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About going off mirtazapine plus venlafaxine (Effexor) aka "California rocket fuel"

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"California rocket fuel" is a combination of mirtazapine and venlafaxine that is a fad among some psychiatrists.

From the Carlat Report at http://pro.psychcentral.com/research-updates-in-psychiatry-6-2/003265.html

 

Does “California Rocket Fuel” Work?
The combination of Effexor (venlafaxine) and Remeron (mirtazapine) has been dubbed “California Rocket Fuel” by Stephen Stahl (see page 290 of his Essential Psychopharmacology, 2nd Edition) because of the multiple ways the combination boosts various neurotransmitter systems. The STAR-D study found that this combination outperformed the MAOI Parnate (tranylcypromine), though the difference was not statistically significant (McGrath PJ et al., Am J Psychiatry 2006; 163(9): 1531-1541). Psychiatrists in Ireland recently reported on a series of 32 patients with refractory depression who were given this combination. The response rate, based on the Clinical Global Impression Scale, was 44% at four weeks and 50% at eight weeks. Most patients who responded were on Effexor XR at 225 mg/day or higher and Remeron 30 mg to 45 mg HS. In terms of side effects, 12% of patients reported moderate to severe weight gain and another 12% reported at least moderate sedation (Hannan N et al., J Psychopharm 2007;21(2):161-164).

TCPR’s Take: Since this is only a case series, it doesn’t prove the value of Effexor/ Remeron, but the combination is fairly well tolerated and certainly worth trying in patients who have not responded to anything else.


Please note that in the Ireland study, 24% of the subjects had serious side effects (plus others not mentioned in the above summary). The study itself http://www.ncbi.nlm.nih.gov/pubmed/17329295reports
 

At 6 month review, 18 patients (56% of the original cohort and 75% of those still receiving treatment) had significantly responded. Clinical response typically occurred at moderate and high dose treatment with both agents. A total of 44% experienced some adverse effects with sedation (19%) and weight gain (19%) most frequent.


In other words, "California rocket fuel" was "effective" (usually this is measured on a depression scale) about half the time, and of those people, 44% had "some" adverse effects.
 
HOWEVER the combination of mirtazapine and venlafaxine can have serious adverse effects http://www.drugs.com/interactions-check.php?drug_list=1640-0,2296-0&types[]=major&types[]=minor&types[]=moderate&types[]=food&types[]=therapeutic_duplication&professional=1
 
 

Interactions between your selected drugs
Major

venlafaxine mirtazapine
Applies to: venlafaxine, mirtazapine

MONITOR CLOSELY: Concomitant use of agents with serotonergic activity such as serotonin reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, 5-HT1 receptor agonists, ergot alkaloids, cyclobenzaprine, lithium, St. John's wort, phenylpiperidine opioids, dextromethorphan, and tryptophan may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: In general, the concomitant use of multiple serotonergic agents should be avoided if possible, or otherwise approached with caution if potential benefit is deemed to outweigh the risk. Patients should be closely monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when increasing the dosages of these agents. The potential risk for serotonin syndrome should be considered even when administering serotonergic agents sequentially, as some agents may demonstrate a prolonged elimination half-life. For example, a 5-week washout may be advisable following use of fluoxetine and 3 weeks following the use of vortioxetine before administering another serotonergic agent. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures.


In effect, psychiatrists know the combination of mirtazapine and Effexor potentially dangerously accelerates nervous system activity, but think it's good for "refractory depression," i.e. "depression" that does not seem to go away with other drugs.


If you are taking this combination, you probably will want to taper the Effexor first with the hope that the remaining mirtazapine will maintain sleep. See 
 
Why taper by 10% of my dosage?
 
Taking multiple psych drugs? Which drug to taper first?
 
Tips for tapering off Effexor (venlafaxine)
 
Also see Tips for tapering off Remeron (mirtazapine) for background.

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Thanks for posting this.

 

If this is how doctors are now going to treat refractory depression protracted ssri/snri withdrawal then this is a most disturbing frightening trend.

 

Look at the high doses they have had to use to bomb and zombie-ize the brain into submission and then no doubt inferring successful treatment.

 

Clinical response typically occurred at moderate and high dose treatment with both agents. ....Most patients who responded were on Effexor XR at 225 mg/day or higher and Remeron 30 mg to 45 mg HS.

 

 

Might i suggest a combination of a bottle of vodka AND a bottle of Sherry might have produced the same result?

 

What a nightmare for anyone trying to get off 225 ven plus 45 rem. These doctors have no idea of the fate that awaits.

 

Lets not forget the Star*D trial from my understanding/reading had no placebo control group.

So since there is no evaluation of what recovery might have been with placebo treatment there is no way of knowing whether their recovery was actually due to the medication they had been given.

 

Decided to look up this  Clinical Global Impression scale  (CGI-I) thingy....

...later.....it requires the CLINICIAN to assess how much the patient's illness has improved (NOT the patient)

 

Its up to the doctor to SUBJECTIVELY determine improvement based on HIS clinical experience. 

I wonder if it takes into account 'stockholm syndrome' ? placebo effect? pharma inducements for a supportive outcome? etc? or dare i say it ...patients opinion???!?

 

 The response rate, based on the Clinical Global Impression Scale, was 44% at four weeks and 50% at eight weeks. Most patients who responded were on Effexor XR at 225 mg/day or higher and Remeron 30 mg to 45 mg HS.

 

Heres the thing most often a 50 % reduction in symptoms is used as a criterion of what is called a 'clinical response'. One problem with this method is that most of the severely  depressed patients who show a clinical response are still depressed at the end of the clinical trial- despite the fact that their depressive symptoms have been cut in half. (Johnson and Kirsch 2008).

 

Do those psychiatrists in Ireland have any conflicts of interest? Just curious thats all !

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I read this article that you have posted as I was on Effexor, then mirtazapine was added back in January 2015 , as you can see you in my history , so I was on the both , Effexor had stopped working and I was and still am in severe w/drawel , mirtazapine was added to help the Effexor and I was told by my gp that this is called California rocket fuel , however because they did not know about protracted withdrawel , both meds were stopped basically cold turkey over a 2 to 4 week period , I believe that the reason my w/d has been so bad is because of the mixing and removing of these two drugs , the worst being some 8 months later mirtazapine was given to me as I was told now that the Effexor is well and truly out of my system the mirtazapine will work better ! Stupid me , currently withdrawing slowly

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This Star*D trial is worth reading about. Sequenced Treatment Alternatives to Relieve Depression or Star* D.

 

Just thought i would add this link to Star*D trial info

 

https://en.wikipedia.org/wiki/STAR*D

Patients entered four different levels of treatment

It looks like one level got the Californian rocket fuel.

 

Level four consisted of the monoamine oxidase inhibitor tranylcypromine or a combination of venlafaxine and mirtazapine.

 

Despite dismal results of this study..

[although approx 67 % of patients recovered the remission of symptoms was temporary with approx half of the patients who recovered relapsed within a year...and because no placebo controlled group we therefore cant say for sure that the recovery of those 50% was due to the drugs with certainty. Im not that clear myself on what actually happened here did those who had their depression go into remission on an ad then, after the 14 week trial get CT off the drug and observed for the rest of the year? Keep in mind that the idea of this trial was to prove the drugs effectiveness in the real world and over longer periods of time. It failed to show that antidepressants were effective at the end of one year.]

 

..it appears it is being used to inform doctors that if one drug doesn't work try another and then another then try a cocktail.

 

(Apparently this is called the 'tailoring hypothesis' - one has to find the right drug for the right person....because supposedly [erroneously] different patients suffer from different chemical imbalances. )

 

Yet why ? since the study doesn't suggest to do this at all. In fact it says:

"Among the patients who were switched to a different antidepressant, there was no significant difference among the different antidepressants."

