A little red meat may help your depression

If you have depression, you are not depressed because there is a deficiency of antidepressants in your body...

...however...

...you may be depressed because you have some basic nutritional deficiencies. One mineral that is involved in numerous brain and nervous system functions, and that has been extensively studied with regards to its role in the development of depression, is zinc.

Various doses of zinc were recently shown to improve immobility time in rats. Immobility in a stressful situation is a common behavior in depression. (When you are not depressed, you have better decision making and response times when it comes to managing stressful situations.)

That's exactly what fluoxetine (Prozac), paroxetine (Paxil), imipramine (Tofranil), desipramine (Norpramin), and bupropion (Wellbutrin) do!

When zinc and antidepressants were administered together, immobility time was reduced by more than either therapy produced on its own.

Practically what that says is that:
(1) if you are at risk for, or have had a history of depression, emphasizing high-zinc dietary choices and/or zinc supplementation would be a smart strategy, and
(2) if you are on an antidepressant, supplementing with zinc would be important to be sure that you get enough medication to do the job without getting so much that you set yourself up for detrimental side effects.

In fact, it seems to me that it should be an automatic recommendation of any physician, when prescribing an antidepressant, to write "zinc supplement" in the script as well...

FYI, your best sources of zinc include: red meats, liver, and oyster. And, when the originating soil is in good condtion...wheat, sweet corn, lettuce, beans, nuts, almonds, whole grains, pumpkin seeds, sunflower seeds and blackcurrant. That's a lot of different options, something for practically everyone, meat eater or not!

Cunha MP, Machado DG, Bettio LE, Capra JC, Rodrigues AL. Interaction of zinc with antidepressants in the tail suspension test. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Dec 12;32(8):1913-20. Epub 2008 Sep 11.

And I thought I was happy after eating at Delhi Palace because the food was so good!

Turmeric is a spice commonly used in Indian cooking that is gaining attention for its health properties. Curcumin, the ingredient in turmeric that provides its yellow color, is thought to be a very powerful antioxidant and anticancer agent.

In Alzheimer's patients, not only can it prevent the accumulation of destructive beta-amyloid proteins, but it is thought to even break up already existing plaques (when I saw this, it made me wonder if this is why the oldest man in the world always seems to be living in some small Indian village.)

Now it's looking like curcumin may also have antidepressant properties. When tested on rats, it had activities mimicking that found in three different categories of antidepressants--monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, and dopamine reuptake inhibitors. Specific medications it was compared to included fluoxetine (Prozac), venlafaxine (Effexor), and bupropion (Wellbutrin).

When rats were already on medication, curcumin seemed to enhance the activity of the medication. Which has me thinking that psychiatrists should be handing out coupons to the closest Indian restaurant along with their medication scripts.

It appears that curcumin absorption is better in the presence of piperidine, a component of black pepper. Curry powder, readily available in most grocery stores, is a combination of coriander, cumin, black pepper, white pepper, turmeric and chillies). Not a bad item to keep stocked in your mental health cooking arsenal.

If you like to cook, Indian food is fun and easy. To get you started, here's a link to some curry recipes. Be sure you cook with olive or canola oil to get the best brain bang for your buck.

Kulkarni SK, Bhutani MK, Bishnoi M. Antidepressant activity of curcumin: involvement of serotonin and dopamine system. Psychopharmacology (Berl). 2008 Dec;201(3):435-42. Epub 2008 Sep 3.

Yang, F; Lim GP; Begum AN; Ubeda OJ; Simmons MR; Ambegaokar SS; Chen PP; Kayed R; Glabe CG; Frautschy SA; Cole GM (February 2005). Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. Journal of Biological Chemistry (American Society for Biochemistry and Molecular Biology) 280 (7): 5892–901.

Pregnant women and psychotropic medications really don't mix

What I hate about this study is that we even have to study whether or not a pregnant woman should be given psychotropic medications during pregnancy. It disturbs me that this many studies surrounding this question are showing up in Pub Med. My common sense would tell me absolutely not, without even having to do the research. However, I guess there are some situations where it is more dangerous to have a pregnant woman's psychopathology left completely untreated for an entire 9 months. So, despite my personal feelings, I'll share the findings.

