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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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{ 58 comments… add one }
  • Joao February 18, 2015, 3:03 am

    I’m a male on Remeron + Sertraline for 2 years now. I had generalized anxiety, during studying, on public transports and in classes, so basically, everywhere. Despite always being a good student with A grades, I couldn’t study anymore without having an anxiety attack, which was making the task nearly impossible. After being accompanied in psychotherapy, which helped me a lot by the way, the psychotherapist suggested that I recurred to medication, since this was affecting every aspect of my life.

    So I went to the doctor and tried 3 different antidepressants, on a monotherapy basis – fluoxetine, sertraline and remeron. Alone, none worked, barely felt any effect. So then he prescribed me Remeron + sertraline, and immediately, I felt really great. Anxiety was gone for at least 95%, and even though I still had some control issues to overcome that I needed to work with my therapist, now my situation didn’t even compare to before. I was no longer fearful of anything and felt joy all the time. Mentally it improved my state quite a lot, and I felt I was on the top of my game again, since anxiety really disturbs your thinking.

    In social situations the same thing – virtually no anxiety, and insecurity thoughts very much diminished, means that I could finally contact with people normally again. It’s like you’re in another dimension all the time, everything seems a bit unreal. Thinking about it, it’s like I had a completely different life for the last 2 years, and it’s not too much to say that my personality changed. Though going out much more and meeting a lot of new people certainly was a factor, I’m much more relaxed now, not so much obsessive in the little things anymore, and much much more secure.

    But, then there was the other side of the coin. What this combination does is that it strongly sedates you, which reduces both your good and bad feelings. I came out of social situations that were supposed to be very enjoyable, and while I flirt with girls and had supposedly interesting conversations with different people, I didn’t feel much about it – it was supposed to be enjoyable, and my behavior was of someone who was having fun, but inside I really just didn’t care, I was just passing the time. Which is part of the reason why I could do that – I didn’t really care if I wasn’t approved or if people didn’t like me, which was something that before would have scared me to death.

    That’s the emotional side effect, but there are others I’m experiencing, and which will make me quit this medication, and that would be scaring me if I wasn’t on this mix (lol). 1 month after I started taking it, I saw my hair thinning on the sides. And the fact that the hair all over my body started thinning as well, made this combination the suspect (it’s known that antidepressants have effects on the hair for a lot of people). That has been worsening ever since, and my hair started falling in the front.

    While there may be some genetic factors involved, it’s highly likely that the medication is having its effect, since it started right after taking it. The other big side effect, is that it greatly reduces your libido. And worse, lately I’m also experiencing a bit of pain in the genitals area. This mix is taking its toll, and I can say it was one hell of a ride, but maybe it’s time to quit.

  • micah April 19, 2015, 4:14 am

    I am on 300 mg effexor and 30 mg remeron and 50 seroquel. It has saved my life, put plain and simple. Went from the state mental hospital to a normal life, good job, normal relationship. Thank the good lord for California rocket fuel.

    • Cody March 28, 2016, 1:10 am

      Hi Micah. Just curious as to how long you’ve been on this combination as I am considering asking my doc about a similar regiment. I suffer from fairly severe depression/anxiety/ocd and was recently hospitalized. I’ve read a lot about the benefits of combining these medications but there is always the worry that it will not work forever. Hopefully it does!

      • John September 2, 2016, 3:20 am

        I highly recommend a benzodiazepine. I just switched back from alprazolam to clonazepam TID plus triazolam 0.25qhs. However, I’m also a full time University student and am on Adderall 30mg BID. I don’t promote narcotics in any way; I just know after years of suffering with GAD/Panic Attacks/Agoraphobia/MajorDepression/ADHD, so I may need a little more potent medications other than SSRI/SNRI and the others.

  • michele April 20, 2015, 7:08 pm

    I have been taking this combo for approximately 4 months and I’ve felt the best I have in years. Over the past few weeks, it seems to have stopped working. I’m finding myself fatigued and uninterested again. My dosage is 150 mg Effexor and 30 mg Remeron. Any suggestions? Thanks.

