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The antipsychotic medication, risperidone, causes global immunosuppression in healthy mice.

ABSTRACT: Atypical antipsychotic medications such as risperidone are widely prescribed for diverse psychiatric indications including schizophrenia, bipolar disorder and depression. These medications have complex pharmacology and are associated with significant endocrine and metabolic side effects. This class of medications also carries FDA black box warnings due to increased risk of death in elderly patients. Clinical reports indicate that patients treated with these medications are more susceptible to infections; however, the underlying mechanisms/pharmacology are unclear. We have previously reported that risperidone and it's active metabolite distributes to the bone marrow in clinically relevant concentrations in preclinical species, leading us to hypothesize that the hematopoietic system may be impacted by these medications. To test this hypothesis, using proteomic and cytokine array technology, we evaluated the expression of genes involved in inflammatory and immune function following short term (5 days) and longer term (4 weeks) treatment in healthy animals. We report that low-dose risperidone treatment results in global immunosuppression in mice, observed following 5 days of dosing and exacerbated with longer term drug treatment (4 weeks). These data are consistent with increased susceptibility to infection in patients administered these medications and have profound implications for the increasing off-label prescribing to vulnerable patient populations including children and the elderly.

SUBMITTER: May M

PROVIDER: S-EPMC6594635 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The antipsychotic medication, risperidone, causes global immunosuppression in healthy mice.

May Meghan M Beauchemin Megan M Vary Calvin C Barlow Deborah D Houseknecht Karen L KL

PloS one 20190626 6

Atypical antipsychotic medications such as risperidone are widely prescribed for diverse psychiatric indications including schizophrenia, bipolar disorder and depression. These medications have complex pharmacology and are associated with significant endocrine and metabolic side effects. This class of medications also carries FDA black box warnings due to increased risk of death in elderly patients. Clinical reports indicate that patients treated with these medications are more susceptible to in ...[more]

PMID: 31242264

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Project description:BACKGROUND:Long-term treatment with antipsychotic medications in early episode schizophrenia spectrum disorders is common, but both short and long-term effects on the illness are unclear. There have been numerous suggestions that people with early episodes of schizophrenia appear to respond differently than those with multiple prior episodes. The number of episodes may moderate response to drug treatment. OBJECTIVES:To assess the effects of antipsychotic medication treatment on people with early episode schizophrenia spectrum disorders. SEARCH STRATEGY:We searched the Cochrane Schizophrenia Group register (July 2007) as well as references of included studies. We contacted authors of studies for further data. SELECTION CRITERIA:Studies with a majority of first and second episode schizophrenia spectrum disorders comparing initial antipsychotic medication treatment with placebo, milieu, or psychosocial treatment. DATA COLLECTION AND ANALYSIS:Working independently, we critically appraised records from 681studies, of which five studies met inclusion criteria. John Rathbone from the Schizophrenia Group supported us with the data extraction. We calculated risk ratios (RR) and their 95% confidence intervals (CI) where possible. For continuous data, we calculated mean difference (MD). We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. MAIN RESULTS:Five studies with a combined N = 998 met inclusion criteria. Four studies (N = 724) provided leaving the study early data and results suggested that individuals treated with a typical antipsychotic medication are less likely to leave the study early than those treated with placebo (Chlorpromazine: 3 RCTs N = 353, RR 0.4 CI 0.3 to 0.5, NNT 3.2, Fluphenaxine: 1 RCT N = 240, RR 0.5 CI 0.3 to 0.8, NNT 5; Thioridazine: 1 RCT N = 236, RR 0.44 CI 0.3 to 0.7, NNT 4.3, Trifulperazine: 1 RCT N = 94, RR 0.96 CI 0.3 to 3.6). Two studies (Cole 1964; May 1976) contributed data to assessment of side effects and present a general pattern of more frequent side effects among individuals treated with typical antipsychotic medications compared to placebo. Rappaport 1978 suggested a higher rehospitalisation rate for those receiving chlorpromazine compared to placebo (N = 80, RR 2.29 CI 1.3 to 4.0, NNH 2.9). However, a higher attrition in the placebo group is likely to have introduced a survivor bias into this comparison, as this difference becomes non-significant in a sensitivity analysis on intent-to-treat participants (N = 127, RR 1.69 CI 0.9 to 3.0). One study (May 1976) contributes data to a comparison of trifluoperazine to psychotherapy on long-term health in favour of the trifluoperazine group (N = 92, MD 5.8 CI 1.6 to 0.0); however, data from this study are also likely to contain biases due to selection and attrition. One study (Mosher 1995) contributes data to a comparison of typical antipsychotic medication to psychosocial treatment on six-week outcome measures of global psychopathology (N = 89, MD 0.01 CI -0.6 to 0.6) and global improvement (N = 89, MD -0.03 CI -0.5 to 0.4), indicating no between-group differences. On the whole, there is very little useable data in the few studies meeting inclusion criteria. AUTHORS' CONCLUSIONS:With only a few studies meeting inclusion criteria, and with limited useable data in these studies, it is not possible to arrive at definitive conclusions. The preliminary pattern of evidence suggests that people with early episode schizophrenia treated with typical antipsychotic medications are less likely to leave the study early, but more likely to experience medication-related side effects. Data are too sparse to assess the effects of antipsychotic medication on outcomes in early episode schizophrenia.

