No 2 patients are alike, and even the same patient may vary from month to month, as needs, medications, and comorbidities change. Because our patients are living longer, they increasingly present with comorbid conditions, including cancers, inflammatory diseases (eg, rheumatoid arthritis), and other chronic conditions (eg, heart disease, metabolic syndrome). Each condition may be treated with 1 or more medications, resulting in complex treatment regimens. For instance, the median number of medications a patient in my practice may be taking at a given time is approximately 4, many of them prescribed by specialists outside of psychiatry who also care for the patient. Prescribing medications is how we and other specialists help our patients, so it is not surprising that patients are taking more than 1 medication. Polypharmacy is the rule in psychiatry, not the exception. As a result, the clinician must look at all the medications a psychiatric patient may be taking and be especially cautious regarding potential drug-drug interactions (DDIs) when making treatment decisions.
Throughout my clinical career, I have noticed a shift in referral patterns with psychiatrists now receiving more patient referrals from other specialists than from primary care providers (PCPs). My interactions with colleagues across different specialties to coordinate care for patients have increased dramatically in the last few years.
An example of a necessary collaboration among specialists is an 84-year-old woman who has congestive heart failure treated by a cardiologist, stress urinary incontinence addressed by a urologist, a recent knee replacement requiring regular visits to an orthopedist, hypertension treated by her PCP, and posttraumatic stress disorder (PTSD) managed by me. She is a fairly healthy patient, comparatively speaking, but she is taking 8 to 9 types of medications, most of which are not prescribed by me. Psychiatrists must recognize that medication changes occur with each provider visit. This challenge isn’t exclusive to older patients; even younger individuals have seen an increase in medication usage. For instance, my 20-year-old patient with bipolar disorder receives multiple medications from me, from an allergist, and from a dermatologist.
Interactions between specialties have improved significantly, as most clinicians have recognized the inadvertent harm that can be caused by DDIs. Contrary to common belief in psychiatry, many specialists are open to collaboration and communication. In my view, this collaboration is underutilized, but when pursued, it often yields positive outcomes.
It is the responsibility of every psychiatric prescriber to recognize that our patients are more than just their minds; they have both a brain and a body that will require lifelong treatment. Therefore, it is on us as clinicians to ensure that there are no DDIs between the treatments we prescribe and those prescribed by other specialists.
Consider my 84-year-old patient. While I was treating her with what I considered an appropriate medication for PTSD, I neglected to investigate that she was also taking an anticholinergic prescribed by her urologist. The combination of psychiatry and urology medications led to an excessive anticholinergic effect, which can include dry mouth, constipation, and urinary retention. Consequently, the patient chose to discontinue both medications. Since neither I nor the urologist performed our due diligence, the patient suffered. Eventually, the mistake was identified and we collaborated to find another urology medication that wasn’t an anticholinergic, allowing her to continue the psychiatric medication for her PTSD.
This is an example of how DDIs can impact a patient’s health, their adherence to their medications, and their belief in the medical system. Patients may stop medications when they experience DDIs, mistakenly attributing the harm to a single medication rather than to the DDIs. We recently published a survey of patients with tardive dyskinesia (TD) which demonstrated that patients discontinue antipsychotics at a high percentage if they perceive them as an offending agent, which impacts management of their underlying mental health condition. Considering DDIs early and often appears to be the mandate of the modern-day clinician.
The optimal time to assess for DDIs is during the early phase of medication initiation; however, many of my patients are in a constant flux of starting and stopping medications. Additionally, it is important to note that certain medications may have a half-life of up to 3 months, which could alter the timing of potential DDIs; initiating a medication today does not guarantee that a DDI won’t manifest months later. This dynamic nature requires a shift in clinical approach—clinicians must now routinely monitor for DDI issues, rather than solely relying on an assessment at the first appointment. Just as checking blood pressure is a routine practice, DDIs must be consistently evaluated. This principle applies universally to all patients; there are no exceptions. It is important to recognize that DDIs can also occur upon cessation of medications. Discontinuing a medication can affect a patient’s oxidative enzymes, leading to changes in the metabolic rates of concomitant medications and altering the plasma levels of active metabolites, thereby influencing their effects. This also applies to patients who discontinue smoking, as it significantly impacts liver metabolic activity.
