Generic, Class Substitution of Meds: Does it Harm Patients?

Should generic medications be substituted at the pharmacy for prescribed brand-name formulations?

In light of widespread public concern about spiraling pharmaceutical drug prices, it’s a question that is receiving some attention.

Psychiatric News spoke with clinicians about “generic substitution”—the practice of substituting a generic formulation of a brand-name drug—and the more controversial cost-control practice known as “therapeutic substitution.” The latter, which is the substitution of a different, lower cost molecule for another prescribed medication in the same “therapeutic class,” was the focus of a recent report in JAMA Internal Medicine that highlighted the potential cost-saving implications of therapeutic substitution.

While generic substitution is widely legal and commonly practiced, clinicians who spoke with Psychiatric News cautioned that how patients respond to generics can differ from how they respond to brand-name drugs.

“I think [generic substitution] is generally safe,” said Philip Muskin, M.D., a professor of psychiatry at Columbia University Medical Center, chief of the Consultation-Liaison Psychiatry Service, and editor of Psychiatric News PsychoPharm. “There is little evidence to support the idea that generics are less effective. However, that doesn’t necessarily mean they are the same. The chemical may be the same, but the preparation may be very different, and that can be important.”

Pill coatings and inert ingredients that go into preparing the generic formulation may produce different, or worse, side effects in individual patients than those they experience with a brand. This may be particularly true for extended-release pills when a different preparation may be absorbed at a very different rate than the brand. “The challenge for the patient and physician is to keep in mind that there may be side effects they have not seen before with a brand-name formulation,” Muskin said.

Child psychiatrist Adelaid Robb, M.D., said she believes the safety of generic substitution depends not only on the patient, but also on the drug being prescribed. Robb noted that when the patent for Prozac ended and patients who had been receiving higher doses of the drug for obsessive-compulsive disorder (OCD) were switched to a generic formulation, some patients experienced the return of some symptoms.

“When they switched to the generic, they lost efficacy because the highest dose on the generic wasn’t as high as on the brand,” she said. “It was almost a quarter dose lower, and some patients experienced breakthrough symptoms.”

University of Michigan SOM

Gregory Dalack, M.D., chair of the Department of Psychiatry at the University of Michigan and a member of APA’s Council on Quality Care, said his own experience treating patients switched from brand name to generics has been generally favorable. “I favor use of generic forms of medications whenever possible,” he said. “I have had a very small number of patients—perhaps five—over the course of my career whom I felt did do better on a brand drug versus the generic, but we have generally come to this after the switch from brand to a newly available generic does not go well and we try some alternative dosing first.”

In light of what is widely regarded as an alarming increase in drug prices, some believe there is an ethical case for the use of generics. “When public or private insurance is paying for the drug, substituting an FDA-approved generic medication for a branded drug serves general welfare by saving money,” Jim Sabin, M.D., director of ethics at the Harvard Pilgrim Healthcare Plan, told Psychiatric News.

But he added, “When an individual is self-paying for a medication, the person should have the right to purchase the branded product. In principle, allowing an individual to have access to the branded product by paying the price difference between the generic and the branded drug is a good policy. It gives the individual choice, but it does not require others to pay for his preferences.

“There should be an easy-to-use appeal mechanism, so that if there is a reason other than preference on the part of the physician or the patient, the branded product can be dispensed,” he said. “Having had a previous allergic reaction to the generic is an example of a justifiable appeal.”

“Overuse” of Branded Drugs?

Therapeutic substitution appears to be a step further—and perhaps a step too far—to address rising drug prices.

A study appearing in the June issue of JAMA Internal Medicine looked at the price differential associated with hypothetically substituting generic medications that were different from prescribed brand-name drugs but were in the same therapeutic class.

That study found that from 2010 to 2012, an estimated $73.0 billion in total excess expenditure and $24.6 billion in out-of-pocket excess expenditure was attributable to what the authors called branded drug “overuse.” The drug classes with the highest excess expenditure included statins ($10.9 billion), atypical antipsychotics ($9.99 billion), proton pump inhibitors ($6.12 billion), selective serotonin reuptake inhibitors ($6.08 billion), and angiotensin receptor blockers ($5.53 billion).

The study authors acknowledged widespread opposition to therapeutic substitution. “There is legitimate concern that therapeutic substitutions could lead to worse clinical outcomes, but this would likely be concentrated in high-risk drug classes,” they stated. “If therapeutic substitution were to become commonplace, more efficient systems that allow for seamless communication among prescribers, pharmacies, and insurance companies should be in place.”

In response to a query from Psychiatric News, lead author Michael Johansen, M.D., of the Department of Family Medicine at Ohio State University, emphasized that he does not favor substitution by a pharmacist without consultation with the prescribing clinician.

“Automatic therapeutic substitution would have the potential to be detrimental to patients’ health,” he said. “There are certainly occasions when use of more expensive branded products is warranted based on a clinical scenario. Within this study, we attempted to mitigate this by decreasing the number of hypothetical substitutions of psychiatric medications. That being said, some of the drug classes with the highest excess expenditure were psychiatric medications. For instance, escitalopram had billions expended on it when there were five other SSRIs available. It is rare that the use of this drug was clinically necessary. 

“The take-home message from the study is that prescribing in United States is inefficient,” Johansen said. “Too many branded drugs are used, when generics will work equally effectively at dramatically lower prices. This does not mean we shouldn’t prescribe branded drugs, but this should be restricted to times when it is absolutely necessary.”

All of the clinicians who spoke with Psychiatric News were unanimous that therapeutic substitution was at least unwise, and possibly dangerous.

Glenn Martin, M.D., immediate past speaker of the APA Assembly, told Psychiatric News that he believes the policy is “problematic and potentially dangerous.” He said, “We know that even within relatively well-defined classes, not all drugs are the same, especially when it comes to side effects, drug interactions, and patient tolerance.”

Martin added, “Psychiatrists understand and value the important role of pharmacists and are happy to collaborate with them. But class substitution without prior specific approval by the physician is not in the patient’s best interest and should definitely not be allowed to be mandated as a cost–saving tactic.”

At APA’s 2016 Annual Meeting, the Assembly approved an action paper requesting the Association to revisit its position on the issue of medication substitution without the express consent of the prescribing psychiatrist. The action paper was in response to a 2013 Arkansas law that appears to be the first in the nation allowing the practice of therapeutic substitution (see related article).

Instead of allowing the decision to be made by pharmacists, Dalack said, a more favorable option might be the inclusion of alerts in a patient’s electronic health record that indicate information about the options for therapeutic substitutions, including cost differentials. “That way I could consider and discuss with my patient.”

Child psychiatrist Robb echoed that comment. “The appropriate time to be thinking about cost is during the initial discussion with a patient, not after he or she has been stabilized on a brand-name drug.” ■