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Discussion Starter · #1 ·
This study just came out. I couldn't help buying the full article. Take a look. This is great! :boogie

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J Affect Disord. 2014 Jun 4;167C:148-152. doi: 10.1016/j.jad.2014.05.047. [Epub ahead of print]
How treatable is refractory depression?
Stewart JW1, Deliyannides DA2, McGrath PJ2.

Abstract
INTRODUCTION:
Patients who do not remit following one or more attempts at treatment present a clinical challenge, as well as prolonged suffering and disability. Discouragement is common, so knowledge of likelihood of eventual remission as well as which treatments might ultimately be effective would help patient and clinician alike.

METHOD:
Thirty-one patients with major depression were recruited, 28 beginning study treatment. All had remained significantly depressed following adequate (4 weeks taking ≥ PDR maximum dose) trials on ≥ two antidepressants having different presumed mechanisms. Patients were begun on tranylcypromine to 60mg/d, were then treated with up to 120mg/d and then had dextroamphetamine added. Following two week wash-out, patients were then treated with nortriptyline+lithium, and then phenelzine was added. Each successive phase was entered only if remission had not been achieved, and phases could be skipped.

RESULTS:
Eighteen of the 28 patients (65%) remitted in one of the five phases of the study, plus 5 additional patients with open post-study treatment (total remitting, 82%). By study phase, Eight of 27 (30%) patients remitted with initial dosing of tranylcypromine up to 60mg/d, 6/18 (33%) remitted with above PDR dosing of tranylcypromine up to 120mg/d, and 1/6 (17%) to adding dextroamphetamine. With nortriptyline, 1/10 (10%) remitted with nortriptyline+lithium, and 1/5 (20%) when phenelzine was added. Eighteen of the 28 patients (64%), or 78% of those who remitted, maintained their good benefit for at least six months.

DISCUSSION:
The majority of depressed patients refractory to two or more adequately utilized differently acting antidepressant medications can still remit and about half may maintain remission for extended periods. "Refractory depression" appears to be a relative description for many unresponsive depressed patients.
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  • This is a 2014 study
  • They took patients who weren't adequately responding (for depression) - and put them on an MAOI (Parnate) and not augment with a bunch of other junk
  • They started with an aggressive/adequate Parnate dose
  • If it failed they used a high Parnate dose up to 120 mg.
  • If that failed they added a stimulant to the MAOI
  • If no good then they restarted on a nortryptiline/lithium combo
  • And next option was to add phenelzine (Nardil) to the TCA/lithium. An MAOI/ NRI /lithium combo
  • They followed them for a nice long time - for six months
  • Ultimately, ~64% remission rate, for treatment-resistant depression from this algorithm.

The results blow modern, conventional antidepressant trials out of the water. (i.e. the SSRI/ SNRI merry go round, "here try a fourth SSRI, maybe this one will work".)

This article might be useful for people who are hoping to have a conversation with their doctor about taking MAOIs, or about MAOI augmentations such as stimulants, TCA's, and lithium.
 

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Tricyclic increase serotonin, stimulants increase catechlomines, nardil inhibits the enzyme which breaks this monoamine and amino acids. So it's no surprise the Guinea pigs have gotten better. That's why I highly recommend rhodiola rosea + 5htp= Heavenly bliss.
 

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Tricyclic increase serotonin, stimulants increase catechlomines, nardil inhibits the enzyme which breaks this monoamine and amino acids. So it's no surprise the Guinea pigs have gotten better. That's why I highly recommend rhodiola rosea + 5htp= Heavenly bliss.
Dude where can I get that stuff?
 

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Good stuff. I haven't seen a journal like this done on MAOI's lately, but then again I haven't been looking.

It makes sense that these powerful antidepressants probably would have a higher effect. But the thing is that's usually understood with the assumption that there will be more side effects than a regular SSRI. There was no discussion of side effects in the blurb you posted.

I can't see how anyone could function on nortriptyline, lithium and phenelzine. That is an incredibly tiring combination. Nortriptyline has anthihistamine properties, lithium = crazy serotonin, phenelzine = gaba-T which usually clouds the mind. I'm sure it diminished the depression, but it probably didn't let them function exceptionally.
 

