Venlafaxine: Drug Effects, Side Effects, Dosage and Uses

Products

Venlafaxine is commercially available in tablet and sustained-release capsule form. In addition to the original Efexor ER (USA: Effexor XR), generic versions are also available. The active ingredient was approved in many countries in 1997.

Structure and properties

Venlafaxine (C17H27NO2, Mr= 277.4 g/mol) is a bicyclic phenylethylamine and cyclohexanol derivative that is structurally closely related to tramadol (Tramal, generics). It exists as a racemate and as venlafaxine hydrochloride, a white crystalline powder that is soluble in water. Venlafaxine is converted by CYP2D6 to its main metabolite desvenlafaxine (= O-desmethylvenlafaxine), which is also active. The metabolite is also marketed in the United States (Pristiq).

Effects

Venlafaxine (ATC N06AX16) has antidepressant properties. The effects are delayed, occurring after one to four weeks, and are due to selective inhibition of the reuptake of serotonin and norepinephrine into the presynaptic neuron. Reuptake of dopamine is only mildly inhibited. Venlafaxine, unlike other antidepressants, does not bind to alpha-adrenoceptors, muscarinic or histamine receptors, is not anticholinergic and is not an MAO inhibitor. The half-life is 5 hours for venlafaxine and 11 hours for the metabolite desvenlafaxine.

Indications

For the treatment of depression, anxiety, and panic disorders:

  • Major depression, treatment and relapse prophylaxis.
  • Generalized anxiety disorder
  • Social anxiety disorder (social phobia)
  • Panic disorder with or without agoraphobia.

Off-label, the drug is used for other complaints (eg, flushing, chronic pain). However, it is not approved for this by the authorities.

Dosage

According to the SmPC. The sustained-release dosage forms are usually taken once daily at the same time of day and with a meal. Dose adjustments are made gradually creeping in or out. The drug should not be discontinued abruptly because discontinuation reactions may result.

Contraindications

  • Hypersensitivity
  • Children and adolescents under 18 years
  • Treatment with MAO inhibitors

For complete precautions, see the drug label.

Interactions

Venlafaxine is metabolized by CYP2D6 and to a lesser extent by CYP3A4. Venlafaxine has a high potential for interaction and numerous drug-drug interactions are possible, for example with MAO inhibitors, serotonergic drugs (serotonin syndrome), and centrally acting drugs.

Adverse effects

The most common potential adverse effects include nausea, dry mouth, headache, drowsiness, insomnia, and sweating. Venlafaxine is considered better tolerated compared with older antidepressants because it is more selective.