 

Whitaker explains why...Apparently its all to do with CPGs

 

Clinical practice guidelines (CPG) are put together and developed by expert panels who review the literature.

 

The CPG committee cited the Star*D study 13 times yet not once mentioned the poor 1 year outcomes.

 

Instead they used the Star* D study to discuss drug switching or drug augmentation strategies for patients who hadn't responded well to a first antidepressant. The Star*D trial the CPG committee wrote, "provided evidence for continued efficacy of medication augmentation."

 

Let me summarize 5 pages:

[Question: Are antidepressants helpful over the long term?

Answer: In summary, data is piling up (including the Star*D study,Rush study, Fava' studies, El-Mallakh - who coined the term tardive dysphoria ) that show evidence that the drugs may have an adverse long-term effect.

"Antidepressants  may worsen the progression of the disease in the long-term." Fava]

 

Whitaker says ...However, the APA's CPG committee did not discuss any of this mounting information.

 

Instead, it recommended that antidepressants could be used as a "maintenance therapy."

 

If this drug treatment failed, the APA recommended that the patient could be "given continuation ECT." Any worry about the long-term negative effects of SSRIs is simply absent from the CPG, even though this is information that prescribing physicians and their patients would surely want to know.

 

So what on earth is going on here ? 

 

Perhaps you are now wanting to ask the same question as me.  Who are these people on the CPG committee?

 

Whitaker gives us an insight into this,

 

"In a 2009 review of the CPG panels for depression, bipolar disorder, and schizophrenia, researchers found that 18 of the 20 members had financial ties to the pharmaceutical companies that manufactured the medications recommended in the guidelines as first-line treatment. (e.g. had equity in a company that made the medication, was a consultant or corporate board member, or received honoraria). 14 of the 20 worked as consultants to pharmaceutical companies.

 

On the CPG panel for bipolar disorder, all of the members had ties to the companies whose drugs were identified as "first-line pharmacological treatment."

 

The CPG for depression listed 9 drugs as optimal medication, and all of the companies that manufactured one of those nine drugs had a financial tie to one or more of the panel members.

 

The same was true for schizophrenia: the CPG listed 16 drugs that were commonly used, and every manufacturer of one of those drugs had a financial tied to one or more of the schizophrenia panel members.

 

None of the three CPG's disclosed the financial conflicts of interest of the panel members.

 

The 2010 CPG contains over 1000 references, 106 of which were papers that had been authored by one of the panel members. On average, each panel members work was cited nearly 20 times in the guideline most of these articles were research reports, reviews, or editorials involving a pharmaceutical.   "

 

p140 Psychiatry under the Influence.

 

"There was a tight web of mutual interest present as psychiatry developed its expert consensus guidelines', and again and again, the experts recommended the new drugs as first-line treatments.... In his report, Rothman summarised the production of the schizophrenia "expert consensus guidelines" in this way: "From the start, the project subverted scientific integrity, appearing to be a purely scientific venture when it was at its core, a marketing venture for Risperdal". p150

 

nz11

Apologies if i got a bit off topic.

Totally ok to move it if you want.

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I have just picked up on this thread. I was on Effexor 150 mg and Mirtazapine 30 mg for 15 years. In retrospect it was terrible 

for me, my life and my relationships. However I had endured a really hideous bout of depression and bought the chemical 

imbalance nonsense. It was widely promulgated and supported. Anyhow I muddled through until about 13 months ago when I rapidly tapered Effexor.

About a month or two after stopping I went into the most awful withdrawals. I ascribed my ill health to a tough treatment 

I had done with Interferon during the previous year. It was only when I was prescribed Lyrica, Dec 2015 ,for the symptoms I was presenting,

that I realised I was in serious protracted withdrawal from the Effexor. I had such a horrible reaction to Pregabalin that I began to investigate 

my situation and history with Ads. I came off Lrica too quickly 2 months ago Am still in protracted withdrawal with the added layer 

of Lryica discontinuation. Am very concerned that my many years of Mirtazapine and Effexor may have caused me irreparable damage. 

