Web Exclusives

Polypharmacy of Psychotropic Drugs Rising

By Jamie Santa Cruz

New research suggests that numbers of prescriptions combining psychotropic medications are increasing.

Research finds that nearly four in 10 individuals over the age of 65 are taking five or more prescription medications simultaneously, indicating a common syndrome among older adults called polypharmacy.1 Although prevalent, combination prescribing is potentially harmful due to possible side effects associated with each drug and the additional risks brought on by drug combinations. Despite concerns, new research suggests that combination prescriptions, specifically of psychotropic medications, are ballooning. In fact, the number of older adults taking multiple central nervous system (CNS)-active medications has more than doubled over the period of a decade.2

The increase is not surprising, says Donovan Maust, MD, MS, an assistant professor of psychiatry at the University of Michigan and lead author of the new study, since other research shows that the use of psychotropic medications has risen generally. But the increased rates of combination prescriptions cause concern. "The hope would be that if, say, a patient was on a medication for anxiety or for pain, and then was really having trouble with sleep—you would hope that people would cut something out before adding something else," Maust says.

Helen C. Kales, MD, a professor of psychiatry at the University of Michigan and another of the study authors, agrees that the increase is alarming. "[It's] something that really raises concern because a lot of these medications have serious risks, especially when they're being coprescribed," she says.

The study, published in JAMA Internal Medicine, was based on data from the Centers for Disease Control and Prevention gathered through the National Ambulatory Medical Care Survey. The researchers found that 1.4% of all physician office visits for patients aged 65 and older between 2011 and 2013 were by patients who were taking at least three psychotropic medications simultaneously—up from just 0.6% of office visits 10 years prior. The data were drawn from a representative sample of physicians' offices for the years 2004 through 2013.2

Although the percentage of older adults impacted by polypharmacy of psychotropic medications is relatively small, Maust stresses that the older adult population is quite large. "That tiny percentage ends up being a big number of people," he says.

Particularly worrisome is the fact that close to one-half (45.9%) of the patients receiving multiple CNS-active medications did not appear to have an official mental health or pain diagnosis to justify those prescriptions. The percentage of patients without a diagnosis could be inflated because the study limited visit diagnoses to three. However, the findings suggest that many prescriptions are being given without sufficient justification. "It appears as though a lot of the prescribing is being done in a nonevidence-based fashion," Kales says.

According to Maust, it is not clear whether there has been an equal growth in the use of all CNS-active medication groups, or whether the overall increase is being driven by increased prescriptions of specific medication groups. He notes, however, that other studies have clearly documented a rise in opioid prescriptions and suggests, "It would be surprising if [opioid prescriptions] were not a key driver of this growth."

Drivers of Growth of Psychotropic Polypharmacy
The dramatic growth in CNS-active polypharmacy is likely due to a combination of factors, Maust says. These include destigmatization of mental illness, increased perception of mental illness as something to be treated, and limited access to nonpharmacologic therapies.

According to Kales, increasing direct-to-consumer drug marketing likely also plays a role. "Patients are increasingly being exposed to the idea that there is a medication to treat every problem they might have," she says. "Older patients may be getting more comfortable than they used to be with the idea of taking more medications."

Greatest Increase in Rural Areas
A significant finding of the study is that the largest increase in usage was in rural areas, where rates of combination psychotropic prescriptions more than tripled during the study period. According to Kales, this finding is likely explained by the fact that specialists in psychiatry are typically concentrated in urban areas. "In rural areas, there's going to be a real deficit in that type of expertise, so of course many patients are going to be seen in primary care settings," she says.

The challenge, she notes, is that many primary care physicians lack training—in the treatment of older adults as well as in psychiatry and the prescription of psychotropic medications. Primary care physicians are doing their best, she adds, but issues relating to prescription of CNS-active medications in older adults may simply lie outside their areas of expertise. Kales says the problem speaks to the need for accessible high-quality training for primary care physicians on issues related to prescribing for older adults.

In addition to the lack of training among primary care physicians, another factor that may explain higher rates of use in rural areas is the lack of availability of therapies other than medications. In rural areas, Kales says, there is often less access to counseling and other treatment modalities, either as alternatives to CNS-active drugs or as combination treatments. "If there are simply no providers to refer to for counseling or therapy, then maybe in that case a benzodiazepine is the only option from the physician's standpoint. So we need to look at what is available to physicians and the support that they themselves need to help patients," Kales says.

Concerns Surrounding Psychotropic Polypharmacy
One of the biggest concerns with psychotropic medication use among older adults is that such medications increase fall risk. Since a fall can easily mean a broken hip in older adults, Maust says, an individual who was functioning well prior to a fall can deteriorate rapidly. "A lot of these meds by themselves seem to increase fall risk, and then there's also evidence that the cumulative burden of psychotropic and opioid medications matters—that is, the greater the burden of medications overall, the higher the fall risk," he says.

According to Maust, fall risk appears to have been the main reason CNS-active combination prescribing was included as potentially inappropriate in the 2015 version of the Beers Criteria, a set of guidelines issued by the American Geriatrics Society regarding safe prescribing for older adults.

New research has shown that in addition to fall risk, other alarming risks related to combinations of opioids, in particular, with other psychotropic drugs. Specifically, several studies have shown an increased risk of both respiratory depression and death with opioid combinations.3-5 These new findings led the FDA in August 2016 to announce a new boxed warning on most such combinations.6

Not All Polypharmacy Is Inappropriate
Although the finding regarding the dramatic increase in CNS-active polypharmacy among older adults creates cause for concern, experts stress that not all combination prescriptions are inappropriate. Indeed, Kales says, there are cases where polypharmacy is "absolutely" justified. "Certainly in people with serious mental illness, for example—they may be on two or three psychotropics and they may very well need that regimen. … I would never recommend taking somebody off of medications without really understanding what they're being used for and whether they're necessary."

According to Todd Semla, PharmD, MS, a clinical associate professor in the departments of medicine and of psychiatry and behavioral sciences at Northwestern University, polypharmacy is usually understood to refer to the simple fact of patients taking multiple medications. Semla, however, prefers to reserve the term for cases in which patients are taking medications for which there is no apparent need, or in which patients are taking one medication to treat the side effects of another medication. Many older adults take multiple medications simultaneously, Semla says, but the rate of inappropriate polypharmacy is lower.

"If you take a patient who has type 2 diabetes, and he has heart disease, he could easily be on five medications just to manage those two conditions—and that doesn't address the joint pain he has from osteoarthritis, etc," Semla says. In other words, specifying a set number of medications and saying that any patient who is above that is a victim of polypharmacy is "a little too simple."

But, he says, any time a physician sees that a patient is taking multiple medications, he or she should stop to consider whether each prescription is actually working and necessary. After all, he says, "If there's no reason to be on the drug, or if the drug is not working, the only thing that can happen is for the drug to have adverse effects."

Takeaways for Physicians
Know why each of your patient's medications has been prescribed. Sometimes patients arrive for an office visit after having taken a particular medication for an extended period of time. But with changes in his or her condition or with changes in other medications, the original medication may no longer be necessary, Semla says.

Avoid prescribing without a corresponding diagnosis. According to Maust, physicians are sometimes tempted to prescribe psychotropic medications for patients complaining of poor sleep, anxiety, or pain, even if the patient does not meet diagnostic criteria for an anxiety disorder, for example. However, the physician may write a prescription, seeking to help the patient and may believe the medication will improve his or her symptoms.

However, Maust says, this may not be ideal. The evidence for benefit of psychotropic medications is typically established through clinical trials that have enrolled only those patients who meet the diagnostic criteria for a specific disorder. Thus, it is unclear that a medication will provide benefits for a patient who doesn't have the disorder. Meanwhile, all medications carry the potential for side effects or other harms regardless of the reason they are prescribed. As Maust explains, "If I prescribe my patient an antidepressant because he is a bit down, but he doesn't actually have major depression, the medication is unlikely to help his mood, but he can experience stomach upset and sexual dysfunction regardless."

Consider alternatives to psychotropic medications wherever possible. For example, Maust says, in the case of a sleep complaint, cognitive behavioral therapy is preferred as a first-line treatment over a psychotropic medication. For anxiety, psychotherapy and antidepressants are both effective and have fewer side effects than benzodiazepines.

Keep in mind risk/benefit analysis. Kales cites the example of antipsychotics prescribed for sleep complaints as a scenario in which the risk/benefit profile is extremely poor. There is significant evidence that antipsychotics are associated with a variety of serious side effects and even mortality for those with dementia, Kales says, and there are alternative treatments, both pharmacologic and nonpharmacologic, that are significantly less risky. "Always think about risk and benefit and whether the risk really is something you're willing to tolerate for the benefit the patient's going to get," she says.

— Jamie Santa Cruz is a freelance writer based in Englewood, Colorado.

1. Kantor ED, Rehm CD, Haas JS, Chan AT, Giovannucci EL. Trends in prescription drug use among adults in the United States from 1999-2012. JAMA. 2015;314(17):1818-1831.

2. Maust DT, Gerlach LB, Gibson A, Kales HC, Blow FC, Olfson M. Trends in central nervous system-active polypharmacy among older adults seen in outpatient care in the United States. JAMA Intern Med. 2017;177(4):583-585.

3. Dasgupta N, Funk MJ, Proescholdbell S, Hirsch A, Ribisl KM, Marshall S. Cohort study of the impact of high-dose opioid analgesics on overdose mortality. Pain Med.2016;17(1):85-98.

4. Park TW, Saitz R, Ganoczy D, Ilgen MA, Bohnert AS. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ. 2015;350:h2698.

5. Jones CM, Mack KA, Paulozzi LJ. Pharmaceutical overdose deaths, United States, 2010. JAMA. 2013;309(7):657-659.

6. FDA drug safety communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. US Food and Drug Administration website. https://www.fda.gov/Drugs/DrugSafety/ucm518473.htm. Updated August 31, 2016. Accessed March 29, 2017.