Risk factors of major infections in schizophrenia. A nationwide Danish register study

Pankiewicz-Dulacz, Monika; Chen, M.; Stenager, Elsebeth

doi:10.1016/j.jpsychores.2019.04.003

Cited by 5 publications

(4 citation statements)

References 41 publications

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“…These symptoms and signs are characteristic of infections. Many studies have confirmed that patients with schizophrenia are at increased risk for developing infections [ 44 , 45 , 46 ] and pneumonia represents one of the major causes for their death [ 46 ]. A retrospective analysis of Japanese patients with schizophrenia found that advanced age, low body mass index, smoking, and use of antipsychotics and their high dosage were risk factors for pneumonia [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Potential Drug-Drug Interactions among Patients with Schizophrenia Spectrum Disorders: Prevalence, Association with Risk Factors, and Replicate Analysis in 2021

et al. 2023

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Background and Objectives: Patients with schizophrenia are often exposed to polypharmacotherapy, which may lead to drug—drug interactions. The aim of the study was to investigate the prevalence of potential drug—drug interactions (pDDIs) in hospitalized patients with schizophrenia spectrum disorders and to identify factors associated with pDDIs and manifested symptoms and signs. Materials and Methods: This cross-sectional observational study included 311 inpatients admitted to a psychiatric hospital. The LexiComp drug interaction program was used to identify pDDIs in 2014. Factors associated with the prevalence of pDDIs and factors related to clinically observed symptoms and signs were assessed using multivariable regression. In addition, replicate analysis of pDDI was performed using 2021 program updates. Results: The prevalence of pDDIs was 88.7%. Our study showed that more than half of the patients received at least one drug combination that should be avoided. The most common pDDIs involved combinations of two antipsychotics or combinations of antipsychotics and benzodiazepines, which can lead to cardio-respiratory depression, sedation, arrhythmias, anticholinergic effects, and neuroleptic malignant syndrome. The number of prescribed drugs was a risk factor for pDDIs (OR 2.85; 95% CI 1.84–5.73). All groups of clinically observed symptoms and signs were associated with the number of drugs. In addition, symptoms and signs characteristic of the nervous system and psychiatric disorders were associated with antipsychotic dosage (IRR 1.33; 95% CI 1.12–1.58), which could contribute to the development of extrapyramidal syndrome, insomnia, anxiety, agitation, and bipolar mania. The 2021 version of the drug interaction program showed a shift in drug interactions toward a lower risk rating, implying less severe patient management and possibly less alert fatigue. Conclusions: Patients with schizophrenia spectrum disorders are at high risk of developing drug—drug interactions. Optimization of drug therapy, patient monitoring, and use of drug interaction programs could help to prevent pDDIs and subsequent adverse drug events.

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Section: Discussionmentioning

confidence: 99%

Potential Drug-Drug Interactions among Patients with Schizophrenia Spectrum Disorders: Prevalence, Association with Risk Factors, and Replicate Analysis in 2021

et al. 2023

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“…For instance, infections have been linked to schizophrenia risk and an increased risk of infections is observed in patients with schizophrenia. [51][52][53] However, the fact that only a subgroup of people received doxycycline for the indication "infections," and that the recorded indications for doxycycline were largely similar between men and women may argue against this mechanism of confounding. Another way of confounding, is that both the exposure (doxycycline prescription) and outcome (psychiatric diagnosis of schizophrenia or personality disorder) may be related to treatment-seeking behavior, which may be different in women vs men.…”

Section: Discussionmentioning

confidence: 99%

A Sex-Dependent Association Between Doxycycline Use and Development of Schizophrenia

