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Effects of alpha-methyl-para-tyrosine (AMPT) in drug-free depressed patients.
Neuropsychopharmacology 1996; 14(3):151-7N

Abstract

A variety of biologic studies have demonstrated abnormal regulation of the norepinephrine (NE) system in patients with major depression, suggesting a role for NE in the etiology of depression. Brain NE and dopamine levels can be rapidly reduced by blocking synthesis with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). In the current investigation, AMPT was administered to drug-free depressed patients to evaluate the effect on mood of diminished catecholamine levels. Seventeen drug-free patients meeting DSM-III-R criteria for major depressive episode were tested with AMPT and an active placebo control, diphenhydramine. Testing was accomplished in a double-blind, crossover fashion, with random assignment to test conditions. Each test included baseline evaluation, 2 days with administration of either AMPT or diphenhydramine, and a follow-up day. Diphenhydramine was used as an active control because of the significant sedation associated with AMPT. Behavioral ratings, including visual analogue scales for a variety of feeling states, the Hamilton Depression Rating Scale (HDRS), and plasma for 3-methoxy-4-hydroxyphenelethyleneglycol (MPHG) and homovanillic acid (HVA) levels, were obtained. AMPT significantly reduced plasma HVA by 70% and MHPG by 50%, but it had no significant effects on the HDRS. AMPT also significantly increased visual analogue ratings of "tired" and decreased ratings of "energetic." Diphenhydramine significantly decreased HDRS scores, but the change was small and was not clinically apparent. The lack of AMPT effects on depressed mood, in conjunction with a prior report that large reductions in plasma tryptophan do not systematically alter depressed mood, indicate that monoamine deficiency by itself is insufficient explanation of the cause of depression. The role of the noradrenergic system needs to be considered in relationship to the many other neurobiologic factors that could be involved in the pathophysiology of depression.

Authors+Show Affiliations

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

8866698

Citation

Miller, H L., et al. "Effects of Alpha-methyl-para-tyrosine (AMPT) in Drug-free Depressed Patients." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 14, no. 3, 1996, pp. 151-7.
Miller HL, Delgado PL, Salomon RM, et al. Effects of alpha-methyl-para-tyrosine (AMPT) in drug-free depressed patients. Neuropsychopharmacology. 1996;14(3):151-7.
Miller, H. L., Delgado, P. L., Salomon, R. M., Heninger, G. R., & Charney, D. S. (1996). Effects of alpha-methyl-para-tyrosine (AMPT) in drug-free depressed patients. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 14(3), pp. 151-7.
Miller HL, et al. Effects of Alpha-methyl-para-tyrosine (AMPT) in Drug-free Depressed Patients. Neuropsychopharmacology. 1996;14(3):151-7. PubMed PMID: 8866698.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of alpha-methyl-para-tyrosine (AMPT) in drug-free depressed patients. AU - Miller,H L, AU - Delgado,P L, AU - Salomon,R M, AU - Heninger,G R, AU - Charney,D S, PY - 1996/3/1/pubmed PY - 1996/3/1/medline PY - 1996/3/1/entrez SP - 151 EP - 7 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 14 IS - 3 N2 - A variety of biologic studies have demonstrated abnormal regulation of the norepinephrine (NE) system in patients with major depression, suggesting a role for NE in the etiology of depression. Brain NE and dopamine levels can be rapidly reduced by blocking synthesis with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). In the current investigation, AMPT was administered to drug-free depressed patients to evaluate the effect on mood of diminished catecholamine levels. Seventeen drug-free patients meeting DSM-III-R criteria for major depressive episode were tested with AMPT and an active placebo control, diphenhydramine. Testing was accomplished in a double-blind, crossover fashion, with random assignment to test conditions. Each test included baseline evaluation, 2 days with administration of either AMPT or diphenhydramine, and a follow-up day. Diphenhydramine was used as an active control because of the significant sedation associated with AMPT. Behavioral ratings, including visual analogue scales for a variety of feeling states, the Hamilton Depression Rating Scale (HDRS), and plasma for 3-methoxy-4-hydroxyphenelethyleneglycol (MPHG) and homovanillic acid (HVA) levels, were obtained. AMPT significantly reduced plasma HVA by 70% and MHPG by 50%, but it had no significant effects on the HDRS. AMPT also significantly increased visual analogue ratings of "tired" and decreased ratings of "energetic." Diphenhydramine significantly decreased HDRS scores, but the change was small and was not clinically apparent. The lack of AMPT effects on depressed mood, in conjunction with a prior report that large reductions in plasma tryptophan do not systematically alter depressed mood, indicate that monoamine deficiency by itself is insufficient explanation of the cause of depression. The role of the noradrenergic system needs to be considered in relationship to the many other neurobiologic factors that could be involved in the pathophysiology of depression. SN - 0893-133X UR - https://www.unboundmedicine.com/medline/citation/8866698/Effects_of_alpha_methyl_para_tyrosine__AMPT__in_drug_free_depressed_patients_ L2 - http://dx.doi.org/10.1016/0893-133X(95)00072-L DB - PRIME DP - Unbound Medicine ER -