CYP2D6-inhibiting drugs and risk of fall injuries after newly initiated antidepressant and antipsychotic therapy in a Swedish, register-based case-crossover study

Leander, Karin; Vikström, Max; Frumerie, Clara; Nordenmalm, Sofia; Möller, Jette; Söderberg-Löfdal, Karin

doi:10.1038/s41598-021-85022-x

Cited by 8 publications

(10 citation statements)

References 42 publications

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“…The large number of concurrent medications in SSRI users may double the fall-related injury risk by the potential drug–drug interactions with the SSRIs. The results from previous case crossover studies relate to the results of this study by reporting the increased risk of fall-related injuries in SSRI users with concomitant use of CYP2D6-inhibiting drugs and the non-significant association with TCA users in the older population (70 years or older) [ 10 ]. The effects of the number of concurrent medications on SSRI users compared to TCA users may be a plausible explanation for the previous observational reporting of the greater risk of falls or fractures for TCA users.…”

Section: Discussionmentioning

confidence: 61%

“…While antidepressant dose and drug choice were investigated as contributing factors to the risks of each antidepressant subclass, the drug–drug interaction in older adults is another aspect that should be considered. A recent case crossover study of SSRI and SNRI users with the concomitant use of CYP2D6-inhibiting drugs reported a significant risk of fall-related injuries in adults aged 70 years or older [ 10 ]. In contrast, the risk of fall-related injuries was not elevated in TCA users with the concomitant use of CYP2D6-inhibiting drugs [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…A recent case crossover study of SSRI and SNRI users with the concomitant use of CYP2D6-inhibiting drugs reported a significant risk of fall-related injuries in adults aged 70 years or older [ 10 ]. In contrast, the risk of fall-related injuries was not elevated in TCA users with the concomitant use of CYP2D6-inhibiting drugs [ 10 ]. This case crossover study conveyed the possible effects of concurrent medications on the risk of fall-related injuries of different antidepressant subclasses.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Risk of Fall-Related Injuries Associated with Antidepressant Use in Elderly Patients: A Nationwide Matched Cohort Study

Jung

Suh

Choi

et al. 2022

IJERPH

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Previous studies have reported a higher risk of falls among tricyclic antidepressant (TCA) users compared to selective serotonin reuptake inhibitor (SSRI) users, yet SSRIs are known as a safer antidepressant class for use in older adults. This study examined the effects of antidepressant use on the risk of fall-related injuries after classifying antidepressant drugs, polypharmacy, and central nervous system (CNS) drugs by therapeutic classes and identifying factors influencing risk of fall-related injuries. A retrospective matched cohort study based on propensity scores was conducted among older adults, aged 70–89 years, who initiated antidepressant use between 1 January 2012 and 31 December 2014 using the national health insurance system senior cohort in Korea. The proportional hazard Cox regression model was used to examine the association between fall-related injuries and antidepressants. The subgroup analyses were performed to assess the risk of fall-related injuries by the number of concurrently administered medications, therapeutic classes of antidepressants, and CNS class medications. This study found that duloxetine, escitalopram, paroxetine, amitriptyline, imipramine, and trazodone significantly increased the risk of fall-related injuries in older adults. When antidepressants were prescribed to older adults, prescribers carefully considered factors including the dose, number of concurrently administered medications, and therapeutic classes of CNS.

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Section: Discussionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Risk of Fall-Related Injuries Associated with Antidepressant Use in Elderly Patients: A Nationwide Matched Cohort Study

Jung

Suh

Choi

et al. 2022

IJERPH

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“…Indeed, drug‒drug interactions can result in toxicity that can lead to hospital admissions [ 29 ]. A recent case crossover study showed that concomitant use of antidepressants, many of which are CYP2D6 substrates, with CYP2D6-inhibiting drugs was associated with an increased risk of fall injuries [ 30 ]. Furthermore, several studies evaluating polypharmacy and drug‒drug interactions have shown that optimizing treatment plans can reduce healthcare and medication costs [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

CYP2D6 Substrate Dispensing Among Patients Dispensed Mirabegron: An Administrative Claims Analysis