  • Joel Schoenbeck May 10, 2015, 2:12 am

    63 Y/O male. Generalized Anxiety Disorder for 35+ years. Tried a lot of monotherapy options. Effexor is what I have been on from 150 to 400 mg/day. Xanax 0.5 mg PRN. I have been on 300 mg Effexor XR and 15 mg Remeron for about 4 weeks now. I have been anxiety free now, since I started. This is the best I have felt in decades.

    I had been on Effexor 300 and buspar prior to California Rocket Fuel, and I was suicidal under that combo. Can’s speak to the long term effectiveness, hoping it’s not just placebo. I do seem to have more energy. My wife asked me what happened to me, since I have been fixing and working on stuff I have been neglecting. Hope this helps others.

  • alicia May 14, 2015, 12:53 pm

    I’ve had chronic treatment-resistant major depression with a heavy overlay of anxiety for 18 years. California rocket fuel is the only thing that had given me lasting remission. I’ve tried monotherapy with almost all available SSRI’s, SNRI’s and tricyclics. Just got out of hospital after my second major nervous breakdown (note to others: do not try to finish a PhD while severely depressed) and am on 30mg mirtazapine and 225mg venlafaxine, working up to 300mg.

    I also use valium as needed. Feeling so much better. Sleeping really well. I do remember the last time I was on this combo becoming a little concerned about blunting of high/low emotional states, similar to a comment above. But it’s minor and it’s pretty much the only side effect. Right now I’m so grateful for the relief. :)

    • alicia September 27, 2015, 7:05 am

      An update for anyone who is interested… CRF stopped working for me pretty quickly, and I ended up back in hospital and having ECT about a month after this comment. :( Stupid ECT didn’t work, just gave me amnesia. I’m now on 60mg mirtazapine, 150mg desvenlafaxine and 50mg lamotrigine. Feel super doped up and sedated, but not as suicidal as I was. Each day that manage to get out of bed, have a shower and not kill myself is a small victory, and often all I can handle. Best wishes and healing vibes to the rest of you out there struggling. <3

      • oandlomom October 21, 2015, 6:33 pm

        Alicia – I did not respond to ECT either except to lose a lot of memories. I am still in a very bad episode although I am having a relatively good day. What you described is no way to live. I try to comfort myself with the thought that if it is ever too bad I can kill myself but I actually can’t, because I have 2 children. Therefore I have to try everything I can. I am longing to try ketamine. My husband and I can’t really afford it but if I don’t get better soon we will do it despite the cost. Here is a list of things that have helped some people. I have found some relief with the flower essences, for a couple days I had the urge to cry and a lump in my throat and after taking Mustard, Gorse and Wild Rose the lump dissolved and I did not feel like crying. Still depressed but it was something. Some people swear by them. Good luck.

        •TMS – Neurostar
        •dTMS – Brainsway
        •Ketamine therapy
        •deep brain stimulation
        •vagus nerve stimulation
        •scopolamine patch
        •botox
        •acupuncture
        •Bach flower remedies
        •hypnotherapy
        •Reiki
        •Fisher Wallace device
        •Chronotherapy
        •getting a full metabolic panel done and taking the indicated supplements
        •testing for pyroluria
        •light box – 10,000 lux
        •joining a clinical trial – http://www.clinicaltrial.gov
        •high doses of niacin
        – neurofeedback
        – brain optimization

      • Brian Marcite January 11, 2016, 10:01 pm

        If the mirtazapine is doing your head in, can’t you see if your doctor can give you an alternative?

      • Nicole February 17, 2016, 10:11 am

        Alicia – I’m not sure how long ago you posted this, but has your psychiatrist ever tried adding lithium? It is effective as augmentation for treatment resistant depression and one of the only medications that can prevent suicide. Just a thought – it really does work great.

  • Ian June 5, 2015, 5:05 am

    45 of mirtazapine ad monotherapy made me stop thinking of wishing I was dead, but I didn’t ever feel good. Added 150mg of venlafaxine and immediately noticed that it was much “quieter” inside my head. I cannot explain it any other way. I haven’t seen this written about, and I never had this with nortriptyline, desipramine, wellbutrin, paxil, or mirtazapine monotherapy.

