Dataset Information

Association of Hydroxylmethyl Glutaryl Coenzyme A Reductase Inhibitors, L-Type Calcium Channel Antagonists, and Biguanides With Rates of Psychiatric Hospitalization and Self-Harm in Individuals With Serious Mental Illness.

ABSTRACT:

Importance

Drug repurposing is potentially cost-effective, low risk, and necessary in psychiatric drug development. The availability of large, routine data sets provides the opportunity to evaluate the potential for currently used medication to benefit people with serious mental illness (SMI).

Objective

To determine whether hydroxylmethyl glutaryl coenzyme A reductase inhibitors (HMG-CoA RIs), L-type calcium channel (LTCC) antagonists, and biguanides are associated with reduced psychiatric hospitalization and self-harm in individuals with SMI.

Design, setting, and participants

These within-individual cohort studies of patients with SMI compared rates of psychiatric hospitalization and self-harm during periods of exposure and nonexposure to the study drugs, with adjusting for a number of time-varying covariates. Participants included 142?691 individuals from the entire population of Sweden with a diagnosis of bipolar disorder (BPD), schizophrenia, or nonaffective psychosis (NAP) who were 15 years or older and who were treated with psychiatric medication from October 1, 2005, through December 31, 2016. Data were analyzed from April 1 through August 31, 2018.

Interventions

Treatment with HMG-CoA RIs, LTCC antagonists, or biguanides.

Main outcomes and measures

Psychiatric hospitalizations and self-harm admissions.

Results

Among the 142?691 eligible participants, the HMG-CoA RI exposure periods were associated with reduced rates of psychiatric hospitalization in BPD (adjusted hazard ratio [aHR], 0.86; 95% CI, 0.83-0.89; P?Conclusions and relevanceThis study provides additional evidence that exposure to HMG-CoA RIs, LTCC antagonists, and biguanides might lead to improved outcomes for individuals with SMI. Given the well-known adverse event profiles of these agents, they should be further investigated as repurposed agents for psychiatric symptoms.

SUBMITTER: Hayes JF

PROVIDER: S-EPMC6450278 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Hydroxylmethyl Glutaryl Coenzyme A Reductase Inhibitors, L-Type Calcium Channel Antagonists, and Biguanides With Rates of Psychiatric Hospitalization and Self-Harm in Individuals With Serious Mental Illness.

Hayes Joseph F JF Lundin Andreas A Wicks Susanne S Lewis Glyn G Wong Ian C K ICK Osborn David P J DPJ Dalman Christina C

JAMA psychiatry 20190401 4

<h4>Importance</h4>Drug repurposing is potentially cost-effective, low risk, and necessary in psychiatric drug development. The availability of large, routine data sets provides the opportunity to evaluate the potential for currently used medication to benefit people with serious mental illness (SMI).<h4>Objective</h4>To determine whether hydroxylmethyl glutaryl coenzyme A reductase inhibitors (HMG-CoA RIs), L-type calcium channel (LTCC) antagonists, and biguanides are associated with reduced ps ...[more]

PMID: 30624557

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Project description:Importance:Some reports have raised concerns regarding a potential psychiatric worsening associated with first-time use of aripiprazole in patients already treated with other antipsychotic medications. Whether aripiprazole use, particularly in the long term, increases the risk for serious psychiatric events is unclear. Objective:To assess whether switching to or adding aripiprazole is associated with serious psychiatric treatment failure compared with switching to or adding another antipsychotic drug in patients previously exposed to antipsychotic medications. Design, Setting, and Participants:This population-based cohort study was conducted from January 1, 2005, to March 31, 2015. Data were obtained from the United Kingdom Clinical Practice Research Datalink, one of the world's largest computerized databases linked to the Hospital Episodes Statistics repository and the Office for National Statistics (ONS) mortality database. Within a base cohort of new users of antipsychotic drugs, patients switching or adding aripiprazole (n = 1643) were propensity matched 1:1 to patients switching to or adding another antipsychotic medication (n = 1643). All patients were followed up until psychiatric treatment failure, for 365 days (1 year) after cohort entry, until death from any cause other than suicide, until end of registration or linkage with the databases, or end of the study period (March 31, 2016). Main Outcomes and Measures:Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs of serious events of psychiatric treatment failure (psychiatric hospitalizations, self-harm, or suicide) associated with switching to or adding aripiprazole compared with other antipsychotic drugs. In addition to propensity score matching, all models were adjusted for age, number of psychiatric hospitalizations or self-harm events in the 6 months before cohort entry, number of different antipsychotic drugs before cohort entry, and quintiles of the Index of Multiple Deprivation. Results:The study cohort included 1643 patients (949 [57.8%] were women with a mean [SD] age of 42.1 [16.8] years) starting aripiprazole use; they were matched 1:1 to 1643 patients (871 [53.0%] were women with a mean [SD] age of 42.4 [17.1] years) starting use of another antipsychotic drug. During 2692 person-years of follow-up, 391 incident serious psychiatric treatment failures occurred, with a crude incidence rate of 14.52 (95% CI, 13.16-16.04) per 100 person-years. First-time use of aripiprazole was not associated with an increased rate of psychiatric treatment failure (HR, 0.87; 95% CI, 0.71-1.06), psychiatric hospitalizations (HR, 0.85; 95% CI, 0.69-1.06), or self-harm or suicide (HR, 0.96; 95% CI, 0.68-1.36) compared with starting use of another antipsychotic drug. Results were consistent across several sensitivity analyses. Conclusions and Relevance:Initiating aripiprazole use, compared with another antipsychotic medication, after a previous antipsychotic exposure did not appear to be associated with psychiatric hospitalization, self-harm, or suicide; these findings warrant replication in large observational studies.

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Dataset Information

Association of Hydroxylmethyl Glutaryl Coenzyme A Reductase Inhibitors, L-Type Calcium Channel Antagonists, and Biguanides With Rates of Psychiatric Hospitalization and Self-Harm in Individuals With Serious Mental Illness.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Publications

Association of Hydroxylmethyl Glutaryl Coenzyme A Reductase Inhibitors, L-Type Calcium Channel Antagonists, and Biguanides With Rates of Psychiatric Hospitalization and Self-Harm in Individuals With Serious Mental Illness.

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