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Information |
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Drug Groups
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approved |
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Description
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Venlafaxine (Effexor) is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class first introduced by Wyeth in 1993. It is prescribed for the treatment of clinical depression and anxiety disorders. Due to the pronounced side effects and suspicions that venlafaxine may significantly increase the risk of suicide it is not recommended as a first line treatment of depression. However, it is often effective for depression not responding to SSRIs. Venlafaxine was the sixth most widely-used antidepressant based on the amount of retail prescriptions in the US (17.1 million) in 2006. [Wikipedia] |
| Indication |
For the management of major depressive disorder (MDD), generalized anxiety disorder (GAD), social anxiety disorder (social phobia), panic disorder with or without agoraphobia, and vasomotor symptoms in women with breast cancer and in postmenopausal women. |
| Pharmacology |
Venlafaxine, an antidepressant agent structurally and pharmacologically unrelated to other antidepressants and agents used to treat generalized anxiety disorder, is used to treat melancholia, generalized anxiety disorder (GAD), panic disorder, post-traumatic stress disorder, and hot flashes in breast cancer survivors. |
| Toxicity |
Most patients overdosing with venlafaxine develop only mild symptoms. However, severe toxicity is reported with the most common symptoms being CNS depression, serotonin toxicity, seizure, or cardiac conduction abnormalities. Venlafaxine's toxicity appears to be higher than other SSRIs, with a fatal toxic dose closer to that of the tricyclic antidepressants than the SSRIs. Doses of 900 mg or more are likely to cause moderate toxicity. Deaths have been reported following large doses. |
| Affected Organisms |
| • |
Humans and other mammals |
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| Biotransformation |
Undergoes extensive first pass metabolism in the liver to its major, active metabolite, ODV, and two minor, less active metabolites, N-desmethylvenlafaxine and N,O-didesmethylvenlafaxine. Formation of ODV is catalyzed by cytochrome P450 (CYP) 2D6, whereas N-demethylation is catalyzed by CYP3A4, 2C19 and 2C9. ODV possesses antidepressant activity that is comparable to that of venlfaxine. |
| Absorption |
Bioavailability is 45% following oral administration. |
| Half Life |
5 hours |
| Protein Binding |
venlafaxine, 27%; ODV, 30% |
| Elimination |
Renal elimination of venlafaxine and its metabolites is the primary route of excretion. |
| Distribution |
* 7.5 ± 3.7 L/kg [venlafaxine]
* 5.7 ± 1.8 L/kg [O-desmethylvenlafaxine(active metabolite)] |
| Clearance |
* 1.3 +/- 0.6 L/h/kg |
| References |
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Golden RN, Nicholas L: Antidepressant efficacy of venlafaxine. Depress Anxiety. 2000;12 Suppl 1:45-9.
[Pubmed]
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Thase ME, Clayton AH, Haight BR, Thompson AH, Modell JG, Johnston JA: A double-blind comparison between bupropion XL and venlafaxine XR: sexual functioning, antidepressant efficacy, and tolerability. J Clin Psychopharmacol. 2006 Oct;26(5):482-8.
[Pubmed]
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Bielski RJ, Ventura D, Chang CC: A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder. J Clin Psychiatry. 2004 Sep;65(9):1190-6.
[Pubmed]
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Rowbotham MC, Goli V, Kunz NR, Lei D: Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain. 2004 Aug;110(3):697-706.
[Pubmed]
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Ozyalcin SN, Talu GK, Kiziltan E, Yucel B, Ertas M, Disci R: The efficacy and safety of venlafaxine in the prophylaxis of migraine. Headache. 2005 Feb;45(2):144-52.
[Pubmed]
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