Psychiatric Polypharmacy Continues to Grow

Psychiatrists who prescribe drugs for their patients today usually give more than one at a time, often with little scientific basis, researchers said.

About 60% of patients with psychiatrist office visits leading to a drug prescription received at least two medications in 2005-2006, according to government survey data analyzed by Ramin Mojtabai, MD, PhD, MPH, of Johns Hopkins University, and Mark Olfson, MD, MPH, of Columbia University.

That was up from about 43% in 1996-1997 (P<0.001), the researchers reported in the January Archives of General Psychiatry.

They also found that 33% of prescription-associated visits led to three or more medications in the latter period, compared with 17% nine years earlier (P<0.001).

These multiple combinations sometimes involved drugs within the same class -- two or more antidepressants for depressed patients, for example -- but more often drugs of different classes.

Gaining in popularity during the study period were combinations of antidepressants and antipsychotic drugs, with an adjusted odds ratio of 1.96 (P<0.001) for each year during the study period.

"While some of these combinations are supported by clinical trials, many are of unproven efficacy," Mojtabai and Olfson wrote. "These trends put patients at increased risk of drug-drug interactions with uncertain gains for quality of care and clinical outcomes."

Jeffrey Lieberman, MD, of Columbia University, who was not involved with the study, told MedPage Today in an interview that the findings were "disturbing and not entirely surprising."

He said earlier studies as well as his own experience had suggested that psychiatric polypharmacy is a growing phenomenon.

The researchers based their findings on data from the CDC's ongoing National Ambulatory Medical Care Survey program. The analysis covered 13,079 psychiatrist office visits over the 11 years from 1996 through 2006.

Drug prescriptions and other survey data were provided by participating physicians' offices after each visit. Mojtabai and Olfson classed the reported drugs into four categories: antidepressants, antipsychotics, mood stabilizers, and sedative-hypnotic drugs. Benzodiazepines and other drugs often used for anxiety disorders were included in the last category.

Overall, the percentage of psychiatrist office visits leading to one or more drug prescriptions increased from 73.1% in 1996-1997 to 86.2% in 2005-2006 (P<0.001), Mojtabai and Olfson found.

While the median number of prescriptions in the earlier period was one, it had risen to two by 2005-2006. The mean increased to 1.99, from 1.42 in the mid-1990s (P not reported).

In addition to the passage of time, other factors significantly associated with psychiatric polypharmacy included the following (all odds ratios adjusted for demographics and clinical characteristics of visits):

* Age 45 to 64: OR 1.31 relative to younger age (P<0.001)
* Female sex: OR 1.30 relative to men (P<0.001)
* Medicaid patient: OR 1.77 relative to private insurance (P<0.001)
* Medicare patient: OR 1.73 relative to private insurance (P<0.001)
* Multiple psychiatric diagnoses: OR 1.61 (P<0.001)

Single diagnoses of major depression, bipolar disorder, anxiety disorder, or schizophrenia were also each significantly associated with multiple prescriptions, with adjusted odds ratios ranging from 1.57 for anxiety to 3.79 for bipolar disorder (all P<0.001) relative to patients with other diagnoses.

Racial minorities were less likely to receive multiple prescriptions than were whites, as were new patients relative to returning patients.

Mojtabai and Olfson found that antidepressants were most often prescribed with sedative-hypnotic drugs, accounting for 22% of all visits in which an antidepressant was prescribed in 1996-1997 and 27% of those in 2005-2006 (not significant).

Some 10% of visits involving antidepressants in the earlier period also included an antipsychotic prescription, which increased to 16% in 2005 to 2006 (P<0.001).

Adding a second (or third) antidepressant also doubled in frequency, from 8% to 16% of visits leading to an antidepressant prescription.

Antidepressants were the most commonly prescribed psychiatric medications at both time points, involved in more than 60% of visits with prescriptions.

Combinations not involving antidepressants also increased in frequency, but Mojtabai and Olfson -- who used a strict P<0.01 standard for statistical significance -- reported that those increases were not significant.

For example, the frequency of antipsychotic and sedative-hypnotic drug combinations increased by about half during the study period, from 8% of antipsychotic-associated visits to 12%, with a P value of 0.02.

"Significant time trends appeared to be mainly limited to concomitant prescription of two or more antidepressants or antipsychotics as well as combinations of antipsychotics and antidepressants," the researchers wrote.

In their discussion of the results, they took a dim view of these trends.

They noted that there was some evidence that combining antidepressants can improve the efficacy. But they also indicated that such combinations raise the risk of adverse effects.

"Some antidepressants inhibit cytochrome P450 enzymes and thus impact the metabolism of other psychotropic medications, including other antidepressants," they pointed out in the report.

"A further potential complication associated with overuse of antidepressant medications is the risk of emerging manic symptoms in susceptible depressed patients and acceleration of mood cycles in patients with bipolar disorder," they wrote.

They expressed similar concerns about combinations of antidepressants and antipsychotics.

Lieberman said there was little evidence to justify multiple drugs for treating depression.

"Are there studies showing that two drugs or three drugs are better than one drug? The answer is no," he said. "There's a potential rationale but it's not all that compelling."

Mojtabai and Olfson indicated that the reasons for the increase in polypharmacy were unclear, but suggested that "a change in the style of psychiatric practice" may be been at least partly responsible.

"Some psychiatrists may be placing greater emphasis on symptom reduction while lowering their concerns over the number of medications required to achieve this clinical goal," the researchers wrote.

In a telephone interview, Lieberman said one factor may be that doctors are "frustrated by the limitations in effectiveness of existing medications," tempting them to simply pile on additional drugs.

Consequently, he said, "they improvise with what might be called innovative psychopharmacology, or trial and error."

He said marketing may also be an influence. Although drugmakers aren't permitted to tout unapproved combinations, their advertising for approved indications may have a "carryover effect" in the minds of physicians as well as patients, Lieberman said.

Lieberman said increased education and perhaps restrictions on drug formularies -- especially in the Medicare and Medicaid programs -- could help rein in the polypharmacy practice, though he noted that limiting access to medications was unpopular with both physicians and patients.

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No external funding for the study was reported.

Lieberman reported receiving research funding from Pfizer, Lilly, AstraZeneca, Merck, and GlaxoSmithKline.
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Primary source: Archives of General Psychiatry
Source reference:
Mojtabai R, et al “National trends in psychotropic medication polypharmacy in office-based psychiatry” Arch Gen Psych 2010; 67: 26-36.