The pharmacologic management of behavioral health conditions has grown considerably more complex over the past decade. As behavioral health diagnoses have increased in prevalence and comorbidity has become the norm rather than the exception, many patients are now managed on two or more concurrent psychiatric medications. While multi-drug regimens are clinically appropriate for a meaningful subset of patients, polypharmacy also carries well-documented risks (e.g., drug-drug interactions, adverse side effects, medication non-adherence and higher total cost of care).
Prior research found that antidepressants ranked as the second most prescribed drug class overall among patients on five or more medications, and the top-ranked class among both men and women ages 18-44.1 However, the dynamics driving psychiatric polypharmacy are distinct from those driving multi-drug use in primary care or chronic disease management. Behavioral health polypharmacy is shaped by a confluence of the high prevalence of comorbid psychiatric diagnoses, inadequate supply of behavioral health providers and the proliferation of direct-to-consumer (DTC) prescribing platforms.
Polypharmacy – broadly defined as the concurrent use of multiple prescription medications – is associated with a 16% higher risk of hospitalization and a 25% higher mortality risk compared to patients on one or two medications, reflecting both the complexity of underlying conditions and the potential for medication-related harm.2 Polypharmacy is more common in older populations, and over half of adults ages 65 and older prescribed five or more medications in 2024 as compared to nearly one in four adults ages 18-44 in the same time period.
Within this broader context, behavioral health polypharmacy represents a clinically distinct and increasingly significant subset, although the clinical rationale is not always straightforward. In some cases, combination regimens reflect evidence-based augmentation strategies (e.g., the addition of atypical antipsychotics to antidepressants in treatment-resistant depression, or stimulants alongside SSRIs in patients with co-occurring ADHD and anxiety). In others, polypharmacy occurs when medications are added in response to partial treatment response or emerging symptoms without systematic deprescribing of agents that are no longer indicated.3 For example, antipsychotic polypharmacy – the concurrent use of two or more antipsychotic agents – is particularly common in the management of schizophrenia and bipolar disorder, despite limited evidence of incremental efficacy and established risks including metabolic syndrome, extrapyramidal side effects and QT prolongation.4
Comorbidity is central to understanding behavioral health polypharmacy since co-occurring psychiatric diagnoses are common. For example, over 40% of individuals with a behavioral health condition have at least one co-occurring condition, and co-occurring mental illness and substance use disorder affects roughly 8% of U.S. adults.5 These presentations frequently require multi-drug management, but they also demand a level of clinical coordination that the current behavioral health delivery system is insufficiently structured to provide. Nationally, the mental health professional adequacy rate is 27.3%, and projected workforce shortfalls suggest demand will continue to outpace supply through at least 2038.6 Prescribing responsibility for complex, multi-diagnosis patients increasingly falls to primary care physicians and general practice nurse practitioners and physician assistants, as opposed to specialized providers.
DTC telehealth platforms have accelerated this dynamic in behavioral health specifically, expanding access to psychiatric prescribing (e.g., stimulants, anxiolytics and antidepressants) often without integration into a patient's broader medication history. When a patient receives a stimulant prescription from a DTC platform, an SSRI from a primary care provider and a sleep aid from an urgent care visit, no single clinician may have full visibility into the cumulative pharmacologic burden. This fragmentation represents a polypharmacy risk that is distinct from the clinical judgment of any individual prescriber and is unlikely to be resolved without deliberate care coordination.
The economic consequences of unmanaged behavioral health polypharmacy are substantial. Adverse drug events attributable to psychiatric medications are among the most common causes of medication-related hospitalizations in the U.S., accounting for an estimated 89,000 emergency department visits annually.7 Patients on complex multi-drug regimens also exhibit lower medication adherence, higher rates of early treatment discontinuation and greater reliance on acute care settings. At the same time, untreated or inadequately treated behavioral health conditions have a material economic impact, currently estimated at $477.5B annually and projected to exceed $1.3T by 2040. The imperative for health economy stakeholders is to ensure that prescribing is clinically appropriate, coordinated and actively monitored for safety and efficacy.
Given the substantial downstream impacts on health status and spending, it is critical to examine how have behavioral health polypharmacy patterns evolved in recent years, particularly amid the growth in fragmented DTC prescribing.
National all-payer claims data were analyzed to examine behavioral health prescribing patterns between 2018 and 2024. To examine trends in behavioral health prescribing, patient volume by drug class – stimulants, anxiolytics, antipsychotics, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) and mood stabilizers – were analyzed.
To assess polypharmacy patterns, patients were categorized by the number of distinct drug classes represented in their behavioral health prescriptions, ranging from one to six classes. The number and share of patients in each category were calculated overall and stratified by age group (0-17, 18-44, 45-64 and over 65) and sex. Among patients prescribed medications spanning two or more drug classes, the share of patients utilizing each of the six drug classes was examined. Additionally, the top 10 most common multi-class drug combinations were identified for 2018, 2021 and 2024.
Between 2018 and 2024, the majority of patients with behavioral health prescriptions were prescribed medications from a single drug class, though this share declined from 68.1% to 64.4% over the period (Figure 1). Notably, that share equates to nearly 29M patients in 2024, up from 24M in 2018. Across the same period, the share of patients prescribed medications spanning two classes – representing 11M patients in 2024 – grew slightly from 23.0% to 24.8%. However, those prescribed three classes – nearly 4M patients in 2024 – increased from 6.9% to 8.3% and those prescribed medications from four to six classes – over 1M patients in 2024 – grew from 2.0% to 2.6%.