Am still on Mirtazapine but not really sleeping or functioning all that well. Any advice would be gratefully received. I have even considered 

a very small reinstatement of Effexor to see if it restored better function. I guess it is a long way out and there has been the added problem of 

pregabalin.

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Somehow this "CA rocket-fuel" combination in "treatment resistant" depression - 

 

brings to mind the overuse of GMO's and glyphosate causing treatment resistant weeds - and the ghastly toxic combinations that they need to use to fight the superweeds....

 

"We've made your depression resistant to our treatment (with our long term treatment), so now we're going to have to bomb your brain into oblivion."

 

I do think that the example is apt.

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Somehow this "CA rocket-fuel" combination in "treatment resistant" depression - 

 

brings to mind the overuse of GMO's and glyphosate causing treatment resistant weeds - and the ghastly toxic combinations that they need to use to fight the superweeds....

 

"We've made your depression resistant to our treatment (with our long term treatment), so now we're going to have to bomb your brain into oblivion."

 

I do think that the example is apt.

Yeah, mirtazapine and it's cousin drug mianserin are actually very effective anti-depressants and are pretty safe, it's the effexor which is the issue.

SSRI's are pretty much all garbage.

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Yeah, mirtazapine and it's cousin drug mianserin are actually very effective anti-depressants and are pretty safe, it's the effexor which is the issue.

 

?!?!

Sorry, I don't see it this way  its same church different pew they are all unsafe, they are all immensley harmful..the whole lot !

 

I have seen many people struggle to get off mirtzapine just like all the others. Don't know about mianserin havent heard of that one before its probably hiding behind lots of names and im too lazy to look it up.

(Effexor like mirtz is a newer antidepressant and effexor is an SNRI...and words like 'newer', 'more effective than' is just marketing hype)

 

 Kirsch  "the differences between one antidepressant  and another are virtually non-existant.

 

Breggin 2014 says

All classes of psychiatric drugs can cause brain damage and lasting mental dysfunction when used for months or years. Although research data is lacking for a few individual drugs in each class, until proven otherwise it is prudent and safest to assume that the risks of brain damage and permanent mental dysfunction apply to every single psychiatric drug. 

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Neither of these drugs is superior to the other or to Effexor as antidepressants, and all have withdrawal issues.

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A person i know who did this combination and thought he was off all ADs is now on Cymbalta and did not know it was an Ad so I had to break it to him... sadly he seems to be losing his marbles and has one eye that acts and looks funny odd... not funny it does not look right to me ...lots of new blood pressure meds is what he did know ... sad and crazy both nobody believes me... I wish I had the magic that made people believe me. 

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It's hard to comprehend that intelligent people prescribe these evil drug combinations

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Somehow this "CA rocket-fuel" combination in "treatment resistant" depression - 

 

brings to mind the overuse of GMO's and glyphosate causing treatment resistant weeds - and the ghastly toxic combinations that they need to use to fight the superweeds....

 

"We've made your depression resistant to our treatment (with our long term treatment), so now we're going to have to bomb your brain into oblivion."

 

I do think that the example is apt.

 

I love your analogy with glyphosate!!  :lol:

At the same time I feel like crying - so many brains are bombed into oblivion, so sad  :mad:

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This is an interesting topic. I am on the so-called Californian Rocket Fuel. The mirtazapine is at a relatively low dose however. I'm not sure how sedating it is although having said that I generally don't have any trouble sleeping. I am over-sleeping at the moment actually and I feel very fatigued a lot of the time. I am tapering the Effexor now which luckily seems to be the advisable route from what I have read here.

 

Thanks for the information.

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