Pregnant mice were given fluoxetine (Prozac) throughout their pregnancy and kept on the medication until their pups were weaned. The pups were then given other medications and their responses to those medications were evaluated. The effects seemed to be more significant in the female offspring, who did not seem to have normal responses related to dopamine function. (Dopamine is important for impulse control, which influences potential for chemical dependencies and troubles such as addictions, gambling, shoplifting, and carbohydrate bingeing). The researchers also suggested that if this relationship existed in humans, daughters of women who took Prozac during pregnancy may not effectively respond to certain medications later in life. Two important classes of medications this might include are Parkinson's medications and antipsychotics, both of which attempt to correct problems in dopamine systems.

So, MY take on this is that given the fact that fish oil is such a powerful antidepressant and it is important to have enough of it during pregnancy for both mother and baby, perhaps we're learning that we should lean more in that direction on behalf of the two individuals involved in a pregnancy.

My CONCERN is that a drug company R and D person is likely to read the very same study and think, "Hmmm...if we get started right now, we can have a new drug ready for all those babies coming down the pike whose dopamine systems aren't responding to anything we can currently script."

We'll see which direction this information takes science. I sure hope it's the one involving fewer trips to the pharmacy in 20 years.

Favaro PN, Costa LC, Moreira EG. Maternal fluoxetine treatment decreases behavioral response to dopaminergic drugs in female pups. Neurotoxicol Teratol. 2008 Nov-Dec;30(6):487-94. Epub 2008 May 14.

Folic acid and brain health--don't forget it!

As my last post discussed, depression is not just about mood. It's about the integrity of neurons and the systems that support them. One very strong connection that research is increasingly supporting, is the link between depression and inflammation. Inflammatory markers commonly used to identify heart disease, such as homocysteine, are being correlated as well with depression.

Here, 27 subjects were divided into two groups. One group was given fluoxetine (Prozac) and folic acid, while the other was given fluoxetine and placebo. (Folic acid was given because it has been shown to help prevent elevated homocysteine.) Another 15 subjects were given nothing at all, for a basis of comparison.

As happens in cardiovascular studies using folate as an intervention, plasma homocysteine levels dropped with folate supplementation. The interesting finding, however, was that when subjects took the Hamilton Depression Rating Score, those who had received the folate showed greater improvement than those who only received the fluoxetine. There was no significant difference in serotonin levels, so the researchers concluded that folate was not affecting the mechanism by which fluoxetine works.

So the bottom line seems to be...you can't just fix depression with a pill. How you take care of yourself (i.e., how you choose to eat) can be a crucial factor in whether or not your brain works at its absolute best.

If you want to add more folate to your diet, here are your best food choices: fortified breakfast cereal, whole wheat products, meat, beans, liver, eggs, sunflower seeds, asparagus, leafy green vegetables, oranges, strawberries, melons.

Resler G, Lavie R, Campos J, Mata S, Urbina M, García A, Apitz R, Lima L. Effect of folic acid combined with fluoxetine in patients with major depression on plasma homocysteine and vitamin B12, and serotonin levels in lymphocytes. Neuroimmunomodulation. 2008;15(3):145-52. Epub 2008 Aug 21.

Aging brains and medicine

How medications work at different points in life can be a very important consideration. I see many, many studies looking at the viability of antidepressant therapy in the elderly. Recently there seems to be a flurry of research looking at how to medicate (note I did not use the word "treat") depression when it occurs as a comorbidity with diagnoses such as stroke or Alzheimer's disease.

In this study, the naturalistic finding was that as rats (and probably humans, too) age, the rate at which they are able to generate new neurons declines. The survival rate of those new cells starts to deteriorate as well.

The good news is that the response to fluoxetine (Prozac) was the same across the board.

The bad news is, that in none of the groups, even the young rats who had a better ability to make new neurons, did fluoxetine enhance that ability.

Hmmm...is it just me, or does it make sense that if a medication is going to work, it needs some brain cells to work on?

Cowen DS, Takase LF, Fornal CA, Jacobs BL. Age-dependent decline in hippocampal neurogenesis is not altered by chronic treatment with fluoxetine. Brain Res. 2008 Sep 4;1228:14-9. Epub 2008 Jun 24.

This study gives new meaning to the term, "mama's boy"...

Several years ago I was diagnosed with uterine fibroids. For all of my medical knowledge and connections, I was very distressed to learn that the treatments for this very common gynecological condition seemed to be very crude and invasive. There really wasn't much research into gentle, natural, or nutritional solutions. Every physician I spoke to just wanted to give me a hysterectomy, despite my young age. Some couldn't figure out why I wouldn't consent, given the fact I was not going to have children and my uterus was, therefore, essentially useless and unnecessary.

