renal compromised patients. Most interactions based oncomorbid medical illnesses or co-administered drugs totreat those comorbid conditions are discovered postap-proval.
Before addressing the issue of potential claims that mayarise from studies of psychotropic drugs in patients havingcomorbid mood disorders and medical illness, it is neces-sary to introduce the concept of pseudospecificity. Aproposed claim for a drug in a psychiatric illness would beconsidered pseudospecific if it was found to be artificiallynarrow (i.e., focusing on a subgroup within the ill popu-lation or on a particular aspect of the illness, such as aparticular symptom) in the absence of any empiricalevidence to support such a restricted focus. Such claimsserve only to permit a promotional advantage for the drug,since they imply an advantage of that drug over otherdrugs in the class for the subgroup or symptom of interest.Since no such advantage has been demonstrated, suchclaims would be misleading. Of course, if superiority overother drugs in the class with regard to the subgroup orsymptom of interest could be demonstrated, the claimwould no longer be considered pseudospecific. Legitimacyof a claim in a subgroup or for a particular symptom couldalso be established by showing that the drug works only inthat subgroup or only for that particular symptom. Whiledemonstrations of superior efficacy for a drug are difficultto accomplish, they are most likely to be feasible insituations where a particular subgroup of an ill populationor a particular symptom of an illness are not well treatedwith existing therapies. The bottom line is FDA considersnarrow claims in subgroups of an ill population or forparticular symptoms of that illness as pseudospecific untilproven otherwise.It is easiest to illustrate pseudospecificity with exam-ples. One type of pseudospecificity would be to focus ona demographic subgroup of a recognized entity (e.g.,major depressive disorder [MDD] in women). A relatedtype of pseudospecificity would be to focus on a recog-nized entity in the context of a comorbid illness (e.g.,MDD in patients with coexisting hypertension). Anothertype of pseudospecificity would be to focus on a specificsymptom of a recognized entity (e.g., targeting hallucina-tions in schizophrenia). Similarly, focusing on psychiatricsymptoms that occur as a normal accompaniment tomedical illness and that improve with the effective treat-ment of the underlying medical illness (e.g., targetinganxiety that occurs in patients with herpes simplex andthat improves as the herpes infection clears) would beconsidered pseudospecific. Finally, claiming an effect in asingle disease model of a recognized nonspecific symptom(e.g., a specific claim for dental pain rather than a moregeneral analgesic claim) would be considered pseudospe-cific. The FDA would consider all of these claims to bepseudospecific in the absence of evidence to show they arelegitimate. While there is the potential for any of theseclaims to be shown to be legitimate, the burden falls to thesponsor of a drug to show that any particular claim is justified.
Claims Arising in the Context of ComorbidMood Disorders and Medical Illnesses
It is easiest to illustrate the regulatory issues that arise inconsidering claims based on studies of psychiatric drugs totreat mood disorders in patients having comorbid medicalillnesses by providing examples. Several possible scenar-ios will be proposed, each involving the psychiatric drugtreatment of mood symptoms or other psychiatric symp-toms occurring in patients having comorbid medical ill-nesses.
Major depressive disorder occurs in patients with seriouscardiovascular disease, and a psychiatric drug is shown tobe superior to placebo in treating the MDD in thispopulation.
The important observation in this exam-ple is that the MDD seen is identical to MDD seenindependently of this medical illness (i.e., it just happensto coexist with this medical illness). Thus, a claim forMDD in serious cardiovascular disease would be consid-ered pseudospecific. Theoretically, it would be possible togain a claim in this very narrow context (e.g., if it could beshown that this drug were effective in treating MDD onlyin the presence of serious cardiovascular disease and nototherwise). Alternatively, if it were possible to show thatthis drug had superior efficacy compared to other drugs inthe class in treating MDD in the presence of seriouscardiovascular disease and not more general superiority toother drugs in the class, a narrow claim might be sup-ported. As noted earlier, it is this kind of superiority that isimplied by such a narrow claim. While such demonstra-tions of differential efficacy are theoretically possible,they are difficult to accomplish.
A depressive syndrome that can be well characterized(phenomenology, course, etc.) and is phenomenologicallydistinct from MDD occurs in patients with Alzheimer
sdisease (AD), and a psychiatric drug is shown to be