Major
Mirtazapine × venlafaxine
Other antidepressants (NaSSA)×SNRI (serotonin-norepinephrine reuptake inhibitor)
Mechanism
'California rocket fuel' augmentation – mirtazapine (5-HT2/3 blocker) + venlafaxine (SNRI). Used in resistant depression. Serotonin syndrome is rare but possible at high doses.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, fever.
Management
The combination is used for augmentation in resistant depression. Keep doses low: mirtazapine 30 mg, venlafaxine 75–150 mg/day. Monitor blood pressure, pulse, and mental status in the early weeks.