Guideline-Concordant Antipsychotic Use and Mortality in Schizophrenia

Cullen, Bernadette; McGinty, Emma E.; Zhang, Yiyi; dosReis, Susan; Steinwachs, Donald M.; Güallar, Eliseo; Daumit, Gail L.

doi:10.1093/schbul/sbs097

Cited by 67 publications

(62 citation statements)

References 53 publications

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“…The results on cumulative exposure to antipsychotics resembled those of Cullen et al (3), as well as those obtained in our preliminary study (2), but the effect sizes changed slightly when we also adjusted for the effect of cumulative exposure to antidepressants and benzodiazepines. In particular, the mortality related to high-dose antipsychotic use decreased when we adjusted for the effect of concomitant high-dose benzodiazepine use.…”

Section: Discussionsupporting

confidence: 87%

“…Especially in Europe, public media have widely claimed that the shorter life expectancy of patients is attributable to long-term exposure to antipsychotics and that the use of such medications should be avoided whenever possible (1). Thus far, only two published studies have described the relationship between risk of death and cumulative antipsychotic dose in representative patient populations (2,3), but those studies did not control for the effect of concomitant psychotropic medications. Another study investigated cardiac mortality and cumulative exposure to antipsychotics (4), but it included only patients who had more than one prescription for oral thioridazine, haloperidol, risperidone, or clozapine.…”

mentioning

confidence: 99%

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Mortality and Cumulative Exposure to Antipsychotics, Antidepressants, and Benzodiazepines in Patients With Schizophrenia: An Observational Follow-Up Study

Tiihonen

Mittendorfer‐Rutz

Torniainen

et al. 2016

AJP

163

137

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Objective: Although mortality related to psychotropic medications has received much attention in recent years, little is known about the relationship between risk of death and cumulative antipsychotic load, and even less about the relationship between mortality and cumulative exposure to antidepressants or benzodiazepines. The authors examined these relationships using nationwide databases. Method:The authors used prospectively collected nationwide databases to identify all individuals 16-65 years of age with a schizophrenia diagnosis (N=21,492) in Sweden. All-cause and cause-specific mortality rates were calculated as a function of cumulative low, moderate, and high exposure to antipsychotics, antidepressants, and benzodiazepines from 2006 through 2010.Results: Compared with no exposure, both moderate (adjusted hazard ratio=0.59, 95% CI=0.49-0.70) and high (adjusted hazard ratio=0.75, 95% CI=0.63-0.89) antipsychotic exposures were associated with substantially lower overall mortality. Moderate antidepressant exposure was associated with a lower mortality (adjusted hazard ratio=0.85, 95% CI=0.73-0.98), and high exposure, even lower (adjusted hazard ratio=0.71, 95% CI=0.59-0.86). Exposure to benzodiazepines showed a dose-response relationship with mortality (hazard ratios up to 1.74 [95% CI=1.50-2.03]).Conclusions: Moderate and high-dose antipsychotic and antidepressant use were associated with 15%-40% lower overall mortality, whereas chronic high-dose use of benzodiazepines was associated with up to a 70% higher risk of death compared with no exposure. Since patients with anxiety and depressive symptoms may have a higher intrinsic risk of death, the finding for benzodiazepines may be attributable to some extent to residual confounding.

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Section: Discussionsupporting

confidence: 87%

mentioning

confidence: 99%

Mortality and Cumulative Exposure to Antipsychotics, Antidepressants, and Benzodiazepines in Patients With Schizophrenia: An Observational Follow-Up Study

Tiihonen

Mittendorfer‐Rutz

Torniainen

et al. 2016

AJP

163

137

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“…Nonadherence to psychopharmacological medications has been found to predict worse outcomes for psychiatric patients,12 including relapse, rehospitalization and delays in achieving remission,13,14 violence such as reported aggression and arrests,15 suicide,16 and premature death 17,18. Furthermore, a relationship has been evidenced between nonadherence to psychopharmacological medications and the economic costs of psychiatric disorders, with higher rates of nonadherence leading to higher treatment costs 19–21…”

Section: Introductionmentioning

confidence: 99%

Factors influencing adherence to psychopharmacological medications in psychiatric patients: a structural equation modeling approach

