Vortioxetine (Brintellix, Trintellix) Side effects Including Sexual

Vortioxetine Side effects that are common include nausea, dyspepsia, diarrhea, constipation, and sexual side effects. Most of the side effects are related to the central nervous system. A detail of the side effects of Vortioxetine is reviewed here. A piece of advice regarding how to overcome these side effects is also discussed.

What is Vortioxetine?

Vortioxetine is an antidepressant drug that acts by activating 5HT-1A receptors and inhibits the activity of 5HT-1D, 5HT-7, and 5HT-3 receptors. It also has a partial agonist activity by binding to 5HT-1B receptors. The exact role of its affinity to various receptors is not yet known.
It increases the serotonin levels in the brain by inhibiting its reuptake by the neurons. Vortioxetine is also called a serotonin modulator because it affects the activity of various serotonin receptors.
The main action of the drug is via binding to and activating 5-HT-1A receptors, while the partial agonist activity at the 5HT-1B receptors enhances its effects.
It is available by the brand names of Brintellix and Trintellix. It is administered orally in a dose of 5 – 20 mg once daily.
vortioxetine moa
Vortioxetine MOA: It has 5HT-1A agonist activity and antagonist activity at other receptors.

Vortioxetine Contraindications: Who should not take Vortioxetine?

  • Patients who are allergic to vortioxetine (Brintellix or Trintellix). Allergic reactions that are of serious nature may manifest as facial and lip swelling, shortness of breath, wheezing, and hypotension.
  • Use of MAO inhibitor to treat psychiatric disorders concurrently or within 21-days of stopping vortioxetine, or within 14-days of ceasing the MAO inhibitor. Co-administration of Vortioxetine with an MAO inhibitor may result in serotonin syndrome.
  • Likewise, the initiation of vortioxetine for patients receiving intravenous methylene blue or linezolid can cause the development of serotonin syndrome.

Side effects of Vortioxetine (Brintellix):

Vortioxetine has a relatively better safety profile compared to most other antidepressant medications. In one 52-weeks trial, side effects were reported in 70.6% of the patients. The most common side effects that were reported with the use of vortioxetine included [Ref]:

  • Nausea (15.2%)
  • headache (12.4%)
  • Nasopharyngitis (9.8%)
  • Diarrhea (7.2%)
  • Dizziness (6.8%)

Another study reported Nausea, headache, dry mouth, and dizziness as the most common side effects of Vortioxetine [Ref]. In other short-term trials, nausea, constipation, and vomiting were reported commonly with vortioxetine 20 mg compared with placebo.

Nausea is the most commonly reported side effect

Studies have shown that side effects of vortioxetine are less common than those of other antidepressants like duloxetine and agomelatine. As an example, a meta-analysis of five randomized trials (n >2000 depressed patients) lasting eight weeks compared vortioxetine (2.5 to 20 mg/day) with duloxetine (60 mg/day) and found that adverse effects were less likely to occur with vortioxetine than duloxetine (relative risk 0.88, 95% CI 0.82-0.94), including nausea (relative risk 0.70, 95% CI 0.56-0.87) [Ref].

Among the serious side effects reported with the use of vortioxetine, suicidal risk, hypertensive crisis, and acute pancreatitis were the most common.

Serious Side effects: Suicide, Hypertensive Crisis, Pancreatitis

Suicidal thoughts:

  • Be aware of the risk of suicidal thoughts and suicidal behaviors before prescribing. Studies done in short term did not find an increase in risk for patients aged >24 years and a decrease in risk for patients 65+.
  • Instruct family members or caregivers to monitor the patient closely and communicate with their health care provider during treatment, especially during the initial few months or periods of dosage adjustments. Each prescription should include a medication guide describing the use of antidepressants.
  • Major depression can lead to suicide attempts. This possibility may continue until remission. Modifying or stopping drug therapy may be necessary for severe suicidal thoughts and worsening depression. High-risk patients should be cautious when initiating therapy.
  • Prescriptions should only be written for the lowest amount of medication that is consistent with patient care. Patients should be notified by their caregiver or family to be on the lookout for signs of suicidality.
  • How to identify an increase in suicidal tendency?

