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Venlafaxine: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on March 15, 2021.

1. How it works

  • Venlafaxine may be used for the treatment of depression and other mood disorders.
  • Experts aren't exactly sure how venlafaxine works but suggest it may potentiate the activity of neurotransmitters in the brain, such as serotonin, norepinephrine, and to some extent dopamine. Venlafaxine and its active metabolite, ODV, are potent inhibitors of serotonin and norepinephrine in the brain and weak inhibitors of dopamine reuptake.
  • Venlafaxine belongs to a class of medicines called Selective Serotonin and Norepinephrine Reuptake Inhibitors (SSNRIs).

2. Upsides

  • May be used for the treatment of significant depression (Major Depressive Disorder), generalized anxiety disorder, panic disorder, and social anxiety disorder (social phobia).
  • May also be used off-label (not an approved use but its use may be recognized by national and international guidelines) for the treatment of vasomotor symptoms (hot flashes), diabetic neuropathy, or migraines.
  • Well absorbed after oral administration.
  • Available as an extended-release capsule. The maximum daily dosage is 225mg daily as extended-release capsules in major depressive disorder, generalized anxiety disorder, social phobia, and panic disorder. The conventional tablets of venlafaxine were discontinued because the extended-release capsules allow once-daily dosing.
  • Has no affinity for muscarinic cholinergic, H1-histaminergic, or alpha1 adrenergic receptors, so less likely to cause side effects such as a dry mouth or constipation than some other antidepressants that act on these receptors.
  • Venlafaxine is not approved as a weight-loss treatment; however, some weight loss has been reported when used for other indications.
  • Generic venlafaxine is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Nausea, headache, sedation, dry mouth, dizziness, insomnia, nervousness, constipation, and sweating are some of the more commonly reported side effects. May also cause weight loss, cholesterol elevation, sexual dysfunction, and several other side effects.
  • May be associated with a sustained, moderate increase in blood pressure (about 10-15mm Hg) in some people; regular monitoring of blood pressure may be required.
  • As with other antidepressants, venlafaxine may increase the risk of suicidal thoughts or behavior in young adults. Not generally recommended for people under the age of 18.
  • May impair judgment or cause drowsiness and affect a person's ability to drive or operate machinery. Avoid alcohol.
  • Reduce the dosage of venlafaxine by 25% to 50% in those with mild-to-moderate kidney disease and by 50% in those undergoing hemodialysis. Reduce the dosage by 50% in those with moderate liver disease.
  • In susceptible people, pupil dilation may lead to an episode of angle-closure glaucoma.
  • Interaction or overdosage may cause serotonin syndrome (symptoms include mental status changes [eg, agitation, hallucinations, coma, delirium], fast heart rate, dizziness, flushing, muscle tremor or rigidity, and stomach symptoms [including nausea, vomiting, and diarrhea]).
  • May increase the risk of bleeding, especially if used with other drugs that also increase bleeding risk.
  • May precipitate a manic episode in people with undiagnosed bipolar disorder.
  • May cause a lowering of sodium levels in the body (this is called hyponatremia). Elderly people or people taking diuretics or who are already dehydrated may be more at risk.
  • May cause a discontinuation syndrome if abruptly stopped; symptoms include flu-like symptoms, irritability, low mood, dizziness, electric shock sensations, a headache, and confusion. Taper the dosage slowly on discontinuation.
  • Rarely causes seizures.
  • May interact with some other medications, including other antidepressants and those metabolized through CYP3A4 or CYP2D6 enzymes, although the degree of interaction appears smaller than with some other antidepressants.
  • Venlafaxine has been associated with some possible complications during pregnancy, such as respiratory support, enteral nutrition, and other forms of supportive care in neonates exposed to venlafaxine late in the third trimester; these may arise immediately upon delivery. Carefully consider the potential risks and benefits of treatment when used during the third trimester of pregnancy and consider cautiously tapering the dose during the third trimester before delivery. Distributed into breast milk; discontinue nursing or the drug.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

  • Venlafaxine is an antidepressant that may also be used for mood disorders and off-label for some other conditions such as hot flashes. It may cause a discontinuation syndrome if abruptly stopped after long-term administration.

5. Tips

  • Take with food. Try to take at the same time each day.
  • Swallow extended-release capsules whole; do not break, crush, or chew or attempt to dissolve in water. If you cannot swallow the capsule whole, the capsule may be opened and the contents sprinkled over a spoonful of applesauce and swallowed without chewing.
  • Be alert for changes in behavior including agitation, depressed mood, and suicide-related events, and seek medical advice if changes are apparent. Venlafaxine may unmask bipolar disorder; be alert for symptoms of bipolar such as extremely elevated mood, risk-taking behaviors, false-belief of superiority, or difficulty falling asleep.
  • Do not drive or operate machinery until full effects of venlafaxine are known as it may impair your judgment and affect your ability to drive or operate machinery.
  • Seek urgent medical advice if symptoms consistent with serotonin syndrome (such as agitation, hallucinations, fast heart rate, dizziness, flushing, nausea, or diarrhea) develop.
  • Alcohol is best avoided when taking venlafaxine.
  • Do not stop taking venlafaxine suddenly. Your doctor will advise you on how to taper it when the time comes to discontinue it.
  • Seek urgent advice from an eye professional if eye pain, changes in vision, or swelling or redness around the eye develop.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using venlafaxine while you are pregnant.

6. Response and effectiveness

  • Peak plasma concentrations occur within one to two hours of taking an immediate-release tablet; however, it may take two to four weeks before a reduction in depressive symptoms is noticed, and up to six to eight weeks before the full effects are seen.
  • Extended-release capsules provide a slower rate of absorption but the same extent of absorption as conventional tablets.
  • The half-lives of venlafaxine and its active metabolite are prolonged by about 30% to 60% in cirrhotic patients, and by about 40% to 50% in renally impaired patients (GFR 10-70 mL/min).

7. Interactions

Medicines that interact with venlafaxine may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with venlafaxine. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with venlafaxine include:

  • anti-anxiety medications, such as diazepam and oxazepam
  • anticoagulants such as warfarin
  • anticonvulsants such as phenytoin
  • antidepressants, such as amitriptyline, imipramine, or nortriptyline
  • antihistamines that cause sedation, such as diphenhydramine
  • antiplatelet agents, such as aspirin, apixaban, clopidogrel, or NSAIDs
  • aprepitant
  • duloxetine
  • HIV medications such as indinavir
  • linezolid or methylene blue
  • methylphenidate
  • migraine treatments, such as rizatriptan and sumatriptan
  • monoamine oxidase inhibitors, such as selegiline, isocarboxazid, or phenelzine (do not use within 2 weeks)
  • omega-3 fatty acids
  • opioid analgesics such as oxycodone and morphine
  • muscle relaxants such as cyclobenzaprine
  • serotonin modulators, such as nefazodone and trazodone
  • sleeping pills, such as zolpidem
  • some chemotherapy treatments
  • some heart medications, such as doxazosin and prazosin
  • some medications used to treat mental illness, such as aripiprazole, clozapine, or thioridazine
  • voriconazole.

Alcohol may worsen the side effects of venlafaxine such as drowsiness, dizziness, and liver toxicity.

Note that this list is not all-inclusive and includes only common medications that may interact with venlafaxine. You should refer to the prescribing information for venlafaxine for a complete list of interactions.

References

Venlafaxine. Revised 01/2021. Drugs.com https://www.drugs.com/pro/venlafaxine.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use venlafaxine only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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