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Desvenlafaxine side effects and how to avoid them

Desvenlafaxine side effects include sexual dysfunction, nausea, dry mouth, and sweating
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By | Nov. 11, 2022 Medically reviewed by Anne Jacobson, MD, MPH

Common desvenlafaxine side effects | Serious side effects | Sexual dysfunction | Side effects timeline | Contraindications | Warnings | Interactions | How to avoid side effects | How to treat side effects

Desvenlafaxine is a generic prescription antidepressant used to treat major depressive disorder (MDD) in adults. It has some off-label uses, as well: relieving nerve pain and, in menopausal women who cannot take estrogen, reducing hot flashes. Desvenlafaxine is closely related to another antidepressant, Effexor (venlafaxine). Like venlafaxine, desvenlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI). By prolonging the duration of these two chemicals in the brain, desvenlafaxine helps increase activity in the part of the brain responsible for mood control. 

Desvenlafaxine and its brand-name versions Pristiq and Khedezla are all taken as extended-release tablets. They have many of the same side effects as other antidepressants, with one major difference: there are fewer drug interactions to worry about when taking desvenlafaxine.

Common side effects of desvenlafaxine

Nausea is the most common side effect of desvenlafaxine. In order of prevalence, the most common side effects of desvenlafaxine are:

  • Nausea
  • Dry mouth
  • Sweating
  • Dizziness
  • Insomnia
  • Constipation
  • Erectile dysfunction
  • Ejaculation problems 
  • Drowsiness
  • Decreased appetite
  • High cholesterol or triglycerides
  • Tremor
  • Vomiting
  • Fatigue
  • Elevated protein in the urine
  • Difficulty having an orgasm
  • Pupil dilation
  • Vertigo
  • Abnormal dreams
  • Yawning
  • Anxiety
  • Blurred vision
  • Jitteriness
  • Elevated blood pressure
  • Abnormal orgasms
  • Hot flushes
  • Troubles with taste
  • Ringing in the ears
  • Trouble urinating

Serious side effects of desvenlafaxine

The most serious side effects of desvenlafaxine include:

  • Seizures
  • Suicidality
  • Worsening of depression
  • Mania
  • Serotonin syndrome
  • Bleeding
  • Angle-closure glaucoma
  • Low sodium
  • High blood pressure
  • Lung diseases
  • Involuntary movements (extrapyramidal symptoms)
  • Heart muscle disease
  • Swollen pancreas
  • Discontinuation syndrome (withdrawal)
  • Blood pressure that drops too fast in older people
  • Severe drug or allergic reactions

Desvenlafaxine and sexual dysfunction

Dose-related sexual dysfunction is commonly experienced by people taking desvenlafaxine, but it affects men more than women. In clinical trials, 3% to 11% of men experienced erectile dysfunction depending on the dose. Up to 8% could not have an orgasm, up to 6% could not easily orgasm, and up to 5% had some form of ejaculation disorder. Other problems experienced by more than 2% of participants included a decrease in sex drive, abnormal orgasms, ejaculation failure, and other types of sexual dysfunction. One to 3% of women taking desvenlafaxine reported an inability to orgasm. For most people, these sexual dysfunctions will resolve when the drug is stopped. If desvenlafaxine is interfering with sex, ask the prescribing healthcare provider for medical advice or treatment options.

How soon do desvenlafaxine side effects start?

Most of the common side effects of desvenlafaxine occur early in treatment. These include nausea, vomiting, dizziness, sleepiness, fatigue, tremor, and weird dreams. Sexual problems are usually delayed side effects, requiring a few weeks of exposure to the drug before becoming obvious. The same applies to most of the serious side effects of desvenlafaxine including lung diseases, high blood pressure, heart problems, pancreas problems, seizures, and suicidality. 

How long do desvenlafaxine side effects last?

Many of the mild side effects of desvenlafaxine may improve over time as the body adapts to the drug. If they don’t, they should improve when the drug is discontinued. Don’t expect to feel better overnight, however. When it’s time to quit taking desvenlafaxine, dosages must be reduced gradually. Some serious side effects, however, may take some time to resolve even after desvenlafaxine has been discontinued. These include pancreatitis, lung diseases, or glaucoma.

What are the long-term side effects of desvenlafaxine?

As a general rule, antidepressant therapy is meant to last anywhere from six to nine months, but some people take antidepressants for a year or longer. Desvenlafaxine has no side effects that are due specifically to long-term or prolonged use. Outside of an initial assessment of depression and suicidality, no special monitoring is required in healthy people taking desvenlafaxine.

