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Augmentation of SSRIs (antidepressants) with creatine

ssris ssri luvox creatine escitalopram antidepressant antidepressants depression

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#1 blood

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Posted 18 August 2014 - 09:59 AM


Interesting study.

Women on SSRIs (Luvox) who were also given 5 grams creatine/ day had a better (faster, stronger) antidepressant response than woman taking an SSRI alone.
 

A Randomized, Double-Blind Placebo-Controlled Trial of Oral Creatine Monohydrate Augmentation for Enhanced Response to a Selective Serotonin Reuptake Inhibitor in Women With Major Depressive Disorder

Abstract

Objective

Antidepressants targeting monoaminergic neurotransmitter systems, despite their immediate effects at the synaptic level, usually require several weeks of administration to achieve clinical efficacy. The authors propose a strategy of adding creatine monohydrate (creatine) to a selective serotonin reuptake inhibitor (SSRI) in the treatment of patients with major depressive disorder. Such augmentation may lead to a more rapid onset of antidepressant effects and a greater treatment response, potentially by restoring brain bioenergetics at the cellular level.

Method
Fifty-two women with major depressive disorder were enrolled in an 8-week double-blind placebo-controlled clinical trial and randomly assigned to receive escitalopram in addition to either creatine (5 g/day, N=25) or placebo (N=27). Efficacy was primarily assessed by changes in the Hamilton Depression Rating Scale (HAM-D) score.

Results
In comparison to the placebo augmentation group, patients receiving creatine augmentation showed significantly greater improvements in HAM-D score, as early as week 2 of treatment. This differential improvement favoring creatine was maintained at weeks 4 and 8. There were no differences between treatment groups in the proportion of patients who discontinued treatment prematurely (creatine: N=8, 32.0%; placebo: N=5, 18.5%) or in the overall frequency of all reported adverse events (creatine: 36 events; placebo: 45 events).

Conclusions
The current study suggests that creatine augmentation of SSRI treatment may be a promising therapeutic approach that exhibits more rapid and efficacious responses in women with major depressive disorder.


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#2 Virtual Reality

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Posted 18 August 2014 - 11:13 AM

Interesting. Do you think its likely that this same effect could be achieved in males?



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#3 Virtual Reality

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Posted 18 August 2014 - 10:51 PM

To my question, I would be likely that it will be the same for males.

But why did they choose for females...  Non the less, this could be a game changer to some.



#4 datrat

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Posted 18 August 2014 - 11:37 PM

I think you're right, that it should also apply to males, but why do the study only on females; the only idea I have is that since many drugs affect women differently than men (60 minutes report - I know best possible cite :) ) they wanted to eliminate any differences in sex response to treatment. I'm glad you posted that study, it could be really helpful for some people.



#5 blood

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Posted 19 August 2014 - 03:46 AM

But why did they choose for females...


In a mouse model of depression, apparently, creatine (taken on its own, with no SSRIs) was found to have antidepressant benefits in female mice, but not male mice.

The people running this "proof of concept" study probably chose all female human subjects to maximise their chances of getting a significant i.e. publishable result:
 

Recent preclinical evidence from an animal model of depression also provides support for the potential antidepressant effects of creatine (17). This antidepressant-like response induced by creatine supplementation was observed in female, but not male, rodents. Although it is not clear why the antidepressant efficacy of creatine supplementation was predominantly in female rodents, sexual dimorphism in expression of creatine kinase levels (18) and beneficial effects of estrogen on mitochondrial function (19, 20)—for example, greater energy-producing capacity and lower reactive oxygen species production—could play a role in these sex-dependent creatine effects in animal models. Furthermore, abnormal cerebral metabolism associated with depression has been reported to be more common in women than in men (12), suggesting that creatine supplementation may be more beneficial in women. On the basis of these preliminary findings, we focused on women in what we believe is the first double-blind placebo-controlled study of creatine augmentation for major depressive disorder.

