Direct to Consumer Drug Advertising: There's a Sucker Born Every Minute

Have you seen them? TV and print ads advocating the use of a new drug called Rexulti as something that can be used to augment an antidepressant when the antidepressant alone does not completely relieve all of your symptoms. These ads are only slightly different than ads you may have seen in the past for Abilify, which was also touted for the exact same indication.

As it turns out, both of these drugs are manufactured and distributed by the same companies: Otsuka Pharmacuetical Company and its marketing partner Bristol-Myers Squibb. And guess what? Abilify recently went generic (which means its original manufacturer has lost its patent protection and therefore its monopoly on the drug) under its chemical name, aripiprazole. 

Rexulti's chemical name seems oddly similar: brexpiprazole. Coincidence?

Well here are pictures of the chemical structures of the two compounds.

Remarkably similar, no? In fact, these drugs have effects on people that are nearly identical, have only slightly different side effects, and they both have the exact same indications. And of course they are not antidepressants at all as many of you have probably been led to believe, but antipsychotics: meant to treat delusions and hallucinations in schizophrenia, bipolar disorder (the real kind), and major depression with psychotic features.

(BTW, we've always known that any antipsychotic medication can augment an antidepressant in some patients. However, they have potentially very toxic side effects, and there are other, safer drugs which can also augment an antidepressant, such as lithium and a thyroid hormone named T3. I think benzodiazepine drugs such as clonazepam do as well, but drug companies are not about to do studies confirming that, because benzo's are so cheap and free of side effects).

There is one very big difference between Rexulti and Aripriprazole: the price. Generic Aripiprazole will be much, much cheaper. Why on earth would anyone ask for an expensive drug when a cheaper, nearly identical drug with the same effectiveness and nearly the same side effects is available?

Well of course they would not. Which is where the direct to consumer ads come in. The company wants to keep up its profits, so it pushes their new drug without any reference to their old one. And people are suckered into demanding it from their doctors. As someone once said, no one ever went broke underestimating the intelligence of the American people.

Now I can't prove that the company developed Rexulti in anticipation of losing its patient protection on Abilify, but the timing is a bit suspicious, wouldn't you say?

Drug companies have lots of tricks to extend their patent protections aside from just coming up with new conditions for which a drug is indicated, coming up with an extended release version of the same drug, or newly combining the drug with a second drug. 

Some drugs are converted to other drugs in the body which are in fact the compounds that have the desired effects (active metabolites). So after the parent drug goes off patent, they release the active metabolite as a "new" drug. Think Effexor vs. Prestique.

Some drug compounds come in two different versions which have the same chemical formula but different geometry - the two molecules (enantiomers) are mirror images of one another. One of the two versions may be effective for a given symptom while the other may have little effect. So drug companies first issue a mix of both versions (racemic mixtures), and when that drug goes off patent, they release a drug which is  the pure, active enantomier. Voila, new more expensive drug, new patent, and the clock keeping track of how long the company retains exclusive ownership of the drug starts to tick anew. Think: Celexa vs. Lexapro, and Prilosec vs. Nexium.

So if you pay attention to those ads, you will be being taken as sucker.

Lexapro and Prestiq: Nothing New Under the Sun

Remember a couple years ago when television was blanketed with ads for Nexium, the purple pill that represented the next "big step" in the treatment of gastric reflux esophagitis? Was this medicine something new? Well, sort of. To understand what the manufacturer did, first you have to know a little simple chemistry.

Molecules, as most of know, are made of atoms of various elements in a fixed ratio, like H20 is two hydrogen atoms and one oxygen atom combined to make water. If a molecule is large enough, two molecules with exactly the same chemical formula and structure can have slightly different geometry. The two molecules can be mirror images of one another, creating what are called enantiomers. The R-enantiomer is the right handed version and the L-enantiomer is the left handed version.

In particular, some drugs can have both L and R versions, but only one of the two versions may be active in the body, while the other is either completely inert (the usual case) or, in a few instances, creates different side effects. A mixture of the L and R versions is called a racemic mixture.The reflux drug prilosec is such a racemic misture. One enantiomer is active and the other is inert.

When prilosec, a highly profitable blockbuster drug, was about to go generic, the manuafacturer did something to preserve its profits. It created Nexium, which was not a racemic mixture but the single active enantiomer. Of course, the inactive enantiomer in Prilosec is inert, so in order to ingest an equivalent amount of "Nexium," all you have to do is take double the dose of prilosec. There would be no difference at all. And there is no evidence that Nexium is any more effective or has fewer side effects than Prilosec!

Lexapro, one of only three anti-depressants that have not already gone generic, is the R-enantiomer of Celexa (Citalopram) and is a lot more expensive than generic Citalopram, but in all other respects is nearly identical. Some people claim to have more side effects on the original drug, but this is debatable. They are equally effective, so why pay more?

Another trick the pharmaceutical companies use to extend sales of expensive, brand-named drugs when they are about to go off patent is to release what is called the active metabolite of the original drug as a new drug. For example, when the old antidepressant Elavil (amitriptylene) was broken down in the body, the first new molecule created was nortriptylene (Pamelor). Nortriptylene was the active drug for depression, not Elavil.

Now, in that case Pamelor was an improvement because the parent drug, which was not psychiatrically active, did have a lot of side effects that its metabolite did not. Elavil also had to be prescribed in much higher doses, which made its overdose potential more of problem.

When the antidepressant Effexor (venlafaxine) was about to go off patent, the drug company came up with Pristiq, which is desvenlafaxine, Effexor's active metabolite. The effectiveness of the two drugs is once again absolutely the same if the proper dosage is prescribed, and in this case, side effect differences are minimal. Pristiq's only advantage is that it has a narrower effective dosage range, so the doctor does not have to slowly increase the dose of the medication to see what the minimal effective dose will be in a given patient.

Still, unless money is no object, a patient might want to go with the cheaper generic alternative. I have no sympathy for insurance companies, but their interests are finally beginning to diverge from those of big PhARMA in a good way. They are starting to push for use of the generic alternatives for their subscribers in order to save money.