Desvenlafaxine contraindications

Desvenlafaxine is never prescribed to people with a known hypersensitivity to desvenlafaxine or venlafaxine. It is also contraindicated in people taking monoamine oxidase inhibitors (MAOIs).

Pregnancy

Desvenlafaxine can be taken during pregnancy and has not been associated with birth defects. However, any use of an SNRI like desvenlafaxine during the third trimester does risk the baby being born with withdrawal symptoms or serotonin syndrome. There also may be increased bleeding after delivery.

Breastfeeding

Desvenlafaxine can be taken while breastfeeding. Only a small amount of the drug is present in breast milk and no adverse effects have been reported in nursing infants.

Children

The Food and Drug Administration (FDA) has not approved the use of desvenlafaxine in anyone younger than 18. 

Seniors

Desvenlafaxine is safe and effective when given to people older than 65. However, there is a slightly higher risk of orthostatic hypotension and fainting in seniors taking desvenlafaxine. 

Desvenlafaxine warnings

Although the FDA has determined desvenlafaxine to be safe, there are some potential hazards outlined in the drug’s warnings.

Black box warning

Like other antidepressants, the FDA has attached a black box warning to desvenlafaxine about the risk of suicidal thoughts and behaviors in children, teens, and young adults. The FDA advises that all those at risk should be monitored carefully for worsening depression or suicidality throughout desvenlafaxine treatment.

Cautions

Some pre-existing medical conditions may be worsened by desvenlafaxine. Alternatively, some medical conditions could increase the risk of desvenlafaxine side effects. These include: 

  • Seizure disorders: Venlafaxine can increase the incidence of seizures in people with seizure disorders. 
  • Bipolar disorder: People with bipolar disorder or a history of mania may become manic or hypomanic when taking desvenlafaxine. 
  • High blood pressure: Desvenlafaxine can worsen high blood pressure. 
  • Uncorrected narrow angles: Because desvenlafaxine can dilate the pupils, people with uncorrected narrow angles in their eyes are at risk for developing angle-closure glaucoma, a serious and vision-threatening eye disorder. 
  • Bleeding disorders: Desvenlafaxine can interfere with the blood’s ability to form blood clots. 
  • Dehydration: Dehydrated people have an increased risk of low sodium when taking desvenlafaxine.
  • Liver impairment or kidney dysfunction: The frequency and severity of desvenlafaxine side effects are higher in people with liver or kidney disease.

Abuse 

Desvenlafaxine is not a controlled substance and does not have a risk for addiction or abuse. 

Dependence and withdrawal

Although desvenlafaxine does not cause physical dependence, its sudden discontinuation could bring on withdrawal symptoms including:

  • Nausea
  • Sweating
  • Rotten mood
  • Irritability
  • Anxiety
  • Mood swings
  • Confusion
  • Low energy
  • Ringing in the ears
  • Trouble sleeping
  • Tingling or other skin sensations

Withdrawal can last for two weeks or several months. Severe symptoms are possible including suicide, thoughts about suicide, and severe aggression. When it is time to stop taking desvenlafaxine, healthcare professionals will use a steadily decreasing dose to prevent discontinuation syndrome.

Overdose

Get immediate medical attention or call a poison control center if too much desvenlafaxine is taken, especially if it’s combined with alcohol or other CNS depressants. Symptoms of an overdose might include racing heartbeats, sleepiness, vomiting, pupil dilation, seizures, or coma. The maximum dosage is 400 mg per day, but this is uncommon. Most people will be prescribed 50 mg per day. Consider the dose prescribed as the maximum dosage.

Desvenlafaxine interactions

Desvenlafaxine has many of the same drug interactions as other SNRIs and SSRIs. However, desvenlafaxine is not primarily broken down by liver enzymes, so it competes with fewer drugs in this area compared with other antidepressants. Still, it does interact with quite a few drugs. Here’s an overview:

  • Drugs that raise serotonin levels: Serotonin syndrome is a potentially serious and life-threatening medical condition in which serotonin levels are too high in the brain. The risk of serotonin syndrome increases when two or more drugs that raise serotonin, like desvenlafaxine, are taken together. Other drugs that raise serotonin levels include other SNRIs, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, anxiety medications, antipsychotic medications, bipolar disorder medications such as lithium, opioids, anticonvulsants, migraine drugs called triptans, and some over-the-counter supplements such as tryptophan and St. John’s wort.
  • Drugs that slow down blood clotting: Since desvenlafaxine interferes with the body’s ability to form blood clots, bleeding episodes are more likely when it’s combined with other drugs that slow down blood clotting including blood thinners and nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin or ibuprofen. 
  • Drugs that are more likely to have side effects when combined with desvenlafaxine: Although not as bad as other SNRIs or SSRIs, desvenlafaxine does block the metabolism of some drugs by the liver, making the side effects of those drugs more likely. Those other drugs may need to have their dosages reduced. Healthcare providers are aware of these drug interactions and will take appropriate steps.

