The fact that you landed on this page means that you were researching California Rocket Fuel. I too have been in your shoes performing this same search (years ago).
What is California Rocket Fuel, you ask? It's an antidepressant cocktail popularized by the celebrity psychiatrist Stephen Stahl.
What's the recipe? It only has two ingredients:
- Venlafaxine (Effexor)
- Mirtazepine (Remeron)
Venlafaxine is an SNRI or serotonin-norepinephrine re-uptake inhibitor. Mirtazepine on the other hand is an unconventional antidepressant. It's technically a noradrenergic and specific serotonergic antidepressant (NaSSA). The key difference is that mirtazepine boosts serotonergic and noradrenergic signaling via a different mechanism than Venlafaxine.
Why Is The Cocktail Called "California Rocket Fuel"?
It's a curious name for an antidepressant combo.
Effexor + Remeron is rocket fuel because it packs a serious punch; it's a very robust antidepressant combination. The "California" aspect is derived from the fact that Dr. Stahl practices in California so this is where the antidepressant cocktail was popularized.
What Are The Advantages of Combining Remeron + Effexor?
Remeron is a robust antidepressant by itself, though its side effects can be hard to tolerate (a ravenous appetite and sedation). That's because Remeron is also a sleep aid. Depression and insomnia go hand-in-hand, so a drug that both elevates mood while promoting sleep can do wonders.
Venlafaxine duplicates some of the effects of Remeron. In other words, it's an SNRI that affects the same neurotransmitters - norepinephrine and serotonin. This has a synergistic effect.
If you combined two SNRIs like Pristiq and Effexor - you wouldn't get much synergy. Pristiq and Effexor are very closely related and have identical mechanisms. Therefore taking both would be no different than simply raising the dose of either drug and taking it alone.
But what about California Rocket Fuel, i.e., Remeron and Effexor? These drugs affect the same neurotransmitters but via different mechanisms:
Remeron antagonizes (blocks) 5-HT2A serotonin autoreceptors receptors which promotes serotonin release.
Effexor blocks serotonin re-uptake, allowing serotonin to build up around neurons (brain cells).
Note that both drugs have analogous effects on norepinephrine, too.
So on the one hand, California Rocket Fuel is boosting serotonin release (Remeron) while preventing serotonin clearance (Effexor). This synergy naturally prompts a conversation about serotonin syndrome.
California Rocket Fuel and Serotonin Syndrome
What is Serotonin Syndrome?
Serotonin syndrome is a potentially life threatening emergency where serotonin becomes dangerously elevated in the brain.
What Causes Serotonin Syndrome
By and large the most common cause of serotonin syndrome is combining different classes of serotonergic antidepressants.
When it comes to serotonin syndrome, the worst offendors are SSRIs and tricyclic antidepressants. MAOIs can also precipitate serotonin syndrome.
It's possible but unlikely for California Rocket Fuel to cause serotonin syndrome. Although both drugs boost serotonergic signaling, Remeron also antagonizes (blocks) many serotonin receptors which limits its propensity to induce serotonin syndrome when combined with other serotonergic drugs.
Nevertheless, there are case reports that characterize serotonin syndrome in connection with mirtazepine (Remeron).
Mirtazapine-Induced Serotonin Syndrome (2003)
An 85-year-old woman developed sudden confusion and dysarthria progressing to mutism, orobuccal dyskinesias, generalized tremors worse with activity, ataxia, and rigidity with cog wheeling without high-grade fevers or dysautonomia. These findings were related temporally to the institution of mirtazapine as monotherapy for a major depressive illness with superimposed anxiety disorder. Withdrawal of the agent resulted in early notable clinical resolution with only residual hypertonia after 2 weeks. This is a rare report of serotonin syndrome induced by mirtazapine monotherapy. The hypothesized pathophysiologic mechanism in this case is overstimulation of serotonin (5-hydroxytryptamine or 5-HT) type 1A receptors (5-HT1A) in the brainstem and spinal cord in an individual with risk factors for hyperserotoninemia resulting from reduced, acquired endogenous serotonin metabolism.
Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine (2004)
SS is a potentially fatal iatrogenic complication of serotonergic polypharmacy. Considered idiopathic in presentation, it typically appears after initiation or dose escalation of the offending agent to a regimen including other serotonergic agents. All drugs that directly or indirectly increase central serotonin neurotransmission at postsynaptic 5-HT(1A) and 5-HT(2A) receptors can produce SS. Individual vulnerability appears to play a role in the development of SS. It is likely that the activation of 5-HT(1A) receptors by mirtazapine, the combined serotonin reuptake inhibition by venlafaxine and tramadol, as well as possible serotonin release by tramadol, contributed to the development of SS in this case.
- Venlafaxine-mirtazapine combination in the treatment of persistent depressive illness (2007)
- Venlafaxine and mirtazapine: different mechanisms of antidepressant action, common opioid-mediated antinociceptive effects--a possible opioid involvement in severe depression? (2002)
- Dual-dual action? Combining venlafaxine and mirtazapine in the treatment of depression (2008)
- A Review of Therapeutic Uses of Mirtazapine in Psychiatric and Medical Conditions (2013)
- California Rocket Fuel is an antidepressant cocktail comprising Effexor (venlafaxine) and Remeron (mirtazepine)
- The combination was popularized by Stephen Stahl and is discussed in Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications 4th Edition
- Remeron + Effexor have synergistic effects that make it a very powerful antidepressant combo in the psychiatrist's armamentarium