Major
Escitalopram × Mirtazapine
Selective serotonin reuptake inhibitors (SSRIs)×Other antidepressants (NaSSA)
Mechanism
Additive serotonergic effect. Mirtazapine blocks 5-HT2A/2C/3 but activates 5-HT1A. Combined with escitalopram (SSRI), serotonin syndrome has been reported, especially at high doses.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.
Management
The combination may be used for augmentation ('California rocket fuel') but requires caution. Escitalopram up to 10 mg, mirtazapine 15–30 mg. Monitor blood pressure, pulse, and mental status in the early weeks.