Generic vs Branded Psychiatric Medications: Is There a Difference?

Jane Lowers; Robert H. Howland, MD

Disclosures

April 25, 2012

In This Article

But Are Generics Really as Effective?

Medscape: There are a lot of anecdotal reports across multiple drug categories of people reporting variability in symptom control or side effects when moving from an innovator to a generic drug or vice versa, but they tend to be small case reports, not randomized controlled trials.[1]What can we say about that issue?

Dr. Howland: If a generic drug is exactly the same in terms of bioequivalence as a brand-name drug, then by definition the FDA assumes that it's therapeutically equivalent, meaning that it's as efficacious and also has the same tolerability and safety profile.

But any time new generic products become available and are used, some individuals may have an experience that's different than what they've been accustomed to with their brand-name product. It might be losing the effectiveness of their drug. In the case of epilepsy, it may be having a seizure if you switch from a brand-name to a generic drug. In psychiatry, you might have a depression relapse if you switch from a brand-name medication to a generic, or develop new or heightened side effects compared with a patient's experience with the brand-name medication.

Relapse risk is certainly a concern in psychiatry. There are 2 products that I know of about which there has been a lot of discussion and reports to the FDA. The first is clozapine -- Clozaril® is the brand name. When generic forms became available, there were some concerns about those not being as effective as the brand-name Clozaril.[2,3]

In more recent years, concerns about certain generic formulations of Wellbutrin (bupropion hydrochloride) were reported to the FDA and led them to examine the experience with various generic Wellbutrin products[4]and also led to the initiation of prospective trials to study whether patients' experiences in switching from brand-name Wellbutrin to generics led to changes in efficacy or adverse effects.

In epilepsy, there has been a lot of debate because of the very specific concerns about the risk for seizures and changing formulations, and how it may affect individuals in terms of driving restrictions and other functional effects of having a seizure.

The concern about anecdotal reports is that they don't necessarily prove that what you observe is caused by the change in medication. There's actually very little evidence, if you look at studies that used a randomized double-blind design to compare a brand-name with a generic medication and assess efficacy, tolerability, and safety, that really demonstrates that a generic is therapeutically different than a brand-name drug.

The clozapine randomized studies have not shown differences. There have been large-scale reviews in the epilepsy and cardiac literature on anticonvulsant medications and cardiovascular medications, which don't support the hypothesis that generics differ therapeutically from brand-name products.[5,6]

Medscape: Could you explain the other factors that can cause variability that is associated with a switch in medications?

Dr. Howland: What gets reported -- and what physicians and patients fear -- is that if they've been on a brand-name medication for a while and they switch to a generic, they will have a relapse or develop a side effect. The vast majority of patients who switch to generic products without any problems don't publicize this. It's certainly possible that a change in medication can lead to a change in efficacy or a change in side effects, but there may be other reasons for a loss of efficacy or development of new side effects.

Think about a randomized trial comparing a drug and placebo. In the placebo arm of these trials, if you look very closely at the data, a significant proportion of those patients get better, and a significant proportion of the patients also report side effects that seem similar to those of patients who are receiving an active drug. Some patients taking an inert substance will still report some type of clinical benefit or an adverse effect. That suggests there is some degree of expectancy or belief that is being conveyed into a clinically measureable effect.

I think this is a good example of what might happen to individuals who switch from a brand-name drug to a generic. If you look at anecdotal reports of a patient switching from a brand-name drug to a generic who became depressed again or developed a side effect, you really can't demonstrate on the basis of the anecdotal report that it was caused by the switch. As part of the natural history of depression, patients can have relapse despite taking the same medication over a certain period or despite being switched to a generic drug.

Nocebo effects might explain the development of side effects in switching from a brand-name drug to a generic. Nocebo effects are adverse effects that patients who are taking a placebo report, which is conversely analogous to the positive clinical benefits of a placebo. In a double-blind, placebo-controlled trial, patients taking the placebo pill who develop side effects are having what would be referred to as a nocebo effect.

My belief is that when patients switch from a medication -- if they've had a very strong feeling that they've done very well with it, if they have inherent fears about changing things, or if they believe that generics are not as good as brand-name medications -- a negative bias about making the switch can lead them to either be more depressed after the switch or to develop side effects, much like a patient in a randomized study who is assigned to placebo may get better or may develop side effects.

We also know from studies[7] that physicians often have very negative biases about whether generic medications are quality medications -- if they're as effective or well tolerated as a brand-name formulation. If patients are treated by a physician who says, "Well, you know, we can try the generic, but I'm kind of concerned about it," that may convey a negative bias to the patient. The interaction between what a physician believes and what a patient believes about the quality or the benefits of a generic compared with a brand-name product may be important.

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