Witte

Laursen

Corcoran

et al. 2023

Schizophrenia Bulletin

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Background Doxycycline and minocycline are brain-penetrant tetracycline antibiotics, which recently gained interest because of their immunomodulatory and neuroprotective properties. Observational studies have suggested that exposure to these drugs may decrease the risk to develop schizophrenia, but results are inconsistent. The aim of this study was to investigate the potential association between doxycycline use and later onset of schizophrenia. Design We used data from 1 647 298 individuals born between 1980 and 2006 available through Danish population registers. 79 078 of those individuals were exposed to doxycycline, defined as redemption of at least 1 prescription. Survival analysis models stratified for sex with time-varying covariates were constructed to assess incidence rate ratios (IRRs) for schizophrenia (ICD-10 code F20.xx), with adjustment for age, calendar year, parental psychiatric status, and educational level. Results In the non-stratified analysis, there was no association between doxycycline exposure and schizophrenia risk. However, men who redeemed doxycycline had a significantly lower incidence rate for schizophrenia onset compared to men that did not (IRR 0.70; 95% CI 0.57–0.86). By contrast, women had a significantly higher incidence rate for schizophrenia onset, compared to women that did not redeem doxycycline prescriptions (IRR 1.23; 95% CI 1.08, 1.40). The effects were not found for other tetracycline antibiotics (IRR 1.00; 95% CI 0.91, 1.09). Conclusions Doxycycline exposure is associated with a sex-dependent effect on schizophrenia risk. The next steps are replication of the results in independent well-characterized population cohorts, as well as preclinical studies to investigate sex-specific effects of doxycycline on biological mechanisms implicated in schizophrenia.

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“…During the pandemic phase of COVID-19, an increased risk of COVID-19 infection was found in patients with a recent diagnosis of schizophrenia, 6 and an increased mortality risk was found in patients with schizophrenia 7 . Risk factors for infection in patients with schizophrenia include young age, female sex, comorbid medical conditions, and substance abuse 8 …”

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confidence: 99%

“…7 Risk factors for infection in patients with schizophrenia include young age, female sex, comorbid medical conditions, and substance abuse. 8 Conversely, there is evidence that antipsychotic medications themselves are associated with increased risk of infection, although findings are inconsistent. Both typical and atypical antipsychotics have been associated with immunomodulatory changes.…”

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confidence: 99%

Long-Acting Injectable Antipsychotics and Infections in Schizophrenia

Malham

Miller

2023

J Clin Psychopharmacol

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PurposeAntipsychotics, particularly long-acting injectable (LAI) agents, are associated with decreased all-cause mortality. Antipsychotics are also associated with an increased prevalence of infections. We performed a systematic review and meta-analysis of the risk of infections in patients with schizophrenia treated with LAIs versus placebo.MethodsWe systematically searched PubMed and Food and Drug Administration package inserts for placebo-controlled studies of LAI antipsychotic use in schizophrenia. Random effects meta-analysis calculating odds ratios and 95% confidence intervals for any and site-specific infections were performed.ResultsThe total study sample consisted of 2559 subjects with schizophrenia, with 867 receiving placebo and 1692 LAI antipsychotics. Long-acting injectable antipsychotic use was associated with a significant 1.75-fold increased odds of any infection versus placebo (2.4% vs 1.5%; odds ratio, 1.75; 95% confidence interval, 1.16–2.66; P = 0.008), although findings for specific infections did not reach statistical significance. The association between LAIs and infection was unrelated to study duration, age, sex, body mass index, and total psychopathology.ConclusionsOur findings suggest that LAIs are associated with a small, but significant, increased risk of infections. This association may be due to immunomodulatory effects of antipsychotics.

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Risk factors of major infections in schizophrenia. A nationwide Danish register study

Cited by 5 publications

References 41 publications

Potential Drug-Drug Interactions among Patients with Schizophrenia Spectrum Disorders: Prevalence, Association with Risk Factors, and Replicate Analysis in 2021

Potential Drug-Drug Interactions among Patients with Schizophrenia Spectrum Disorders: Prevalence, Association with Risk Factors, and Replicate Analysis in 2021

A Sex-Dependent Association Between Doxycycline Use and Development of Schizophrenia

Long-Acting Injectable Antipsychotics and Infections in Schizophrenia

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