Project description:BackgroundAlthough antipsychotics are used for treatment of delirium/agitation in hospitalized patients, their scope of use has not been investigated in a large, multicenter cohort.ObjectiveTo determine rates of use and hospital variation in use of antipsychotics in nonpsychiatric admissions.Design, setting, patientsCohort study of adult, nonpsychiatric admissions to 300 US hospitals contributing data to the Premier database, from July 1, 2009 to June 30, 2010.MeasurementsAntipsychotic exposure defined using pharmacy charges. Potentially excessive dosing defined using guidelines for long-term care facilities.ResultsOur cohort included 2,695,081 admissions (median age, 63 years; 56% female). Antipsychotic exposure occurred in 160,773 (6%) admissions; 102,148 (64%) received atypical antipsychotics, 76,979 (48%) received typical, and 18,354 (11%) received both. Among exposed admissions, 47% received ≥1 potentially excessive daily dose. Among the variables we analyzed, the strongest predictors of antipsychotic receipt were delirium (relative risk [RR]: 2.93, 95% CI: 2.88-2.98) and dementia (RR: 2.78, 95% CI: 2.72-2.83). After adjustment for patient characteristics, patients admitted to hospitals in the highest antipsychotic prescribing quintile were more than twice as likely to be exposed compared to patients admitted to hospitals in the lowest prescribing quintile (RR: 2.56, 95% CI: 2.50-2.61). This relationship was similar across subgroups of admissions with delirium and dementia.ConclusionsAntipsychotic medication exposure is common in nonpsychiatric admissions to US hospitals. The observed variation in antipsychotic prescribing was not fully explained by measured patient characteristics, suggesting the possibility of differing hospital prescribing cultures. Additional research and guidelines are necessary to define appropriate use of these potentially harmful medications in the hospital setting. Journal of Hospital Medicine 2016;11:543-549. © 2016 Society of Hospital Medicine.

Project description:ObjectiveTo characterize the role of antipsychotic medications in the community treatment of adult depression.MethodsWe identified adults (aged 18-64 years) with new episodes of depression treatment (ICD-9-CM 296.2, 296.3, 300.4, or 311) in US national Medicaid data (2001-2010). Patients with alternative ICD-9-CM antipsychotic indications, such as schizophrenia or bipolar disorder, were excluded. Each patient was followed for at least 1 year to characterize antipsychotic and antidepressant treatment and emerging alternative antipsychotic indications. For patients without alternative indications through day 45 following start of antipsychotic treatment, antipsychotics were considered to be intended for treatment of depression. Among this group, we determined whether antipsychotic initiation was preceded by minimally adequate treatment with antidepressants, defined as active antidepressant treatment for ≥ 31 days prior to and including the day of antipsychotic initiation.ResultsWithin 1 year following onset, 14.0% of patients started an antipsychotic medication. A total of 41.3% of antipsychotic initiators developed an antipsychotic indication other than depression through day 45 following antipsychotic initiation, most often bipolar disorder or depression with psychotic features. The remaining 58.7% of antipsychotic initiators presumably started antipsychotics for nonpsychotic depression. Of these, 71.3% did not have minimally adequate antidepressant treatment prior to starting the antipsychotic medication.ConclusionAntipsychotic medications are used in approximately 1 in 7 patients with a new episode of depression. For 1 in 12 patients, the antipsychotic was considered to be intended for nonpsychotic depression. Almost three-quarters of these patients did not receive minimally adequate treatment with antidepressants prior to antipsychotic initiation. This pattern suggests potentially inappropriate and premature initiation of a drug class with substantial adverse effects and medical risks.

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The antipsychotic medication, risperidone, causes global immunosuppression in healthy mice.

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The antipsychotic medication, risperidone, causes global immunosuppression in healthy mice.

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