In this clinical trial, the efficacy, safety, and tolerability of creatine augmentation of escitalopram were assessed in individuals with major depression. Given the nature of the proof-of-concept study, only depressed women were selected as study subjects because creatine’s antidepressant-like effects have been shown preclinically only in female animals.


Edited by blood, 19 August 2014 - 03:49 AM.

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#6 datrat

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Posted 19 August 2014 - 03:52 AM

Thanks, really interesting find.



#7 blood

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Posted 19 August 2014 - 03:54 AM

Here is Examine.com's take:
 

5.9. Depression

Creatine has been sought after for its effects on depression, due to the significant changes occurring in brain morphology and neuronal structure associated with depression[247] and low brain bioenergetic turnover in depression[248], perhaps related to abnormal mitochondrial functioning, which reduces available energy for the brain.[249][250] The general association of low or otherwise impaired phosphate energy systems (of which creatine forms the energetic basis of) with depression, has been noted previously.[251][248][252] Due to associations with cellular death and impaired bioenergetics with depression, creatine was subsequently investigated.

Oral ingestion of 1-1000mg/kg bodyweight of creatine in mice was able to exert an anti-depressive effect, which was blocked by dopamine receptor antagonists. A low dose of creatine (0.1mg/kg) was able to enhance the dopaminergic effects of dopamine receptor activators, suggesting supplemental creatine can positively influence dopamine signalling and neurotransmission.[253]

Anti-depressive effects have been noted in humans, where 5g of creatine monohydrate daily for 8 weeks was able to augment the efficay of SSRI anti-depressants. Benefits were seen at week two and were maintained until the end of the 8 week trial[254]. These effects were noted before in a preliminary study of depressed adolescents (with no placebo group) showing a 55% reduction in depressive symptoms at 4g daily when brain phosphocreatine levels increased.[233] Other prelimnary human studies suggest creatine might lessen unipolar depression[255] and one study on Post-Traumatic Stress Disorder (PTSD) noted improved mood as assessed by the Hamilton Depression Rating Scale.[234]

It is possible that females could benefit more than males due to a combined lower creatine kinase activity as well as having altered purine metabolism during depression,[256] but no human comparative studies have been conducted yet. One rat study noted that creatine monohydrate at 2-4% of feed had 4% creatine able to exert anti-depressive and anxiolytic effects in female rats only.[230]

Intervention studies with creatine supplementation and depression show promise, but only one well conducted study (used alongside SSRI pharmaceuticals) has been done, while other studies have flaws. Promising, but no conclusions can be made at this time.



Note: people with bipolar disorder should possibly be cautious wrt creatine supplementation (in one study, two folks with bipolar developed mania on creatine) - see here.

Edited by blood, 19 August 2014 - 04:00 AM.

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#8 Zenfood

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Posted 29 August 2014 - 06:48 PM

This is "off topic", but:

 

I have taken 10g of creatine twice and I experienced major brain fog from this. I got really disoriented and lost my working memory, short term memory, motoric skills, experienced fatigue, etc.

 

Not really sure if I ever noticed anything from 5g.

 

Any ideas why this happened? Yes, I drank lots of water.



#9 Area-1255

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Posted 01 September 2014 - 05:38 AM

This is "off topic", but:

 

I have taken 10g of creatine twice and I experienced major brain fog from this. I got really disoriented and lost my working memory, short term memory, motoric skills, experienced fatigue, etc.

 

Not really sure if I ever noticed anything from 5g.

 

Any ideas why this happened? Yes, I drank lots of water.

The same reason creatine can have anti-depressant effects, I'm surprised nobody has gone over this yet.

Creatine is a methylated amino acid - thus it increases rates of methylation in the body / CNS.

However it can also take up methylation reserves in very high doses - thus suggesting dose specific methylation modulation.

Methylation leads to break down of histamine, and enhancement of norepinephrine,serotonin and dopamine levels.