How to avoid desvenlafaxine side effects

While side effects are common when taking desvenlafaxine, a few steps can help minimize trouble.

1. Tell the prescriber about all medical conditions

The more serious problems can be avoided by making sure the prescriber has a complete medical history. Tell the prescriber about past and present medical conditions, especially:

  • Suicidal thoughts
  • Depression
  • Seizures
  • Bipolar disorder 
  • High blood pressure
  • Problems with bleeding or bruising
  • Heart problems
  • Stroke
  • Dehydration
  • Low sodium
  • High cholesterol
  • High triglycerides
  • Uncorrected narrow angles
  • Any past bout with closed-angle glaucoma
  • Liver disease
  • Kidney disease
  • Pregnant or plans to get pregnant
  • Breastfeeding or plans to breastfeed

2. Give the prescriber a list of all drugs being taken

The second way to avoid problems with desvenlafaxine is to share with the prescriber a list of all the prescription drugs, over-the-counter medications, and supplements being taken, especially:

  • MAOI inhibitors
  • Antidepressants, anxiety drugs, antipsychotics, bipolar medications, or other drugs that treat psychiatric disorders such as buspirone
  • Amphetamines
  • Migraine medications called triptans 
  • Opioids like tramadol or fentanyl
  • Blood thinners such as warfarin
  • NSAIDs
  • Supplements or herbal remedies like St. John’s wort or tryptophan

3. Follow instructions when taking this medicine

Take each dose as prescribed at the time of day prescribed. Take only one dose per day. If a dose is missed, take it on the day it’s due. If it’s already the next day, skip the missed dose and take the next dose on time.

4. Try taking each dose in the morning

Taking a dose in the morning can help avoid trouble sleeping at night.

5. Try taking the dose with food

To prevent nausea and stomach upset, take the tablet with a meal or a snack.

6. Avoid alcohol and other medications that cause drowsiness

Alcohol, over-the-counter antihistamines, and other drugs that cause drowsiness can worsen sleepiness, dizziness, vertigo, or postural hypotension caused by desvenlafaxine.

7. Avoid medications containing NSAIDs

Over-the-counter pain relievers or cold medications containing aspirin, ibuprofen, or naproxen could worsen bleeding and digestive problems caused by desvenlafaxine. Use acetaminophen products instead for pain, fever, or cold relief.

How to treat side effects of desvenlafaxine

Many people will have mild problems with desvenlafaxine, at least at first. A few tips can help manage these problems. Other adverse effects, though, will require medical care.

Drowsiness and dizziness

The best way to handle drowsiness, dizziness, or vertigo is to simply sit down and wait it out. If driving, pull over and wait it out. The goal is not to fall or have an accident. When it passes, then stand up slowly. Resume what you were doing with caution.

Low sodium

Call the prescriber if any of the signs of low sodium are noticed. The prescriber may give some advice for handling the problem or ask that you get immediate care. The symptoms to watch for are: headache, weakness, unsteadiness, memory problems, and confusion. If sodium levels drop too low, it could cause seizures or a coma; seek medical attention immediately if this occurs.

Serotonin syndrome

Serotonin syndrome is a rare but potentially serious side effect of taking antidepressants like desvenlafaxine. Get immediate medical attention if any of the signs of serotonin syndrome occur:

  • Agitation
  • Dizziness
  • Flushing
  • Fever
  • Sweating
  • Fast heart rate
  • Changes in blood pressure
  • Hallucinations
  • Muscle stiffness
  • Seizures or convulsions

Suicidal thoughts and behaviors

Young adults taking desvenlafaxine have to be monitored for suicide. It can happen at any time during treatment. Call the prescriber or a mental health professional if the person taking desvenlafaxine shows any of the following signs of suicidality:

  • Suicidal thoughts
  • Suicidal behaviors
  • Talking about death
  • Changes in mood or behavior
  • New or worsening depression or anxiety
  • Panic attacks
  • Irritability, agitation, or restlessness
  • Aggressiveness, anger, hostility, or violence
  • Risk-taking
  • Hyperactivity or uncontrolled talking
  • Insomnia

Eye problems

Desvenlafaxine can cause a potentially catastrophic eye condition called narrow-angle glaucoma. Stop taking desvenlafaxine and get immediate medical attention if experiencing changes in vision or eye pain.

Allergic reactions

Stop taking desvenlafaxine and get immediate medical attention at any sign of an allergic reaction including skin rash, hives, or trouble breathing.

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