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Venlafaxine (Effexor) Uses + Side Effects

Written by Mathew Eng, PharmD | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Mathew Eng, PharmD | Last updated:
Venlafaxine

Venlafaxine is an FDA-approved antidepressant for the treatment of major depression, generalized anxiety disorder, social anxiety disorder, and panic disorder. Research also shows that venlafaxine may be effective in other diseases and disorders. Read on to find out how this drug works in your body and the possible side effects accompanying its use.

What is Venlafaxine?

Venlafaxine (commonly known as Effexor) is an antidepressant medication that is FDA-approved for the treatment of depression, anxiety, and panic attacks.

Venlafaxine belongs to a group of drugs known as selective serotoninnorepinephrine reuptake inhibitors (SNRIs). These drugs work by preventing the neurons in the brain from taking up serotonin and norepinephrine, which results in increased levels of these two types of neurotransmitters [1].

Besides its FDA-approved uses, there is also evidence that venlafaxine may have beneficial effects on some other conditions, which will be discussed further in this article.

Mechanism of Action

Venlafaxine primarily works by binding to the proteins that are responsible for the removal of serotonin and norepinephrine from synapses in the nervous system. By binding to these proteins, venlafaxine blocks the removal of serotonin and norepinephrine, which ultimately increases their levels [2].

There is also some evidence that venlafaxine blocks the reuptake of dopamine as well, although this effect is much weaker. This also may result in slightly higher dopamine levels [3].

Serotonin, venlafaxine, and dopamine are all types of neurotransmitters that regulate many biological processes such as mood, learning, and memory, to name a few [2].

However, it’s also important to note that the mechanism of action behind venlafaxine’s therapeutic effects is not fully understood [2].

Uses of Venlafaxine

Venlafaxine is a prescription medication that should only be used as directed by a doctor. The FDA has approved venlafaxine for the treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder. Venlafaxine is also sometimes used off-label to treat several other conditions.

FDA-Approved Uses

1) Major Depressive Disorder

Venlafaxine is commonly used for the treatment of depression. The FDA approved venlafaxine for major depressive disorder after multiple short-term and long-term clinical trials established its effectiveness [4].

A large systematic review of 522 clinical trials including 116,477 people found that venlafaxine may be more effective for depression than several other antidepressants. However, researchers also suggest that patients taking venlafaxine may be less likely to be adherent to the medication [5].

It’s important to note that each person will respond to antidepressants differently and the treatment of depression requires a personalized approach. A doctor will weigh the benefits and risks to determine the best type of antidepressant for each patient.

2) Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) is defined as excessive worrying and tension about everyday events for at least 6 months. This anxiety often makes performing day-to-day tasks difficult [6].

According to two short-term (8 weeks) double-blind randomized placebo-controlled trials including 365 and 377 patients with GAD, venlafaxine may reduce anxiety and tension scores [7, 8].

Two long-term (24 and 28 weeks) double-blind randomized placebo-controlled trials of 251 and 541 patients with generalized anxiety disorder found that venlafaxine may improve anxiety symptoms, starting as early as the second week of treatment [9, 10].

3) Social Anxiety Disorder

Social anxiety disorder (SAD), also known as social phobia, is a condition where one experiences intense anxiety or fear during social situations, which can severely disrupt daily life.

Multiple randomized double-blind placebo-controlled trials suggest that venlafaxine is a safe and effective treatment for social anxiety disorder, even as a long-term option [11, 1213, 14].

4) Panic Disorder

Panic disorder is a chronic and recurring disorder characterized by seemingly unexpected panic attacks, which can negatively impact an individual’s wellbeing.

A number of randomized double-blind placebo-controlled trials have found that venlafaxine may be a safe and effective treatment for panic disorder. These studies suggest that low or high doses of venlafaxine may reduce the frequency of full-symptom panic attacks, including improving anticipatory anxiety, fear, and avoidance symptoms [15, 16, 17, 18].

There is also evidence that venlafaxine may help prevent relapse in panic disorder patients after treatment [17, 18].

Off-Label Uses

Venlafaxine is sometimes used for several off-label conditions, which we’ll discuss in the following sections. If you are prescribed venlafaxine, always take the medication as directed by your doctor.

