK is hyoscine hydrobromide but this may aggravate cognitive deficits in patients with schizophrenia while glycopyrrolate may be an effective alternative with a more tolerable side effect profile. There is currently no convincing evidence for hyoscine, or any other medication, as an effective treatment for CIH. METHODS/DESIGN This is a multicentre randomised, double-blind, placebo-controlled feasibility study of glycopyrronium bromide (glycopyrrolate) and hyoscine hydrobromide (hyoscine) in patients with clozapine-induced hypersalivation. We aim to recruit 42 patients who have been prescribed clozapine and are experiencing hypersalivation, and randomise them to one of three study arms (either hyoscine, glycopyrrolate or placebo). The primary outcome measures will be the participant recruitment and attrition rates, and the secondary outcome will be the metrics of the daytime hypersalivation measure. After a 1-week washout period (discontinuing CIH medication, if any), there will be a 4-week treatment period where participants will be titrated up to the maximum tolerated dose of hyoscine, glycopyrrolate or placebo. Measurements of daytime salivation, nocturnal salivation, cognition and side effects will be taken during home visits in week 2 and week 5. Information on salivation and side effects will also be taken through telephone calls in week 3 and week 4. To gather information on the experience of study participants, exit interviews will also be requested with all participants who drop out of the study and a sample of participants who complete the study. DISCUSSION There is currently no convincing evidence for hyoscine, or any other medication, as an effective treatment for CIH. There is promising evidence that glycopyrrolate may be more successful in the treatment of CIH causing fewer cognitive side effects. We propose to conduct a randomised placebo-controlled feasibility study of glycopyrrolate and hyoscine in the treatment of clozapine-induced hypersalivation to inform the design of a future efficacy trial. TRIAL REGISTRATION Clinicaltrials.gov NCT02613494 , 23 November 2015.
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A Randomized Comparison of Aripiprazole and Risperidone for the Acute Treatment of First-Episode Schizophrenia and Related Disorders: 3-Month Outcomes.
Robinson, DG, Gallego, JA, John, M, Petrides, G, Hassoun, Y, Zhang, JP, Lopez, L, Braga, RJ, Sevy, SM, Addington, J, et al
Schizophrenia bulletin. 2015;(6):1227-36
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Research findings are particularly important for medication choice for first-episode patients as individual prior medication response to guide treatment decisions is unavailable. We describe the first large-scale double-masked randomized comparison with first-episode patients of aripiprazole and risperidone, 2 commonly used first-episode treatment agents. One hundred ninety-eight participants aged 15-40 years with schizophrenia, schizophreniform disorder, schizoaffective disorder or psychotic disorder Not Otherwise Specified, and who had been treated in their lifetime with antipsychotics for 2 weeks or less were randomly assigned to double-masked aripiprazole (5-30 mg/d) or risperidone (1-6 mg/d) and followed for 12 weeks. Positive symptom response rates did not differ (62.8% vs 56.8%) nor did time to response. Aripiprazole-treated participants had better negative symptom outcomes but experienced more akathisia. Body mass index change did not differ between treatments but advantages were found for aripiprazole treatment for total and low-density lipoprotein cholesterol, fasting glucose, and prolactin levels. Post hoc analyses suggested advantages for aripiprazole on depressed mood. Overall, if the potential for akathisia is a concern, low-dose risperidone as used in this trial maybe a preferred choice over aripiprazole. Otherwise, aripiprazole would be the preferred choice over risperidone in most situations based upon metabolic outcome advantages and some symptom advantages within the context of similar positive symptom response between medications.
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The prevalence and predictors of type two diabetes mellitus in people with schizophrenia: a systematic review and comparative meta-analysis.
Stubbs, B, Vancampfort, D, De Hert, M, Mitchell, AJ
Acta psychiatrica Scandinavica. 2015;(2):144-57
Abstract
OBJECTIVE To conduct a meta-analysis investigating the prevalence of type two diabetes mellitus (T2DM) in people with schizophrenia compared to controls. METHOD Systematic review of electronic databases from inception till November 2014. Articles reporting the prevalence of T2DM in people with schizophrenia and healthy controls (without mental illness) were included. Two independent authors conducted searches and extracted data. A random effects relative risks (RR) meta-analysis was conducted. RESULTS Twenty-five studies including 145,718 individuals with schizophrenia (22.5-54.4 years) and 4,343,407 controls were included. The prevalence of T2DM in people with schizophrenia was 9.5% (95% CI = 7.0-12.8, n = 145,718) and 10.75% (95% CI 7.44-14.5%, n = 2698) in studies capturing T2DM according to recognized criteria. The pooled RR across all studies was 1.82 (95% CI = 1.56-2.13; = 4,489,125). Subgroup analyses found a RR of 2.53 (95% CI = 1.68-3.799, n = 17,727) in studies ascertaining T2DM according to recognized criteria and RR 1.65 (95% CI = 1.34-2.03, n = 4,243,389) in studies relying on T2DM determined through medical records. CONCLUSION People with schizophrenia are at least double the risk of developing T2DM according to recognized T2DM criteria. Proactive lifestyle and screening programmes should be given clinical priority.