    A few weeks later I started to actually feel good sometimes for the first time in years. The quietness has subsided over time and I feel even better. Then 2 months ago I started taking 400mg SAMe twice a day and 3grams a day of omega-3s in addition to mirtazepine and effexor and I really bumped up a quantum leap again, and now feel like I am in full remission. Like the comment above I am getting things done that have been on my list forever.

    It’s great. Now the downside. Libido way way down, hunger up, need viagra sometimes to have sex. Libido was gone for the first month when things were really quiet in my head, but this has recovered some. But I never want to stop taking this combo. Feeling really good again after a decade of enjoying very little is worth almost anything.

    • yvonne November 15, 2016, 4:09 pm

      “Quieter in my head” – yes! This is what I’ve been feeling and couldn’t think of a way to describe it.

  • Jayne June 17, 2015, 1:09 pm

    I was prescribed a “California Rocket Fuel” combination 4 years ago (in Australia) when I was 21. I had been on a combination of 150mg Effexor and 1000mg Epilem daily for severe depression and mood instability, which worked for a time, but after the death of my mother, no longer served. My psychiatrist gradually increased my Effexor as high as she dared (around 275-300mg) when she decided to try what she called “California Rocket Fuel”. She added a low dose of Avanxa (Remeron) to the mix.

    In the first couple of days I began feeling side effects – fogginess, lethargy and agitation- but I knew that antidepressants could take some time to adjust so this wasn’t unexpected. However on the fourth day I “wasn’t feeling right in the head” and, long story short, an emotional trigger led to an almost-immediate suicide attempt. While I had had suicidal ideation through out my depression, I had never had intent or a plan. Within 4 days of starting this medication combination I began feeling really emotionally unwell, and within an hour of an emotional trigger I had contemplated, decided on and begun acting out a suicide attempt. This medication cocktail seemed to be the catalyst that moved me from merely severely depressed, to severely depressed and motivated to do something about it.

    Coming out of this (thankfully failed) attempt I tried Cymbalta which made me nauseous, and then, in conjunction with some intensive therapeutic intervention, found stability on Lovan for the next 3 years, and for about a year and a half took 25mg of seroquel before bed for my insomnia, until my body responded in a way that showed I know longer needed it. 4 years later and I am antidepressant free, started and finished a degree in counselling, and have begun working in the field of mental health rehabilitation.

    I do not blame either this combination, nor my psychiatrist for what transpired- obviously CRF works for a lot of people, and everyone responds differently to psychotropic drugs. But my experience was not only scary, but almost fatal. In my neurochemistry, this combination gave me the burst of energy before having time to impact my mood for the better – a dangerous combination in someone who is severely depressed. As long as anyone starting a new psychotropic drug is closely monitored and also engaging in appropriate psychotherapeutic treatment, the potential benefits likely outweigh the risks.

  • Brad June 30, 2015, 10:17 am

    Hi. I’m a 50 y/o male with a 25 yr history of depression and major panic disorder. Finally after all these years I’m actually feeling normal again. I was on 90mg Mirtazapine (Axit) for 12 months with minimal success, then had a major panic episode that shut me down for over a year (stopped doing ‘normal’ things like driving, shopping etc.). I saw a psychiatrist who reduced the Mirt to 60 mg and put me on 75mg Venlafaxine (Effexor).

    The change really crept up on me until one day (about 8 weeks later) I realized that I had been doing all of the things that I normally avoided due to anxiety and panic. I now know why they call this combination ‘California Rocket Fuel’. My confidence is at an all time high and I feel like I did 25 years ago when I was a very confident and positive young man. No anxiety whatsoever, in fact I deliberately put myself in my associated ‘Panic’ situations to test myself out and have had zero emotional response.

    It isn’t a ‘speedy’ kind of high or ‘dopey’ kind of relax, as these drugs don’t work that way. There is a down side, I wouldn’t suggest drinking much alcohol at all as this has twice led to regretful situations (way over confident). I don’t really need booze anyhow. Hopefully this may help someone reading the forum.

  • Pepo August 5, 2015, 3:00 am

    I tried this combo for about a year and it worked well. Unfortunately it also gave me permanent sexual dysfunction for the rest of my life. But I guess you can’t have everything, right?

