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The Effect of Long-term Desipramine Treatment

Dennis S. Charney, MD; George R. Heninger, MD; David E. Sternberg, MD; D. Eugene Redmond, MD; James F. Leckman, MD; James W. Maas, MD; Robert H. Roth, PhD

Arch Gen Psychiatry. 1981;38(12):1334-1340.

Abstract
• Stimulation of presynaptic ₂-adrenergic receptors located on norepinephrine (NE)-containing cells in the brain decreases the firing rate and turnover of NE in these neurons. To assess whether abnormalities in the regulation of the NE system during desipramine hydrochloride treatment may be present in depressed patients, the effects of an ₂-agonist, clonidine hydrochloride, on plasma levels of the NE metabolite 3-methoxy-4-hydroxy/phenethyleneglycol (MHPG) and on blood pressure (BP) were evaluated in ten depressed patients before and during long-term desipramine treatment. Long-term desipramine treatment significantly attenuated the effects of clonidine on plasma MHPG level and BP, indicating that during desipramine treatment ₂-adrenergic receptors had become supsensitive. In addition, plasma MHPG levels were significantly reduced during long-term desipramine treatment. These findings are discussed in relation to the hypothesized therapeutic mechanism of action of desipramine and the hypotheses relating noradrenergic function and depression.

Author Affiliations
From the Department of Psychiatry, Yale University School of Medicine, and the Connecticut Mental Health Center, New Haven, Conn.

Footnotes
Accepted for publication June 12, 1981.

Reprint requests to Clinical Research Unit, Connecticut Mental Health Center, 34 Park St, New Haven, CT 06519 (Dr Charney).

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