When I shared my situation with another female friend, she immediately said, "Well, if it was men who got fibroids on THEIR reproductive organs, you can guarantee there would be a gazillion dollars devoted to researching any possible way to treat them without removing the affected body part!"

Ever since, when I see some kind of gender inequity in medicine, I think of that conversation and remind myself that, unfortunately, sometimes men have to hurt in a unique and most unexpected place in order for them to think more creatively about how they treat women, personally and clinically.

This study is about depression and not fibroids, but it makes my point. Something I find very frustrating with my work in polycystic ovary syndrome is the reluctance on the part of some endocrinologists who treat the disorder to acknowledge the extreme anxiety, depression, and mood swings this disorder promotes. Even though 85% of the over 1,000 women who answered a survey on my website reported at least one of these problems, there are physicians who will flat out say depression is not part of the disorder. Or, rather than trying to understand what may be driving the depression, they simply write a script for an antidepressant.

Well...here's what might happen if you treat depression so superficially. Female rats were treated, throughout pregnancy and lactation, with fluoxetine (Prozac). Later on, the sexual behavior of their male offspring was observed. They appeared to have less incentive to participate in sexual activity. This lack of libido wasn't coming from any measurable, explainable change in hormones, these guys just didn't seem to want any.

With all due respect, knowing that fish oil/omega-3 fatty acids are a great option for depression as well as promoting libido, this kind of problem simply shouldn't be something we have to encounter or research. Except to identify and define precisely why we shouldn't be encountering or researching it.

Oh! And if you're male and you're feeling a little uncomfortable while reading this, you've just experienced what every woman in history has felt when she was told she had to have a hysterectomy that may have been unnecessary. Welcome to the world of medicine without compassion.

Gouvêa TS, Morimoto HK, de Faria MJ, Moreira EG, Gerardin DC. Maternal exposure to the antidepressant fluoxetine impairs sexual motivation in adult male mice. Pharmacol Biochem Behav. 2008 Sep;90(3):416-9. Epub 2008 Apr 4.

Modulation of serotonin transporter function during fetal development causes dilated heart cardiomyopathy and lifelong behavioral abnormalities.

While I've drifted into the topic of antidepressants, I thought I'd share this piece on using them when pregnant. Two different antidepressants, fluoxetine (Prozac) and fluvoxamine (Luvox) were given to pregnant mice. Luvox reportedly did not as easily cross the placenta as Prozac. (This means that Luvox was not as available to the developing baby as Prozac was.)

Most of the rats' babies that were prenatally exposed to Prozac died after birth of a type heart failure known as dilated cardiomyopathy. This is a condition in which the heart becomes enlarged and too weak to pump enough blood to the rest of the body. These rats also showed alterations in serotonin receptor levels in the raphe nucleus, the part of the brain that is in charge of serotonin release. There was also an increased incidence of behaviors in these mice indicating anxiety and depression.

If you are female and you are choosing to treat your depression with an antidepressant, and you are at an age where you can conceive, you may wish to discuss this study with your prescribing caregiver. Your medication decisions are affecting two people, both deserving of consideration.

Noorlander CW, Ververs FF, Nikkels PG, van Echteld CJ, Visser GH, Smidt MP. Modulation of serotonin transporter function during fetal development causes dilated heart cardiomyopathy and lifelong behavioral abnormalities. PLoS ONE. 2008 Jul 23;3(7):e2782.

Now if I could just remember where I found this article...

If I were to be able to tally the time I've spent over a lifetime looking for lost things...especially my keys...there would probably be enough time there to pursue my Ph. D in neuroscience. And I'd likely find myself in a program conducting studies like this one, which looked at how stress affects the memory center (and why mine doesn't seem to ever register "last key location" in any functional part of my neurons).

Most researchers in the area of depression agree that a characteristic biological marker of depression is an elevated level of cortisol, a stress hormone. The researchers in this study decided to see just what cortisol does to the hippocampus, the brain's memory center, both short- and long-term.

Chronic exposure to cortisol decreased the ability of the hippocampus to regenerate neurons, and the volume of existing neurons decreased. These changes could be prevented with the administration of two different antidepressants, imipramine (Tofranil), and fluoxetine (Prozac).

