Chapter

Progress in Drug Research

Volume 58 of the series Progress in Drug Research pp 169-222

Dual serotonin and noradrenaline uptake inhibitor class of antidepressants — Potential for greater efficacy or just hype?

  • David T. WongAffiliated withNeurobiology Program Department of Psychiatry, Indiana University Medical School
  • , Frank P. BymasterAffiliated withNeuroscience Research Lilly Research Laboratories, Eli Lilly and Company Lilly Corporate Center

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Summary

Preclinical and clinical studies support the rationale that development of single molecules, which would promote serotonergic and noradrenergic neurotransmission by inhibiting simultaneously the uptake of both monoamines, would potentially result in improved antidepressant drugs. Currently, the dual inhibitors of serotonin and noradrenaline uptake are venlafaxine, milnacipran and duloxetine. Based on the preclinical studies, the three drugs do show properties of inhibiting uptake of both monoamines in vitro and in vivo in the following order of decreasing potency: duloxetine, venlafaxine and milnacipran, and all exhibit low affinity at neuronal receptors of neurotransmitters, suggesting low side-effect potential. In double-blind, controlled studies, venlafaxine and milnacipran were repeatedly shown to be as efficacious as tricyclic antidepressant drugs in treating major depressive disorder, while one double-blind, placebo-controlled trial showed the antidepressant efficacy of duloxetine. Specifically designed comparative trials of dual uptake inhibitors against the other agents are needed to establish whether the dual uptake inhibitors show improvement in efficacy, rate of responders, antidepressive effects and/or remission.

Key words

Depression antidepressants tricyclic antidepressants SSRI serotonin selective reuptake inhibitors dual uptake inhibitors norepinephrine serotonin dopamine duloxetine venlafaxine milnacipran fluoxetine