# Chromium picolinate for atypical depression



## lepton7 (Sep 17, 2014)

*Background* (you can skip this section if you just want the science)

I've had intense rejection sensitivity / social anxiety for most of my life, and within the past year have acquired depression. In January, I went on Prozac, but abandoned it after a month (for reasons unrelated to the Prozac).

Eight months later, my depression and social anxiety have peaked to levels where I seriously dread the idea of feeling like this for another 60 years, give or take a few. So I began researching my symptoms online. Nothing really seemed to fit that well (major depressive order didn't quite match), until I stumbled across the concept of atypical depression. This disorder is commonly described as having five characteristics: interpersonal rejection sensitivity, hypersomnia (fatigue/oversleeping), mood reactivity (the ability to feel happy in response to a positive event), leaden paralysis, and increased appetite / weight gain. I have the first three symptoms, with rejection sensitivity being by far the strongest. Interestingly, there are a few studies nowadays indicating that the last three characteristics of the disorder were somewhat hastily thrown in its diagnostic description and should be removed. The studies also indicate that rejection sensitivity may be the strongest differentiator of atypical depression from major depressive disorder. (In fact the DSM V completely recategorized all these descriptors anyway.) But I'll save that info for another forum post.

Anyway, of course I stumbled on all the MAOI research and managed to get a prescription from my psychiatrist (I had about 12 scientific studies printed and waiting in my backpack in the event that he didn't want to prescribe it, but he agreed to give it a try surprisingly quickly ).

So I currently just began taking phenelzine/Nardil. _However_, my scientific literature search also turned up something interesting in the process: that chromium picolinate also works effectively for treating atypical depression. Since I already got the prescription for phenelzine and since there's so much user testimony behind it, I'm going to try it first, but I thought the information on chromium picolinate would be valuable to this community for those where MAOIs did not work for their illness or the side effects were too unbearable.

*Effect of chromium picolinate on atypical depression*

The study of the effects of chromium on depression began in 1999 and 2000 with the McLeod group [1, 2]. These are case studies, but they focus on major depressive disorder, dysthymia, and bipolar disorder rather than atypical depression. They are quite interesting though in how dramatically the chromium picolinate affected the patients in a single-blind trial compared to placebos. I'd highly recommend giving the two studies a read (they're short).

The science gets interesting with [3]. In this study, the authors took 15 patients with atypical depression and gave 10 chromium picolinate (CP) and 5 a placebo. Subjects quickly ramped up to 600 µg daily of CP for 8 weeks. 70% of CP patients and 0% of placebo patients met responder criteria (p = 0.02) at the end of the study. (It's notable that the 70% responder rate is similar to the responder rate of MAOIs like phenelzine.)

Various assessment tools were used to assess improvement, including the HAM-D and CGI-I scale.

HAM-D scores for CP went from 30.9 to 12.7 over 8 weeks, while the scores went from 29.8 to 19.0 for placebo. It's important to note that HAM-D is more reflective of generalized depressive symptoms rather than those of atypical depression.

However, of those given CP, the responders differed dramatically from the nonresponders with final HAM-D scores of 2, 3, 3, 3, 4, 7, and 11 compared to 23, 31, and 38 (initial scores of 25, 35, 27, 34, 23, 25, 36 and 42, 31, and 31). So it seems there is a pretty huge improvement or none at all. My guess is that the responders have a somehow different type of depression than the nonresponders. (For comparison, the placebo scores went 24 → 9, 33 → 30, 22 → 26, and 32 → 20).

The SCL-90 assessment is more interesting, because it breaks down the improvements into different categories. The most notable categories that CP affected were:

Interpersonal sensitivity - "This dimension focuses on feelings of personal inadequacy and inferiority in comparisons with others. Self-deprecation, uneasiness, and discomfort during interpersonal interactions are included here." [5]

p-value 0.07, effect size 1.21

Paranoia - "Paranoid ideation is represented here as a disordered mode of thinking. Projective thinking, hostility, suspiciousness, grandiosity, centrality, fear of loss of autonomy, and delusions are viewed as primary reflections of this disorder." [5]

p-value 0.08, effect size 1.21

Hostility - "Thoughts, feelings, or actions characteristic of the negative affect state of anger are reflected here. Qualities such as aggression, irritability, rage, and resentment are included." [5]

