Comorbidities raise risk of resistant depression fivefold.

VIENNA -- Patients with unipolar major depression and anxiety disorder are at more than fivefold greater risk of treatment-resistant depression than are those without this common comorbid condition, Dr. Julien Mendlewicz reported at the annual congress of the European College of Neuropsychopharmacology.

An ongoing multicenter European study--the largest ever undertaken on treatment-resistant depression--identified five independent risk factors for this condition in a multivariate logistic regression analysis with comorbid anxiety disorder topping the list, according to Dr. Mendlewicz, immediate past president of the college and professor of psychiatry at the Free University of Brussels. Those five risk factors are comorbid anxiety disorder, lack of response to the first antidepressant prescribed in the patient's lifetime, melancholic features, and severe vs. moderate intensity.

To date, the seven-center study has enrolled 702 patients with unipolar major depression and even more with bipolar depression.

The goal is to identify clinical, psychosocial, biologic, and genetic predictors of treatment resistance and remission. Dr. Mendlewicz confined his analysis to the 346 patients with treatment-responsive unipolar depression and the 356 with treatment-resistant depression as defined by failure to achieve a Hamilton Depression Rating Scale score below 17 after at least two consecutive trials of antidepressants of adequate dose and duration during their last depressive episode.

The multicenter study, supported by H. Lundbeck A/S, a pharmaceutical company based in Denmark, was undertaken because treatment-resistant depression is an extremely common and underexamined clinical problem, Dr. Mendlewicz said.

Numerous studies have documented that 29%-46% of depressed patients show partial or no response to an adequate trial of the first antidepressant prescribed.

"Many patients whom we traditionally call responders--for example, those with a 50% improvement on our depression symptom scales--are really only partial responders who have a number of residual symptoms, including suboptimal quality of life, and secondary drug side effects," he said.

In an interview, Dr. Hans-Jurgen Moller predicted that this ongoing study of treatment-resistant depression would be "very important" in clinical practice. He said he is particularly excited about the planned genetic profiling. "The sample size is huge. The message that comorbidity is an important driver of treatment resistance is very important," observed Dr. Moller, professor and chairman of the department of psychiatry at Ludwig-Maximilians University, Munich.

Roughly 40% of patients with unipolar major depression have a comorbid anxiety disorder, noted Dr. Moller, who has served as an adviser to and received research support from Lundbeck.

BY BRUCE JANCIN

Denver Bureau