# California Rocket Fuel



## db0255 (Jul 20, 2009)

As a great responder to Prozac that pooped out after only some months, I've been looking to get that response back.

I was wondering if Remeron + Celexa + Strattera would be that combination. I'm already on the Celexa and Strattera, but don't get the social effects and self esteem boost that I got with Prozac. 

Thoughts?


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## arth67 (Aug 6, 2009)

upping the prozac dose may get it working again, max is around 60


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## db0255 (Jul 20, 2009)

Upping the Prozac dose didn't work once it pooped out. I'm thinking maybe the good effects of Prozac had to do with its 5-HT2C antagonism? In this way Remeron would be a good substitute, but I'm not sure. 

My anxiety is definitely very specific in terms of what medications will work. Obviously benzos work very well, but other SSRIs and SNRIs haven't, and I've wanted to research which 5-HT (or other) receptors are at play here.


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## jim_morrison (Aug 17, 2008)

db0255 said:


> Upping the Prozac dose didn't work once it pooped out. I'm thinking maybe the good effects of Prozac had to do with its 5-HT2C antagonism? In this way Remeron would be a good substitute, but I'm not sure.
> 
> My anxiety is definitely very specific in terms of what medications will work. Obviously benzos work very well, but other SSRIs and SNRIs haven't, and I've wanted to research which 5-HT (or other) receptors are at play here.


I beleive that the 5-HT2C antagonism of remeron is stronger than that of prozac.


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## robotaffliction (Jul 24, 2009)

california rocket fuel is supposedly remeron plus effexor. i had been prescribed this combo in addition to neurontin, worked great but i had a seizure on this combination of the three (and neurontin is supposedly a weak-ish anticonvulsant). there's one paper suggesting that mirtazapine can cause epileptiform patterns on EEGs in quite a number of patients, and there's also some small risk of seizure with effexor, but probably this is just robotaffliction-specific and the two together just clobbered my brain. the seizure i had was secondarily generalized tonic-clonic.


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## jim_morrison (Aug 17, 2008)

robotaffliction said:


> california rocket fuel is supposedly remeron plus effexor. i had been prescribed this combo in addition to neurontin, worked great but i had a seizure on this combination of the three (and neurontin is supposedly a weak-ish anticonvulsant). there's one paper suggesting that mirtazapine can cause epileptiform patterns on EEGs in quite a number of patients, and there's also some small risk of seizure with effexor, but probably this is just robotaffliction-specific and the two together just clobbered my brain. the seizure i had was secondarily generalized tonic-clonic.


california rocket fuel is usually effexor + remeron, but can also apply to cymbalta or other SNRI's + remeron.

According to Dr Stephen Stahl -

"california rocket fuel (SNRI plus mirtazapine) is a combination that has a great degree of theoretical synergy, norepinephrine reuptake blockade plus aplha 2 blockade, serotonin reuptake plus 5HT2A and 5HT2C antagonism, and thus many 5HT actions plus norephinephrine actions. 
Specifically, 5HT is quadruple-boosted (with reuptake blockade, alpha 2 antagonism, 5HT2A antagonism, and 5HT2C antagonism). Norepinephrine is quadruple-boosted (with reuptake blockade, aplha 2 antagonism, 5HT2A antagonism, and 5HT2C antagonism.) And there may even be a double boost of dopamine (with 5HT2A and 5HT2C antagonism.)"

It is also important to note that since dopamine is inactivated by norepinephrine reuptake in frontal cortex, which largely lacks dopamine transporters, SNRI's can increase dopamine neurotransmission in this part of the brain through it's norepinephrine reuptake action.

So all of this may explain the efficacy of california rocket fuel in treating severe depression.


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## robotaffliction (Jul 24, 2009)

jim_morrison said:


> california rocket fuel is usually effexor + remeron, but can also apply to cymbalta or other SNRI's + remeron.
> 
> According to Dr Stephen Stahl -
> 
> ...


i'd been taking a combination of nardil and remeron, i guess it could be called lunar rocket fuel... made weight gain much worse though, i'd wake up and go feeding all the time like some crazy animal! not sure of the real risk of serotonin syndrome, there's some doubt whether remeron is very serotonergic at all (alpha-2 i could understand boosting serotonin transmission, but not 5-HT2A/C) and my doctor was ok with it.