    • Chris August 3, 2016, 5:00 am

      One week was bad enough but I was on the Effexor longer which causes ED, lack of climax, lack of desire, and a sense if you take the blue pill you’re just a set of pipes for two drops of semen. These drugs should only be used with the help of a psychiatrist that still has their brain. Then only carefully.

  • john September 3, 2015, 12:33 am

    Currently 225mg ven., 15mg mirtaz., sleep well but awake in hell. Feel anti-d’s have saved my life but triggered life-wrecking, unbidden behaviors.

  • Margaret September 20, 2015, 5:01 pm

    I suffered for over a year with severe depression, I tried to tackle it myself and went for CBT which had helped in the past, however it was not working on its own so attended my GP and eventually found a very caring and empathetic locus who took her time researching and carefully looking at my history. I started on a combination of venlafaxine/mirtazipine for which I have taken for over a year and the difference has been life saving. No more waking up with a horrendous sense of dread and anxiety. I am grateful to that locus, as I do not know what would have happened to me.

  • John September 21, 2015, 11:07 pm

    I have been on this combo for six years (Venlafaxine 300 mg and Mirtazapine 30 mg). After a severe nervous breakdown with depression and burnout I tried many mono treatments and some combinations. The “rocket fuel” lifted my mood and gave me enough energy to finish my PhD and start a career as a research scientist. So far so good. How about side effects? My sex drive totally dissapeared. (For six years!) That really sucked.

    So pretty steep side effects for me but compared the level of depression, fatigue and anxiety that I experienced before this combo I still found it tolerable. Over the last year I have gradually lost the effect of the treatment so now I am switching to Voxra in an attempt to get more energy. I am keeping the Mirtazapine though.

  • B Clarke November 7, 2015, 12:15 am

    A combination of cymbalta 60 mg and remeron 15mg have almost eliminated my anxiety disorder symptoms, for the 2 weeks I have been taking it.

  • Michael (UK) November 20, 2015, 3:15 pm

    I had frequent drug refractory severe depressive episodes with infrequent hypomania as part of a bipolar mood disorder. Was on 225mg venlafaxine MR once daily, and 300mg Quetiapine at night with poor response. Added 30mg of Mirtazapine at night by Psychiatrist just over 1 year ago. Depressive episodes completely gone. My mood has been a steady subclinical ‘high’ for the past year, but with no features of mania/hypomania.

    I spend each day fully motivated, smiling, and productive. I sleep like a baby every night. Personally I have improved my relationships with my spouse, family, and friends. I have excelled in my work, and have lost 5 stone through diet and CV exercise. Result – I am symptom free and living the life I always wanted. I can’t say exclusively that this is all ‘pharmacological’, but I am sure as hell sticking to this regime ?

  • hellyn (UK) November 21, 2015, 2:43 pm

    Hello, I have just gone down from 300mg venlafaxine to 225mg with 15mg mirtazapine. This is my third day after two dose changes… is it common to plummet first? feeling low and demotivated, etc… It would be good to hear from others experiences. Been battling this last episode for 3 months and just can’t get this shutdown numb feeling to shift this time. Grateful.

    • Ann September 25, 2016, 11:46 pm

      Lowering effexor (name brand) is hard and will feel withdraw, vertigo like at first.

  • andrew November 25, 2015, 12:52 pm

    I wonder how many lives could have been saved with CRF.

  • Rae December 13, 2015, 7:52 am

    Thanks for sharing your experience everyone. Came across this while doing some research. I am currently on 200mg Pristiq for depression and anxiety, Hubby has just started CRF treatment (depression, anxiety and PTSD) – 400mg Venlafaxine and 15mg Mirtazapine. He had success with Mirt. previously but hated the side effects (having to get up at all hrs to pee), so GP and Psych suggested Venl. which he also had some success with – except for some side effects – cant win them all huh?

    I mentioned to him that he seemed to be making progress in some areas but really regressing in others, which is why I guess his medical team suggested trying CRF. Day 2 and he is ready to quit. Getting very negative about it all (which I totally understand!) as he is feeling very lethargic and sleepy. Am hoping his body adjusts soon and he is able to remain safe!! Anyone else had experience with these dosages?