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Discussion Starter · #5 ·
Tricyclic increase serotonin, stimulants increase catechlomines, nardil inhibits the enzyme which breaks this monoamine and amino acids. So it's no surprise the Guinea pigs have gotten better. That's why I highly recommend rhodiola rosea + 5htp= Heavenly bliss.
I know you are probably making the troll rounds but this is too important to allow misinformation. In this particular case the details matter, and accuracy matters.

A note: the study is on patients with treatment resistant depression. Patients have a right to effective, ethical treatment, and I object to the pejorative "guinea pigs" term.

1. Nortryptiline is a tricyclic which primarily affects norepinephrine, not serotonin, at the doses used. It is a reuptake inhibitor. That is important because
  • It does not increase "levels" of any neurotransmitters. It keeps the neurotransmitters in the synaptic gap longer.
  • A serotonin reuptake inhibitor would carry a risk of serotonin toxicity, and would be too dangerous to use with an MAOI.
  • By blocking NE reuptake, nortryptiline potentiates norepinephrine. This is important because MAOIs have paradoxical effects on NE, sometimes causing hypotension. An NRI can mitigate this effect. Use of an NRI such as nortryptiline also assists to prevent tyramine toxicity ("cheese reaction"). It blocks tyramine uptake because it blocks the transporter used.

2. Stimulants (amphetamines vs methylphenidate) work differently. Dextroamphetamine was used, which causes release of existing NE and DA as well as causing reuptake inhibition of those neurotransmitters. That mechanism matters, because the MAOI makes more catecholamines available for the stimulant to work. You're on the right track, but realize there is a feedback loop at play between the stimulant and the MAOI.

3. Keep in mind both Parnate and Nardil were used in the study

4.
rhodiola rosea + 5htp= Heavenly bliss
Not even close to comparable. My guess is, you may as well throw in some M&Ms.

But, people need to avoid carelessly adding herbal supplements. Unconventional MAOI augmentation requires careful, evidence-based strategies. Many herbal remedies have multiple effects, and some may be unsafe. Doses of active ingredients are not standardized in the same way. I would not utilize untested herbal supplements. It's either a waste of money, or a needless risk, or (probably) both.
 

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Discussion Starter · #6 ·
I can't see how anyone could function on nortriptyline, lithium and phenelzine. That is an incredibly tiring combination. Nortriptyline has anthihistamine properties, lithium = crazy serotonin, phenelzine = gaba-T which usually clouds the mind. I'm sure it diminished the depression, but it probably didn't let them function exceptionally.
They had 10 patients on nortryptiline/lithium but 3 turned down lithium due to prior intolerance. 2 remitted, 5 did not, so those 5 moved onto the combo w/ Nardil.

The TCA/lithium/phenelzine had 5 patients with 2 remitting and 3 did not.

It's hard to summarize what they have for adverse effects because it's all listed as a table. What stands out to me is the higher rates of side effects on the TCA/lithium combo... adding phenelzine didn't cause a huge increase in problems. But there were far more side effects than for Parnate at either dose, or for Parnate + dex.

All they write is "nortryptiline + lithium + phenelzine. This was also generally well tolerated, although orthostatic hypotension was problematic in one patient."
 

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Not even close to comparable. My guess is, you may as well throw in some M&Ms.

(probably) both.
A bit of copy and pasta.

Anti-aging medicine is all the rage but what really works that is safe and effective? I have previously written about the anti-aging benefits of Reishi mushroom extract but I would like to introduce you to another herb known as Rhodiola rosea. Rhodiola also known as "golden root" has been used for centuries in Europe and Asia with the following benefits:
=>Increases energy and stamina
=>Improves brain function
=>Enhances blood sugar metabolism
=>Helps the body adapt to all forms of stress
=>Antioxidant properties
=>Slows tumor growth progression
=>Prevents altitude sickness
=>Stimulates healing
=>Reduces anxiety
=>Improves mood by increasing serotonin levels in the brain
=>Balances the feel good brain chemical dopamine
=>Decreases adrenaline levels
=>Protects your heart from damage
Rhodiola is in a class of herbal medicines known as adrenal adaptogens meaning they help your body reduce the negative effects of stress as well as adapting to it.
In addition to these benefits, a recent study out of the University of California Irvine found that Rhodiola rosea can increase the lifespan of the fruit fly, worms, and yeast. But what about humans?
- See more at: http://drhedberg.com/2013/07/08/rhodiola-rosea-could-increase-your-lifespan/#sthash.E9K6Nisf.dpuf