5) Vasomotor Symptoms of Menopause

Vasomotor symptoms, more commonly known as hot flashes or night sweats, are the most commonly reported symptoms associated with menopause. Hot flashes can also be a problem for women with a history of breast cancer [19].

A randomized placebo-controlled trial of 80 postmenopausal (and otherwise healthy) women lasting 12 weeks found that venlafaxine may be effective at reducing hot flash symptoms. Interestingly, 93% of the women who were given venlafaxine choose to continue with the treatment once the study ended [20].

Multiple clinical trials also suggest that venlafaxine may improve hot flash symptoms associated with breast cancer. A systematic review of 5 clinical trials including 525 participants found that venlafaxine may reduce the frequency and severity of hot flashes associated with breast cancer. However, some researchers suggest side effects may limit the long-term use of venlafaxine [21, 22, 23, 24, 25].

A double-blind randomized controlled trial of 339 postmenopausal women found that venlafaxine may be as effective as estrogen hormonal therapy in reducing hot flash symptoms [26].

6) Neuropathic Pain

Neuropathic pain is caused by damage to the nerves and can be difficult to treat. Antidepressants are sometimes used off-label to treat this condition, including venlafaxine [27].

A small randomized double-blind trial of 13 patients who suffered from neuropathic pain following breast cancer treatment found that venlafaxine may reduce average pain intensity and maximum pain intensity [28].

Another randomized placebo-controlled trial of 150 patients who experienced neuropathic pain after breast cancer surgery suggests that venlafaxine may decrease the incidence of chronic pain and its intensity 6 months later [29].

However, in a systematic review of 6 clinical trials including 460 patients, researchers concluded that there was not enough evidence to support the use of venlafaxine for neuropathic pain [27].

7) Migraines and Headaches

According to a randomized placebo-controlled trial of 60 migraine patients, venlafaxine may reduce the number of migraines [30].

In a randomized controlled trial of 64 patients, researchers found that venlafaxine may be effective for vertigo symptoms in migraine-associated vertigo [31].

A randomized double-blind controlled trial of 60 patients suggests that venlafaxine may help with tension-type headaches, the most common type of headache that is often described as feeling like a tight band around the head [32].

8) Depression in Bipolar Disorder

A single-blind randomized trial of 60 bipolar patients on mood-stabilizing drugs found that venlafaxine treatment for 6 weeks may help treat depressive breakthrough episodes [33].

A double-blind randomized trial of 129 patients found that venlafaxine may be more effective for short-term treatment of bipolar II depression compared to lithium [34].

However, there is also evidence that venlafaxine use may increase the risk of bipolar patients experiencing hypomania or mania, also known as “mood switch.” A double-blind randomized trial of 174 bipolar patients found that there may be an increased risk of switching to hypomania or mania in patients who took venlafaxine compared to bupropion or sertraline [35].

9) Behavioral Symptoms in Autism

A small study of 10 autistic subjects (8 children and adolescents, 2 adults) suggests that low dose venlafaxine may improve behavioral symptoms in autism, including repetitive behaviors, communication, inattention, and hyperactivity [36].

Another double-blind randomized placebo-controlled trial of 13 patients found that venlafaxine may improve behavioral abnormalities in autistic patients [37].

10) Obsessive-Compulsive Disorder (OCD) Symptoms

Two randomized controlled trials of 73 and 150 OCD patients found that venlafaxine may help improve OCD symptoms. Researchers also suggest that venlafaxine may have fewer side effects than clomipramine, another antidepressant commonly used to treat OCD [38, 39].

11) PTSD Symptoms

A double-blind randomized placebo-controlled trial of 329 post-traumatic stress disorder (PTSD) patients found that venlafaxine may reduce PTSD symptoms after 24 weeks of treatment [40].

Similarly, a double-blind randomized placebo-controlled trial in 538 PTSD patients reported that venlafaxine may improve symptoms of PTSD at the end of 12 weeks of treatment [41].

