Venlafaxine (Effexor XR®) for Fibromyalgia

What is Effexor?

Venlafaxine hydrochloride (Effexor®, Effexor XR®) is an antidepressant (mood elevator) from SNRI class. It is indicated for the treatment of depression, generalized anxiety disorder, social anxiety disorder (social phobia) and panic disorder. Venlafaxine blocks the ability of the nerve terminals in the brain to bind and break down serotonin and norepinephrine so that more is available for the brain to use. Abnormally low levels of serotonin and norepinephrine may play a role in conditions such as depression and anxiety disorders.

Venlafaxine Efficacy for Fibromyalgia

Fibromyalgia (FM) is a chronic widespread musculoskeletal pain for which no alternative cause can be detected.

Venlafaxine has been investigated in the treatment of fibromyalgia because of its potential analgesic properties. Several small studies have shown that venlafaxine may be modest effective for fibromyalgia 11, 12. Although it is not entirely clear how Venlafaxine works for fibromyalgia, the drug may help block the nerve pain signals in the spinal cord or brain. This may help with the pain caused by fibromyalgia. Clinical research has shown that venlafaxine can provide pain relief and decrease disability due to fibromyalgia. Venlafaxine also improves anxiety and depression associated with fibromyalgia pain.

Dosage for Fibromyalgia

The dose of 75-150 mg is effective for various types of chronic pain6. In clinical trial that studied venlafaxine for the treatment of fibromyalgia the dosage of immediate-release venlafaxine ranged from 37.5 to 375 mg per day12.

Benefits

• Alleviates the pain and disability caused by fibromyalgia
• Relieves chronic pain14
• May be a good choice for fibromyalgia accompanied by depression or anxiety4

Concerns

• Lack of scientific evidence of efficacy - only two small open-label trials have evaluated the use of venlafaxine in the treatment of fibromyalgia10, 12
• Can increase blood pressure
• High rate of nausea and vomiting
• Venlafaxine does not last long in the body so abrupt discontinuation can cause a very troublesome withdrawal syndrome 3
• Toxicity in overdose (cardiovascular toxicity, rhabdomyolysis) 19, 20.
• High risk of suicide 1

Pharmacological characteristics

• Absorption: Absolute bioavailability is 45% and well absorbed (at least 92%). Steady-state concentrations of venlafaxine and O-desmethylvenlafaxine (ODV) in plasma are attained within 3 days. Exhibits linear kinetics over dose range 75 to 450 mg/day.
• Metabolism: Extensively metabolized in the liver. The only major metabolite is O-desmethylvenlafaxine, which is active.
• Elimination half-life: elimination half-life of venlafaxine is 5 ± 2 and 11 ± 2 hours of O-desmethylvenlafaxine (ODV).
• Excretion: Renal elimination of venlafaxine and its metabolite is the primary route of excretion. Approximately 87% of a venlafaxine is recovered in the urine within 48 hours as either unchanged venlafaxine (5%), unconjugated ODV (29%), conjugated ODV (26%), or other minor inactive metabolites (27%).

Mechanism of action

Effexor (venlafaxine) blocks the reuptake of serotonin, noradrenaline and, to a lesser extent, dopamine. The drug has the flexibility of being an SSRI at lower doses and an SNRI at higher doses.

Venlafaxine antinociceptive action
Effexor (venlafaxine) has an analgesic effect that is independent of its antidepressant activity. The study has shown that antinociceptive effect of venlafaxine is mainly influenced by the kappa- and delta-opioid receptor subtypes combined with the alpha2-adrenergic receptor. These results suggest a potential use of venlafaxine in some pain syndromes 9.

Venlafaxine Alternatives

Alternatives drugs officially licensed by the US FDA for the treatment of fibromyalgia:

• Duloxetine (Cymbalta®)
• Pregabalin (Lyrica®)
• Milnacipran (Savella®)

References

• 1. Tiihonen J, Lönnqvist J, Wahlbeck K, Klaukka T, Tanskanen A, Haukka J. Antidepressants and the risk of suicide, attempted suicide, and overall mortality in a nationwide cohort. Arch Gen Psychiatry. 2006 Dec;63(12):1358-67. PubMed
• 2. Traynor LM, Thiessen CN, Traynor AP. Pharmacotherapy of fibromyalgia. Am J Health Syst Pharm. 2011 Jul 15;68(14):1307-19.
• 3. Fava M, Mulroy R, Alpert J, Nierenberg AA, Rosenbaum JF. Emergence of adverse events following discontinuation of treatment with extended-release venlafaxine. Am J Psychiatry. 1997 Dec;154(12):1760-2. PubMed
• 4. Thieme K, Turk DC, Flor H. Comorbid depression and anxiety in fibromyalgia syndrome: relationship to somatic and psychosocial variables. Psychosom Med. 2004 Nov-Dec;66(6):837-44. PubMed
• 6. Gálvez R, Caballero J, Atero M, Ruiz S, Romero J. Venlafaxine extended release for the treatment of chronic pain. Actas Esp Psiquiatr. 2004 Mar-Apr;32(2):92-7. PubMed
• 9. Schreiber S, Backer MM, Pick CG. The antinociceptive effect of venlafaxine in mice is mediated through opioid and adrenergic mechanisms. Neurosci Lett. 1999 Oct 1;273(2):85-8.
• 10. Sayar K, Aksu G, Ak I, Tosun M. Venlafaxine treatment of fibromyalgia. Ann Pharmacother. 2003 Nov;37(11):1561-5. PubMed
• 11. VanderWeide LA, Smith SM, Trinkley KE. A systematic review of the efficacy of venlafaxine for the treatment of fibromyalgia. J Clin Pharm Ther. 2015 Feb;40(1):1-6. PubMed
• 12. Dwight MM, Arnold LM, O'Brien H, Metzger R, Morris-Park E, Keck PE Jr. Venlafaxine in fibromyalgia. Psychosomatics. 1998 Jan-Feb;39(1):14-7
• 14. Taylor K, Rowbotham MC. Venlafaxine hydrochloride and chronic pain. West J Med. 1996 Sep;165(3):147-8.
• 16. Sindrup SH, Bach FW, Madsen C, Gram LF, Jensen TS. Venlafaxine versus imipramine in painful polyneuropathy. Neurology. 2003 Apr 22;60(8):1284-9. PubMed
• 18. Andrews JM, Ninan PT, Nemeroff CB. Venlafaxine: a novel antidepressant that has a dual mechanism of action. Depression. 1996;4(2):48-56.
• 19. Howell C, Wilson AD, Waring WS. Cardiovascular toxicity due to venlafaxine poisoning in adults: 235 consecutive cases. Br J Clin Pharmacol. 2007 Aug;64(2):192-7. PubMedCentral
• 20. Pascale P, Oddo M, Pacher P, Augsburger M, Liaudet L. Severe rhabdomyolysis following venlafaxine overdose. Ther Drug Monit. 2005 Oct;27(5):562-4.

By HealthyStock Research Group, September 2009
Medical resources reviewed: August 2018