UK Clinical Pharmacy Association


Issues for surgery

Risk of serotonin syndrome if continued (see Interactions with common anaesthetic agents and Interactions with other common medicines used in the perioperative period).

Risk of bleeding if continued (see Further information).

Advice in the perioperative period

Elective and emergency surgery


Check sodium levels pre-operatively (see Further information).

Post-operative advice

If a long nil by mouth (NBM) period is anticipated, or if there are concerns with enteral absorption, advice on alternative preparations / routes should be sought from a psychiatrist.

Monitor electrolytes, particularly sodium, if risk factors for hyponatraemia (see Further information).

Interactions with common anaesthetic agents

CNS excitation (serotonin syndrome)

Some opioids act as weak serotonin reuptake inhibitors (SRIs) and can precipitate serotonin syndrome in conjunction with other serotonergic medication e.g. vortioxetine. Symptoms of serotonin syndrome may occur if vortioxetine is given concomitantly with:

  • fentanyl
  • methadone
  • pentazocine
  • pethidine
  • tapentadol
  • tramadol

Patients should be monitored closely and the possibility of serotonin toxicity considered if patients experience altered mental state, autonomic dysfunction or neuromuscular adverse effects with concomitant treatment.

Interactions with other common medicines used in the perioperative period

CNS excitation (serotonin syndrome)


For a discussion of opioids see Interactions with common anaesthetic agents

In addition, vortioxetine can lower the seizure threshold; concurrent use with tramadol that also lowers the seizure threshold may have an additive effect on the risk of seizures.

Methylthioninium chloride (methylene blue)

There have been case reports of serotonin syndrome in patients taking serotonergic drugs who were also given methylthioninium chloride. The MHRA advise that methylthioninium chloride should be avoided in patients taking drugs that enhance serotonergic transmission. If concurrent use is necessary the lowest possible dose of methylthioninium chloride should be given and the patients should be closely monitored for signs of CNS toxicity for 4 hours after administration. However, this advice is contested in one report which suggests doses as low as 1mg/kg may be sufficient to inhibit monoamine oxidase-A, thus causing a reaction.

Other medications

There is also an increased risk of developing serotonin syndrome when vortioxetine is used concurrently with the following: 

  • granisetron
  • ondansetron
  • linezolid

Monitor patients for symptoms of serotonin syndrome such as fever, tremors, diarrhoea, and agitation. Concurrent treatment should be stopped if serotonin syndrome occurs.

Increased risk of bleeding 

See also Further information.

Concomitant use of vortioxetine with other medications that can increase the risk of bleeding e.g. Non-Steroidal Anti-inflammatory Drugs (NSAIDs) may have an additive effect.

Increased risk of hyponatraemia 

See also Further information.

Concomitant use of SSRIs with NSAIDS may increase the risk of hyponatraemia.

Further information

Cessation of treatment

The manufacturer advises treatment can be stopped abruptly without need for gradual dose reduction, although transient withdrawal symptoms such as headache and muscle tension have been reported at higher doses.


Serotonin released from platelets potentiates platelet aggregation. SSRIs can block platelet reuptake of serotonin from the bloodstream leading to serotonin depletion, impairment of haemostatic function and an increased risk of bleeding. There are reports of prolonged bleeding time and/or bleeding abnormalities (gastrointestinal bleeding, gynaecological haemorrhages, ecchymoses, cutaneous or mucous bleedings) in patients receiving vortioxetine. This risk is further increased with concomitant use of other medications known to affect platelet function (see Interactions with other common medicines used in the perioperative period).


Hyponatraemia, possibly as a result of inappropriate secretion of antidiuretic hormone, has been associated with vortioxetine. Caution is required in patients at increased risk of hyponatraemia, such as elderly, or volume depleted / dehydrated patients or patients treated with diuretics.


Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. [Accessed on 24th July 2019]

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. [Accessed on 24th July 2019]

Summary of Product Characteristics – Brintellix® (vortioxetine) 10mg film-coated tablets. Lundbeck Limited. Accessed via 24/07/2019 [date of revision of the text June 2019]

Taylor D, Barnes T, Young A. The Maudsley Prescribing Guidelines in Psychiatry. 13th ed. Chichester: Wiley- Blackwell; 2018

Vortioxetine. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. Electronic version. Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: [Accessed 24th July 2019]