California Rocket Fuel – the combination of mirtazapine and venlafaxine Review article

Abstract

The combination of mirtazapine and venlafaxine, known as the „California rocket fuel”, has been attracting growing interest due to its potential application in the treatment of depression resistant to conventional therapies. This review paper examines the available data on the mechanisms of action and the clinical use of the mirtazapine-venlafaxine combination in medical practice. A key aspect of its action lies in its impact on the monoaminergic system, including increased release of serotonin (5-HT) and norepinephrine (NE) through interactions with presynaptic receptors, which may lead to a rapid improvement in depressive symptoms. This combination may also exert its effects by inhibiting presynaptic alpha-2 autoreceptors, thereby enhancing noradrenergic, serotonergic and dopaminergic transmission. Mirtazapine and venlafaxine demonstrate synergistic action in the treatment of depression. Clinical studies have reported improvements in patients with treatment-resistant depression, and there is a growing suggestion that this combination could also be used as a first-line treatment for depression. However, the safety aspects of this pharmacotherapy must be carefully considered before initiating combination treatment. It should be closely monitored for potential adverse effects to ensure the optimal safety and efficacy of the intervention.