Cuevas¹,

León²,

Peñate³

et al. 2017

PPA

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PurposeTo evaluate pathways through which sociodemographic, clinical, attitudinal, and perceived health control variables impact psychiatric patients’ adherence to psychopharmacological medications.MethodA sample of 966 consecutive psychiatric outpatients was studied. The variables were sociodemographic (age, gender, and education), clinical (diagnoses, drug treatment, and treatment duration), attitudinal (attitudes toward psychopharmacological medication and preferences regarding participation in decision-making), perception of control over health (health locus of control, self-efficacy, and psychological reactance), and level of adherence to psychopharmacological medications. Structural equation modeling was applied to examine the nonstraightforward relationships and the interactive effects among the analyzed variables.ResultsStructural equation modeling demonstrated that psychiatric patients’ treatment adherence was associated: 1) negatively with cognitive psychological reactance (adherence decreased as cognitive psychological reactance increased), 2) positively with patients’ trust in their psychiatrists (doctors’ subscale), 3) negatively with patients’ belief that they are in control of their mental health and that their mental health depends on their own actions (internal subscale), and 4) positively (although weakly) with age. Self-efficacy indirectly influenced treatment adherence through internal health locus of control.ConclusionThis study provides support for the hypothesis that perceived health control variables play a relevant role in psychiatric patients’ adherence to psychopharmacological medications. The findings highlight the importance of considering prospective studies of patients’ psychological reactance and health locus of control as they may be clinically relevant factors contributing to adherence to psychopharmacological medications.

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“…Although antipsychotics are the cornerstone of FES treatment 27 and reduce psychiatric symptoms and overall mortality, 28,29 they can cause cardiometabolic adverse effects 20,21 that should be prevented. 30 Unfortunately, little is known about the trajectory of cardiometabolic risk as patients progress through their illness.…”

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confidence: 99%

Cardiometabolic Risk in Patients With First-Episode Schizophrenia Spectrum Disorders

et al. 2014

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IMPORTANCEThe fact that individuals with schizophrenia have high cardiovascular morbidity and mortality is well established. However, risk status and moderators or mediators in the earliest stages of illness are less clear.OBJECTIVE To assess cardiometabolic risk in first-episode schizophrenia spectrum disorders (FES) and its relationship to illness duration, antipsychotic treatment duration and type, sex, and race/ethnicity. DESIGN, SETTING, AND PARTICIPANTS Baseline results of the Recovery After an Initial Schizophrenia Episode (RAISE) study, collected between July 22, 2010, and July 5, 2012, from 34 community mental health facilities without major research, teaching, or clinical FES programs. Patients were aged 15 to 40 years, had research-confirmed diagnoses of FES, and had less than 6 months of lifetime antipsychotic treatment. EXPOSURE Prebaseline antipsychotic treatment was based on the community clinician's and/or patient's decision. MAIN OUTCOMES AND MEASURES Body composition and fasting lipid, glucose, and insulin parameters. RESULTS In 394 of 404 patients with cardiometabolic data (mean [SD] age, 23.6 [5.0] years; mean [SD] lifetime antipsychotic treatment, 47.3 [46.1] days), 48.3% were obese or overweight, 50.8% smoked, 56.5% had dyslipidemia, 39.9% had prehypertension, 10.0% had hypertension, and 13.2% had metabolic syndrome. Prediabetes (glucose based, 4.0%; hemoglobin A 1c based, 15.4%) and diabetes (glucose based, 3.0%; hemoglobin A 1c based, 2.9%) were less frequent. Total psychiatric illness duration correlated significantly with higher body mass index, fat mass, fat percentage, and waist circumference (all P < .01) but not elevated metabolic parameters (except triglycerides to HDL-C ratio [P = .04]). Conversely, antipsychotic treatment duration correlated significantly with higher non-HDL-C, triglycerides, and triglycerides to HDL-C ratio and lower HDL-C and systolic blood pressure (all P Յ .01). Olanzapine was significantly associated with higher triglycerides, insulin, and insulin resistance, whereas quetiapine fumarate was associated with significantly higher triglycerides to HDL-C ratio (all P Յ .02). CONCLUSIONS AND RELEVANCEIn patients with FES, cardiometabolic risk factors and abnormalities are present early in the illness and likely related to the underlying illness, unhealthy lifestyle, and antipsychotic medications, which interact with each other. Prevention of and early interventions for psychiatric illness and treatment with lower-risk agents, routine antipsychotic adverse effect monitoring, and smoking cessation interventions are needed from the earliest illness phases.

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Guideline-Concordant Antipsychotic Use and Mortality in Schizophrenia

Abstract: Adherence to PORT pharmacological guidelines is associated with reduced mortality among patients with schizophrenia. Adoption of outcomes monitoring systems and innovative service delivery programs to improve adherence to the PORT guidelines should be considered.

Cited by 67 publications

References 53 publications

Mortality and Cumulative Exposure to Antipsychotics, Antidepressants, and Benzodiazepines in Patients With Schizophrenia: An Observational Follow-Up Study

Mortality and Cumulative Exposure to Antipsychotics, Antidepressants, and Benzodiazepines in Patients With Schizophrenia: An Observational Follow-Up Study

Factors influencing adherence to psychopharmacological medications in psychiatric patients: a structural equation modeling approach

Cardiometabolic Risk in Patients With First-Episode Schizophrenia Spectrum Disorders

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