  • James January 17, 2016, 10:29 pm

    Well another day wasted trying to figure this disease out. 63 year old grandpa of 8 wonderful grand children wonderful wife & three children. Duration of this disease on and off for 40 years. Zoloft was really great required constant dosage increases over the years but eventually it wore out. Venlafaxine worked for quite sometime with dosage increases and when it wore out, we added lamictal.

    It eventually gave me a dangerous rash so we switched to mirtzapine along with venlafaxine taking maximum dosages when combined as of late seems they have worn out as well. My only side effect has been erectile, but that could be age related :(. So yes I would recommend California Rocket fuel, it got me through a few more years. Hope I’m not in the treatment-resistant zone. I’m making an appointment with my doctor tomorrow hoping he can find another cocktail that works. Thanks.

  • Margaret Rose January 26, 2016, 4:58 am

    I’ve been taking various psychotropics for 30 years. CRF has saved my life. (60 mg Remeron, 300 mg Effexor, plus 200 mg Lamictal.) My diagnosis is bipolar two. I’ve taken just about everything, alone and in combination. SSRI’s, SNRI’s, lithium, atypical anti-psychotics, amphetamine + a benzo, ECT (don’t even consider it, it will mess up your brain for years), MAOI’s, tricyclics, tetracyclics.

    I made a list once and there were 25 different drugs on my list. Some of the meds helped me to keep the anger and anxiety in check, but nothing ever touched the depression; I never felt good. Until CRF. I’ve been on this combo for four years and I feel good 95% of the time. When I feel crappy, I take two Klonopin and go to sleep. It helps that I’m on disability, this doesn’t work for people who are trying to hold down a job, obviously.

    I should mention that my initial (and long-time) diagnosis was MDA, not bipolar. Which is why my psy-docs kept trying all of the above anti-depressants on me. As far as I know, I’ve only had two manic episodes in a lifetime of crazy. One of my docs just happened to witness the latest episode. So that is why I take the Lamictal. And I think there is some overlap between MDA and BP2. So many other psych diagnoses overlap, so why not these two?

    • Jamie February 2, 2016, 12:10 am

      Hi Margaret, I’m on precisely the same medication as you and am also Bipolar 2. Had been on Parnate 60mg for three years but the side effects became a bit of a burden and I asked my Pdoc for a change. Reading your post is like reading my own personal experience. I’ve only just started two weeks ago today on CRF. Found Mirt very sedating at 30mg – but upped it to 60 last night after reading it is more activating at higher doses – and this morning, I do feel more with it.

      Have also titrated up to 300mg Ven in the last couple of days. Have been on 200mg Lamictal for years. I can feel the fog starting to lift so hopefully in the next week or so, everything should have settled in. Anyhow – just wanted to say it was good to read your post and read someone’s experience that’s been the same as mine. Best wishes and good health, Jamie.

  • Bobby C March 19, 2016, 6:20 pm

    I have been dealing with major depression for the past 15 years. At the start, I was on several different anti-depressants, but nothing seemed to work. Once I started taking the CRF (Remeron and Effexor XR) I was a changed man. I had so much energy and was accomplishing so many things, it was amazing. I then went to my PCP for an annual checkup with blood work, and my cholesterol was up from 200 to 350.

    I checked with my Psychiatrist and he said this was a possible side effect. We dropped the Remeron and my cholesterol went back down, but so did my energy level. I have been stuck at 300 mg of Effecxor EX for the past 14 years and I am doing well, as long as I do not try to lower my dosage. However, I would sure love to get back to the high energy level again, but there is a history of Heart Disease in my family and I need to keep my cholesterol in check.

    If anyone out there has has similar experiences, please let me know, especially if you found a solution to the increase in cholesterol levels.

  • Justin M March 26, 2016, 8:29 pm

    I started taking mirtazapine a few years ago and venlafaxine was added a few weeks ago and it has really helped my severe depression. I’ve been on antidepressants for over 20 years but the mix of mirtazapine and venlafaxine has, up to now, seen the best results. The side effects are very manageable, which is a big bonus. Long may this feeling last. I feel a HUGE weight has been lifted and didn’t realise how low I actually was.