Abstract
AIM OF THE STUDY:
Rhodiola rosea L. (Crassulaceae) is traditionally used in Eastern Europe and Asia to stimulate the nervous system, enhance physical and mental performance, treat fatigue, psychological stress and depression. In order to investigate the influence of Rhodiola rosea L. roots on mood disorders, three extracts were tested against monoamine oxidases (MAOs A and B) in a microtitre plate bioassay.
MATERIALS AND METHODS:
Methanol and water extracts gave the highest inhibitory activity against MAOs. Twelve compounds were then isolated by bioassay-guided fractionation using chromatographic methods. The structures were determined by 1H, 13C NMR and HR-MS.
RESULTS:
The methanol and water extracts exhibited respectively inhibitions of 92.5% and 84.3% on MAO A and 81.8% and 88.9% on MAO B, at a concentration of 100 microg/ml. The most active compound (rosiridin) presented an inhibition over 80% on MAO B at a concentration of 10(-5) M (pIC50=5.38+/-0.05).
CONCLUSIONS:
The present investigation demonstrates that Rhodiola rosea L. roots have potent anti-depressant activity by inhibiting MAO A and may also find application in the control of senile dementia by their inhibition of MAO B.
http://www.ncbi.nlm.nih.gov/pubmed/19168123

Extracts of Hypericum perforatum (St. John's Wort) are widely used for the treatment of depressive disorders and are unspecific inhibitors of the neuronal uptake of several neurotransmitters. Previous studies have shown that hyperforin represents the reuptake inhibiting constituent. To characterize the mechanism of serotonin reuptake inhibition, kinetic analyses in synaptosomes of mouse brain were performed. Michaelis-Menten kinetics revealed that hyperforin (2 microM) induces a decrease in V(max) by more than 50% while only slightly decreasing K(m), indicating mainly noncompetitive inhibition. By contrast, citalopram (1 nM) leads to an elevation of K(m) without changing V(max). Monensin, a Na(+)/H(+) exchanger, showed similar properties as hyperforin (decrease of V(max) without changing K(m)). Compared with classical antidepressants, such as selective serotonin reuptake inhibitors and tricyclic antidepressants, hyperforin is only a weak inhibitor of [(3)H]paroxetine binding relative to its effects on serotonin uptake. As monensin decreases serotonin uptake by increasing Na(+)/H(+) exchange, we compared the effects of hyperforin and monensin on the free intracellular sodium concentration ([Na(+)](i)) in platelets by measuring 1,3-benzenedicarboxylic acid, 4,4'-[1,4,10-trioxa-7, 13-diazacyclopentadecan-7,13-diylbis(5-methoxy-6, 2-benzofurandiyl)]bis-, tetraammonium salt (SBFI/AM) fluorescence. Both drugs elevated [Na(+)](i) over basal levels, with a maximal [Na(+)](i) of 69 +/- 16.1 mM (50 microM hyperforin) and 140 +/- 9.1 mM (10 microM monensin). Citalopram at concentrations relevant for [(3)H]serotonin uptake inhibition had no effect on [Na(+)](i). Although the mode of action of hyperforin seems to be associated with elevated [Na(+)](i) similar to those levels found with monensin, the molecular mechanism might be different, as even at high concentrations, hyperforin does not elevate free intracellular sodium concentration ([Na(+)](i)) up to the extracellular level, as monensin does. Hyperforin represents the first substance with a known preclinical antidepressant profile that inhibits serotonin uptake by elevating [Na(+)](i).
http://www.ncbi.nlm.nih.gov/pubmed/10454515

This study looks to compare the antidepressant efficacy and safety of a standardized extract of St John's wort with both placebo and fluoxetine.
METHOD:
After a 1-week single-blind washout, patients with major depressive disorder diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were randomized to 12 weeks of double-blind treatment with LI-160 St John's wort extract (900 mg/d), fluoxetine (20 mg/d), or placebo. The 17-item Hamilton Rating Scale for Depression (HAMD-17) was the primary efficacy measure, and analysis of covariance was used to compare differences in end point HAMD-17 scores across the 3 treatment groups, treating the baseline HAMD-17 as the covariate.
RESULTS:
One hundred thirty-five patients (57% women; mean age, 37.3 +/- 11.0; mean HAMD-17, 19.7 +/- 3.2) were randomized to double-blind treatment and were included in the intent-to-treat analyses. Analysis of covariance analyses showed lower mean HAMD-17 scores at end point in the St John's wort group (n = 45; mean +/- SD, 10.2 +/- 6.6) compared with the fluoxetine group (n = 47; 13.3 +/- 7.3; P < 0.03) and a trend toward a similar finding relative to the placebo group (n = 43; 12.6 +/- 6.4; P = 0.096). There was also a trend toward higher rates of remission (HAMD-17 <8) in the St John's wort group (38%) compared with the fluoxetine group (30%) and the placebo group (21%). Overall, St John's wort appeared to be safe and well tolerated.
CONCLUSION:
St John's wort was significantly more effective than fluoxetine and showed a trend toward superiority over placebo. A (25%) smaller than planned sample size is likely to account for the lack of statistical significance for the advantage (indicating a moderate effect size, d = 0.45) of St John's wort over placebo.
http://www.ncbi.nlm.nih.gov/pubmed/16160619