Short-term exposure to stress brought out "depressed" behaviors in the rats. Long-term exposure seemed to create more of an anxious presentation.

The researchers concluded that the physically damaging effects of stress could be prevented with antidepressants.

I conclude that the next time I lose my keys, if I can remember to do so, I'm going to use that as an indicator that I may be trying to do too many things in too short a time. And that I need to do something to reduce my stress level. I really don't think I need to be taking an antidepressant to prevent memory loss!

Murray F, Smith DW, Hutson PH. Chronic low dose corticosterone exposure decreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice. Eur J Pharmacol. 2008 Mar 31;583(1):115-27.

There's something fishy about depression treatment...

Here's the study I've been looking for. There are plenty of studies showing the effectiveness of antidepressant medications. And there are plenty of studies showing the effectiveness of fish oil in treating depression. But no one had compared the two. Until now.

In Iran, researchers compared the separate relative effectiveness of eicosapentaenoic acid (EPA), one of the chemicals commonly referred to as fish oil, and fluoxetine (Prozac). What they found was that EPA was equally as effective as fluoxetine, in an 8 week trial, in reducing symptoms of depression. The most superior outcome was found in subjects who received both EPA and fluoxetine.

If you're wanting to try this at home, as always, discuss this with your physician. The risk of using fish oil in conjunction with antidepressants is almost always outweighed by the potential benefits--however, it is not advised that you discontinue any prescription medications you are on without consulting with the prescribing party.

A word about EPA. There is a lot of confusion about what it means to use fish oil. Most products available in the grocery store that are labeled as containing "omega-3 fatty acids" actually contain ALA, a great omega-3 but not the one that has been associated with improved mental health. If you're using omega-3 eggs, or vegan (marine algae-based) omega-3's, you're getting DHA, not EPA. That primarily comes from fish. Even though you will read that there are conversions to EPA from both ALA and DHA, the efficiency of these conversions is great and likely not enough to achieve results such as were seen in this study.

If your diet is high in pro-inflammatory oils (those "S" and "C" oils you see me routinely discuss in this blog), it will be harder to get effects described in this study. You're going to need to tweak your diet in order to get the most bang for your buck. And, realistically, that means you're going to have to get rid of most processed foods and salad dressings.

But, for those individuals motivated to make these changes, the results can be profound. I see it routinely in my private counseling. It is certainly my first recommended item of action when someone is trying to reduce the number of medications they are on.

Finally, for physicians who prescribe antidepressants, this study suggests that if you do so without strong nutritional guidance as well, you're not as helpful to your patients as you have the potential to be. It's not just about pills. Your patients did not become depressed because they were antidepressant-deficient!

Jazayeri S, Tehrani-Doost M, Keshavarz SA, Hosseini M, Djazayery A, Amini H, Jalali M, Peet M. Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder. Aust N Z J Psychiatry. 2008 Mar;42(3):192-8.

Folic acid, depression, and Prozac

Folic acid is clearly essential for brain and nervous system health.

When animals are depressed, they have a delayed response to stressful situations. Researchers in this study reported that rats given folic acid who were then forced to swim (a standard test for depression in lab rats, believe it or not!) started swimming sooner than rats who did not receive the supplement.

Folic acid also seemed to promote a synergistic effect with fluoxetine (Prozac), meaning in the presence of folic acid, Prozac was more effective. What this finding has the potential to translate into...is that if you DO need an antidepressant, eating well (or at least taking a multivitamin at the same time)may reduce the dose of the medication you actually need, which in turn reduces the potential for side effects. And side effects are a major reason why people do not maintain compliance with their psychotropic medications.

This seems like it's too simple to be true. But the reality is, when you're depressed, you may not feel like making the effort to eat well. Or, you grab something quick and easy (and likely low in essential vitamins/minerals and high in the wrong kind of fats), which only worsens the depression. If you have time to do only one thing a day that is just for YOU...make it eating well.

Whether it's a Flintstones or a One A Day, consider a multi as an essential part of your mental health bag of tricks!

Brocardo PS, Budni J, Kaster MP, Santos AR, Rodrigues AL. Folic acid administration produces an antidepressant-like effect in mice: Evidence for the involvement of the serotonergic and noradrenergic systems. Neuropharmacology. 2008 Feb;54(2):464-73. Epub 2007 Nov 5.

