Can electroconvulsive therapy (ECT) induce serotonin syndrome in patients taking medications that increase serotonin levels, such as selective serotonin reuptake inhibitors (SSRIs)?

Can Electroconvulsive Therapy (ECT) Induce Serotonin Syndrome?

Yes, electroconvulsive therapy can induce serotonin syndrome, particularly when administered to patients taking serotonergic medications such as SSRIs, SNRIs, or other drugs that increase serotonin levels. Multiple case reports document this potentially dangerous interaction, which appears to be related to transient blood-brain barrier changes caused by ECT.

Mechanism and Risk Factors

• ECT may transiently increase blood-brain barrier permeability, enhancing the central nervous system effects of serotonergic medications even at standard doses 1
• This increased permeability appears to be temporary, typically resolving within days after ECT 2
• The combination of ECT with serotonergic medications can lead to excessive serotonin stimulation in the central nervous system, triggering serotonin syndrome 3

Documented Cases

• Case reports show serotonin syndrome developing after the first session of ECT in patients taking:

  • Paroxetine (an SSRI) 1
  • Fluoxetine (an SSRI) 4
  • Combination of trazodone, bupropion, and quetiapine 3
  • Lithium in combination with escitalopram 2

• In these cases, symptoms typically developed shortly after ECT and resolved within days after discontinuation of the serotonergic medications 2, 3, 1

Clinical Presentation of Serotonin Syndrome

• Serotonin syndrome presents with a triad of symptoms 5:
  • Mental status changes (confusion, agitation)
  • Neuromuscular hyperactivity (tremor, clonus, hyperreflexia)
  • Autonomic instability (hyperthermia, tachycardia, diaphoresis)
• Symptoms typically develop within 24-48 hours after the triggering event 5
• Severe cases can progress to fever, seizures, arrhythmias, unconsciousness, and potentially death 5

Management Recommendations

• For patients requiring ECT who are on serotonergic medications:

  • Consider temporarily discontinuing serotonergic medications before initiating ECT when clinically feasible 6
  • If discontinuation is not possible, use the lowest effective dose of serotonergic medications 5
  • Monitor closely for signs of serotonin syndrome after each ECT session 3, 1

• If serotonin syndrome is suspected:

  • Immediately discontinue all serotonergic agents 5
  • Provide supportive care, including IV fluids and cardiac monitoring 5
  • Consider serotonin antagonists such as cyproheptadine for severe cases 5
  • Be aware that symptoms typically resolve within 24-72 hours after discontinuation of the causative agents 2, 1

High-Risk Medication Combinations

• Particular caution is needed when ECT is combined with:
  • Multiple serotonergic agents simultaneously 5
  • MAOIs (monoamine oxidase inhibitors) 6, 5
  • Opioids with serotonergic properties (meperidine, fentanyl, methadone, tapentadol, tramadol) 6
  • Lithium 6
  • Trazodone 6, 3

Important Clinical Considerations

• The risk appears highest with the first ECT session and may diminish with subsequent treatments 1
• Hypersensitivity to serotonergic medications during ECT appears to be transient 2
• Patients may tolerate the same medication combinations weeks after completing ECT 2
• When restarting serotonergic medications after ECT, begin with low doses and titrate slowly 5

This phenomenon highlights the importance of careful medication management during ECT and vigilant monitoring for signs of serotonin syndrome, especially after the initial treatment sessions.