    • It is important to note and report if there is a change in behavior or the person develops any of the following symptoms:
      • Thoughts about harming yourself
      • an increase in irritability, aggression, and agitation
      • panic attacks and new symptoms of worsening depression and anxiety
      • change in mood and sleep timings
      • abnormal dietary changes
  • What to do if the person develops an increased risk of suicidal ideations?

    • Since the patient might not help himself, it is the responsibility of the family members and caregivers to take care of the patient. To protect the patient and other people from getting injured, the caregivers should call 911 and get the person admitted to a hospital.
    • It is also important to keep all the objects that can harm the patient or other people away from the patient including knives, guns, acids, washroom cleaners, and medications.
    • Caregivers must listen to the patient and avoid arguing with the patient. Caregivers must be advised not to shout or yell at the patient and never threaten the patient.

Bleeding Risk with Vortioxetine:

  • Since serotonin is an important mediator released by the dense granules of platelets that help in platelet aggregations. Serotonin-reuptake inhibitors can result in an impairment of platelet aggregation especially when it is taken with Aspirin, NSAIDs, warfarin, or novel anticoagulants like rivaroxaban and apixaban.
  • Bleeding is usually mild to moderate and does not require any specific intervention in most cases other than reducing the dose, discontinuing the anticoagulant temporarily, or local measures.
  • In cases of severe bleeding, patients may need hospitalization. Occasionally, factors and platelet concentrates may be required.

Use Vortioxetine with caution in patients on anticoagulants

Drowsiness with Vortioxetine:

  • CNS depression can cause impairments in mental or physical abilities. Patients should be cautious about driving or operating machinery that requires mental alertness.
  • Drowsiness, abnormal dreams, or memory impairment may all result. Patients may take the drug at night if daytime drowsiness is a problem. It may also be helpful to start the drug from a low dose and gradually increase the dose as tolerated.

Fracture Risk With Vortioxetine:

  • Antidepressant treatment has been linked to bone fractures. Consider the possibility of a fragility fracture if an antidepressant-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising.
  • The exact mechanism of bone fractures is not yet understood, however, SSRIs can result in demineralization of bones, a reduction in bone mineral density, and frequent falls that can result in fractures.
  • Patients may be asked to take adequate amounts of calcium and indulge in activities like aerobic exercises and weight lifting. In high-risk patients, prescribing bisphosphonate may be helpful.

SSRIs increase the risk of fractures

Eye-related Side effects of Vortioxetine:

  • Ocular side effects may include mild pupillary dilation, which can in some cases lead to narrow-angle glaucoma. Patients with narrow-angle glaucoma who have not had an Iridectomy should be evaluated for the benefits and risks associated with the drug.
  • The association is not strong, however, patients with pre-existing glaucoma may be at an increased risk of worsening eye disease. Furthermore, mydriatic agents that dilate the pupils may exacerbate the problem.

Serotonin Syndrome:

  • Serotonin Syndrome is a potentially life-threatening condition that can be caused by serotonergic antidepressants (eg SSRIs, SNRIs) when combined with serotonergic agents such as triptans, tricyclic antidepressants, fentanyl, and lithium.
  • Watch out for signs and symptoms of SS, such as:
    • mental changes such as agitation or hallucinations, delirium, and coma
    • autonomic changes like tachycardia, labile blood pressure, and sweating
    • neuromuscular changes such as tremors, rigidity, and myoclonus,
    • GI symptoms like nausea, vomiting, diarrhea; and/or
    • Seizures.
  • If you notice any symptoms, discontinue treatment.

