The association venlafaxine-mirtazapine is currently known as California Rocket Fuel (CRF). Studies show advantage in terms of efficacy and rapid control of depressive symptoms compared to other associations. Venlafaxine is a selective serotonin-noradrenalin reuptake inhibitor and mirtazapine is a noradrenergic-specific serotonergic antidepressant: the result is a potent noradrenergic and serotonergic effect. Studies say that CRF should be performed only for drug-resistant depression; however, there are case reports of its use as a first line treatment, in selected patients.

To summarize the latest literature about this field and to present a case report.

To explore and critically review the controversies of venlafaxine-mirtazapine association as a first line antidepressants strategy.

A brief review of the latest literature was performed, using PubMed and the keywords “venlafaxine-mirtazapine association”. A case report about a depressed woman is presented.

Despite most studies are referent to its utility in drug-resistant depression, there are recent pilot studies that recommend CRF as a first line option.

M., a 64-year-old woman, had her first psychiatric consultation. She had been depressed for 2 years, she lost 10kg, had total insomnia and suicidal thoughts. CRF was started up to 150/15mg, daily. An improvement was noticed after two weeks of treatment and the stabilization of depressive symptoms were achieved by the fourth month.

CRF seems to be effective and useful. Patients with insomnia and weight loss may benefit from CRF as a first line option. However, more studies are needed.