Your antidepressants and your baby's future drug habit

Whether it's food or drugs, the compounds in your body while your baby is developing can have a significant impact on your child. In this study, it is reported that (in rats) the offspring of mothers who were exposed to fluoxetine (Prozac) had fewer neurons in their nucleus accumbens, as well as less serotonin activity in their raphe nucleus. The nucleus accumbens is a brain region thought to be important in, among other things, reward, addiction, and pleasure. The raphe nucleus, a part of the brain stem, is responsible for releasing serotonin to other parts of the brain. With fewer neurons to tell the brain it's pleased, and less serotonin to help regulate mood, scientists wondered about the practical implications of these findings.

So....they put the offspring in a situation where they had free access to cocaine. Using a maze, they conditioned rats to associate a specific location of that maze with cocaine. Actually, the rats exposed to their mother's Prozac were a lot less active in the maze than rats who didn't have this exposure. However, those rats who did use the maze showed a preference for the location that had been associated with cocaine. When the cocaine was gradually removed from the protocol, Prozac-exposed rats took 350% longer to stop looking for the cocaine.

I don't need to add a comment, this study speaks for itself.

Forcelli PA, Heinrichs SC. Teratogenic effects of maternal antidepressant exposure on neural substrates of drug-seeking behavior in offspring. Addict Biol. 2008 Mar;13(1):52-62. Epub 2007 Sep 11.

Caffeine and antidepressant medications

Over the short term (one day on meds), imipramine (Tofranil)and amitriptyline (Elavil) decreased, while fluoxetine (Prozac) accelerated the overall metabolism of caffeine. Nefazodone(Serzone) also stimulated metabolism, but through a more indirect pathway. To say it another way, the body more rapidly broke down and inactivated caffeine under the influence of these medications.

Fluoxetine given chronically increased an indirect pathway of caffeine metabolism. Sertraline (Zoloft) and mirtazapine (Remeron) enhanced the rates of all caffeine oxidation pathways.

I must qualify this study was done on rats, not humans, and I can't remember the last time I saw a rat in line chumming it up with the barista. Even so, it's not unreasonable to assume the same effects could be seen in humans.

So...if you're feeling like your Prozac may have reduced the effect of your double caf skinny no foam morning treat into a half caf regular cup of joe...it may not be your imagination!

Don't let that drug influence tempt you into buying a frequent flyer card at your local coffee haunt, though. Excess caffeine is associated with insulin resistance which can aggravate weight gain. Better to focus on better sleep habits (and less late night web sudoku)than on better productivity through chemical stimulation.

Kot M, Wójcikowski J, Daniel WA. Caffeine metabolism during prolonged treatment of rats with antidepressant drugs. Pharmacol Rep. 2007 Nov-Dec;59(6):727-33.

Antidepressants and risk of bone fracture

Are broken bones the price paid for a better attitude? Some researchers may think so. In a rather large study (124,655 fracture cases and 373,962 age and gender matched controls), relationships between fractures were seen with the following psychiatric medications:

Amitriptyline (Elavil), clomipramine (Anafranil), citalopram (Celexa), fluoxetine (Prozac), and sertraline (Zoloft) were all associated with an increased risk of fractures. Imipramine (Tofranil) and nortriptyline (Pamelor) did not demonstrate this association. Paroxetine (Paxil) showed a slight relationship but statistically it was insignificant.

No medication is perfect, ever. However, antidepressants are used for a wide variety of medical problems, and as you know if you read my blog, many of these uses are off-label. For anyone with a family history of osteoporosis, or in a demographic group at risk for osteoporosis, it is important to (1) weight the risks vs. benefits of your prescribed medication before taking it, and(2) consider consulting with a dietitian to enhance your diet and lifestyle choices to minimize the risk of bone-debilitating side effects.

Many of the lifestyle choices you are likely to be advised to adopt to prevent osteoporosis (more exercise, less soda, wider variety of foods) also enhance brain health. And what do you know--that may reduce your depressive symptoms as well.

(If you're getting tired of hearing that exercise, healthy food, adequate sleep, and less stress might be your answer...maybe that means you should try them...tee hee!!)

Vestergaard P, Rejnmark L, Mosekilde L. Selective Serotonin Reuptake Inhibitors and Other Antidepressants and Risk of Fracture. Calcif Tissue Int. 2008 Jan 25 [Epub ahead of print]