. he influence of the co-factor pyridoxine, vitamin B6, on the activity of aromatic amino acid decarboxylase enzyme was studied by positron emission tomography, PET in the brain of the Rhesus monkey using the precursor for serotonin synthesis 5-hydroxy-L-tryptophan (5-HTP) radiolabelled with 11C in the beta-position. The rate constant for the formation of serotonin in the corpus striatum was calculated using a two tissue compartment model with reference area in the brain. In baseline investigations, the mean rate constants (+/-S.D:) for selective utilization of [11C]5-HTP to form [11C]serotonin in the corpus striatum was 0.0080 +/- 0.0011 min(-1). Pretreatment with intravenous pyridoxine hydrochloride 10 mg/kg bodyweight before doing a second PET study resulted in an enhanced rate constant by a mean of 20%. The rate increase was statistically significant. The increase varied considerably in different monkeys from no effect to more than 60%. The effect of pyridoxine on aromatic amino acid decarboxylase activity supported a regulatory role of pyridoxine on the synthesis of neurotransmitter in vivo, and may be of importance in diseases with deficiencies in neurotransmitter functio
http://www.ncbi.nlm.nih.gov/pubmed/8748674
 

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Discussion Starter · #11 ·
A bit of copy and pasta.
You only produced two potential sources:
  • 1 link to a creepy guy, claiming to be a chiropracter, selling a book and other stuff, and just kind of saying things about it. (Btw, generally anything that solves everything is just snake oil.)
  • 1 reference to a study done in petri dishes stating that X concentration had an enzyme reaction in methanol and water media.

The others were not relevant. They related to other topics.

Compare to MAOI/ MAOI augmentation strategies listed here. These are medication strategies with multiple clinical studies, conducted over several months at standardized doses, using multiple measures, with research investigating every level of mechanisms from intracellular to gross physiology, replicated over time, and backed by decades of clinical use by psychiatrists who specialize in treatment-resistant depression.

I am aware of no evidence, at this time, that rhodiola rosea supplements have clinically reliable antidepressant efficacy that exceeds placebo. Much less, have efficacy similar to the meds I mentioned, in the same context.

Maybe over time this plant will receive more research, and can be processed to deliver standardized amounts of an active compound, and that compound can be studied in patients. But we are not there yet and there is no reason to buy something without evidence that it will work.

The only thing I want to take is something that works, safely.
 

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Fighting demons!
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You only produced two potential sources:
  • 1 link to a creepy guy, claiming to be a chiropracter, selling a book and other stuff, and just kind of saying things about it. (Btw, generally anything that solves everything is just snake oil.)
  • 1 reference to a study done in petri dishes stating that X concentration had an enzyme reaction in methanol and water media.

The others were not relevant. They related to other topics.

Compare to MAOI/ MAOI augmentation strategies listed here. These are medication strategies with multiple clinical studies, conducted over several months at standardized doses, using multiple measures, with research investigating every level of mechanisms from intracellular to gross physiology, replicated over time, and backed by decades of clinical use by psychiatrists who specialize in treatment-resistant depression.

I am aware of no evidence, at this time, that rhodiola rosea supplements have clinically reliable antidepressant efficacy that exceeds placebo. Much less, have efficacy similar to the meds I mentioned, in the same context.

Maybe over time this plant will receive more research, and can be processed to deliver standardized amounts of an active compound, and that compound can be studied in patients. But we are not there yet and there is no reason to buy something without evidence that it will work.