Collecting information about a patient’s medication regimen from as many sources as possible, including the patient themselves, medical records, caregivers, PCPs, and other specialists, is essential. Requesting that patients bring all their medications to appointments can enhance accuracy, as they may struggle to identify or describe all their medications or adhere to prescriptions. Additionally, cross-referencing pharmacy records can provide valuable insights, as patients may forget or intentionally discontinue a medication. Given the complexity of patients’ lives, clarity is paramount, and the practice of bringing medications to appointments is invaluable. Routine clinical examination might include asking, “Since our last meeting, have you or your providers made any changes to your medication regimen?” This could entail the addition of a new medication, discontinuation of an old one, or adjustments in dosage or scheduling.
Healthcare professionals (HCPs) can mitigate the risk of DDIs by maintaining a comprehensive list of a patient’s medications, including dietary supplements, as well as over-the-counter and illicit drugs. They should also leverage online tools to implement a reliable system for DDI checks and involve a pharmacist in the process. Reviewing the patient’s history for reactions to other medications can also provide valuable insights. Patients can already be experiencing difficulties with memory, motivation, scheduling, or medication adherence, and these challenges only worsen with polypharmacy and should be consistently addressed.
The significance of this question lies in the number of medications capable of causing DDIs. It is insufficient to merely warn about a single medication, as numerous medications across the different medical specialties can lead to DDIs. Even within the same class of medications, such as antidepressants, there are over 30 distinct members, each with their own unique characteristics regarding absorption, metabolism, and excretion. Consequently, DDIs may occur within and across medication classes. HCPs can strategically “play the odds” for evaluating their patients’ psychiatric treatment for DDIs by focusing on the 2 most significant pathways: CYP2D6 and CYP3A4/5. The majority, up to 80%, of psychiatric medications are metabolized through these pathways; it’s crucial for HCPs to consider them to prevent complications.
Medical literature reports that about 100,000 Americans die each year due to DDIs, but the number of patients harmed by them is far greater. Therefore, it is inaccurate to assume that only 1 or 2 combinations of medications warrant screening for potential problems. A better approach if you are practicing in psychiatry is to understand: (1) DDIs are dynamic, not static; (2) your patient may receive treatment from other specialists; (3) patients are often prescribed medications that utilize CYP2D6 and CYP3A4/5 pathways; (4) while daunting, the risk can be mitigated by proactively assessing patients for DDIs on a routine basis; and (5) it is always preferable to utilize a medication with minimal potential DDIs and the greatest range of doses available for treating patients. These principles apply to all disorders, not just TD.
This is an important conversation to have, as there are 2 treatment options for patients with TD, each carrying significant considerations for the clinician. AUSTEDO XR is the only FDA-approved vesicular monoamine transporter 2 inhibitor with no dose restrictions for patients taking strong CYP3A4/5 inducers or inhibitors. As such, AUSTEDO XR should be considered for concomitant use in patients with TD receiving treatment with strong CYP3A4/5 inducers or inhibitors for underlying conditions. For a treatment regimen that includes a strong CYP2D6 inhibitor or if the patient is genetically a poor CYP2D6 metabolizer, the maximum daily dose of AUSTEDO XR should not exceed 36 mg; however, the FDA has approved 5 different dose options of AUSTEDO XR of 36 mg/day or less for use in these patients, providing the HCP and patient with flexibility to adjust the dose as needed. This allows me to tailor my treatment decisions for each patient. AUSTEDO XR has clearly emerged as an important option for clinicians to consider when DDI issues are present.
