Desipramine-yohimbine combination treatment of refractory depression. Implications for the beta-adrenergic receptor hypothesis of antidepressant action.
Preclinical investigations have shown that combined administration of the alpha 2-adrenergic receptor antagonist yohimbine hydrochloride and the tricyclic antidepressant desipramine hydrochloride produces a reduction in brain beta-adrenergic receptor function within four days. Since the ability of antidepressant treatments to reduce beta-adrenergic receptor function has been hypothesized to mediate antidepressant efficacy, it was predicted that combined desipramine-yohimbine treatment would be a more rapid-acting and potent antidepressant regimen than desipramine alone. In the present investigation, the effects of desipramine (N = 11) and desipramine-yohimbine (N = 10) treatment on depressive symptoms, norepinephrine turnover, and blood pressure were determined in patients with major depression who had a history of nonresponse to standard antidepressant treatments. Neither desipramine nor desipramine-yohimbine proved to be an effective treatment, although concomitant yohimbine administration did attenuate the ability of desipramine to decrease plasma free and 24-hour urinary 3-methoxy-4-hydroxyphenyl-ethyleneglycol levels and blood pressure. Fifteen of the 21 patients eventually had a good response to pharmacologic treatments, particularly a desipramine-lithium carbonate or lithium carbonate-tranylcypromine sulfate combination treatment (11 of 14 responded). This study provides evidence against the beta-adrenergic receptor hypothesis of antidepressant action.
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002986:Clinical Trials as Topic; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D003891:Desipramine / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008094:Lithium / Q000627:therapeutic use; D016651:Lithium Carbonate; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D014191:Tranylcypromine / Q000627:therapeutic use; D015016:Yohimbine / Q000494:pharmacology / Q000627:therapeutic use*
D011943:Receptors, Adrenergic, beta; D016651:Lithium Carbonate; D015016:Yohimbine; D014191:Tranylcypromine; D008734:Methoxyhydroxyphenylglycol; D008094:Lithium; D003891:Desipramine; D009638:Norepinephrine