Across both 2018 and 2024, women accounted for a disproportionately higher share of behavioral health prescribing at every level. In 2024, women accounted for 59.9% of patients on one class, increasing to 67.3% among those on four to six classes, which remained largely unchanged across the study period. Overall, women accounted for a larger share of polypharmacy prescribing in both years.
Polypharmacy patterns varied meaningfully by age group in both 2018 and 2024. Pediatric patients ages 0-17 had the highest share prescribed a single drug class in both years (79.5% in 2018 and 74.5% in 2024), while adults ages 18-44 and 45-64 had the greatest multi-class prescribing (Figure 3). By 2024, patients ages 18-44 had the lowest single-class prescribing share at 62.0% and the highest two-class share prescribing at 26.0%, while patients ages 45–64 followed closely with 64.1% on one class and 25.2% on two. Across all age groups, the share on a single class declined between 2018 and 2024, with corresponding increases in two- and three-class prescribing.
Among patients prescribed medications from two or more drug classes, anxiolytics and SSRIs were the most prevalent classes throughout the study period, with anxiolytics present in 68.6% of this population in 2018 and 67.0% in 2024, and SSRIs in 65.7% and 64.1%, respectively (Figure 4). Antipsychotics were present in roughly one-third of polypharmacy patients, increasing slightly from 34.5% in 2018 to 36.6% by 2024. Stimulant use among this population grew most notably, increasing from 22.4% in 2018 to 29.3% in 2024. SNRIs remained relatively stable as a share of patients, decreasing slightly from 24.6% to 22.9%, while mood stabilizers also declined modestly from 19.7% to 18.7%.
The anxiolytic/SSRI combination ranked first among all behavioral health drug class pairings in 2018, 2021 and 2024 (Figure 5). The most notable shift across the three index years was the rise of SSRI/stimulant prescribing, which changed from third position in 2018 to second in 2021 and 2024. The anxiolytic/SNRI combination fell from second position in 2018 to third in both 2021 and 2024, displaced by stimulant pairings. The bottom of the top 10 list showed more volatility. SNRI/SSRI and Anxiolytic/SNRI/SSRI combinations were among the top combinations in 2018 but dropped out of the top 10 by 2024, replaced by anxiolytic/SSRI/stimulant and antipsychotic/anxiolytic/mood stabilizer, reflecting the growing complexity and stimulant involvement in multi-class regimens over time.
Growing behavioral health polypharmacy is simultaneously a symptom and a driver of the broader U.S. behavioral health crisis. Between 2018 and 2024, the share of patients on a single behavioral health drug class fell from 68.1% to 64.4%, while those on three or more classes grew from 8.9% to 10.9%. Adults ages 18-44 now carry the highest polypharmacy burden of any age group, and women account for a disproportionate share of multi-class prescribing at every level of complexity. As comorbid diagnoses become more prevalent among younger adults, multi-drug regimens are increasingly the norm rather than an exception. The continued growth in polypharmacy is almost certain, which raises many uncomfortable questions. What are the root causes of these concerning trends, and what solutions are available to society other than a steady increase in polypharmacy? In the interim, what regulatory changes are required to provide more effective oversight to prioritize patient safety?
The rapid growth of stimulant and SSRI/SNRI co-prescribing warrants particular attention. Stimulant use among patients on two or more behavioral health drug classes grew faster than any other class between 2018 and 2024, rising from 22.4% to 29.3%, and the SSRI/stimulant combination climbed from third to second among all drug class pairings over the same period. This pattern reflects the growing prevalence of co-occurring ADHD and anxiety and seemingly correlates with the proliferation of DTC telehealth platforms that have lowered prescribing barriers without corresponding evidence of improved care coordination. When prescribing occurs across disconnected providers and platforms, the risk is both pharmacologic and systemic.
Managing concurrent psychiatric medications requires familiarity with drug-drug interactions, tolerance for diagnostic uncertainty and the clinical bandwidth to monitor patients longitudinally. These are not trivial competencies, and the infrastructure to support non-specialist prescribers – including clinical decision support tools, supervision frameworks and structured medication review protocols – has not kept pace. For providers, these findings reinforce the importance of medication reconciliation, measurement-based care and structured deprescribing protocols – particularly as patient panels grow more diagnostically complex. Research presented consistently demonstrates that medication regimens tend to grow incrementally over time, with additions outpacing systematic review. Integrating structured deprescribing protocols into routine care workflows, rather than relying on episodic clinical judgment, is associated with more appropriate prescribing outcomes. For health systems, investment in clinical decision support at the point of prescribing for non-specialist providers is a high-priority intervention for managing polypharmacy risk without restricting access to care.
For payers, the growing prevalence of behavioral health polypharmacy has direct implications for benefit design and total cost projections. This population drives disproportionate spending and carries elevated risk for adverse outcomes and avoidable acute utilization. Reimbursement structures that reward longitudinal medication management are better aligned with the clinical demands of these patients. Prior authorization policies, often applied broadly across behavioral health drug classes, should be tailored to flag clinically questionable combinations rather than simply restricting access to any individual agent.
For policymakers, the challenge is to design programs that expand behavioral health access without catalyzing an increase in the volume of unsafe prescribing. This means investing in training and supervision for non-specialist prescribers, strengthening care coordination requirements for telehealth platforms and ensuring that mental health parity enforcement extends to coverage of medication management services. The September 2024 update to the Mental Health Parity and Addiction Equity Act took a step in this direction, and its subsequent non-enforcement has reintroduced the coverage variability that makes fragmented, uncoordinated prescribing more likely. Without deliberate attention to the quality and coordination of behavioral health prescribing, rising utilization will continue to outpace the system's capacity to deliver care that is not only accessible, but safe.