Special Article:

Are antipsychotics mood stabilizers?

Maintenance “enriched” studies are questionable

Chocolate and vanilla cake

Do you like chocolate cake?

Suppose that a pharmaceutical company decided to market chocolate cake. It wanted a Food and Drug Administration (FDA) indication for maintenance treatment with chocolate cake. It consulted with the FDA and got approval to design the pivotal research study this way: First, a sample of research subjects would eat chocolate cake and vanilla cake. If they liked vanilla cake only they would be excluded from further study. If they liked chocolate cake only, they would now be entered into a research study where they would be randomized to continue eating chocolate cake or eat vanilla cake instead. 

What do you think the results of the “randomized” clinical trial would show?  Have we  now proven that chocolate cake is better than vanilla cake? 

This is how the FDA approves maintenance treatment for antipsychotics for bipolar illness (and also for antidepressants in major depressive disorder).

“Enriched” but not better

The key issue in adjudicating the question of whether antipsychotics are mood stabilizers involves how the research studies test that question. The maintenance studies of dopamine blockers all use a similar basic design: they are “enriched” studies, also called randomized discontinuation trials (RDTs). The term “enriched” refers to the fact that the sample is enhanced in such a way that it is more likely to show a treatment effect. Put another way, the sample is preselected for subjects who have already responded to the medication being studied. The problem...

As described in the Classic Article of the Month,  the basic enriched design of a RDT is as follows:  a dopamine blocker is given to a group of patients with acute mania;  those who don’t respond or don’t tolerate medication are then excluded; the remaining patients who have responded to the dopamine blocker for acute mania are then entered into the randomized maintenance trial, in which they either stay...

To the complete article, including a complete analysis of the RDT design and implications in FDA's drug indications, click here or subscribe!

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