 

So in summary, no it's not just in your head that Creatine has a stimulant effect, it's just not a traditional stimulant by any means; rather an indirect one. ;)

 

 

http://www.lef.org/m...creatine_01.htm

http://www.longecity...nd-methylation/

http://www.bodybuild.../drobson181.htm

 

 

 

 

 

As explained previously in this article, creatine's erogenic actions work to assist energy production and power output, resulting in muscle size and strength, and improved performance. Additionally, it has been found creatine provides a powerful anabolic boost through its enhancing of systemic methylation (the regulation of gene expression, protein synthesis and RNA metabolism through enzymatic catalyzation) status 14.

Indeed, methylation is a process that is essential for the supporting of life itself. A molecule known as SAM (S-Adenosyl Methionine) is the body's principal methyl donor, and a breakdown in its production can adversely affect whole-body anabolism.

Creatine drains the body's SAM reserves like nothing else, which, in turn, deleteriously impacts methylation status (during its synthesisation by the liver and kidneys, creatine draws heavily from the SAM reserves). Supplementing creatine will enhance methylation status, as it will lessen the drain on the liver and kidneys, and alleviate the body's need to synthesize creatine from amino acids.

 

 

 

Also, creatine increases DHT in men - and this may allow for more 3a/5a steroid activity, which can lead to an anti-depressant response and higher CNS activity in general. I've always liked Creatine, it's one of my core supplements but I always get it alone - can't stand the concept of "Proprietary Blends" for the most part. 

 

 

 

 

Clin J Sport Med.

 

 

2009 Sep;19(5):399-404. doi: 10.1097/JSM.0b013e3181b8b52f.

Three weeks of creatine monohydrate supplementation affects dihydrotestosterone to testosterone ratio in college-aged rugby players.

Abstract
OBJECTIVE:

This study investigated resting concentrations of selected androgens after 3 weeks of creatine supplementation in male rugby players. It was hypothesized that the ratio of dihydrotestosterone (DHT, a biologically more active androgen) to testosterone (T) would change with creatine supplementation.

DESIGN:

Double-blind placebo-controlled crossover study with a 6-week washout period.

SETTING:

Rugby Institute in South Africa.

PARTICIPANTS:

College-aged rugby players (n = 20) volunteered for the study, which took place during the competitive season.

INTERVENTIONS:

Subjects loaded with creatine (25 g/day creatine with 25 g/day glucose) or placebo (50 g/day glucose) for 7 days followed by 14 days of maintenance (5 g/day creatine with 25 g/day glucose or 30 g/day glucose placebo).

MAIN OUTCOME MEASURES:

Serum T and DHT were measured and ratio calculated at baseline and after 7 days and 21 days of creatine supplementation (or placebo). Body composition measurements were taken at each time point.

RESULTS:

After 7 days of creatine loading, or a further 14 days of creatine maintenance dose, serum T levels did not change. However, Levels of DHT increased by 56% after 7 days of creatine loading and remained 40% above baseline after 14 days maintenance (P < 0.001). The ratio of DHT:T also increased by 36% after 7 days creatine supplementation and remained elevated by 22% after the maintenance dose (P < 0.01).

CONCLUSIONS:

Creatine supplementation may, in part, act through an increased rate of conversion of T to DHT. Further investigation is warranted as a result of the high frequency of individuals using creatine supplementation and the long-term safety of alterations in circulating androgen composition. STATEMENT OF CLINICAL RELEVANCE: Although creatine is a widely used ergogenic aid, the mechanisms of action are incompletely understood, particularly in relation to dihydrotestosterone, and therefore the long-term clinical safety cannot be guaranteed.

 

 

 

METHODS OF INCREASING DHT NATURALLY


Edited by Area-1255, 01 September 2014 - 05:44 AM.


#10 nashi

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Posted 01 September 2014 - 03:41 PM

How do you guys take creatine?