p-value 0.08, effect size 0.90

Depression - "Symptoms of dysphoric mood and affect as well as signs of withdrawal of life interest, lack of motivation, and loss of vital energy are represented. Feelings of hopelessness, thoughts of suicide, and cognitive and somatic correlates of depression are included." [5]

p-value 0.22, effect size 0.84

Anxiety - "This dimension is composed of symptoms that are associated with manifest anxiety. Nervousness, tension, and trembling as well as feelings of terror and panic are included." [5]

p-value 0.08, effect size 0.84

Psychoticism - "The scale provides a continuum from mild interpersonal alienation to dramatic evidence of psychosis. Items include withdrawal, isolation, and schizoid lifestyle as well as first-rank schizophrenia symptoms such as hallucinations and thought-broadcasting." [5]

p-value 0.08, effect size 0.76

Categories with small effect sizes were somatization, obsessive compulsive, and phobic anxiety. Effect sizes are roughly categorized as small (0.2), medium (0.5), and large (0.8).

What is the mechanism of action of chromium picolinate? The study's comments on this are out of my area of expertise, but the authors hypothesize that chromium increases insulin sensitivity, perhaps by increasing the number of insulin receptors, and this in turn brings about enhanced central noradrenergic and serotonergic activity. Also postsynaptic 5HT2A receptor downregulation by chromium has been found in humans, an effect that could be of relevance to insulin sensitivity and depression.

Studies [1, 2, 3] all indicate that response to CP is very rapid, with a strong effect seen in 2-4 days, along with a strong and swift 2-4 day return of symptoms upon discontinuation of CP. This is a significantly different timeframe than antidepressants like SSRIs and MAOIs, which often work on a scale of weeks or months.

Study [4] basically repeated the protocol of [3] with 110 patients, with an emphasis on what happened to the subset of patients with intense carb cravings. The CP treated patients showed significant improvement on 4 HAM-D-29 items: appetite increase, increased eating, carbohydrate craving, and diurnal variation of feelings. The subset with high carb cravings (and high BMI = 31.1) showed significantly greater response on total HAM-D-29 scores than the placebo group (65% vs 33%, p < 0.05).

Side effects include of chromium picolinate include:

Intense, unusually vivid dreams within the first few days of taking the supplement
Initial insomnia
Disappearance of food cravings, particularly carbs (also reported in other studies as a possible weight loss method)
Mild psychomotor activation ('caffeine-like effect')

In my opinion, CP is a very effective alternative to some of the antidepressants used to treat atypical depression (and as evidenced by [1, 2], major depressive disorder, dysthymia, and bipolar disorder to some unknown degree as well). It would be very interesting to see a head-to-head comparison study of phenelzine, fluoxetine, chromium picolinate, and a placebo, because CP definitely has far less side effects than the other substances.

Also, it seems that CP could be easily combined with a MAOI like Nardil for an enhanced effect. MAOIs seem to increase carb carvings, while CP reduces them, so I hypothesize that the two could cancel out. I'm not yet willing to combine the two myself because I want to see the isolated effect of phenelzine first. Only if the phenelzine fails me will I add CP, and if that doesn't work, then ultimately I'll try CP alone.

Oh yeah, I forgot to mention - chromium picolinate *doesn't require a prescription*.  You can pick it up in any vitamin store.


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## lepton7 (Sep 17, 2014)

*References*

As a researcher myself, I feel kind of bad for listing the impact factors of the journals since that doesn't necessarily correspond with "good" science; however, it does allow one to rule out quack journals / pay-to-publish.

I have included the main studies centering on chromium picolinate's role in improving atypical depression. There aren't many of them; these are actually the only four I could find on the subject that aren't review articles. For the last two studies listed you will need university access or a subscription to read more than the abstract.

[1] Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in 5 patients
Journal of Clinical Psychiatry 60, 237-240 (Impact factor: 5.812, 12/40)
McLeod, M.N., Gaynes, B.N., Golden, R.N., 1999

[2] Chromium treatment of depression
International Journal of Neuropsychopharmacology 3, 311-314 (Impact factor: 5.641 13/40)
McLeod, M.N., Golden, R.N., 2000

[3] Effectiveness of chromium in atypical depression: a placebo-controlled trial
Biological Psychiatry 53, 3, 261-264 (Impact factor: 9.247, 4/40)
Davidson, J., Abraham, K., Connor, K.M., McLeod, M.N., 2003

[4] A double-blind, placebo-controlled, exploratory trial of chromium picolinate in atypical depression:
effect on carbohydrate craving
Journal of Psychiatric Practice 11, 5, 302-314(Impact factor: 1.349, not ranked)
Docherty, J.P., Sack, D.A., Roffman, M., Finch, M., Komorowski, J.R., 2005

[5]
Assessment of psychiatric symptoms using the SCL-90
Academic dissertation, University of Helsinki
Matti Holi, 2003


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## Caedmon (Dec 14, 2003)

LOVE YOUR POST!