  • SJ April 6, 2016, 12:04 pm

    I was on 150mg of Effexor and 15mg of mirtazapine for 10 years. It definitely helped my mood and got rid of the depression. Felt amazing. But….the side effects weren’t fun: constipation and bloating. Some days I actually looked pregnant. But I kind of put up with it until it stopped working and the depression returned. And to be honest, the side effects started to make me miserable.

    So now I am only on 20mg of Lovan. (Tried pristiq, but it made me crazy!!) Digestion normal again, but mood not as good as when I was on the Effexor and Mirtazapine. I’m really sensitive to side effects though. I would still recommend trying this combination if you’re really depressed, because you might not even experience the side effects I did.

  • Niall April 10, 2016, 4:48 pm

    My psych doc is planning adding Remeron to my existing dose of 375mg of Effexor. What I want to know is whether, like me, anyone has experienced no or extremely mild benefit from Effexor at comparable doses but did see a big benefit when Remeron was added. After 2 months of being on Effexor I have nothing but sexual dysfunction to show for it.

  • Russ April 12, 2016, 7:44 pm

    I’m just starting the combination of the two drugs. But after two days of taking the mirtazapine I’m like a zombie. Sleeping up to 20 hours a day and feeling useless. How long do I persist with this? Venlafaxine is fine, but when I add the other one it just knocks me out.

    • mlahor April 13, 2016, 7:36 pm

      Hi! I had the same problem with 30 mg of mirtazapine (together with 225 mg venlafaxine, 2 mg risperidone and 250 mg of lamotrigine) but after the mirtazapine and risperidone have been scaled down to 22.5 and 1.5 mg – I no longer needed excess sleep and have optimal amounts of energy, feel excellent, like finally there is something that actually works very well for me and not only mildly improves my mood.

    • alex September 4, 2016, 1:21 pm

      I realize this is a few months ago but hoping someone can answer. I have just been given this CRF combo: 50 mg Pristiq (desvenlafaxine) and 15 mg Mirtazapine both to be taken at night together and it sounds scary. Has anyone started both of these at the same time or has one tablet been introduced and the other added later? Is it ok to start both at the same time?

  • mlahor April 13, 2016, 7:29 pm

    I have tried probably all antidepressant drugs both in monotherapy and in combination with one another. I would usually experience mild, if any, improvement of my symptoms. Finally I was given a combination of Remeron and Effexor (together with Risperdal and Lamictal that have been pretty much a constant in my therapy) and I FINALLY can say that I actually do feel SIGNIFICANTLY better.

    However dosages had to be scaled down as 30 mg Remeron and 2 mg Risperdal made me terribly sleepy. Now on 225 mg Effexor, 250 mg Lamictal, 22.5 mg Remeron and 1.5 mg Risperdal. I tolerate it very well, have optimal amounts of energy and feel better than ever in the last 15 years or so. :-)

  • Grant April 16, 2016, 11:07 pm

    (Male 44 next week). I’m on day 2 of the combination having had 60mg of mirtazapine every day for last 3 years. I also take lithium (22 years) I’ve had various anti d’s over the years. The only medication I would say had a positive effect is modafinil but I have to take the lower dose of 100mg because of side effects (my lips developed sores). I have high expectations for CRF.

    • Grant May 2, 2016, 9:30 am

      My mood is lifting! I often wake with a zing and as Lorraine says below absolute clarity. Dr is very cautious as there are possible side effect issues with Bipolar 2 whilst taking CRF. I’m keeping track of my mood using moodscope and my score is definitely higher.

    • Francesco September 22, 2016, 3:41 pm

      Hello, Grant. So you’ve been taking CRF + lithium? How have you been? I’m on a version of CRF (Pristiq 200mg + Miratazapine 30mg) and it has been the best combination so far, at least, regarding depression. Anxiety, though, is still an issue.

  • lorraine cummings April 23, 2016, 7:17 pm

    Three days on CRF and wondering how long side effects last e.g. hot flashes, dizziness and sporadic palpitations. In saying that this morning, I woke up with absolute clarity of mind! Something to definitely hooray about!

