Unless a person is dealing with treatment-resistant depression, it’s relatively uncommon for a person to be taking multiple antidepressants. If a person ends up taking multiple antidepressants, they are generally from different classes such as an SSRI (e.g. Prozac) with an atypical (e.g. Wellbutrin). Prescribing multiple antidepressants of the same class such as multiple SSRIs can lead to a potentially fatal condition known as “serotonin syndrome.”
For this reason, medical professionals generally exercise caution when prescribing multiple antidepressants to ensure that the patient will be safe. In other words, all potential interaction effects should be thoroughly investigated prior to ever taking multiple antidepressants or any combination of treatments. Although many antidepressant augmentation strategies involve prescribing an antidepressant with anxiolytics, stimulants, or antipsychotics, sometimes using multiple antidepressants works better than other options.
When multiple antidepressants are prescribed, the theory is that they will both elicit differing, yet beneficial mechanisms by which they help improve depressive symptoms. In some cases the drugs have synergistic effects which results in amplification of the antidepressant response. One such combination that has been proven effective at treating the most severe cases of depression is referred to as “California rocket fuel.”
What is “California Rocket Fuel?”
California rocket fuel is a slang term created by the psychiatric community (and some medical professionals) that refers to a combined treatment with Remeron (Mirtazapine) and Effexor (Venlafaxine). The reason this combination is referred to as “California rocket fuel” is due to the its higher than average potency and efficacy. Rockets blast off with extreme speed, and in many cases, people given this particular combination notice a rapid improvement in their depressive symptoms.
Remeron (Mirtazapine): This drug functions as an “NaSSA” antidepressant. It was approved in the U.S. to treat depression in 1996 and some comparison studies go as far as to suggest that it has the single highest efficacy of any antidepressant on the market. Although it has relatively average tolerability, for many people with severe forms of depression, there’s nothing that works better than Remeron. This drug also can be effective at treating anxiety, insomnia, and stimulating the appetite. It can be classified as an atypical antidepressant (or TeCA antidepressant).
- NaSSA: The classification of Remeron is that of a noradrenergic and specific serotonergic antidepressant (NaSSA). It drug functions by acting as an antagonist at the Alpha-2 adrenergic receptor, as well as the 5-HT2A, 5-HT2C, 5-HT3, and 5-HT6 serotonergic receptors. When it inhibits the Alpha-2 adrenergic receptors, it improves the neurotransmission of norepinephrine and serotonin, which in turn helps regulate mood. This drug particularly impacts the 5-HT1A receptor as an agonist. The fact that this drug does not target all serotonin receptors (like an SSRI), it is considered a “specific serotonergic” antidepressant. It is believed that the specific targeting of serotonin receptors may lead to less unwanted side effects.
Effexor (Venlafaxine): This is considered the first SNRI (serotonin-norepinephrine reuptake inhibitor) antidepressant to ever get approval from the FDA. It hit the U.S. market in 1993 for the treatment of major depression, but is also prescribed for various anxiety disorders and phobias. Many people consider this drug to be more effective than SSRIs, but it tends to be less tolerable due to the fact that it inhibits reuptake of norepinephrine.
- SNRI: This type of drug functions by inhibiting the reuptake of the neurotransmitters serotonin and norepinephrine. By inhibiting their reuptake, the drug raises extracellular levels of these neurotransmitters, resulting in improvements in mood. Although it inhibits reuptake of both serotonin and norepinephrine, it inhibits serotonin to 30 times the extent that it does norepinephrine. Therefore some would consider Effexor as being one of the most serotonergic-oriented SNRIs. The SNRI class of medication tends to elicit unwanted side effects such as: nausea, headaches, insomnia, and sweating. The upside is that the drug tends to be less likely to cause weight gain or fatigue in comparison to an SSRI.
Studies involving “California Rocket Fuel”
Although research with this particular combination strategy is not extensive, there are several studies demonstrating its high degree of efficacy among those with refractory depression. In all studies, the “rocket fuel” proved to be more effective than other antidepressant combinations. Whether this is universally the most effective combination of multiple antidepressants is subject to debate.
A study conducted in 2006 compared the efficacy of Remeron in conjunction with either Parnate or Effexor. These were administered to patients that weren’t able to get benefit from at least 3 previous medication trials. This study had a sample size of 109 total participants, with 58 assigned to the Remeron + Parnate treatment and the remaining 51 to the Remeron + Effexor treatment. Results were interpreted based on the HAM-D scores which was administered via telephone interview. Below is the percentage of individuals that experienced improvement on each of the treatments.
- 6.9% Remeron + Parnate
13.7% Remeron + Effexor
Although the researchers determined that both treatments can be effective, they stated the fact that the Remeron and Effexor group experienced more symptom reduction and superior tolerability (compared to the group taking Remeron and Parnate). The researchers in this study recommend Remeron and Effexor as being a great option to consider for those who have found no benefit from 3 different antidepressant medications.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16946177
In a 2009 double-blind, randomized trial, various antidepressant combination treatments were investigated to determine their efficacies. Researchers conducted this study due to the fact that only one-third (~33%) of patients taking antidepressants tend to experience improvement in their depressive symptoms from monotherapy. What caught their attention was when the number of individuals that experienced an improvement in depressive symptoms nearly doubled when Paxil was added to Remeron as an adjunct.