12) Fibromyalgia

A systematic review of 5 studies found that venlafaxine may be at least modestly effective in treating fibromyalgia. However, researchers also state that the quality of the available evidence is low [42].

Safety of Venlafaxine

Side Effects

There are many side effects associated with venlafaxine with some being more common than others. Certain side effects may disappear with time as the body adjusts to the medication. This list does not cover all possible side effects. Let your doctor know of any side effects you may be experiencing [4, 43].

Common Side Effects

  • Nausea
  • Headaches
  • Insomnia/experiencing trouble sleeping
  • Drowsiness
  • Sweating
  • Nervousness
  • Dry mouth
  • Dizziness
  • Constipation
  • Lack of energy
  • Blurred vision
  • Loss of appetite
  • Decreased sex drive
  • Erectile dysfunction
  • Impotence
  • Numbness/tingling

Rare Side Effects

  • Suicidal thoughts
  • Irritability
  • A feeling of uncontrollable euphoria/excessive excitement
  • High fever
  • Shortness of breath
  • Irregular heartbeat
  • Chest pains
  • Restlessness
  • Muscle pain/weakness
  • Increased blood pressure
  • Abnormal bleeding
  • Severe dizziness/feeling of passing out
  • Yellow eyes/skin
  • Menstrual changes like heavy bleeding/spotting/bleeding between periods
  • Difficult/painful urination
  • Seizures
  • Eye pain/changes in vision/swelling or redness in and around the eye

Withdrawal Symptoms

Withdrawal symptoms may appear in patients who intentionally or unintentionally discontinue venlafaxine therapy without medical consultation.

For those that need to stop venlafaxine, a doctor will gradually taper off the dose of venlafaxine to minimize any risk of developing withdrawal symptoms [4].

Physical withdrawal symptoms of abruptly discontinuing venlafaxine therapy may include [44, 45, 46, 47]:

  • Headaches
  • Nausea
  • Diarrhea
  • Sweating
  • Increased blood pressure
  • Vertigo
  • Irritable Mood
  • ‘Pins and needles’ sensation
  • Restlessness
  • Fatigue

Mental withdrawal symptoms of abruptly stopping venlafaxine therapy include [44, 45, 46, 47]:

  • Visual and auditory hallucinations
  • Bizarre dreams
  • Feelings of dissatisfaction and agitation
  • Delirium
  • Electric shock-like sensations/brain zaps
  • Worsening of depressive symptoms

Precautions

1) Higher Suicide Risk

Venlafaxine is associated with a higher risk of suicidal thinking and behavior, especially in children and young adults. Those taking venlafaxine should be monitored and any changes in behavior should be reported to a doctor [4].

2) Withdrawal Symptoms

There is a high risk of experiencing adverse events or withdrawal symptoms after abruptly discontinuing venlafaxine therapy, in as little as 12 hours. Consult with your doctor before stopping this medication [4].

Withdrawal symptoms may occur in patients who were taking either a low, moderate, or high dose of venlafaxine.

The accompanying dizziness, disorientation, and impaired coordination as part of the withdrawal symptoms can severely interfere with an individual’s ability to carry out everyday tasks such as driving a car [48].

3) Serotonin Syndrome

Serotonin syndrome is a life-threatening disorder that can occur when taking one or more medications that increase serotonin levels, such as venlafaxine. Always let your doctor know of all the medications and supplements you are taking to avoid harmful interactions.

Some common symptoms of serotonin syndrome include high body temperature, agitation, tremors, sweating, and dilated pupils, which can lead to seizures and death. Seek immediate medical attention if you suspect you are experiencing this disorder [4].

4) Elevations in Blood Pressure

A meta-analysis of 3,744 patients with depression reported that venlafaxine may cause clinically significant increases in blood pressure in a dose-dependent manner [49].

The FDA recommends managing high blood pressure before starting venlafaxine therapy and regularly monitoring blood pressure during treatment [4].

5) Activation of Mania/Hypomania

Venlafaxine is associated with an increased risk of causing mania/hypomania in short- and long-term treatment of bipolar disorder when used as an adjunct to standard mood stabilizers [50, 51].

Venlafaxine should be used cautiously in patients with bipolar disorder [4].

