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Published Online:https://doi.org/10.1176/ajp.123.6.690

Urinary excretion of normetanephrine, the metabolite of norepinephrine which may reflect noradrenergic activity, showed a gradual increase during the period of definitive clinical improvement in depressed patients treated with imipramine. These and other findings of the study suggest that noradrenergic activity may gradually increase during clinical improvement from depression, and that noradrenergic activity may be relatively decreased in retarded depression and increased in mania. The pharmacological action of imipramine may initiate increases in noradrenergic activity and clinical improvement, in depressed patients, that are subsequently maintained after discontinuation of the drug.

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