Adverse drug events (ADEs) are injuries resulting from medical intervention related to a drug. ADEs can occur during medical treatment and can affect both inpatients and outpatients across all demographics. Understanding the epidemiology of ADEs, including the most common types, is important for improving medication safety.
Adverse drug events are a major public health issue. ADEs are one of the leading causes of morbidity and mortality in health care, resulting in more than 3.5 million physician office visits, 1 million emergency department visits, and 125,000 hospital admissions each year in the United States alone. ADEs can occur at any point during medical care and treatment with a drug. They can result from medical errors as well as from adverse drug reactions that are not due to errors.
Many different types of ADEs have been identified. They range in severity from mild side effects to life-threatening conditions. Certain types of ADEs occur more frequently than others. Understanding the epidemiology of the different categories of ADEs, including the most common types, is essential to guide prevention efforts and improve patient safety during medical care.
Definitions of Adverse Drug Events
According to the Institute of Medicine, adverse drug events are injuries resulting from medical intervention related to a drug. This encompasses both harm caused by the inherent properties of the drug (adverse drug reactions) as well as harm from errors associated with drugs (medication errors).
More specifically, an adverse drug reaction refers to any harmful, unintended effect of a drug that occurs during proper use and normal dosage. Adverse reactions are caused by the pharmacological properties of the drug. They can occur even when the drug is appropriately prescribed and taken as directed.
In contrast, a medication error is any preventable event that leads to inappropriate medication use or potential patient harm. Medication errors may be related to professional practice, healthcare products, procedures and systems. Examples include prescribing errors, dispensing errors, and administration errors.
Prevalence of Adverse Drug Events
Many studies have been conducted to estimate the prevalence of adverse drug events among hospitalized patients. In a systematic review of 25 studies, the median overall prevalence of ADEs in hospitalized patients was 6.3% (range 0-90%). The pooled incidence density was 10 ADEs per 100 admissions.
In the outpatient setting, a systematic review of 12 studies found that the median prevalence of ADEs was 12% across all ages and settings. The incidence ranged widely from 1.8 to 41 ADEs per 100 person-months.
Overall, adverse drug events affect millions of patients each year and are one of the leading causes of morbidity and mortality associated with medical care. One study estimated that in the United States, there are over 3.5 million ADE-related physician office visits, 1 million ADE-related emergency department visits, and 125,000 ADE-related hospital admissions annually.
Types of Adverse Drug Events
Many classification systems have been developed to categorize the different types of adverse drug events. One commonly used system divides ADEs into the following categories:
- Type A: Augmented pharmacologic effects – Exaggerated but expected pharmacologic effects from appropriate drug usage. Examples include bleeding from warfarin, hypoglycemia from insulin.
- Type B: Bizarre/idiosyncratic effects – Uncommon, delayed, or unexpected effects not clearly related to the drug’s pharmacology. Examples include anaphylaxis, hepatotoxicity.
- Type C: Chronic effects – Effects from cumulative drug toxicity after repeated usage. Examples include adrenal insufficiency from corticosteroids, tardive dyskinesia from antipsychotics.
- Type D: Delayed effects – Effects that appear after discontinuation of drug therapy. Examples include withdrawal symptoms, rebound hypertension.
- Type E: End-of-treatment effects – Signs of underlyng disease unmasked after discontinuation of drug therapy. Examples include recurrence of ulcers after stopping NSAIDs, myxedema after stopping thyroid hormone.
- Type F: Failure – Failure of pharmacologic therapy to produce the desired effect. May be due to subtherapeutic dosing, drug interactions, or resistance.
- Type G: Genetic – ADEs caused by genetically-determined variation in drug metabolism. Examples include prolonged neuromuscular blockade seen in persons with plasma cholinesterase deficiency.
- Type H: Hypersensitivity – Immunologically-mediated reactions to drugs. Usually unpredictable. Examples include rash, anaphylaxis, serum sickness.
This system categorizes ADEs based on the underlying mechanism. However, most ADEs can fall under multiple categories. Other classification systems organize ADEs based on severity, preventability, stage of medication process involved, organ systems affected, and more.
