Bupropion Normalizes Cognitive Performance in Patients With Depression

C. Thomas Gualtieri, MD; Lynda G. Johnson, PhD

Disclosures
In This Article

Discussion

Patients with depression are subject to neuropsychological deficits in attention, memory, psychomotor speed, processing speed, and executive function. When they are treated, they perform better, but they do not perform as well as normal controls.[1,17] They improve, at least to a degree, but do not "normalize." The data reported here suggest that how well they perform on neurocognitive testing may be a function of the antidepressant with which they are treated. What our data show is that depressed patients on bupropion perform as well as normals do on a battery of neurocognitive tests. Patients on venlafaxine and SSRIs do not.

These results are consistent with the hypothesis that cognitive benefit may occur relative to an antidepressant's norepinephrine activity, while lack of benefit may relate to its serotonergic activity. The noradrenergic/dopaminergic antidepressant bupropion is associated with normal function. The mixed serotonin/norepinephrine reuptake venlafaxine performs less well than bupropion but better than the SSRIs (Figure). This is consistent with the principle that enhanced norepinephrine metabolism is associated with better cognitive performance of a variety of neurocognitive tasks.

Relative summary performance of antidepressants.

A naturalistic, cross-sectional study is not an optimal environment for dealing with the complexities of the questions at hand. One would prefer to have data from a more controlled environment. The ideal way to examine drug-related changes in neurocognition is to test patients at baseline, and then to test them again after they have achieved a therapeutic result. It would also be useful to have a comparison group of patients who were treated with placebo. The severity of patients' depression at baseline and how well they have responded to treatment should have been calibrated with more precision than we have done. In addition, the only unbiased way to compare one treatment with another is to use random assignment.

Patients were not randomly assigned to medication. Antidepressants were selected on the basis of clinicians' professional good judgment. This is a flaw, but not a fatal flaw. The choice of which antidepressant to use was made by 9 experienced clinicians operating independently in 2 different clinics. No specific pattern was detected in the clinician's choice. If there was bias in drug selection, it would have worked against bupropion and venlafaxine. Psychiatrists, aware of the beneficial neurocognitive effects of bupropion, sometimes prescribe the drug for depressed patients who complain of problems with concentration or memory. Psychiatrists often prescribe venlafaxine for patients with more severe depression or who have failed to respond to SSRIs. If either of these factors had been operative in this study, one would have expected patients on bupropion or venlafaxine to do less well than patients on SSRIs.

The reason why it is important to report these data, in spite of the obvious shortcomings, is that the relative neurocognitive effects of antidepressants are rarely addressed in the medical literature, and when they are, the research has been done in laboratory settings. Not only is it important to address the issue of neurocognition with respect to the antidepressants, it is important to do so using practical tools in a real-world environment. Computerized testing allows clinicians to evaluate the cognitive effects of drug treatment in the clinic setting.

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