Summary: A study of over 500,000 older adults in Ireland identified five prevalent prescribing cascades, where side effects of one drug led to prescriptions for additional medications—some potentially avoidable. Two cascades are particularly relevant to sleep specialists, involving SSRIs/SNRIs followed by sleep agents, and benzodiazepines followed by antipsychotics. The findings underscore the importance of recognizing adverse drug reactions to reduce unnecessary prescriptions and patient harm.
Key takeaways:
- SSRIs/SNRIs often lead to sleep agent prescriptions, with 2.5% of patients receiving a sleep medication within one year—translating to one cascade per 115 patients.
- Benzodiazepines may trigger antipsychotic use, occurring in 3.2% of users, or one cascade per 242 patients.
- The most frequent cascade involved calcium channel blockers followed by diuretics, with one in every 78 patients affected.
New research published in Annals of Family Medicine identifies five clinically relevant prescribing cascades in a national sample of more than half a million older adults in Ireland. The findings show how unrecognized drug side effects can trigger extra prescriptions and potentially avoidable harm in primary care.
Prescribing cascades occur when one medication is used to treat or prevent a side effect of another drug. An unintentional cascade can arise when a patient’s symptoms are mistaken for a new illness. In that case, the patient not only experiences the original side effect but also faces added risks from the second medication.
Funded by the Health Research Board of Ireland, the study was led by researchers at University College Cork in Ireland. They analyzed national prescription data for 533,464 community-dwelling Irish adults aged 65 years and older, covering prescriptions dispensed between 2017 and 2020. A prescription sequence symmetry analysis was performed with a 365-day window to examine nine expert-defined ‘ThinkCascades.’ It is important to note that this study examined dispensed prescriptions data only for potential prescribing cascades. There may be alternative explanations as to why patients are prescribed these medications, such as new health conditions.
Two Prescribing Cascades Relevant to Sleep Specialists
Selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) leading to sleep agent prescribing
SSRIs and SNRIs are commonly prescribed for depression. Approximately 2.5% of those on an SSRI or SNRI went on to receive a sleep agent prescription within one year. The authors estimated one additional sleep agent prescription for every 115 patients who start a SSRI or SNRI.
Benzodiazepine leading to antipsychotic prescribing
Benzodiazepines are often used to treat anxiety disorders and sometimes, off-label, for insomnia disorder. This cascade appeared in 3.2% of benzodiazepine initiators. The authors estimated one additional antipsychotic prescription for every 242 patients who start a benzodiazepine.
Study Found Three Other Prominent Prescribing Cascades
Calcium channel blocker leading to diuretic prescribing
This cascade was the most prominent. About 2.6% of those who started a calcium channel blocker, often used to treat high blood pressure, went on to receive a diuretic within one year. The authors estimated one extra diuretic prescription for every 78 patients started on a calcium channel blocker.
Alpha-1-receptor blocker leading to vestibular sedative prescribing
Alpha-1 receptor blockers are used to ease symptoms of an enlarged prostate. About 3% of alpha-1 blocker users went on to receive a vestibular sedative (used to relieve vertigo and dizziness) within one year. The authors estimated one additional vestibular sedative prescription for every 85 patients who start an alpha-1-receptor blocker.
Antipsychotic leading to antiparkinsonian agent prescribing
Antipsychotics can cause movement-related side effects. About 0.4% of antipsychotic users went on to receive an antiparkinsonian agent prescription within one year. The authors estimated one extra antiparkinsonian agent prescription for every 1,644 antipsychotic users.
Physicians Seem to Avoid Specific Cascades
Three other drug pairs showed significant negative associations, suggesting physicians may already be intentionally avoiding these cascades. These three cascades are:
- a diuretic to overactive bladder medication;
- benzodiazepine to antidementia agent; and
- nonsteroidal anti-inflammatory drugs to antihypertensive medication.
“An increasing number of medications in older people is strongly associated with an increased risk of medication-related harm and serious adverse drug reactions,” the authors write. “For clinicians, considering adverse drug reactions as part of the differential in patients presenting with new symptoms in primary care is an important step in identifying and mitigating the risk of medication-related harm. Furthermore, identifying prescribing cascades and deprescribing when appropriate offers potential to reduce pill counts and associated treatment burden for patients.”
