Effects of amitriptyline and imipramine on brain amine neurotransmitter metabolites in cerebrospinal fluid

The effects of amitriptyline (AMI) or imipramine (IMI) on levels of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) (the major brain metabolites of the neurotransmitters norepinephrine [NE], serotonin [5-HT], and dopamine [DA]) in cerebrospinal fluid were determined in 66 subjects with unipolar and bipolar depression. There were significant reductions in MHPG and 5-HIAA levels for the depressed group taken as a whole, but levels of HVA did not change significantly. The changes were similar when subjects were grouped as treated with AMI and IMI and with unipolar and bipolar depression. Reductions in MHPG and 5-HIAA levels were greater in women than in men. In all subjects with depression and in those treated with AMI and IMI, amine metabolite changes did not differ significantly between those who had a positive clinical response to drug therapy and those who did not. Responders with bipolar depression had smaller reductions in MHPG levels than did responders with unipolar depression. The similar effects of AMI and IMI on MHPG and 5-HIAA differ from the dissimilar effects of the two drugs on NE and 5-HT amine uptake systems reported in animal and in in vitro studies. Results provide conclusive evidence of the effects of AMI and IMI on noradrenergic and serotonergic (but not dopaminergic) systems in patients with depression.