Venlafaxine

Venlafaxine is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) used to treat major depression, generalized or social anxiety disorder, and panic disorder.

Use and indications

Venlafaxine is primarily used for the treatment of major depression, generalized anxiety disorder, social phobia, panic disorder, and vasomotor symptoms. Venlafaxine is also sometimes used "off-label" for the treatment of diabetic neuropathies, chronic pain, and prevention of migraine. A positive effect on patients with ADHD and post-traumatic stress syndrome (PTSD) is discussed. Administration is peroral in the form of tablets.

History

Venlafaxine was first approved by the FDA in 1993, and the extended-release formulation was introduced in 1997. It has been available as a generic drug since 2008.

Pharmacodynamics and mechanism of action

The exact mechanism of action of venlafaxine in the treatment of various psychiatric disorders is not fully understood, but it is known that venlafaxine and its metabolites effectively and selectively inhibit the reuptake of serotonin and norepinephrine at the presynaptic cleft. This results in an increased concentration of neurotransmitters available at the synapse to stimulate postsynaptic receptors. Venlafaxine is thought to have 30-fold selectivity for serotonin compared to norepinephrine. Venlafaxine only inhibits serotonin reuptake at low doses and only has an additional effect on norepinephrine reuptake at higher doses.

Pharmacokinetics

Venlafaxine is rapidly absorbed after oral administration and has an absolute bioavailability of approximately 45%. Venlafaxine is 27% bound to plasma proteins. After absorption, venlafaxine undergoes extensive hepatic metabolism. It is degraded primarily by CYP2D6-mediated demethylation to its active metabolite, O-desmethylvenlafaxine. The elimination half-life of venlafaxine is 3-7 hours.

Drug Interactions

Many drugs may interact with venlafaxine, in particular:

• other antidepressants
• Cimetidine
• Tramadol
• St. John's wort
• L-tryptophan
• weight loss medicines (eg, phentermine)
• blood thinners like warfarin or phenprocoumon
• lithium
• sumatriptan and zolmitriptan

Contraindications

This drug should not be used

• if there is a known allergy to the active substance
• in untreated narrow-angle glaucoma
• if MAO inhibitors have been taken less than 14 days before taking venlafaxine

Side effects

Venlafaxine may cause serious side effects. Immediate medical attention should be sought if the following symptoms occur:

• blurred vision, eye pain or redness, seeing halos around lights
• cough, chest tightness, difficulty breathing
• seizure (convulsions)
• Abnormal bleeding - nosebleeds, bleeding gums, abnormal vaginal bleeding, any bleeding that does not stop
• Confusion, thinking or memory problems, weakness, unsteadiness
• very stiff (rigid) muscles, high fever, sweating, confusion, fast or irregular heartbeat, tremor

Common side effects of venlafaxine may include:

• Headache
• dizziness
• drowsiness or tiredness
• anxiety and nervousness
• trouble sleeping, unusual dreams
• tremors
• fast heartbeat
• blurred vision
• vomiting
• diarrhea
• constipation
• changes in weight or appetite
• dry mouth
• increased sweating
• sexual problems

Pregnancy and breastfeeding

Taking venlafaxine during pregnancy may have a negative effect on the baby and is therefore not recommended.

Venlafaxine passes into breast milk and may therefore have an effect on the baby. Therefore, it is not recommended to take it during breastfeeding.