    • Grant May 2, 2016, 9:26 am

      I’ve also had mornings waking up with absolute clarity of mind and it’s amazing. Quite startling, but it’s been uncomfortable on a couple of occasions, I’ve had flashbacks and racing thoughts.

  • D. Stanaland April 26, 2016, 2:09 pm

    **This comment is posted so that others that suffer from major depression and anxiety, hopefully can have a better, happier, life. I have used each of these me medications individually many years ago having only mild to moderate improvement.** I have suffered with major depression and anxiety for over twenty years.

    When I refused to do trial and error on medications over and over again, and I knew that I must use something that works well quickly, I searched for that specifically and “California Rocket Fuel” came to the front. I told my Family Physician about it and said, “I want to try This”. So months later I am still feeling wonderful.

    While I understand that others may respond differently, I responded to the combination of Effexor and Remeron faster than I had hoped, and faster than with any other medication in it’s class. A mild side effect from both medications lasted only 2-3 days and I saw immediate improvement. The doctor made a dosage adjustment and I am better than with anything other single or combination medication therapy that I have ever been prescribed.

    I don’t do word dress-up. That is the facts of my success with these two medications.

  • Niall May 23, 2016, 5:29 pm

    After a month, Californian Rocket Fuel failed to ignite for me. At maximum dosages too. Lithium here I come (sigh).

  • Andy (Scotland) June 3, 2016, 8:58 am

    Not a great fan of internet forums in general but guess if my story helps only one person or saves one life. Suffered several episodes of clinical depression since my mid 20’s. A short course of isotretinoin (Roaccutane) for severe acne on my chest may have been the trigger although will never know for sure. Turned 50 last month.

    Fluoxetine worked wonders in my late 20s to get me well. Stopped fluoxetine with no problems but when again prescribed fluoxetine for a subsequent episode of depression, never worked at all and was unable to tolerate sertraline. Fast forward to around 2002. Unwell again. Started venlafaxine under the supervision of a Consultant Psychiatrist.

    Dose adjustments (upwards) and time got me well again. Over next few years tried gradually reducing venlafaxine dosage but crashed quite quickly both times, needing to re-initiate higher doses of venlafaxine than had been taking previously in order to get well again. By this time taking 375mg venlafaxine daily and stayed on this dose for years. Fast forward to around 2008.

    Unwell again, whilst still taking 375mg venlafaxine daily. At this point 15mg mirtazapine at night was prescribed in addition to venlafaxine I was already taking. Think I took 15mg mirtazapine at night for just two nights and thought at that time “this ain’t for me!” Had the most bizarre side-effect. Can only compare it to how my face would have felt if someone had been punching me all through the night! Weird eh?

    So, the box of mirtazapine tablets sat in my bedside drawer unopened again for the next two years. Continued with the 375mg daily of venlafaxine as before. Now, fast forward again until 2013. Ill again. Lay on my bed pretty much continuously for about a month (live on my own and was unemployed at the time).

    In desperation, as a last resort decided to try the mirtazapine again (this time 30mg at night) as by this time could not remember the previous side-effects, only the fact that I gave up after only a couple of days. Hey presto – got exactly the same primary side-effect as previously. Felt like my face had been bashed in. BUT this time I somehow persevered with the mirtazapine for three days and then WOW!!! – I made an almost Lazarus like recovery from the dead within a only a further 24 hours.

    With zero effort on my part, got up, showered, dressed, cleaned my flat. Energised, depression minimal, anxiety non-existent and previous dependence on codeine painkillers vanished. It was unbelievable and definitely not a placebo effect as had absolutely no expectation of the mirtazapine helping.

    Ended up on 45mg mirtazapine and existing 375mg venlafaxine and was generally well for next two years. However have had recent major relapses and currently seeing another psychiatrist next week re what next?

    • Lou July 29, 2016, 11:32 pm

      Andy, please let us know how you are now. Take care.

  • A June 12, 2016, 1:25 pm

    Currently taking 400mg seroquel IR, 150 mg pristiq and 30 mg mirtazapine. Certainly not a zombie but mirtazapine helped with sleep. Seroquel helps with overwhelming anxiety and depression but still don’t see flowers instead of weeds.

