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California Rocket Fuel: Remeron and Effexor Combination

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.

Study #1

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

Study #2

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.

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{ 85 comments… add one }
  • Barb September 9, 2018, 3:30 pm

    I just started taking 75 mg of Effexor and 15 mg of Mirtazapine and have had two horrible nights of sleep. I wake up frequently and have had really disturbing dreams. Wondering if increasing the dosage of Effexor or Mirtazapine would solve the bad dreams. Does it take time to get used to?

  • Nigel August 4, 2018, 10:28 am

    I take 45 mg Mirtazapine at night and 150 mg Venlafaxine prolonged release in the morning. I have been on this combination since January/February 2018. The combination seems to work well for me. I am still very depressed, but I am more functional.

    Before this combination I took just 45 mg Mirtazapine and 375 mg Pregabalin for my anxiety. 45 mg Mirtazapine is the highest dose prescribed in the UK, but on it’s own was not effective. The Pregabalin had no effect on my anxiety and made me even more irritable than normal.

    My GP also prescribed 20 mg of Nortriptyline for my chronic migraine, this only made the symptoms of the migraine worse and increased the risk of Serotonin Syndrome. The Nortriptyline was stopped. I am still waiting for an appointment with a neurologist.

    • Margaret September 1, 2018, 1:59 pm

      Do you feel tired the next day from Remeron? I am on 30mg at bedtime. Thank you.

  • Pam July 8, 2018, 10:43 pm

    I take 30 remeron and 75 Effexor, for anxiety. Still haven’t gotten much relief from the anxiety. I take remeron at night and Effexor in the morning. Is that how everyone takes these meds? Or does anyone take them together at bedtime?

    • Pasta July 10, 2018, 5:46 am

      Maybe you need to up the effexor? My doctor says anything less than 150 mg is a waste of time. At one point I was on 300mg effexor and 30mg remeron. It worked great. Tried to come off, solo, was an absolute disaster.

      Was suicidal and hospitalized. They put me back on 150mg and 15mg and it had me stabilized in 4 days… Says a lot.

  • Sabine July 1, 2018, 6:30 pm

    I have had recurrent depression for 8 years, with various combinations of Citalopram and Mirtazapine. After hospitalization following a medication withdrawal, I was put on Citalopram, Mirtazapine and Lithium.

    I was stable but my mood kept being low. After 9 months my psychiatrist put me on Mirtazapine 30 mg and Venlafaxine 225mg. Immediately I felt better and especially more active and energetic.

    I have taken the combination for 4 years now and have felt good and like my old self ever since. The only downside is I that I gained 20 pounds and feel slightly less emotional, but that is a small price to pay for the immense benefits of this combination.

  • Catherine June 23, 2018, 1:56 am

    I took 300mg of effexor, 45mg of remeron, and 150mg of hydroxyzine for about 6 years and worked every well. Effexor had some rough side effects like sweating… how embarrassing. However it was worth it.

    I think my doctor thought is wasn’t working as well as it used to for me – so he switched me over to prozac and I feel pretty good again and no more sweating! If you’re having a hard time working through your depression – it might be worth a try and ask your doctor.

    If prozac starts to not work for me I will try to get back on effexor.

  • Margaret May 27, 2018, 1:19 am

    After 25 years of taking just about every kind of med you can think of (SSRI, SNRI, tricyclics, tetracyclics, amphetamine, klonopin, atypical antipsychotics, mood stabilizers, alone and in various combinations).

    I was prescribed 300 mg Effexor, 60 mg Remeron, and 400 mg Lamictal for my treatment resistant bipolar depression. (My BPD went undiagnosed because I have so few hypo manic periods.) The CRF and lamictal combination has me feeling better than I have ever felt.

    I don’t have the euphoria some have described; I still have the occasional bout of depression, but I function pretty well most days. I wish I had this combination when I was working. I might still be working and not on disability (sigh).

  • Terri May 26, 2018, 4:24 am

    I’ve been battling recurrent, severe major depression since 1983. Included with this is PTSD, GAD and DID. Throughout all these years I’ve been on every psych med on the market (including meds that were totally inappropriate for my diagnoses).

    To say nothing has ever worked for me would be a gross understatement. I just began seeing a new psychiatrist (gosh, he seems very young), and he presents me with this idea of CRF. I have absolutely zero faith in psych meds and have experienced such bizarre side effects previously that I don’t expect anything good from these but if I don’t do something different I will soon finalize my suicide plans.

    The fact that I’m still alive today after all these years is a miracle (it certainly isn’t from my lack of trying). Reading all of your comments gives me the strength to at least try this combination. Thanks to everyone for sharing.

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