My impression was that this piece is the central mechanism:

_"chromium increases insulin sensitivity, perhaps by increasing the number of insulin receptors, and this in turn brings about enhanced central noradrenergic and serotonergic activity"_

I noticed that the Docherty et al 2005 study found differences related to food and energy from chromium intake in peeps with a BMI ~30. So that is potentially pre-diabetes level anyway. It sounds to me like the chromium is basically treating the insulin issue, which contributed to mood dysfunction.

Perhaps medical management would be helpful i.e. get insulin testing done?

I'd like someone smarter than me to take a look at the mechanisms that Nardil uses to cause weight gain and see if chromium can affect that. *Can you take chromium to offset insulin dysfunction from Nardil and enhance the antidepressant effect? *This would be hugely cool, if it did.


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## watertouch (Nov 4, 2013)

Having tried Krom (as we call it here) specially made after the Dr,s orders. (wasn't cover by the healtinsurence)
It did not have a possetive effect on either hunger or bloodsuger or cravings...:no
One should probably use it anyway... Methabolic syndrom or Diabietes would really ruin my mood...


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## llodell88 (May 15, 2011)

Thanks, I don't know if I have atypical depression but because there is a lot of overlap between Atypical Depression and SA, I think anything that what works good for one is worth a try for treating the other. I think of depression as more of a transitory thing and sa as something i'm stuck w/ so the SA label makes more sense to/for me. I was actually looking specifically for supplements that treat atypical depression (to treat SA) a few days ago lol. Also I found 200 caps for $2.50 so I don't think price should deter anyone from trying this.


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## Caedmon (Dec 14, 2003)

Been taking 200 mcg with breakfast, lunch, and dinner (600 total) what can I say, I like this stuff. Not a panacea, but energy levels are distinctly more even keeled. A keeper!


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## hworth (Mar 31, 2013)

This sounds promising! I'll have to pick some up today while I'm running errands


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## lepton7 (Sep 17, 2014)

Caedmon said:


> Been taking 200 mcg with breakfast, lunch, and dinner (600 total) what can I say, I like this stuff. Not a panacea, but energy levels are distinctly more even keeled. A keeper!


Awesome! Have you noticed any improvement in interpersonal sensitivity (rejection sensitivity)? This seems to be the aspect that chromium picolinate has the biggest effect on.


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## Caedmon (Dec 14, 2003)

Maybe... Most of my shutdowns or difficulties involve feeling overwhelmed by work and daily life. Those have improved. As to interpersonal sensitivities, hard to tease that apart from some recent life event problems and (un)fortunately now starting Topamax which introduces another factor. The Topamax is soothing, dang it.


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## Weston (Sep 23, 2006)

I was prescribed Nardil by Quitkin who I believe authored the original study on atypical depression. I don't have all the symptoms though. This was many years ago. Maoi's have been very effective for me regardless


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## lepton7 (Sep 17, 2014)

Hey Caedmon, just wondering, are you still taking the chromium picolinate? Any thoughts on it?


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## Caedmon (Dec 14, 2003)

Over time I found it was actually increasing my anxiety somewhat, so I stopped taking it. I think it may have lowered blood sugar too much. It didn't have that effect at first but it built up over time. Weird.


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## butterz (Aug 8, 2013)

Is CP safe? I remember reading that there is a kind of chrome which
can damage the DNA.


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## sadness (May 9, 2006)

I picked some of this up today. Going to see if it helps w/ Nardil.


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## sadness (May 9, 2006)

sadness said:


> I picked some of this up today. Going to see if it helps w/ Nardil.


I haven't noticed any difference. I suppose its hard to measure given the variables of every day life. Plus I don't know if its the Nardil working or what.

I am concerned on the post that says it was increasing his anxiety...


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