  • Roz June 20, 2016, 2:25 pm

    I have had treatment-resistant depression with GAD (generalized anxiety disorder) for most of my life (untreated, except with therapy, until I was 42). I have found the combination of Remeron and Wellbutrin, with a low dose of Abilify to be the most effective for me. I currently take half a 22.5 mg. (half a 45) of the former, 450 Wellbutrin XR 150 mg, and 5 mg Abilify daily.

    When I first went on the Wellbutrin (added to the Remeron and Abilify) three years ago, I felt better than I had in many years, and, I should, add, I have a very stressful job in which I function quite well. Recently, I have had some episodes of fairly intense depression and tried upping my dose of Remeron. It worked beautifully, except I am having to be really careful about my weight because of increased appetite. (Currently I’m 5’2″ and weigh 128.)

  • laura June 23, 2016, 6:53 pm

    I have been on effoxor (225mg) and mirtazapine (45mg) for approx. 3 years. Although it has helped my mood, I still struggle. Sadly… I gained 50 lbs on this medication. Every time I try to decrease the amounts, I physically feel sick, and “out of it”. I have not felt the upbeat energetic feelings talked about, but I can function better now. My fear is I will never be able to get off this medication now and that is terrifying to me.

  • test June 27, 2016, 7:43 pm

    Test to see if comments are legit and postable and not fake. If this shows, the comments on this page are written by real people and not pharmacy reps!

  • Pedro July 30, 2016, 10:56 pm

    This combination gave me some good years – improved mood, easier to focus, and virtually no anxiety or depression feelings. It’s a pretty strong combination though, and if you don’t wanna be on meds all your life, I can say getting off it is a real hell. Even feeling better, trying to get off one of the meds (Remeron or the SSRI), I get depressed pretty quickly and much more than I previously was before starting.

    This is supported by studies that show double antidepressants treatment has about 50% remission rate, compared to 25% on monotherapy. Your brain becomes used to being stimulated all the time, and when it’s reduced, the serotonin levels are constantly low. Only use this as last resource, always make sure monotherapy doesn’t work for you before going on a combo.

  • Paula August 12, 2016, 5:51 pm

    It’s a brilliant combo. Feeling fantastic!

  • Maggie August 17, 2016, 5:40 pm

    Anybody came off venlafaxine and mirtazapine together successfully? I am suffering horrendous protracted withdrawal still a yr off third awful combination. I am worse than I’ve been in my life. Can’t function at ALL can’t sleep wash dress leave house and am much much iller than I have ever been.

  • Michael Breton August 18, 2016, 11:20 pm

    I was prescribed Remeron and Effexor by my medical doctor without consulting a mental health professional at any point in time and caused Serotonin Syndrome. He told me specifically this combination was used for insomnia and chronic pain. I was in a coma for two days. NEVER let a normal M.D. prescribed you this medication.

    • Ann September 26, 2016, 12:40 am

      I felt this with effexor and ADHD vyvanse. They both had a same chemical in them. Getting off was horrible as well. So sorry you had to go through this.

  • watford August 26, 2016, 4:17 am

    A very stressful financial and property situation triggered me into severe anxiety and depression. First line of attack was lexapro – titrated up to 20 mg/day but found it did help a bit but after a few months I felt relapse. Under doctor supervision, added mirtzapine 7.5 mg which helped with sleep then went to 15 mg while continuing with lexapro.

    Thinking of increasing to 22.5 mg mirtazapine and winding back gradually on lexapro. With reduction in lexapro, thinking of introducing zoloft or effexor – not sure yet and will discuss with doctor – I don’t remember the correct spelling for the chemical names so sorry for the mixed names. I use a normal general practitioner who is experienced and flexible in trying new combinations. I don’t want to spend the big bucks on psych doctor. Any advice appreciated on which way to go.

    • Eric September 4, 2016, 5:22 am

      I wouldn’t let a GP handle my brain mess just like I would let a dentist give me a colonoscopy. Spend the money to see a psych. They know more about anti depressants/mood stabilizers than you could even imagine.

  • Zack October 25, 2016, 8:03 pm

    I’ve been taking california rocket fuel for about a month and a half now and it has put my depression into complete remission!

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