The articles by Arline Kaplan and Hagop Asiskal, MD, in the November 2011 issue of Psychiatric Times1,2 highlight the race to patent bio-tests for schizophrenia and depression. Alas, this drive is destined to fail for the same reason that earlier biotests failed—the heterogeneity of the populations for these disorders as defined by the DSM criteria. The failure of the STAR*D, STEP-BD, and CATIE studies to find assured efficacy for the treatments in the trials is sufficient evidence to question the DSM criteria.
Dr Akiskal notes that “the dexamethasone(Drug information on dexamethasone) suppression test [DST] was considered to have acceptable sensitivity and specificity for melancholia, rather than broadly defined depression.”2 But it was the view of key opinion leaders of an NIMH committee in 1982 and the 1986 Glassman APA Commission that the failure of the DST to define “major depression” doomed it for rejection in the clinic.
In the past decade, the question has been asked whether the DST could be used to identify the melancholic patients who fail to respond to SSRI, SNRI, MAOI, and the psychotherapies, but do respond to tricyclic antidepressants (TCAs) and elecroconvulsive therapy (ECT). The evidence that hypercortisolemia is a biomarker of melancholic mood disorders is compelling.
In the STAR*D study, the patient records were examined for the DSM “melancholia specifier.”3 Overall 42% to 55% of the sample were considered treatment failures. Additionally, 23.5% were positive for the melancholic specifier; their inclusion reduced the remission rates by 24.1%. Had they been excluded and treated by TCA and ECT, the overall remission rate for the SSRI would have been salvaged.
The sad history of the rejection of the DST and its present exclusion from clinical use (failure of reimbursement by insurers is a tragic consequence of the present teaching) is described by Edward Shorter and Max Fink in Endocrine Psychiatry.4 Additional references (all not reviewed by the major journals) are Taylor and Fink’s Melancholia: A Clinician’s Guide5 and the proceedings of the 2006 Copenhagen conference on Melancholia published as “Melancholia: Beyond DSM, Beyond Neurotransmitters.”6
Dr Asiskal’s opinion that “biomarkers for mental disorders [are a] field whose time has come” is correct. We have many markers that are in use—EEG criteria for epilepsy, serum tests for neurosyphilis, the lorazepam(Drug information on lorazepam) test for catatonia. Tests for hypercortisolemia are freely available for melancholia and warrant study and use.
It is timely to reconsider the DSM division of major depression and bipolar disorder that serve patients and doctors poorly and seek a new split of the mood disorders as melancholia and non-melancholia.