Following this finding, they decided to explore whether other combinations of antidepressants with Remeron would offer superior benefit as well. The medications used in their study as adjuncts to Remeron included: 20 mg Prozac (Fluoxetine), 150 mg Wellbutrin (Bupropion), and 225 mg Effexor (Venlafaxine). These combinations were taken over a period of 6-weeks by 105 individuals and depression ratings were determined by HAM-D (Hamilton Depression Rating Scale) scores.
In comparison to standardized Prozac monotherapy, all three combination strategies resulted in significantly greater improvement in depressive symptoms based on HAM-D scores. In standard Prozac monotherapy, 25% of people experienced relief. The percentage of improvement was significantly greater under all combination treatment strategies. Below are the percentage of people that improved with combined options.
- 46% Remeron + Wellbutrin
- 52% Remeron + Prozac
- 58% Remeron + Effexor
It should be highlighted that the greatest overall benefit was derived from the group given the “California rocket fuel.”
- Source: http://ajp.psychiatryonline.org/doi/abs/10.1176/appi.ajp.2009.09020186
When is California Rocket Fuel prescribed?
Generally, this combination is prescribed only when someone is faced with a severe case of major depression that hasn’t responded to at least three prior antidepressant trials. In some cases, depending on the psychiatrist, all monotherapeutic options will first need to be explored before practicing poly-pharmacology. Therefore someone will likely have tried many different antidepressants, and in some cases several augmentation options before a psychiatrist will consider prescribing this potent combination.
The response you experience when taking Effexor and/or Remeron may dictate whether this combination strategy is pursued. If you poorly tolerate one drug or the other, this particular strategy may not even be an option. However, if you respond fairly well to one drug, but it’s not helping your depression enough, sometimes the other drug will be added to treatment to create the “rocket fuel” – which could provide more substantial relief.
Benefits of California Rocket Fuel…
There are several benefits of taking “California rocket fuel” to treat depression. The major benefit is that this combination tends to have a moderate degree of efficacy among individuals diagnosed with treatment-resistant depression.
- Antidepressant boost: In the event that you respond fairly well to either Effexor or Remeron (or have in the past), a psychiatrist may prescribe the other medication to provide further relief from depressive symptoms. Another example could be someone that has been on one of these drugs for an extended period of time, has developed some tolerability, and needs their depression to improve.
- Highly effective: In comparison studies evaluating combination options for the treatment of depression, this particular treatment option proved superior in efficacy. Although there weren’t a significant number of studies, the fact that this combination outperformed all other combinations suggests that the drugs may work synergistically or perfectly complement each other’s effects.
- Synergistic effect: Some have speculated that the mechanisms of these medications work in synergy and/or complement each other. Remeron is an NaSSA and it blocks various receptors to enhance neurotransmission of both norepinephrine and serotonin. Effexor is an SNRI and inhibits reuptake of serotonin and norepinephrine. Both target the same neurotransmitters and have differing effects, potentially resulting in synergism.
- Tolerability: While taking multiple antidepressants generally has inferior tolerability to taking a standalone medication, some have suggested that this particular combination may be more tolerable than other combinations. Although Remeron causes weight gain, Effexor may help offset the weight gain by providing an activating, energetic effect. However, some people still experience weight gain from Effexor, thus an increase in weight may be one potential drawback.
- Treatment-resistant depression: This combination is usually reserved only for those with treatment-resistant forms of depression. This is due to the fact that neither of these medications are considered first-line treatment options. Each carries side effects, and in some cases, the side effects are intolerable. Therefore it is best to first test these on an individual basis to establish tolerability prior to taking them together.
What about Remeron and Pristiq? Is it upgraded Rocket fuel?
Logically it would make sense that if Remeron and Effexor is considered “California Rocket Fuel” then Remeron and Pristiq would be something similar. Some pharmaceutical reps may argue that it should be considered upgraded rocket fuel or something. This is due to the promotion that Pristiq is a superior version of the drug Effexor.
Pristiq (Desvenlafaxine) is a newer medication than Effexor, and is the active metabolite of Effexor. Thus it should (in theory) result in relatively similar effects to that of Effexor. The notable differences between these two medications though is that they have different ratios of serotonin to norpinephrine reuptake inhibition. Effexor inhibits serotonin to 30x the extent of norepinephrine, whereas Pristiq inhibits at a ratio of 10 to 1 (serotonin to norepinephrine).
In theory, the combination should work somewhat similar to Remeron and Effexor, but this will largely depend on how well you tolerate Pristiq. Obviously if you are considering any such combinations, it is best to work with a psychiatrist. Due to the success of Remeron and Effexor, studies should be conducted with Pristiq (and possibly other new SNRIs) to determine the degree of efficacy in the treatment of refractory depression.
Have you taken California Rocket Fuel?
If you have experience taking Remeron in combination with Effexor, feel free to share your experience in the comments section below. Discuss how well it worked, whether it worked for a long period of time, and be sure to mention any unwanted side effects that you endured while on this combination. If you are merely intrigued at this potential combination, keep in mind that there isn’t extensive research on this touted “rocket fuel” and that several small studies doesn’t necessarily indicate that this is a superior combination strategy to others.