Brintellix withdrawal is no joke. Abruptly stopping Brintillix can leave you feeling unwell and depressed. Zaps, agitation, insomnia – these are just a few of the symptoms of SSRI discontinuation syndrome.

But there is a light at the end of the tunnel. Most if not all of the symptoms of Brintellix discontinuation/withdrawal resolve over time.

If you’re abruptly stopping Brintellix on your own, we strongly suggest that you taper off of Brintellix gradually under the care of a physician. If you’re physician instructed you to stop Brintellix, heed their advice.

If you’re withdrawing from Brintellix because you ran out of medication, your best bet is calling your physician or visiting an urgent care clinic. At an urgent care clinic you can also get a temporary prescription until you’re able to get an appointment with your psychiatrist or primary care physician to renew the prescription.

Treatments for Depression

First line treatments for depression often target the serotonin system.

Serotonin modulates several behaviors including mood. To be frank, it’s not fully understood how serotonin contributes to depression and anxiety

Boosting serotonin may reduce depression and anxiety by suppressing hyperactivity of the amygdala. This brain region plays a role in emotional responses. Another mechanism is that serotonin can enhance neurogenesis 1.

Types of Serotonergic Antidepressants:

  • Selective Serotonin Reuptake Inhibitors (SSRIs). An example is Lexapro (escitalopram). Drugs like Lexapro block removal of serotonin. This increases serotonin activity because more neurotransmitter lingers at synapses.
  • Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs). These drugs block removal of both neurotransmitters, boostign their effects.

Strictly speaking, vortioxetine isn’t a pure SSRI or SNRI. It does block serotonin removal (reuptake) just like SSRIs. But it interacts with other receptors, so its mechanism is nuanced.

Why Was Brintellix Developed?

Vortioxetine is a new antidepressant approved for the treatment of major depression.

Pharmacologists created vortioxetine as a novel antidepressant to target more pathways than current drugs.

Vortioxetine modulates serotonin in many ways:

  • blocking serotonin re-uptake
  • activating serotonin receptor 5-HT1A
  • partially activating 5-HT1B
  • blocking 5-HT1D, 5-HT3 and 5-HT7 receptors

Vortioxetine’s effect on serotonin is complex. It’s not only globally increasing serotonin like conventional SSRIs. Vortioxetine also activates and blocks specific serotonin receptors. Vortioxetine also affects other neurotransmitters involved in depression including norepinephrine, dopamine, and histamine.

Vortioxetine may also improve learning and memory, particularly in depressed patients 2.

Vortioxetine FDA Approval

Vortioxetine was approved by the US Food and Drug Administration (FDA) on September 30, 2013, to treat MDD in adults.

It’s sold under the brand names Trintellix and Brintellix which contain the beta-polymorph of vortioxetine hydrobromide.

Physical Appearance

Vortioxetine is a slightly beige powder that is partially soluble in water.

How to Take

Vortioxetine is administered as a tablet at four different dosages: 5, 10, 15 or 20mg. The tablet is taken orally.


The half-life of Vortioxetine is relatively long at nearly 66 hours.

A steady-state concentration can be reached in approximately 2 weeks after administration of the initial dose.

Despite achieving steady state in a short amount of time, vortioxetine is not effective until 6-8 weeks following the initial treatment. Patients are started on 10mg per day. If vortioxetine is well-tolerated, the dose is increased to 20mg per day 3.

Side Effects of Vortioxetine

Since blocking serotonin receptors can result in light-headedness and nausea, it is no surprise that the most common side effects of vortioxetine used to treat MDD were nausea constipation and vomiting. However, cases of diarrhea, dry mouth, constipation, vomiting, dizziness and abnormal dreams have been reported. Sexual dysfunction in a small percentage of men has also been reported.

Vortioxetine Withdrawal

As with any antidepressant, stopping medication can be accompanied by withdrawal symptoms. Vortioxetine is no exception.

Several factors influence the severity and duration of withdrawal symptoms. These factors include:

  • Duration of therapy with Brintellix. The longer you’ve been taking Brintellix, the harder it is to discontinue.
  • Dosage. It’s harder for your brain to re-equilibrate after stopping higher doses.
  • Sensitivity to medication
  • Unique neurophysiology

Higher doses of vortioxetine are more potent than lower doses, resulting in greater changes to the nervous system function that needed to be readjusted to after discontinuation.

If you’re contemplating voluntarily stopping vortioxetine please taper your dose.

The longer your course of vortioxetine and the higher dosage, the time it will take for withdrawal symptoms to subside. Unsurprsingly, withdrawal symptoms can also felt to a greater extent when treatment ends abruptly.

To reiterate, your withdrawal symptoms will be more pronounced if you’ve been on th drug for a long time and you stop suddenly.

Tapering Brintellix

Tapering allows the nervous system to adjust to the drop in drug concentrations.

Other factors desides dosage, tapering schedule, concurrent use of other medicines or duration influence Brintellix withdrawal symptoms 4.

Common Symptoms of Vortioxetine

Sudden discontinuation of vortioxetine is associated with multiple withdrawal symptoms.

Physical withdrawal symptoms include:

  • Muscle tension
  • Rebound depression
  • Brain zaps/sensation of an electrical shock
  • Depersonalization
  • Not feeling like yourself
  • Dizziness
  • Flu-like symptoms
  • Nausea and vomiting
  • Sweating
  • Headaches
  • Suicidal thoughts

Serotonin influences activity in the amygdala, a region of the brain responsible for emotional responses. Thus it’s not surprising that cessation of vortioxetine treatment can be emotionally destabilizing.

Vortioxetine’s emotional withdrawal symptoms include anxiety, random outburst of anger, irritability, and mood swings.

Learning and Memory

Because vortioxetine may enhance learning and memory, discontinuation could also result in temporary difficulty concentrating.

Rebound Depression

The least surprising withdrawal symptom is depression. Depressive symptoms may be more intense than prior to vortioxetine therapy. That’s because stopping treatment could skew neurochemistry more severely than that originally experienced until the brain begins to compensate.


Another common withdrawal symptom is fatigue. Serotonin and norepinephrine influence arousal and the sleep/wake cycle. Thus a altered neurophysiology due to treatment cessation may leave you feeling fatigued. Paradoxically, you might even have insomnia despite being fatigued.

You may also have a runny nose. This is a withdrawal symptom unique to vortioxetine 5.


In summary, vortioxetine is an effective new therapy to treat MDD that modulates serotonin, and to a lesser extent norepinephrine, dopamine, and histamine.

But discontinuation of vortioxetine can result in severe withdrawal effects. To prevent these symptoms, patients and care providers should be sure to slowly taper treatment to help make the transition as comfortable as possible.


  1. Cowen PJ, Browning M. What has serotonin to do with depression?. World Psychiatry. 2015;14(2):158-60. 
  2. Available at: Accessed August 5, 2016. 
  3. D’agostino A, English CD, Rey JA. Vortioxetine (brintellix): a new serotonergic antidepressant. P T. 2015;40(1):36-40. 
  4. Katona CL, Katona CP. New generation multi-modal antidepressants: focus on vortioxetine for major depressive disorder. Neuropsychiatr Dis Treat. 2014;10:349-54. 
  5. Kelliny M, Croarkin PE, Moore KM, Bobo WV. Profile of vortioxetine in the treatment of major depressive disorder: an overview of the primary and secondary literature. Ther Clin Risk Manag. 2015;11:1193-212.