Bupropion (Zyban) - risk of serotonin syndrome with use with other serotonergic drugs

Review of cases of serotonin syndrome

• a European review of safety data for Zyban identified at least 8 cases of serotonin syndrome, a potentially life-threatening condition, where a possible interaction between bupropion and a serotonergic drug was thought to have led to serotonin syndrome. The review also identified 6 cases with good evidence of an association with an overdose of bupropion. In the majority of these cases the patients had intentionally taken more than the prescribed dose.

Advice for healthcare professionals:

• cases of serotonin syndrome have been reported in association with bupropion and coadministration with serotonergic drugs, for example
  • selective serotonin reuptake inhibitors (SSRIs)
  • serotonin norepinephrine re-uptake inhibitors (SNRI)
• if concomitant prescribing with other serotonergic drugs is clinically warranted:
  • do not exceed the recommended dose
  • remind patients of the milder symptoms of serotonin syndrome at initiation of treatment and at any change of dose and the importance of seeking medical advice if they occur
• if serotonin syndrome is suspected, either decrease the dose of bupropion or withdraw therapy depending on the severity of the symptoms

Advice to give to patients

• if you are told you may be at risk of serotonin syndrome, be aware of symptoms, including mild signs such as nausea, vomiting, and diarrhoea or increased heart rate and agitation (see full list below) and talk to your prescriber if you experience these
• never exceed the prescribed dose of bupropion
• always read the patient information leaflet for side effects to be aware of and when to seek medical advice

Serotonin syndrome – signs and symptoms

• serotonin syndrome is an iatrogenic disorder of serotonergic hyperstimulation in which the underlying mechanism is thought to involve excessive stimulation of 5-HT1A receptors
• occurs most commonly when two or more serotonergic agents with different pharmacological mechanisms are administered either concurrently or sequentially without a sufficient washout period. However, it can also be associated with a single serotonergic agent, particularly at a high dose
• signs and symptoms of serotonin syndrome may include:
  • mental-status changes (for example, agitation, hallucinations, coma),
  • autonomic instability (for example, tachycardia, labile blood pressure, hyperthermia),
  • neuromuscular abnormalities (for example, hyperreflexia, incoordination, rigidity)
  • and gastrointestinal symptoms (for example, nausea, vomiting, diarrhoea)

If serotonin syndrome is suspected, a dose reduction or discontinuation of bupropion therapy should be considered, depending on the severity of the symptoms.

Reference:

• Drug Safety Update volume 14, issue 4: November 2020: 4.