 

I read that simply taking pure creatine with water is ineffective and that you need to take it with a high glucose transport matrix.

Does this mean that buying pure creatine isn't good and instead you need something like celltech?

 

I don't want to have to digest huge loads of sugars just to get the creatine absorbed.



#11 opusensemble

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Posted 02 March 2016 - 11:50 PM

 

As explained previously in this article, creatine's erogenic actions work to assist energy production and power output, resulting in muscle size and strength, and improved performance. Additionally, it has been found creatine provides a powerful anabolic boost through its enhancing of systemic methylation (the regulation of gene expression, protein synthesis and RNA metabolism through enzymatic catalyzation) status 14.

Indeed, methylation is a process that is essential for the supporting of life itself. A molecule known as SAM (S-Adenosyl Methionine) is the body's principal methyl donor, and a breakdown in its production can adversely affect whole-body anabolism.

Creatine drains the body's SAM reserves like nothing else, which, in turn, deleteriously impacts methylation status (during its synthesisation by the liver and kidneys, creatine draws heavily from the SAM reserves). Supplementing creatine will enhance methylation status, as it will lessen the drain on the liver and kidneys, and alleviate the body's need to synthesize creatine from amino acids.

 

 

Sounds so
B-vitamins.jpg
What brought me to this thread was the curiosity of knowing if adenosine supplementation would help depression (considering its involvement in MDD symptom improvement after sleep deprivation). 

This paper (attached) sheds some light on the attempts of doing so in mice: 
 

"In contrast, infusion of adenosine, an ATP hydrolysis product, worsened the depressive-like behavior of Itpr2−/− mice. The infusion of ATP-γ-S or adenosine had no effect on locomotor activity (Supplementary Fig. 13), indicating that it was ATP, not adenosine, that rescued depressive-like behaviors in Itpr2−/− mice."

The involved formulas in Creatine function and Muscle Metabolism and Fatigue are: 
ATP --> ADP + P + ENERGY
ADP + PCr --> ATP + Cr   (creatine kinase formula)
Sources: 
https://www.youtube....h?v=szV_RMoN8QU
http://www.edb.utexa...s & Fiction.PDF

So, in the paper above, the ATP administration (not adenosine) had fast antidepressant effect. And according to the creatine kinase formula, Phosphocreatine would have a similar (albeit more indirect effect). 
Whether this can be achieved through the commonly available creatine monohydrate (not in Phosphocreatine form), is beyond me, but seems to make some sense, regardless of gender.
 

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#12 medievil

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Posted 04 March 2016 - 07:10 PM

Dipyridamole is a adenosine reuptake inhibitor, those pathways warrent their own thread, you go ahead with your post as a start or ill make one once ive done more research.



#13 Junk Master

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Posted 04 March 2016 - 08:45 PM

For what it's worth, I've taken numerous ssri's and pounds of Creatine together and never "felt" much of a synergistic effect.



#14 medievil

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Posted 04 March 2016 - 09:11 PM

Its said that creatine increaes methyliation while excessive methylation is implicated in alot of disorders such as shizophrenia and bipolar, that you didnt notice much makes sense with the succes rate of most antidepressants and treatment resistance which is extremely commom, i often see ignorant ppl recommending to switch antidepressants like remission is easily achieved, if only that was true.



#15 jaiho

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Posted 06 March 2016 - 04:02 AM

Huh, interesting. When i do my workouts on my sri+tca combo, i also take creatine before.

I get some awesome post workout highs, great endorphin rush, feel on top of the world.

 

With no meds, i actually crash hard after workouts and feel miserable. 



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#16 Junk Master

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Posted 06 March 2016 - 05:07 AM

I find there's no need to take creatine mono with anything but water and no necessity for a "loading phase."  As long as you take it on a daily basis and you are using a decent brand.  BTW it's one of my favorite supplements after more than 20 years of trying various supplements.  It works and with minimal sides.  Just don't expect too much from it.

 

Good find!







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