Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression

Helen L. Miller, Pedro L. Delgado, Ronald M. Salomon, Robert Berman, John H. Krystal, George R. Heninger, Dennis S. Charney

Research output: Contribution to journalArticle

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Abstract

Background: Most hypotheses of the therapeutic mechanism of action of antidepressant drugs have focused on the role of the monoamines. We examined the effect of catecholamine depletion on antidepressant-induced remission. Method: The tyrosine hydroxylase inhibitor α-methylparatyrosine and the antihistamine diphenhydramine hydrochloride were administered, during separate test sessions, to depressed patients in remission maintained with either norepinephrine reuptake inhibitors (desipramine [n=7] or mazindol [n=2]) or serotonin reuptake inhibitors (fluoxetine hydrochloride [n=9] or sertraline hydrochloride [n=1]). Because of considerable sedation associated with α-methylparatyrosine testing, diphenhydramine was used as an active control rather than an inactive placebo. The effects of α-methylparatyrosine and diphenhydramine on depression, anxiety, and plasma catecholamine metabolites were assessed. Results: α-Methylparatyrosine produced similar significant decreases in plasma 3-methoxy-4-hydroxyphenyl-ethyleneglycol and homovanillic acid levels in the treatment groups. α-Methylparatyrosine produced a robust increase in depressive symptoms on the Hamilton Depression Rating Scale, including depressed mood, decreased concentration, anhedonia, loss of interest, and feelings of worthlessness, helplessness, and hopelessness, in the desipramine-mazindol but not in the fluoxetine- sertraline group. Diphenhydramine had no effects on mood in either treatment group. Conclusions: The therapeutic effects of norepinephrine reuptake inhibitors, but not serotonin reuptake inhibitors, are reversed by catecholamine depletion. Considered with previous reports that serotonin depletion produces depressive relapses in patients in remission maintained with serotonin reuptake inhibitors, but not norepinephrine reuptake inhibitors, these findings suggest that antidepressants may not work via a single monoamine-related mechanism.

Original languageEnglish (US)
Pages (from-to)117-128
Number of pages12
JournalArchives of General Psychiatry
Volume53
Issue number2
StatePublished - Feb 1996
Externally publishedYes

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Diphenhydramine
Antidepressive Agents
Catecholamines
Mazindol
Depression
Sertraline
Desipramine
Fluoxetine
Serotonin Uptake Inhibitors
Norepinephrine
Anhedonia
Homovanillic Acid
Histamine Antagonists
Tyrosine 3-Monooxygenase
Therapeutic Uses
Serotonin
Emotions
Therapeutics
Anxiety
Placebos

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Miller, H. L., Delgado, P. L., Salomon, R. M., Berman, R., Krystal, J. H., Heninger, G. R., & Charney, D. S. (1996). Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression. Archives of General Psychiatry, 53(2), 117-128.

Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression. / Miller, Helen L.; Delgado, Pedro L.; Salomon, Ronald M.; Berman, Robert; Krystal, John H.; Heninger, George R.; Charney, Dennis S.

In: Archives of General Psychiatry, Vol. 53, No. 2, 02.1996, p. 117-128.

Research output: Contribution to journalArticle

Miller, HL, Delgado, PL, Salomon, RM, Berman, R, Krystal, JH, Heninger, GR & Charney, DS 1996, 'Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression', Archives of General Psychiatry, vol. 53, no. 2, pp. 117-128.
Miller HL, Delgado PL, Salomon RM, Berman R, Krystal JH, Heninger GR et al. Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression. Archives of General Psychiatry. 1996 Feb;53(2):117-128.
Miller, Helen L. ; Delgado, Pedro L. ; Salomon, Ronald M. ; Berman, Robert ; Krystal, John H. ; Heninger, George R. ; Charney, Dennis S. / Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression. In: Archives of General Psychiatry. 1996 ; Vol. 53, No. 2. pp. 117-128.
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