Med-Psych.com

Found an interesting article:
Comparison of Pharmacokinetic Profiles of Brand-Name and Generic Formulations of Citalopram and Venlafaxine: A Crossover Study

Typically I find Journal of Clinical Psychiatry to be biased towards pharmaceutical companies, so this may be just one more example. The authors receive grants and funding from multiple pharmaceutical companies but I doubt any of it comes from the generic manufacturers.

Nonetheless, it likely is a valid result and it is a very straightforward study. The results are concerning, yet understandable. Basically, the long acting Effexor XR produces lower blood levels than the generic version, novo-venlafaxine XR 75mg at a fixed interval after ingestion (they don't mention the time in the abstract, and I will assume it was selected shortly after ingestion to maximize the chances of finding an impact of long acting formulation vs an immediate release formulation). Because the steady state blood levels are the same, I'd say that the effect on treatment is minimal; however, the abstract makes a point of saying that the generic group had 3x the reported side effects, which would fit with a higher blood level. I'm curious what the rest of the article shows as far as which side effects were more frequently reported and whether they were mild, moderate, or severe.

My understanding is that the FDA is supposed to make sure that not only are the pill contents of the active ingredient are the same (which in this study they were) but also that the delivery time is similar. I'll need to do a bit more research into this.

The bottom line in my mind is that even if the release times are different, the active ingredient is the same and the dosage and timing should be able to be adjusted to have comparable efficacy. It is probably a non-issue when first starting out with the medication (perhaps starting with a lower dose or BID dosing until steady state if you know the formulation doesn't have as much of delayed release), but this is more of an issue if someone has been on one formulation and is switching to another.

Just to follow up, the FDA does require testing to show that the generic has the same bioavailability as the brand name drug.

You can get the full details here on the FDA website.

From the above referenced page on the FDA website:

MYTH: Generics take longer to act in the body.
FACT: The firm seeking to sell a generic drug must show that its drug delivers the same amount of active ingredient in the same timeframe as the original product.

and:

One way scientists demonstrate bioequivalence is to measure the time it takes the generic drug to reach the bloodstream and its concentration in the bloodstream in 24 to 36 healthy, normal volunteers. This gives them the rate and extent of absorption-or bioavailability-of the generic drug, which they then compare to that of the pioneer drug. The generic version must deliver the same amount of active ingredients into a patient's bloodstream in the same amount of time as the pioneer drug.

So, according to the FDA, adequate studies must be provided to show that the generic drug is equivalent to the brand name drug. The above referenced study seems to indicate that the blood levels were higher in the generic group and that side effect rates were higher. The question is who to believe? My own bias is against the pharmaceutical companies as they have an inherent bias in supporting studies that will be to their favor. The authors of the above referenced study have received grants and support from the manufacturer of Effexor (Wyeth). My own impression (and just my opinion) is that Journal of Clinical Psychiatry tends to publish articles that favor the pharmaceutical industry.

Nonetheless, the article has served its purpose in created doubt amongst people that the generic drug may not be equal to the brand name.

After doing a little more research, it is interesting that they did not find differences in bioavailability between citalopram and Celexa. The history of this finding was interesting enough that I'll be creating a separate thread here on the topic soon.