Cognitive Impairment Found in Patients With Treatment-Resistant Depression

SAN DIEGO —In a study exploring the role of cognitive impairment in treatment-resistant depression, patients exhibited considerably more cognitive deficits than healthy controls. These results, reported by Philip D. Harvey, PhD, Professor of Psychiatry at Emory University in Atlanta, and colleagues, were presented at the 160th Annual Meeting of the American Psychiatric Association.

Treatment-resistant depression is known to involve neuropsychological deficits. However, studies on cognitive impairment in treatment-resistant depression using normative reference data are lacking, the researchers said.

“While use of normative standards using regression analysis is an established methodology, this is the first study of cognitive impairment in treatment-resistant depression patients, comparing performance to that of age-, gender-, and education-matched healthy controls,” the investigators said. “Evaluating the severity and profile of cognitive impairment in treatment-resistant depression patients is a substantial step in understanding the determinants of disability in this condition.”

The study included 497 patients with treatment-resistant depression, a sample of participants from a multinational trial of atypical antipsychotic augmentation of antidepressant therapy. These patients met DSM-IV criteria for major depressive disorder, had single or recurrent episodes with or without psychotic symptoms, and at baseline had a score of 20 or higher on the Hamilton Rating Scale for Depression. In addition, patients in the treatment-resistant depression group did not respond to a range of one to three antidepressants (excluding citalopram and escitalopram) for six weeks or longer.

The control subjects were selected from various research sites and had no history of lifetime major depression, bipolar disorder, or psychosis. Participants in both groups were excluded if they presented with mental retardation, substance dependence, seizure disorder, or head injury with loss of consciousness.

Five computerized cognitive tests were used to assess participants at baseline. The Auditory Number Sequencing evaluated working memory, whereas the Face Memory Test measured secondary memory. The investigators used the Continuous Performance Test and the Set-Shifting Test (SST) to gauge executive function; the SST also examined processing speed and procedural learning. The Tapping Speed Test measured simple motor speed.

Of the 272 participants with treatment-resistant depression and 63 healthy subjects, patients with treatment-resistant depression performed consistently more poorly than controls in all of the tests administered. The only nonsignificant differences were in two reaction tasks (mean imitation reaction time and mean reversal reaction time) on the SST. The treatment-resistant depression group had the most severe impairments in motor speed, episodic memory, and attention. Although patients with treatment-resistant depression performed slightly worse than previously evaluated patients with bipolar depression, their impairments were more substantial than those expected for patients with major depression experiencing remission.

Cognitive assessments were not completed on all patients enrolled, and only patients younger than 55 were examined. Further research, the investigators noted, should concentrate on the functional significance of these cognitive impairments and their response to various treatments.

—Jessica Jannicelli

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