Dr. Yu: How to assess for possible drug-drug interactions
Medication errors due to system-, provider-, or patient-related factors contribute significantly to increased costs, adverse drug events (ADEs), and morbidity and mortality.1 One study found >60% of ADEs that led to hospitalization could have been prevented by strategies such as adequate monitoring or appropriate prescribing.2 Psychiatrists have an opportunity to reduce rates of ADEs; however, the possibility of disease symptoms overlapping with these adverse events is 1 of many obstacles prescribing clinicians face.1 Prescribers also must contend with adverse effects of polypharmacy, which are common among psychiatric patients. Patient-related factors of concern include:
- seeing multiple prescribers
- medication nonadherence
- failure to communicate use of herbal or over-the-counter products
- lack of insight
- comorbid medical and psychiatric diagnoses, such as dementia.1
This article highlights potential ADEs and major medication safety concerns that may contribute to morbidity and mortality among patients taking psychotropics. Although many factors are beyond the prescribing clinician’s control—such as medication dispensing and administration errors—psychiatrists can substantially reduce ADEs. We will cover potential adverse events associated with key medications or medication classes, drug interactions with potentially devastating consequences, and strategies to minimize risks of ADEs, including enhanced awareness and monitoring (Table 1).
Table 1
How to avoid ADEs with psychotropics
| Establish a collaborative practice among physicians, pharmacists, nurses, and social workers to enhance patient care and reduce the risk of medication errors and negative outcomes |
| Educate patients to increase their understanding of psychiatric diseases and medications and increase compliance with therapy. This may lead the patient to self-monitor drug efficacy and adverse effects |
| Be aware of psychotropic medications’ ‘black-box’ warnings that guide their safe use |
| Pay particular attention to drugs with a narrow therapeutic index, such as lithium and tricyclic antidepressants, which have small safety margins and are lethal in overdose |
| Avoid using 1 drug to treat the side effects of another. Minimizing polypharmacy can reduce medication errors, DDIs, and ADEs |
| Remain vigilant for DDIs, which can be serious and life-threatening. Examples include sudden cardiac death from additive QTc prolongation effects and NMS. Early detection of NMS and discontinuing the offending agent(s) can help prevent patient morbidity and mortality |
| Stay up-to-date on literature and drug warnings to employ best practices and avoid potentially serious adverse and/or lethal outcomes |
| Encourage patients to disclose any prescription drugs, over-the-counter medications, and herbal therapies they are taking |
| Develop strategies to prevent ADEs, such as personal formularies, suicide assessments, prescribing limited quantities, ‘eyes on’ medication administration, therapeutic drug monitoring, utilizing databases and resources for drug information, and patient education |
| ADEs: adverse drug events; DDIs: drug-drug interactions; NMS: neuroleptic malignant syndrome |
Prescription drug overdose
Each year, unintentional drug overdoses account for >20,000 deaths in the United States.3 Prescription medications, particularly opioid analgesics, have contributed to the doubling of overdose mortality rates in recent years. A recent study reported that nearly 50% of unintentional drug overdose deaths were associated with psychotropics and one-third of these deaths were associated with benzodiazepines, many of which were not prescribed to the individual.4
The risk of mortality from intentional drug overdose also must be assessed. Tricyclic antidepressants (TCAs) are a particularly lethal class of medications in suicide attempts and may result in arrhythmias, coma, seizures, respiratory failure, and death.5 Venlafaxine and mirtazapine are associated with greater risk of death and toxicity in overdose, respectively, than selective serotonin reuptake inhibitors (SSRIs).6 Lithium toxicity in overdose may lead to bradycardia, seizure, coma, hyperventilation, serotonin syndrome, respiratory failure, or death.5 The risk of death with lithium or benzodiazepine monotherapy is low when these agents are taken as prescribed. However, prescribers must exercise caution when these agents are used in combination. Interactions involving drugs with a narrow therapeutic index—such as lithium and TCAs—are more likely to be clinically significant because small increases in drug concentration can lead to serious adverse effects or death. See Related Resources for a review article on appropriate use and monitoring of lithium.
Drug-drug interactions
Many Americans take multiple prescription and nonprescription drugs, and psychiatric patients are more likely than other individuals to have more complex medication regimens.7 This can result in polypharmacy and drug-drug interactions (DDIs), which can lead to undesired medication effects and serious, potentially fatal ADEs.
Pharmacokinetic interactions typically affect drug concentrations and occur when 1 drug interferes with the absorption, distribution, metabolism, or excretion of another drug. Many common pharmacokinetic interactions involve the liver cytochrome P450 (CYP) system, which is responsible for metabolizing many medications.8 DDIs can occur when CYP enzymes are modified by inhibitors or inducers, which can decrease or increase drug clearance, respectively. Table 2 5,7,9 provides examples of common CYP450 substrates, inhibitors, and inducers. Polymorphisms in the pharmacogenetics of CYP450 also can affect overall drug clearance and the impact of DDIs.8