Is your chia pet a hidden nutritional surprise?

Risperidone (Risperdal) is a common antipsychotic medication that was recently investigated for its influence on omega-3 fatty acid metabolism.

Rats were placed on two different diets, one containing alpha-linolenic acid (ALA) and one that was ALA-deficient. Then both groups were administered a dose of risperidone.

This research design was used because ALA can be converted to docosahexaenoic acid (DHA), and the purpose of the study was to evaluate the influence of risperidone on this conversion.

In rats not fed ALA, there was a significant increase in tissue DHA in the presence of risperidone, suggesting that this medication helps to increase the conversion of ALA to DHA. When there was ALA in the diet, this was not observed, suggesting that when there is enough ALA available, there is no need for any augmentation of pre-existing mechanisms.

Some questions and comments:

1. This will be an interesting line of research to follow...to determine whether schizophrenia is related to nutritional imbalances and/or deficiencies, whether there might be different types of schizophrenia, some nutritionally instigated and aggravated, others not.

2. Seems that a dietary strategy of increased ALA isn't a bad idea if you struggle with schizophrenia.

3. At this point, it is NOT rational to assume that increasing dietary ALA will eliminate the need for antipsychotic medications.

4. At the same time, it doesn't make sense to use a prescription medication to correct a nutritionally-relevant problem.

If you balance the diet and focus on adequate ALA, the amount of medication you might actually need might decrease, therefore reducing the risk of metabolic side effects.

For those who are interested, foods that are good sources of ALA include: canola oil, whole soybeans, walnuts, salva (chia), ground flaxseeds, and flaxseed oil.

McNamara RK, Able JA, Jandacek R, Rider T, Tso P. Chronic risperidone treatment preferentially increases rat erythrocyte and prefrontal cortex omega-3 fatty acid composition: Evidence for augmented biosynthesis. Schizophr Res. 2009 Feb;107(2-3):150-7. Epub 2008 Nov 7.

When you play with antipsychotics, you play with fire.

Antipsychotic medications have worked wonders to enhance the lives of many people. However, in recent years, antipsychotics have also been used for an increasing number of off-label uses and in progressively younger populations than they ever were before. Before handing these medications out like they are candy, it's important to evaluate the risks associated with using these medications. A recent study suggested that we should be much more careful about choosing our treatment populations than we have been to date.

Before I get to the meat of the study, I'd like to preface this post with an explanation of the study design. The authors of this study are concerned about safety risks in young children and pregnant women when they are given antipsychotic medications. However, they had to develop a research model that did not place young children and pregnant women at risk in the process of looking into this issue. So...rather than give antipsychotics to these two populations, they chose to administer a battery of antipsychotics to a group of roundworms. Roundworms were chosen because they are an accepted research model for investigating matters related to brain and nervous system development. That is definitely a limitation of the study, as most people I know would not say they have much in common with this guy...but that's one of the tough things about studying medications and their risks...how to investigate those risks without causing more damage.

Anyway...when the roundworms were given three of these medications, clozapine (Clozaril), fluphenazine (Prolixin), and haloperidol (Haldol), there was less development of neurons in general and axons (a specific anatomical feature of a neuron) in neurons devoted to mechanosensory function (that's touching and registering what you're touching). Neurons that were produced also tended to not migrate to the location where they would be expected to migrate, meaning there might have been neurons there, but they were, so to speak, all dressed up with no place to go.

In some neurons, axons grew past their functional anatomical size. And some had abnormal anatomical features.

Other antipsychotics produced similar results, although not to as significant a degree. The drugs mentioned included: risperidone (Risperdal), aripiprazole (Abilify), quetiapine (Seroquel), trifluoperazine (Stelazine) and olanzapine (Zyprexa).

I'm not going to pontificate about the ethical dilemma encountered when treating a pregnant woman with schizophrenia. The choices made in those situations involve complex risk/benefit considerations that are the responsibility of the patient and her physician.

However, I will say that responsible use of these medications in women of childbearing age is imperative. Forty-nine percent of all pregnancies ending in childbirth in 1994 were unintended, and 48% of all women aged 15-44 in 1994 had had at least one unintended pregnancy at some point in their life. It happens, and it happens a lot.

So if you're a physician and you're handing out prescriptions for antipsychotics for off-label uses to women of childbearing age...no matter how much judgment, education, evaluation, etc. you think you're providing, you really are playing with fire.