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## jim_morrison (Aug 17, 2008)

robotaffliction said:


> i'd been taking a combination of nardil and remeron, i guess it could be called lunar rocket fuel... made weight gain much worse though, i'd wake up and go feeding all the time like some crazy animal! not sure of the real risk of serotonin syndrome, there's some doubt whether remeron is very serotonergic at all (alpha-2 i could understand boosting serotonin transmission, but not 5-HT2A/C) and my doctor was ok with it.


Wow now thats a combo!, I think somebody else on this site was also on that combo too.
How did it work for you anyway?

Yeah there seems to be much debate over mirtazapines alleged serotonergic activity, however in his book, Dr stahl goes on to explain thats it's actually a complex interaction between relatively potent alpha-2 blockade, and relatively weak alpha-1 blockade which gives mirtazapine far more serotonergic potential then it's parent compound mianserin (a potent alpha 1 & 2 antagonist), this is supposedly because once the noradrenaline has been released (via alpha 2 blockade) it then stimulates the excitable alpha 1 receptors on the serotonin cell body, this is in addition to also releaseing serotonin via alpha 2 blockade, which he refers to as "both cutting the break cable (alpha 2 antagonism) and stepping on the accelerator (alpha 1 stimulation) of serotonin. As for his hypothosis that 5-HT2A/C antagonism leads to boosting serotonin transmission, my guess is that hes suggesting that by blocking 2 key receptors that serotonin would usually bind to, their may be more available in the synapse, and more left to be released via 5HT1A.


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## robotaffliction (Jul 24, 2009)

jim_morrison said:


> Wow now thats a combo!, I think somebody else on this site was also on that combo too.
> How did it work for you anyway?
> 
> Yeah there seems to be much debate over mirtazapines alleged serotonergic activity, however in his book, Dr stahl goes on to explain thats it's actually a complex interaction between relatively potent alpha-2 blockade, and relatively weak alpha-1 blockade which gives mirtazapine far more serotonergic potential then it's parent compound mianserin (a potent alpha 1 & 2 antagonist), this is supposedly because once the noradrenaline has been released (via alpha 2 blockade) it then stimulates the excitable alpha 1 receptors on the serotonin cell body, this is in addition to also releaseing serotonin via alpha 2 blockade, which he refers to as "both cutting the break cable (alpha 2 antagonism) and stepping on the accelerator (alpha 1 stimulation) of serotonin. As for his hypothosis that 5-HT2A/C antagonism leads to boosting serotonin transmission, my guess is that hes suggesting that by blocking 2 key receptors that serotonin would usually bind to, their may be more available in the synapse, and more left to be released via 5HT1A.


well Stahl has some nice ideas and hypotheses there, but im guessing he's never actually taken mirtazapine  i've heard the 5HT1A hypothesis before but don't know any kind of measurement that supports it. perhaps in some ways its actually more meaningful if we know nothing about the mechanism and blindly observe the effects.. same with phenelzine, so much data about other auxiliary mechanisms besides MAOI but so many varying effects under different circumstances and people!

so my experience, it was great combination (phenelzine + mirtazapine) for focus. i'd just sit in the same place for about 12 hours and work, chew some nicotine gum (why smoke when you have the MAO inhibition already?), maybe just get up a couple times to stretch, get some coffee and go to the bathroom. problem was id dose mirtazapine at 15mg at bed and it would make me hungry and then wake up lots to eat.

tried not having food in the apartment, that worked better but the combo had pooped out eventually. even eating less though, i didnt seem to lose the weight. i do think it might have had something to do with tolerance to the MAO inhibition and also weight gain probably leading to reduced MAO inhibition. i was going to try a higher dose of phenelzine (90mg vs. 60mg previously) without the mirtazapine next after having done a 2 week washout.

ps - wasnt helpful for SA much eventually because id be so focused on working that i'd forget to go out and be social! at first it was really good though, kept meeting girls when id go out, and i was in sweden where it was kinda even harder for me to meet people due to the language barrier.. a drink or two and i was good (bottled, not tap beer!)


