Discontinuing Trazodone in Patients with Prior Serotonin Syndrome

Rationale for Discontinuation

The American Academy of Sleep Medicine recommends against using trazodone for treatment of sleep onset or sleep maintenance insomnia in adults, due to insufficient evidence supporting its efficacy 1.
The American Academy of Sleep Medicine's 2017 clinical practice guideline explicitly states that trazodone should not be used for insomnia treatment in adults, reflecting its limited evidence base 1.

Trazodone can be discontinued abruptly at 100mg without significant withdrawal risk, as discontinuation syndrome is more commonly associated with shorter-acting SSRIs 5, 6, 7.
A minimum washout period of 5-7 days after trazodone discontinuation is recommended before initiating trintellix, to allow for clearance of trazodone and reduce cumulative serotonergic burden 3, 4.
Trintellix should be started at the lowest dose (5mg daily) and titrated slowly, with intensive monitoring for serotonin syndrome symptoms during the first 24-48 hours after each dose increase 3, 4, 2.

Mental status changes, such as confusion, agitation, and anxiety, should be monitored as potential signs of serotonin syndrome 3, 4, 9, 2.
Neuromuscular hyperactivity, including tremors, clonus, hyperreflexia, muscle rigidity, and myoclonus, should be monitored as potential signs of serotonin syndrome 3, 4, 9, 2.
Autonomic hyperactivity, including hypertension, tachycardia, tachypnea, diaphoresis, and hyperthermia, should be monitored as potential signs of serotonin syndrome 3, 4, 9, 2.
Myoclonus occurs in 57% of serotonin syndrome cases and is the most common finding, while clonus and hyperreflexia are highly diagnostic 9, 2, 8.

Severe complications of serotonin syndrome, including temperature >41.1°C (106°F), seizures, rhabdomyolysis, metabolic acidosis, renal failure, and disseminated intravascular coagulopathy, require emergency care 9, 2.
The mortality rate for severe serotonin syndrome is approximately 11%, with 25% of patients requiring ICU admission with mechanical ventilation 9, 2, 8.