Serotonin syndrome is life-threatening


  • The development of SIADH has been linked to the use of serotonergic drugs. Hyponatremia (including severe cases involving serum sodium 110 mmol/L) has been reported.
  • Risk factors include age (the elderly), volume depletion, and/or concurrent diuretics use. Patients with symptoms of hyponatremia should avoid taking the drug.

Brintellix Side effects: Mania and Hypomania:

  • Mania and hypomania have been reported in patients using vortioxetine. Before initiating therapy, screen patients for any history or family history with bipolar disorder, hypomania, or mania.
  • This may lead to a shift towards mania or hypomania in patients suffering from bipolar disorder. Patients with bipolar disorder should not be treated with monotherapy. Combining antidepressant therapy with a mood stabilizer can be helpful for the acute treatment of major bipolar episodes.
  • However, it should not be used in cases of severe mania or mixed episodes. Bipolar disorder should be checked for patients who present with depressive symptoms.
  • Vortioxetine has not been approved by the FDA for the treatment of bipolar disorder.

Vortioxetine is not approved for Bipolar disorder

Seizures Risk With Vortioxetine:

  • Patients with seizure disorders, a history of seizure disorder or conditions that predispose to seizures (like brain trauma or tumors) should be cautious when using vortioxetine (Brintellix). Rarely, seizures have been reported in patients who do not have a history of seizures.
  • Seizures may also occur in patients using Vortioxetine if they have hyponatremia or if the patient develops serotonin syndrome.

Seizures may occur in high-risk patients

Discontinuation Syndrome:

  • Discontinuation syndrome is abrupt discontinuation or interruption in antidepressant treatment. Although symptoms may vary, most patients report symptoms of nausea, vomiting, diarrhea, lightheadedness as well as dizziness. The less common symptoms include electrical shock-like sensations and cardiac arrhythmias.
  • Anxiety, panic attacks, and irritability are all possible symptoms. Antidepressants that have shorter half-lives, longer treatment durations, or abrupt discontinuation are more likely to develop a discontinuation syndrome.
  • Symptoms may develop within two to five days of treatment discontinuation for antidepressants with intermediate or short half-lives. They can last seven to fourteen days.

Vortioxetine Weight Gain:

Vortioxetine does not cause significant weight gain compared to other antidepressants, especially when administered for a duration of six months or less. In one long-term clinical trial, vortioxetine cause a weight gain of 0.67 kgs when the drug was administered over 52 weeks [Ref].

Among the antidepressants, bupropion causes the least weight gain. In fact, Bupropion is FDA-approved for weight loss.

Vortioxetine does not cause significant weight gain

Vortioxetine Sexual Side effects:

Depression and anxiety have been associated with abnormal sexual health. The situation is worsened by the use of antidepressants. Most antidepressants cause some degree of impotence and sexual side effects.

In one clinical trial, the incidence of sexual side effects was higher in patients who were using vortioxetine compared to those who received a placebo. Side effects were observed in both men and women.

In patients who did not have sexual dysfunction at baseline, vortioxetine administered in a dose of 20 mg once daily resulted in a higher percentage of patients developing sexual side effects compared to placebo [Ref].

In the above clinical trial, sexual dysfunction was measured by the ASEX (Arizona Sexual Experience Scale) that has five different questions. Each question covers a different aspect of sexual function and has 6 points each.

The ASEX score evaluates Desire, Arousal, Penile erection in men and vaginal lubrication in women, orgasm, and satisfaction. Sexual dysfunction is labeled when the patient has a total score of 19 or more, OR 5 or more on any item, OR 4 or more on three items [Ref].

sexual side effects of vortioxetine 20 mg
Vortioxetine Sexual side effects compared with placebo

Vortioxetine Overdose:

Vortioxetine overdose is only known from clinical trials where subjects consumed between 40 and 75 mg of the drug. This was associated with increased nausea, vomiting, diarrhea, cramping, flushing, and pruritus.

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