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## jim_morrison (Aug 17, 2008)

robotaffliction said:


> well Stahl has some nice ideas and hypotheses there, but im guessing he's never actually taken mirtazapine  i've heard the 5HT1A hypothesis before but don't know any kind of measurement that supports it. perhaps in some ways its actually more meaningful if we know nothing about the mechanism and blindly observe the effects.. same with phenelzine, so much data about other auxiliary mechanisms besides MAOI but so many varying effects under different circumstances and people!
> 
> so my experience, it was great combination (phenelzine + mirtazapine) for focus. i'd just sit in the same place for about 12 hours and work, chew some nicotine gum (why smoke when you have the MAO inhibition already?), maybe just get up a couple times to stretch, get some coffee and go to the bathroom. problem was id dose mirtazapine at 15mg at bed and it would make me hungry and then wake up lots to eat.
> 
> ...


I tend to agree that at the end of the day it doesnt really matter "how" a medication might work as long as it yields good results, and obviously isnt highly dangerous. For example no matter what the mechanism may be, in my expererience mirtazapine works!, it's been the only antidepressant thats ever managed to actually lift me out of the bounds of my severe depression, and according to that big study they did awhile ago of all the new generation antiderpessants it came out as number 1 in terms of efficiacy, so seems like I'm not the only one.

http://www.wellsphere.com/depression-article/scientists-rate-the-top-antidepressants/596658

However I think that Stahls observations, and that of the monoamine hypothesis of depression in general may be sound one, when you consider that Nardil, Parnate, California Rocket fuel, and ECT, the common last line treatments in treatment resistant or severe depression all have the same common dependant variable in the fact that they all significantly and reliably boost 5HT, Noradrenaline and Dopamine. Could it be that they all have another unkown mechanims of action in common? Ofcourse it's possible.


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## robotaffliction (Jul 24, 2009)

jim_morrison said:


> I tend to agree that at the end of the day it doesnt really matter "how" a medication might work as long as it yields good results, and obviously isnt highly dangerous. For example no matter what the mechanism may be, in my expererience mirtazapine works!, it's been the only antidepressant thats ever managed to actually lift me out of the bounds of my severe depression, and according to that big study they did awhile ago of all the new generation antiderpessants it came out as number 1 in terms of efficiacy, so seems like I'm not the only one.
> 
> http://www.wellsphere.com/depression-article/scientists-rate-the-top-antidepressants/596658
> 
> However I think that Stahls observations, and that of the monoamine hypothesis of depression in general may be sound one, when you consider that Nardil, Parnate, California Rocket fuel, and ECT, the common last line treatments in treatment resistant or severe depression all have the same common dependant variable in the fact that they all significantly and reliably boost 5HT, Noradrenaline and Dopamine. Could it be that they all have another unkown mechanims of action in common? Ofcourse it's possible.


yep, could also be some action resulting from increased monoamine transmission too (i.e., monoamines might not be necessary if you could effect this action directly), or maybe some effect that's coupled to the increased transmission so that you'd get both in any situation. so what are the doses that have been effective for depression with mirtazapine for you, and was it difficult to overcome the sedation? i personally find that too much daytime sedation can really ruin an antidepressant for me, perhaps thats why i couldnt benefit from the higher doses (like i was sayin, it wasn't actually more stimulating for me, like you related too)


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## jim_morrison (Aug 17, 2008)

robotaffliction said:


> yep, could also be some action resulting from increased monoamine transmission too (i.e., monoamines might not be necessary if you could effect this action directly), or maybe some effect that's coupled to the increased transmission so that you'd get both in any situation. so what are the doses that have been effective for depression with mirtazapine for you, and was it difficult to overcome the sedation? i personally find that too much daytime sedation can really ruin an antidepressant for me, perhaps thats why i couldnt benefit from the higher doses (like i was sayin, it wasn't actually more stimulating for me, like you related too)


Yeah, unfortunately I found the higher the dosage I got to, the better antidepressant effect I got but also the more sedated I'd become, which sort of undermined the AD effect.


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## euphoria (Jan 21, 2009)

^ Tolerance happens to the sedation after a few weeks. In the meantime you can just drink a lot of coffee...


