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We investigated sympathoadrenal and sympathetic nervous system activity, catecholamine disposition, and clinical state in 19 hospitalized manic patients. Severity of the core manic syndrome, anxiety, and hostility correlated with 24-hour urinary excretion of epinephrine relative to its metabolites, but only weakly with norepinephrine. Agitation, however, correlated most strongly and significantly with norepinephrine. Eight of the patients had mixed states: concurrent manic and depressive syndromes. There were no differences between mixed and pure manic patients with respect to catecholamine or metabolite excretion or precursor/product ratios, but mixed manic patients tended to have higher excretion of norepinephrine and had increased variance with respect to catecholamine measures. These data suggest that the function of the adrenal medulla, whether directly or indirectly, is important in the symptoms of both mixed and pure mania.

The effects of treatment with amitriptyline (AMI) or imipramine (IMI) on changes in catecholamines and their metabolites in urine were studied in 95 unipolar and bipolar depressed patients. For the entire group, not separated by drug, substantial reduction in concentrations of all metabolites, but not catecholamines, occurred. Although catecholamine and metabolite change was similar for most substances assayed, there were some specific drug and diagnostic group differences. Vanillylmandelic acid (VMA) reduction was limited to bipolar patients; metanephrine (M) reduction to unipolar patients. Greater M and 3-methoxy-4-hydroxyphenylglycol (MHPG) reduction were associated with response in unipolar, but not bipolar patients. In bipolar, but not unipolar patients, norepinephrine (NE) rose in responders in contrast to reductions among nonresponding bipolar patients. The results suggest that effectiveness of blockade of reuptake of norepinephrine may be relatively more important for recovery in bipolar than in unipolar patients. Study of a battery of amine substances may contribute more information to our understanding of antidepressant drug effects on aminergic systems than analyses of MHPG alone.

Depressed patients as a group have been found to excrete greater amounts of catecholamines (CAs) and metabolites than healthy control subjects, but these differences were not uniform for all metabolites. Patients may differ from controls in the metabolism and/or disposition of CAs. We analyzed the suggested metabolic-dispositional differences by determining 24-hour urine values for norepinephrine (NE), epinephrine (E), normetanephrine (NM), metanephrine (M), vanillylmandelic acid (VMA), and 3-methoxy-4-hydroxyphenylglycol (MHPG). For each subject, we calculated ratios of CAs or metabolites to an estimate of CA synthesis and determined ratios of CAs and metabolites to each other based on a precursor-product paradigm. The results indicate that as a group, patients have modestly but significantly greater CA synthesis rates than controls; patients excrete disproportionately more NE and E and disproportionately less MHPG relative to estimated CA synthesis, as well as other metabolites, than do controls; in contrast to NE, E, and MHPG, the increased NM, M, and VMA excretion rates by patients are proportional to each other as well as to the increase in CA synthesis; and the differences in NE, E, and metabolite excretion in the patients as a group are due principally to unipolar rather than bipolar depressives. The differences would be expected if patients, relative to controls, released more NE and E into the circulation. These data indicate the need to measure several CAs and metabolites when evaluating differences between groups since the significance of any given metabolite value needs to be examined in the context of total CA and metabolite production and excretion.