Donohoe DR, Weeks K, Aamodt EJ, Dwyer DS. Antipsychotic drugs alter neuronal development including ALM neuroblast migration and PLM axonal outgrowth in Caenorhabditis elegans. Int J Dev Neurosci. 2008 May-Jun;26(3-4):371-80.

http://www.guttmacher.org/pubs/journals/3002498.html

Keeping your brains right where they belong

A few years ago I was working with a client with polycystic ovary syndrome. In the course of giving her medical history, she'd also disclosed that she had hyperprolactinemia, a condition in which milk production and let down occurs, even in men, and even in women who are not nursing, if their blood levels of prolactin are too high. She told me that she continued to produce and release milk for four years after delivering her last child, and not a single physician she'd asked about it here in Arizona or over in California seemed to think it was a situation worthy of medical intervention. So she lived with it, until it eventually went away.

As we progressed through our consultation, I explained to her why omega-3 fatty acids are so important--as they are an integral part of the brain's structure and functioning. I then explained to her that breast milk is high in omega-3 fatty acids, and that babies who are nursed are more likely to get these crucial fatty acids than babies on formula.

I looked up from my notepad to see my client red-faced. If steam could have come out of her ears, it would have.



Thinking I'd said something hurtful or offensive, I asked her if something was wrong.

She looked at me and asked, "So you mean to tell me...for four whole years...my brains were leaking out of my boobs and no one seemed to think that was a problem?"

I was the professional in that situation and so it fell on me to keep a completely straight face and answer a serious "yes, yes that's true."

Hyperprolactinemia really is a condition that needs to be taken seriously. As my client correctly deduced, it can drain the body of some of its most essential compounds, which can promote inflammation and potentially disrupt healthy brain function. Some psychiatric medications can increase the risk of hyperprolactinemia. One that has this reputation is risperidone (Risperdal).

A group of Chinese researchers recently tested an herbal remedy for hyperprolactinemia, peony-glycyrrhiza decoction, against a more traditional treatment, a medication called bromocryptine. Their subjects were women whose hyperprolactinemia was a direct result of risperidone use. For the purposes of this study, the women were also experiencing irregular periods (oligomenorrhea) or absence of periods (amenorrhea). Each group was exposed to both the herbal and the pharmaceutical treatment, with one group starting on herbs and switching to medication. The second group received the treatments in the reverse order. Psychotic symptoms, negative side effects, and levels of the hormones prolactin, estradiol, testosterone, and progesterone were all measured at the beginning and end of the study.

Not only did the herbal preparation produce a decrease in prolactin similar to the medication, other hormones were not affected, and psychosis was not worsened. And, more often in the herbal than the pharmaceutical remedy, there were improvements in negative side effects of hyperprolactinemia.

Whether or not you are on a medication, if you're producing breast milk and you are not nursing a baby, it is a medical problem and it does need to be addressed.

And now that you've read this post, you won't need to wait four years until a nutritionist mentions in passing that you should insist that your problem be taken seriously.

Yuan HN, Wang CY, Sze CW, Tong Y, Tan QR, Feng XJ, Liu RM, Zhang JZ, Zhang YB, Zhang ZJ. A randomized, crossover comparison of herbal medicine and bromocriptine against risperidone-induced hyperprolactinemia in patients with schizophrenia. J Clin Psychopharmacol. 2008 Jun;28(3):264-370.

Bowden CR, Voina SJ, Woestenborghs R, Do costerR, Heykants J. Stimulation by risperidone of rat prolactin secretion in vivo and in cultured pituitary cells in vitro. J Pharmacol Exp Ther 1992 Aug;262(2): 699-706.

Kinon BJ, Stauffer VL, McGuire HC, Kaiser CJ, Dickson RA, Kennedy JS. The effects of antipsychotic drug treatment on prolactin concentrations in elderly patients. J Am Med Dir Assoc 2003 Jul-Aug; 4(4): 189-94.

Lee BH, Kim YK. The relationship between prolactin response and clinical efficacy of risperidone in acute psychotic inpatients. Prog Neuropsychopharmacol Biol Psychiatry 2006 Jun;30(4):658-62.

Holzer L, Eap CB. Risperidone-induced symptomatic hyperprolactinaemia in adolescents. J Clin Psychopharmacol 2006 Apr;26(2):167-71.

Foley KF, Kast RE. Review of evidence that posttransplantation psychiatric treatment commonly affects prolactin levels and thereby influences graft fate. Gen Hosp Psychiatry 2006 May-Jun;28(3):230-3.

Anderson GM, Scahill L, McCracken JT, McDougle CJ, Aman MG, Tierney E, Arnold LE, Martin A, Katsovich L, Posey DJ, Shah B, Vitiello B. Effects of short- and long-term risperidone treatment on prolactin levels in children with autism. Biol Psychiatry 2007 Feb 15;61(4):545-50.