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## jim_morrison (Aug 17, 2008)

euphoria said:


> ^ Tolerance happens to the sedation after a few weeks. In the meantime you can just drink a lot of coffee...


I've never developed tolerance to the sedation of mirtazapine and I've been taking it nightly for over 4 months.


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## db0255 (Jul 20, 2009)

Thanks for the responses. For those on Remeron, do you notice any social effects? Like increased fluency of thought, more sociability, self-confidence, and the like? 

Prozac had these effects, and I'm trying to figure out if it's because of the 5-HT2C antagonism, and if that's the way to go, or if I should be considering an MAOI, if I really want to see a difference.


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## jim_morrison (Aug 17, 2008)

db0255 said:


> Thanks for the responses. For those on Remeron, do you notice any social effects? Like increased fluency of thought, more sociability, self-confidence, and the like?
> 
> Prozac had these effects, and I'm trying to figure out if it's because of the 5-HT2C antagonism, and if that's the way to go, or if I should be considering an MAOI, if I really want to see a difference.


I didn't really notice much effect on SA unfortunately.


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## robotaffliction (Jul 24, 2009)

For serious SA, i dont think nardil and klonopin are really always necessary or best tho. for me, its actually just the only crap i have scripts for (and leftover mirtazapine), wish i had something else that i knew worked. moclobemide can be quite good too but for many MAOI responders I bet amphetamines would be even better, and neurontin is REALLY good for some, better than the klonopin because when it works well it doesn't cause the same kind of lethargy that can be involved with klonopin and benzos

ps - the mechanism of mirtazapine might also be lowering cortisol levels. i have a reference to that if you are interested.


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## euphoria (Jan 21, 2009)

jim_morrison said:


> I've never developed tolerance to the sedation of mirtazapine and I've been taking it nightly for over 4 months.


Really? I've been on it about 2-3 weeks and still get a bit of sedation at night (after the dose), but nothing during the day time.


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## jim_morrison (Aug 17, 2008)

euphoria said:


> Really? I've been on it about 2-3 weeks and still get a bit of sedation at night (after the dose), but nothing during the day time.


Yep, I never seem to gain tolerance to the sedation. But I deff do to most sedatives (Benzos, etc).


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## jim_morrison (Aug 17, 2008)

Another suggested mechanism regarding california rocket fuels efficiacy, is discussed in this study; 'Venlafaxine and mirtazapine: Different mechanisms of antidepressant action, common opioid-mediated antinociceptive effects-A possible opioid involvement in severe depression?'

http://www.springerlink.com/content/2kx87825w7017h47/



> When mice were tested with a hotplate analgesia meter, both venlafaxine and mirtazapine induced a dose-dependent, naloxone-reversible antinociceptive effect following ip administration. Summing up the various interactions of venlafaxine and mirtazapine with opioid, noradrenergic and serotonergic agonists and antagonists, we found that the antinociceptive effect of venlafaxine is influenced by opioid receptor subtypes (μ-, κ1- κ3- and δ-opioid receptor subtypes) combined with the α2-adrenergic receptor, whereas the antinociceptive effect of mirtazapine mainly involves μ- and κ3-opioid mechanisms. This opioid profile of the two drugs may be one of the explanations to their efficacy in severe depression, unlike the SSRIs and other antidepressants which lack opioid activity.


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## mark555666 (May 1, 2008)

So anyone having success with Cali rocket fuel? I want add cymbalta to my currently prescribed remeron.


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## AbsentSince2003 (Aug 28, 2011)

Looking for a way out? Been on 375mg Effexor for 7 years because of anxiety and it helped to a degree, but I felt really numb for years. After seeing my psychiatrist he advised me to change in November last year. Since then I have been on Duloxetine, Duloxetine plus Seraquel, Duloxetine plus Mirtazapine and now just 45mg of Mirtazapine. It's been a year of hell and now I have been on Mirtazapine for a month and feel sad all the time and having trouble going to work and everything else. I want to go back to effexor but then this year of hell seems pointless. I'm blabbing now, basically venlaflaxine plus Mirtazapine, could it be the answer?


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