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Decreased peripheral brain-derived neurotrophic factor levels are a biomarker of disease activity in major psychiatric disorders: a comparative meta-analysis.
Fernandes, BS, Berk, M, Turck, CW, Steiner, J, Gonçalves, CA
Molecular psychiatry. 2014;(7):750-1
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A randomized, 12-week study of the effects of extended-release paliperidone (paliperidone ER) and olanzapine on metabolic profile, weight, insulin resistance, and β-cell function in schizophrenic patients.
Hu, S, Yao, M, Peterson, BS, Xu, D, Hu, J, Tang, J, Fan, B, Liao, Z, Yuan, T, Li, Y, et al
Psychopharmacology. 2013;(1):3-13
Abstract
OBJECTIVE To compare matched paliperidone-ER- and olanzapine-treated schizophrenic patients on measures of glucose and lipid metabolism. METHODS Eighty hospitalized patients with schizophrenia (DSM-IV) were randomly assigned to treatment with paliperidone ER or olanzapine for a period of 12 weeks. At baseline and every 4 weeks, we assessed weight, subcutaneous fat, waist and hip circumferences, fasting glucose, insulin, glycohemoglobin A1, cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, and prolactin. We also assessed at every time point body mass index (BMI), homeostasis insulin resistance (HOMA-IR), and homeostasis β-cell function (HOMA-B). RESULTS Thirty-three patients randomly assigned to paliperidone ER and 23 patients randomly assigned to olanzapine groups completed the entire 12-week treatment. Within-group analyses showed that fasting measures in both groups increased for weight, BMI, waist circumferences, hip circumference, subcutaneous fat, cholesterol, triglycerides, and prolactin. In contrast, fasting glucose, LDL, and HOMA-B increased during treatment only in the olanzapine group. We also detected significantly different serum prolactin levels at all time point between the paliperidone ER- and olanzapine-treated groups, as well as a statistical trend for HOMA-B to increase more in the olanzapine compared to paliperidone-ER group over the 12 weeks of the trial. We did not detect, however, differential drug effects over the 12 weeks of the trial on fasting measures of BMI, glucose, glycohemoglobin A1, insulin, HDL, LDL, cholesterol, triglyceride, or HOMA-IR. CONCLUSION This study reinforces the necessity of regularly monitoring metabolic parameters in patients with schizophrenia taking atypical antipsychotics, including paliperidone ER.
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A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia.
Adams, DH, Kinon, BJ, Baygani, S, Millen, BA, Velona, I, Kollack-Walker, S, Walling, DP
BMC psychiatry. 2013;:143
Abstract
BACKGROUND We compared the time to discontinuation due to lack of tolerability over 24 weeks in patients suffering from schizophrenia treated with pomaglumetad methionil (LY2140023 monohydrate, the prodrug of metabotropic glutamate 2/3 receptor agonist, LY404039) or standard of care (SOC: olanzapine, risperidone, or aripiprazole). METHODS Study HBBR was a multicenter, randomized, open-label study comparing the long-term safety and tolerability of LY2140023 with SOC for schizophrenia. Patients had moderate symptomatology with prominent negative symptoms and evidence of functional impairment. Those who met entry criteria were randomized to open-label treatment with either LY2140023 (target dose: 40 mg twice daily [BID]; n = 130) or SOC (n = 131). RESULTS There was no statistically significant difference between LY2140023 and SOC for time to discontinuation due to lack of tolerability (primary objective; P = .184). The Kaplan-Meier estimates revealed comparable time to event profiles. Only 27% of LY2140023 and 45% of SOC patients completed the 24-week open-label, active treatment phase. Twenty-seven patients (20.8%) in the LY2140023 group and 15 patients (11.5%) in the SOC group discontinued due to lack of efficacy (P = .044). Twenty-three patients (17.7%) in the LY2140023 group and 19 patients (14.5%) in the SOC group discontinued due to adverse events (physician and subject decision combined, P = .505). The incidence of serious adverse events was comparable between groups. LY2140023-treated patients reported significantly more treatment-emergent adverse events of vomiting, agitation, and dyspepsia, while SOC-treated patients reported significantly more akathisia and weight gain. The incidence of treatment-emergent parkinsonism (P = .011) and akathisia (P = .029) was significantly greater in SOC group. Improvement in PANSS total score over the initial 6 to 8 weeks of treatment was similar between groups, but improvement was significantly greater in the SOC group at 24-week endpoint (P = .004). LY2140023 and SOC groups had comparable negative symptom improvement at 24-week endpoint (P = .444). CONCLUSION These data provide further evidence that the potential antipsychotic LY2140023 monohydrate, with a glutamatergic mechanism of action, may have a unique tolerability profile characterized by a low association with some adverse events such as extrapyramidal symptoms and weight gain that may characterize currently available dopaminergic antipsychotics. TRIALS REGISTRATION A Long-term, Phase 2, Multicenter, Randomized, Open-label, Comparative Safety Study of LY2140023 Versus Atypical Antipsychotic Standard of Care in Patients with DSM-IV-TR Schizophrenia.