Ritchey

Wang

Young

et al. 2022

Drugs - Real World Outcomes

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Background Overactive bladder (OAB) is characterized by the presence of bothersome urinary symptoms. Pharmacologic treatment options for OAB include anticholinergics and β 3 -adrenergic agonists. Use of β 3 -adrenergic agonists may result in similar treatment efficacy with a decreased side effect profile compared with anticholinergics because high anticholinergic burden is associated with cardiovascular and neurologic side effects. However, the β 3 -adrenergic agonist mirabegron, one of two approved drugs within this class, is a moderate cytochrome P450 (CYP) 2D6 inhibitor, and coadministration of drugs that are CYP2D6 substrates with mirabegron may lead to adverse drug effects. Objective The aim of this study was to quantify how often CYP2D6 substrates were dispensed in patients receiving mirabegron among adults of any age and among those ≥ 65 years of age. Methods In this retrospective descriptive analysis, a deidentified administrative claims database in the United States, IQVIA PharMetrics ® Plus, was used to identify dispensing claims for CYP2D6 substrates and mirabegron from November 2012 to September 2019. Prevalence of CYP2D6 substrate dispensing was assessed in patients dispensed mirabegron among all adults ≥ 18 years old and additionally among a cohort of those ≥ 65 years old. Patient baseline profiles at the time of mirabegron and CYP2D6 substrate codispensing and at the time of mirabegron dispensing were compared. CYP2D6 substrates were categorized as those with the potential for increased risk of QT prolongation, with anticholinergic properties, with narrow therapeutic index (NTI), contraindicated or having a black box warning when used with CYP2D6 inhibitors, or used for depression or other psychiatric disease. Dispensing data and patient profiles were summarized descriptively. Results Overall, 68.5% of adults ≥ 18 years old dispensed mirabegron had overlapping dispensings for one or more CYP2D6 substrate; 60.6% and 53.6% had overlapping dispensings for CYP2D6 substrates with anticholinergic properties or risk of QT prolongation, respectively. CYP2D6 substrates with NTI, contraindicated with CYP2D6 inhibitors, or for psychiatric use were codispensed in 17.7%, 16.6%, and 38.0% of adult mirabegron users, respectively. Mirabegron users receiving one or more concurrent CYP2D6 substrate were more likely to be older, have more comorbidities and baseline polypharmacy, and have increased healthcare resource utilization compared with those without concurrent CYP2D6 substrates. Commonly codispensed CYP2D6 substrates included hydrocodone, oxycodone, tramadol, metoprolol, and tamsulosin. Findings were similar for patients in the older cohort (≥ 65 years old), with 72.1% receiving overlapping CYP2D6 substrates. Conclusions Codispensing of CYP2D6 substrates, especially those w...

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“…Most of the unintentional poisoning events are acute (86.8%) while a much smaller proportion seem to be due to chronic exposure (9.55%) [ 10 ]. Regarding the vulnerability to adverse drug events due to age-related changes, multimorbidity, or polypharmacy, older adults may be more vulnerable (e.g., a high risk of fall injuries and injurious road traffic crashes) at the start of a newly prescribed drug [ 11 , 12 ], and it is hence important to pay more attention to the short-term effects of medications.…”

Section: Introductionmentioning

confidence: 99%

Short-Term Risk of Unintentional Poisoning After New Initiation of Central Nervous System Medications in Swedish Older Adults: A Register-Based Case-Crossover Study

et al. 2022

Self Cite

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Introduction Medications acting on the central nervous system (CNS) are common causes of medication-related unintentional poisoning. Little is known about the short-term effects of CNS medications on unintentional poisoning. Objective This study aims to determine the short-term association between newly prescribed CNS drugs and unintentional poisoning. Methods We conducted a register-based case-crossover study of 9354 patients (age ≥ 50 years) with first-time hospitalization for unintentional poisoning in Sweden between 1 July, 2006 and 30 September, 2018. Newly initiated CNS medication was identified based on dispensations from the Swedish Prescribed Drug Register during 28 days prior to the unintentional poisoning event and compared with dispensations during an equally long control period. Conditional logistic regression was used to estimate the odds ratio and 95% confidence intervals. Results After a newly initiated CNS treatment, we found an increased risk of unintentional poisoning during the following 2 weeks with an odds ratio (95%) being 2.52 (1.98-3.21) and 1.47 (1.08-2.00) for the first and second week, respectively. The risk was elevated in all sub-groups but to a different degree with odds ratio ranges of 1.73-2.47 by age, 1.91-2.21 by sex, 1.40-2.30 by Charlson Comorbidity Index, 2.00-2.07 by neuropsychiatric comorbidity, and 1.63-2.82 by number of other medications. Conclusions The risk of unintentional poisoning doubles in 2 weeks following a new initiation of CNS drugs and the risk is increased across a range of population groups. Clinicians should carefully monitor signs of poisoning after such initiation among not only multimorbid older adults but also those with less comorbidity and polypharmacy.

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CYP2D6-inhibiting drugs and risk of fall injuries after newly initiated antidepressant and antipsychotic therapy in a Swedish, register-based case-crossover study

Cited by 8 publications

References 42 publications

Risk of Fall-Related Injuries Associated with Antidepressant Use in Elderly Patients: A Nationwide Matched Cohort Study

Risk of Fall-Related Injuries Associated with Antidepressant Use in Elderly Patients: A Nationwide Matched Cohort Study

CYP2D6 Substrate Dispensing Among Patients Dispensed Mirabegron: An Administrative Claims Analysis

Short-Term Risk of Unintentional Poisoning After New Initiation of Central Nervous System Medications in Swedish Older Adults: A Register-Based Case-Crossover Study

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