The only thing I want to take is something that works, safely.
The active ingredient of rhodiola rosea which is responsible for the adaptogen effects and as you seen in the study above they used methanol and water extracts and found the methanol extract is much more potent inhibitor of monoamine oxidize. The proof is in the pudding, their are literally thousands of brands of rhodiola roses along with St. John's worts and al, of the are rubbish except for two brands .........." Perika St. John's worts " a German brand made by dr schwabbe. And " jarrow rhodiola rosea 5% rosavins" the highest rosavins " active ingredient on the market. The rosavins are not only responsible for the monoamine oxidize inhibiton, but also the powerful psychostimulants effects of rhodiola rosea, it's more stronger than Ritalin in terms of psychostimulants effects, while at the same time relaxing you. It's unbelievable herb.
 

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Rhodiola rosea had been used since ancient times, Vikings used it, ancient chinese emperors used it, even genghis khan was a big fan of it due to its strong energizing effects and stress relieving effects. It's been used since ancient times why do you need to see thousands of studies to proof something used for thousands of years? I think ppl laugh when they see the word herb, but they didn't realize marihuana is a herb and it's active ingredients thc is what's responsible for its effects.
 

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This " herb" is nothing short of a miracle but I would call it the limitless pill, have you seen limitless 2011 starring Bradley cooper? Well I think he was taking rhodiola rosea.

The incidence of human urinary bladder cancer increases markedly with age, suggesting a mechanistic connection between aging and bladder carcinogenesis and a potential use of anti-aging agents in bladder cancer chemoprevention. Rhodiola rosea, growing in high altitude or cold regions of the world, has been reported to have anti-aging effects in Drosophila. We demonstrated that a R. rosea extract and one of its bioactive components, salidroside, inhibited the growth of bladder cancer cell lines with a minimal effect on nonmalignant bladder epithelial cells TEU-2. Interestingly, the R. rosea extract and salidroside component exhibited a selective ability to inhibit the growth of p53 knockout primary mouse embryo fibroblasts (p53-/- MEFs) compared to their wild-type counterparts. The growth inhibitory effects of the R. rosea extract and salidroside were, however, attenuated in TSC2 and p53 double knock MEFs (TSC2-/-, p53-/- MEFs), suggesting that TSC2 protein is, at least in part, required for the growth inhibitory effects of the R. rosea extract and salidroside. The R. rosea extract and salidroside treatment of UMUC3 cells resulted in an increase of AMP-activated protein kinase (AMPK)-α phosphorylation and a decrease of 4E-BP1 phosphorylation, leading to increased binding of 4E-BP1 to m7 GTP. These results indicate that the R. rosea extract and salidroside inhibit translation initiation. Furthermore, both the R. rosea extract and salidroside treatment of UMUC3 cells caused a significant percentage of cells undergoing autophagy. Therefore, the R. rosea extract and salidroside deserve further study as novel agents for chemoprevention of bladder carcinogenes
Rhodiola rosea reduces cancer cell growth.
 

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^ Does this troll ever stop? Rhodiola Rosea is a decent herb that could possibly help with energy and mood, but it's not going to treat any severe mood disorders. This troll thinks Magnesium and Rhodiola are going to treat extreme cases of mental conditions. Refers to the use of herbs and supplements as heavenly bliss... No one should take Mufasa serious on this board or listen to any of his advice. He continuously talks out of his ***
 

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Fighting demons!
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^ Does this troll ever stop? Rhodiola Rosea is a decent herb that could possibly help with energy and mood, but it's not going to treat any severe mood disorders. This troll thinks Magnesium and Rhodiola are going to treat extreme cases of mental conditions. Refers to the use of herbs and supplements as heavenly bliss... No one should take Mufasa serious on this board or listen to any of his advice. He continuously talks out of his ***
Propecia:teeth
 

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Do you think Nardil and Parnate are interchangeable in the algorithm? Can a stimulant be added to Nardil? Can Parnate be taken with TCA/lithium?
 

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Discussion Starter · #20 ·
I should clarify, the topic is mainly regarding depression treatment more so than social anxiety, though of course the two go hand in hand.

Do you think Nardil and Parnate are interchangeable in the algorithm? Can a stimulant be added to Nardil? Can Parnate be taken with TCA/lithium?
Absolutely :) Only difference is that I am unaware of high-dose Nardil treatment. I probably wouldn't go there.

Stimulants and norepinephrine reuptake inhibitors (such as TCAs) would pair very well with Nardil because of its side effect profile.
 
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