Tolerability of serotonin norepinephrine reuptake inhibitor antidepressants.
All three serotonin norepinephrine reuptake inhibitors (SNRIs) inhibit the reuptake of both serotonin and norepinephrine but they do so with differing affinity ratios. Venlafaxine has a 30-fold higher affinity for serotonin than for norepinephrine while duloxetine has a 10-fold selectivity for serotonin. Milnacipran has a balanced (1:1) ratio of potency for inhibition of reuptake of the two neurotransmitters. The most frequent adverse event with SNRIs is nausea. Not unexpectedly, adverse effects related to a noradrenergic stimulation, such as dry mouth, sweating, and constipation, are found more frequently with SNRIs than with selective serotonin reuptake inhibitors. At true SNRI doses, venlafaxine is associated with dose-dependent cardiovascular phenomena (principally increased blood pressure), an effect which is less frequent with duloxetine and rare with milnacipran. Serious and potentially fatal hepatotoxity has been reported with duloxetine. This problem appears to be unique to duloxetine and not a characteristic of the SNRI class. There are differences in overdose toxicity between venlafaxine and the other SNRIs, possibly related to its increased cardiotoxicity.
Montgomery
Stuart A
SA
Imperial College School of Medicine, University of London, London, United Kingdom. stuart@samontgomery.co.uk
D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced; D056486:Chemical and Drug Induced Liver Injury; D003863:Depression / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004361:Drug Tolerance / Q000502:physiology*; D006801:Humans; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012735:Sexual Dysfunction, Physiological / Q000139:chemically induced; D013375:Substance Withdrawal Syndrome / Q000209:etiology
D018759:Adrenergic Uptake Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors