Dopamine in Depressed Patients with Psychomotor Retardation

Editor, Primary Psychiatry and Psychiatry Weekly, Professor of Psychiatry, New York University School of Medicine

Introduction

Findings from a just-published study suggest that depressed patients who exhibit motor retardation also have abnormalities in their striatal dopamine system, and in theory would benefit from treatments that raise brain dopamine activity. In contrast to earlier studies, which attempted to assess brain DA function in depressed patients by measuring levels of the DA metabolite homovanillic acid (HVA) in cerebrospinal fluid (CSF), the new study uses positron emission tomography (PET) to study D₂ type receptor binding. This is the first time this technology has been used in depressed patients not recently or currently exposed to antidepressant drugs. Like the older CSF HVA studies, the new findings support the hypothesis that there is a decrease in dopamine function among depressed patients, particularly those patients with marked psychomotor retardation.

The finding that extracellular dopamine is lower in patients with major depression characterized by motor retardation, as opposed to psychomotor retardation, led the authors to speculate that this depressive subtype might “preferentially benefit from dopamine-increasing medications and should be targeted in future clinical trials of dopamine reuptake inhibitors.”

Bupropion

In terms of currently available antidepressants, only bupropion (Wellbutrin XL and generics) produces a sustained dopamine agonist effect. Bupropion is a dopamine reuptake inhibitor that is several magnitudes more selective for that neurotransmitter than sertraline, the only SSRI with some dopaminergic activity. Lending support to the idea that there is a preferential response to dopamine-enhancing antidepressants is the recent approval of bupropion as a treatment for seasonal affective disorder (SAD). That subtype of depression is characterized by extreme lethargy and somnolence. Bupropion is the only antidepressant to get FDA approval for that indication

A hint of how useful a highly selective dopamine reuptake inhibitor might be in clinical practice came when nomifensine (Merital), was briefly available in 1985 and 1986. Now largely forgotten and used only for research purposes, nomifensine produced dramatic improvement in many patients. Unfortunately, nomifensine was found to be associated with an increased incidence of hemolytic anemia and was pulled from the market.

In addition to bupropion, clinicians sometimes rely on non-antidepressant, stimulant drugs to help treat depression. These agents have long been known to increase motivation, mood, energy, and wakefulness. Amphetamines, methylphenidate, and more recently, modafinil (Provigil) are sometimes used as add-on therapy with antidepressants, particularly among patients who report being tired or fatigued.

Treatment Specificity

Publication of this study would seem to somewhat contradict the results of the STAR*D trial, which suggest that, regardless of antidepressant drug regimen, expected outcomes are the same. While all antidepressants might be equivalent in terms of their overall efficacy, certain types of symptoms are more likely to respond to a particular intervention. In the case of patients who have prominent symptoms of motor retardation, the best choice may be a treatment that boosts dopamine.

Disclosure: Dr. Sussman reports no affiliations with or financial interests in any organization that may pose a conflict of interest.

References

Fawcett J. Sympathomimietics and dopamine receptor agonists. In Sadock BJ, Sadock VA (editors). Kaplan & Sadocks Comprehensive Textbook of Psychiatry. Eighth edition, pp 2938-2944. Lippincott Williams & Wilkins, Philadelphia 2005

Meyer JH, McNeely HE, Sagrati S, et al. Elevated Putamen D₂ Receptor Binding Potential in Major Depression With Motor Retardation: An [11C]Raclopride Positron Emission Tomography Study. Am J Psychiatry 2006;163:1594-1602