Most Common Types of Adverse Drug Events
Many studies have aimed to identify the most frequent categories and examples of adverse drug events. The distribution varies depending on the clinical setting.
In the outpatient setting, hypersensitivity reactions, idiosyncratic reactions, and augmented pharmacologic effects are most common. According to one metanalysis, the most frequent outpatient ADEs are:
- Rash
- Gastrointestinal bleeding
- Kidney impairment
- Electrolyte/metabolic abnormality
- Gastrointestinal symptoms
- Anemia
- Hypotension
Among hospitalized patients, augmented pharmacologic effects followed by errors in dosing/monitoring are the most prevalent categories. Frequent examples include:
- Bleeding
- Electrolyte/metabolic abnormality
- Kidney impairment
- Gastrointestinal symptoms
- Delirium/confusion
- Hypotension
- Hypoglycemia
The table below summarizes the most common types of ADEs seen in the inpatient and outpatient settings:
| Outpatient Setting | Inpatient Setting |
|---|---|
|
|
Overall, the most frequent categories are Type A (augmented pharmacologic effects), Type B (bizarre/idiosyncratic effects), and Type H (hypersensitivity reactions). The specific examples differ but bleeding, kidney dysfunction, electrolyte abnormalities, and GI symptoms are consistently among the most common.
Factors that Increase Risk of Adverse Drug Events
Many factors can increase a patient’s risk of experiencing an adverse drug event. These include:
- Polypharmacy – Use of multiple medications raises risk of drug-drug interactions.
- Age – The very young and very old are at higher risk.
- Gender – Females experience more ADEs than males.
- Narrow therapeutic index drugs – Certain drug classes like anticoagulants have higher risk.
- Renal insufficiency – Decreased drug elimination can lead to toxicity.
- Genetic factors – Pharmacogenomic variability affects drug response.
- Comorbidities – Chronic diseases can increase susceptibility.
Studies demonstrate that risk of ADEs is highest among patients with factors like advanced age, polypharmacy, and renal impairment. Preventative strategies should target these high risk groups.
Preventing Adverse Drug Events
Various interventions have been implemented to try to reduce the occurrence of adverse drug events. Common prevention strategies include:
- Medication reconciliation to obtain accurate drug histories
- Computerized physician order entry with clinical decision support
- Pharmacist-led medication review and optimization
- Drug allergy and intolerability documentation
- Dose adjustment protocols for renal impairment
- Anticoagulation management services
- Education on high-alert medications
- Pharmacogenomic testing
While some progress has been made, adverse drug events remain common, indicating medication safety still needs improvement. A multifaceted approach targeting both system-related and patient-related factors will be important for reducing preventable ADEs.
The Cost Burden of Adverse Drug Events
In addition to the human cost, adverse drug events also impose a major financial burden on the healthcare system. Studies estimate the total cost of all ADEs to be over $30 billion annually in the United States, with hospital ADEs costing over $7,000 per occurrence.
Factors contributing to the high costs include:
- Prolonged length of hospital stay
- Additional medications needed to treat ADEs
- Extra healthcare provider time
- Added laboratory and diagnostic testing
- Increased utilization of other services (ICU, etc)
The table below summarizes estimated costs associated with adverse drug events:
| Setting | Estimated Cost per ADE |
|---|---|
| Outpatient | $1,000-$5,000 |
| Emergency Department | $2,000-$7,000 |
| Inpatient | $2,000-$7,000 |
| Long-term Care | $2,000-$9,000 |
Clearly, adverse drug events have staggering economic consequences. Preventing ADEs represents an opportunity to reduce harmful patient outcomes as well as unnecessary medical spending.
Conclusion
Adverse drug events are a major contributor to iatrogenic harm across all areas of healthcare, affecting millions of patients and costing billions of dollars each year. Augmented pharmacologic effects, bizarre/idiosyncratic reactions, and hypersensitivity reactions are the most prevalent categories.
Common examples include bleeding, kidney dysfunction, electrolyte abnormalities, and GI symptoms. Patients at highest risk include the elderly, those with polypharmacy or renal impairment, and other vulnerable groups. Ongoing efforts to improve medication safety are critical for reducing this modifiable source of patient harm and expense.