6) Risk of Bleeding

There’s some evidence that venlafaxine may increase the risk of bleeding. Caution should be used in patients taking other medications with bleeding risks, such as aspirin or anticoagulation medications [4].

7) Caution in Pregnancy and Breastfeeding

Some research suggests that venlafaxine may be associated with birth defects and miscarriages, although strong clinical evidence is lacking. Venlafaxine should only be used during pregnancy if a doctor determines that the benefits outweigh risks [4].

Small amounts of venlafaxine are excreted in breast milk. Again, a doctor will decide if venlafaxine can be used during breastfeeding [4].

Contraindications

Hypersensitivity

People who are sensitive or allergic to venlafaxine, desvenlafaxine (another SNRI drug that is similar to venlafaxine), or any other excipients (substances that are present in the medication along with the drug) should refrain from using venlafaxine.

Concomitant Use with Monoamine Oxidase Inhibitors (MAOIs)

The concomitant use of venlafaxine with monoamine oxidase inhibitors (another type of antidepressant) is contraindicated since both drugs result in elevated serotonin levels. This may lead to potentially toxic serotonin syndrome [52, 53].

It is not advisable to start any MAOI treatment 7 days after discontinuing venlafaxine treatment due to the increased risk of serotonin syndrome [53].

The effects of MAOIs in the brain may persist for a while after their discontinuation. Hence, venlafaxine medication is also contraindicated within 14 days of discontinuing treatment with MAOIs [54, 55].

Drug Interactions

Medications That Increase Serotonin

As discussed earlier, drugs that increase serotonin (such as venlafaxine) can potentially cause serotonin syndrome.

The following drugs have been reported to interact with venlafaxine, resulting in serotonin syndrome. However, this is not a complete list, let your doctor know of all the medications you are currently taking to avoid any unexpected interactions:

  • Linezolid (an antibiotic that is also a monoamine oxidase inhibitor) [56, 57]
  • Lithium [58, 59, 60]
  • Mirtazapine [61, 62]
  • St John’s wort (herbal product) [63]
  • Tramadol [62]
  • Tranylcypromine [64, 65]
  • Trazodone [66]
  • Triptans (drugs used to treat migraine headaches) [67]

Medications That Affect Bleeding Risk

There is some evidence that venlafaxine may impair the function of platelets, potentially increasing the risk of bleeding events [53, 68].

Venlafaxine should be used cautiously in patients who are taking other medications that may increase the risk of bleeding. The following drugs are some examples of drugs that may increase bleeding risk, but keep in mind this is not a complete list [4].

  • NSAIDs, such as aspirin or ibuprofen
  • Anticoagulants, such as warfarin

Venlafaxine Dosing

Venlafaxine is only available in an extended-release (XR) form, which is taken by mouth, typically in a single dose with food in the morning or evening. The following sections detail the recommended dosing according to the FDA [4].

It’s important to note that each patient will respond to antidepressants differently and it may take time to find the right dose for you. Antidepressants like venlafaxine also take time to work and patients may not feel benefits for 1-3 weeks or more. Always take venlafaxine as directed by a doctor and do not discontinue the medication abruptly.

Major Depression and Generalized Anxiety Disorder

According to the FDA, patients should start at a venlafaxine dose of 37.5 -75 mg per day.

The recommended dose is 75 mg, patients taking lower doses should slowly increase until this target dose is reached.

However, patients that are not experiencing benefits from the recommended venlafaxine dose may be prescribed doses as high as 225 mg per day, which is the maximum dose.

Social Anxiety Disorder

For social anxiety disorder, the recommended venlafaxine dosage is 75 mg per day administered as a single dose. There is no evidence that a higher venlafaxine dose results in any additional benefits.

Panic Disorder

Patients with panic disorder should start on a venlafaxine dosage of 37.5 mg per day for a week.

After at least a week, the dose should be increased to 75 mg, which is the recommended dose.

However, patients that are not experiencing benefits from the recommended venlafaxine dose may be prescribed doses as high as 225 mg per day, which is the maximum dose.

About the Author

Mathew Eng

Mathew Eng

PharmD
Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.
Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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