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Venlafaxine and Mirtazapine Different Mechanisms of Antidepressant Action, Common Opioid-Mediated An

Venlafaxine and Mirtazapine Different Mechanisms of Antidepressant Action, Common Opioid-Mediated An

  1. NeuroChi
    Venlafaxine and Mirtazapine

    Different Mechanisms of Antidepressant Action, Common Opioid-Mediated
    Antinociceptive Effects—A Possible Opioid Involvement in Severe Depression?

    Shaul Schreiber,1 Avi Bleich,1 and Chaim G. Pick*,2
    1Department of Psychiatry, Tel Aviv Sourasky Medical Center, and Tel-Aviv University Sackler School of
    Medicine, Tel-Aviv, Israel; and 2Department of Anatomy and Anthropology, Tel-Aviv University Sackler
    School of Medicine, Tel-Aviv, Israel
    Received May 6, 2001; Accepted July 1, 2001
    Abstract
    The efficacy of each antidepressant available has been found equal to that of amitriptyline in double-blind
    studies as far as mild to moderate depression is involved. However, it seems that some antidepressants are more
    effective than others in the treatment of severe types of depression (i.e., delusional depression and refractory
    depression). Following studies regarding the antinociceptive mechanisms of various antidepressants, we speculate
    that the involvement of the opioid system in the antidepressants’ mechanism of action may be necessary,
    in order to prove effective in the treatment of severe depression. Among the antidepressants of the newer generations,
    that involvement occurs only with venlafaxine (a presynaptic drug which blocks the synaptosomal
    uptake of noradrenaline and serotonin and, to a lesser degree, of dopamine) and with mirtazapine (a postsynaptic
    drug which enhances noradrenergic and 5-HT1A-mediated serotonergic neurotransmission via antagonism
    of central α2-auto- and hetero-adrenoreceptors). When mice were tested with a hotplate analgesia meter,
    both venlafaxine and mirtazapine induced a dose-dependent, naloxone-reversible antinociceptive effect following
    ip administration. Summing up the various interactions of venlafaxine and mirtazapine with opioid,
    noradrenergic and serotonergic agonists and antagonists, we found that the antinociceptive effect of venlafaxine
    is influenced by opioid receptor subtypes (μ-, κ1- κ3- and δ-opioid receptor subtypes) combined with the
    α2-adrenergic receptor, whereas the antinociceptive effect of mirtazapine mainly involves μ- and κ3-opioid
    mechanisms. This opioid profile of the two drugs may be one of the explanations to their efficacy in severe
    depression, unlike the SSRIs and other antidepressants which lack opioid activity.