Reserpine augmentation of desipramine in refractory depression: clinical and neurobiological effects.
Early studies showed dramatic improvement in some depressed patients when a brief course of parenteral reserpine was added to ineffective tricyclic antidepressant (TCA) treatment. We treated eight patients with DSM-III melancholic major depression with desipramine (DMI) greater than or equal to 2.5 mg/kg/day (plasma levels greater than 125 ng/ml) for at least 4 weeks. All patients failed to respond and received reserpine 5 mg IM b.i.d. over 2 days, in seven cases as a placebo-controlled, double-blind trial. One patient had dramatic resolution of depressive and psychotic symptoms within 48 h, but relapsed within 2 weeks; two other patients had transient hypomanic symptoms. Depression ratings did not significantly change for the sample as a whole, but plasma and cerebrospinal fluid (CSF) levels of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) decreased and CSF levels of homovanillic acid (HVA) and 5-hydroxy-indoleacetic acid (5-HIAA) increased. Despite robust effects on central monoamine metabolism, reserpine augmentation appears insufficiently effective for routine use in managing refractory depression.
D000328:Adult; D000368:Aged; D001519:Behavior / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D003866:Depressive Disorder / Q000188:drug therapy*; D003891:Desipramine / Q000009:adverse effects / Q000627:therapeutic use*; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D008875:Middle Aged; D012110:Reserpine / Q000009:adverse effects / Q000627:therapeutic use*
D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D012110:Reserpine; D003891:Desipramine; D006719:Homovanillic Acid