Staller J. The effect of long-term antipsychotic treatment on prolactin. J Child Adolesc Psychopharmacol 2006 Jun;16(3):317-26.

Madhusoodanan S, Moise D. Risperidone-induced hyperprolactinemia in adolescents: A case series. J Clin Psychiatry 2006 Jul;67(7):1110-3.

Meldersson KI. Prolactin elevation of the antipsychotic risperidone is predominantly related to its 9-hydroxy metabolite. Hum Psychopharmacol 2006 Dec;21(8):529-32.

Kopecek M, Bares M, Horacik J, Mohr P. Low-dose risperidone augmentation of antidepressants or anxiolytics is associated with hyperprolactinemia. Neuro Endocrinol Lett 2006 Dec;27(6):803-6.

Troost PW, Althaus M, Lahuis BE, Buitelaar JK, Minderaa RB, Hoekstra PJ. Neuropsychological effects of risperidone in children with pervasive developmental disorders: a blinded discontinuation study. J Child Adolesc Psychopharmacol 2006 Oct;16(5):561-73.

Eberhard J, Lindstrom E, Holstad M, Levander S. Prolactin level during 5 years of risperidone treatment in patients with psychotic disorders. Acta Psychiatry Scand 2007 Apr;115(4):268-76.

Bushe C, Shaw M. Prevalence of hyperprolactinaemia in a naturalistic cohort of schizophrenia and bipolar outpatients during treatment with typical and atypical antipsychotics. J Psychopharmacol 2007 Sep;21(7):768-73.

Duval F. Guillon MS, Mokrani MC, Crocq MA, Garcia Duarte F. Relationship between prolactin secretion, and plasma risperidone and 9-hydroxyrisperidone concentrations in adolescents with schizophreniform disorder. Psychoneuroendocrinology 2007 Nov 27.

Synek O, Svestka J, Tomanova J, Rodakova I, Cejpkova A. Differences in the effect of second-generation antipsychotics on prolactinaemia: Six weeks open-label trial in female in-patients. Neuro Endocrinol Lett 2007 Dec 6;28(6).

Togo T, Iseki E, Shoji M, Oyama I, Kase A, Uchikado H, Katsuse O, Kosaka K. Prolactin levels in schizophrenic patients receiving perospirone in comparison to risperidone. Neurology 2003 Apr 8;60(7): 1130-5.

Brunelleschi S, Zeppegno P, Risso F, Cattaneo CI, Torre E. Risperidone-associated hyperprolactinemia: evaluation in twenty psychiatry outpatients. Pharmacol Res 2003 Oct;48(4): 405-9.

Volavka J, Czobor P, Cooper TB, Sheitman B, Lindenmayer JP, Citrome L, McEvoy JP, Lieberman JA. Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol. J Clin Psychiatry. 2004 Jan;65(1):57-61.

Speak up! There may be options that don't cause weight gain

Schizophrenia is a challenging problem to manage. I'm not a huge fan of medication, but I AM a huge fan of keeping people safe as well as healthy. And in the case of schizophrenia, that often means medication MUST be part of the treatment plan.

I wish, though, that in the process of keeping our schizophrenic loved ones safe with regards to reducing self-harming and otherwise destructive behaviors, we could keep them metabolically safe. In other words, I wish we could also create an antipsychotic that didn't significantly increase weight gain, as well as risk of diabetes and heart disease. The most we seem to be able to do, right now, it seems, is be aware of the relative health risks that medications in this category pose.

One medication that seems to be working well, is ziprasidone (Geodon). One hundred eighty five individuals with schizophrenia or schizoaffective disorder who were initially on either risperidone (Risperdal), olanzapine (Zyprexa), or conventional antipsychotic agents, were switched to ziprasidone, and maintained on this medication for one year. Cholesterol, triglyceride, weight, and behavioral measures were recorded at regular follow-up intervals during this time.

In the individuals who had been switched from risperidone or olanzapine, there were overall significant improvements in weight, total cholesterol, and triglyceride levels. These changes did not seem to show up, however, in those who were switched over from other antipsychotics.

The take home message here is that there seems to be a spectrum along which these medications lie, from most weight-neutral to least weight-neutral. It's important to be aware that if you or someone you know is on medications and you notice changes in metabolic health, that you ask about alternatives.

I know that there are many other reasons why psychiatrists make medication choices in their treatment planning. I have several clients in my case load who simply are not well managed unless they are using the weight-promoting antipsychotics. Their treatment goals are different than what I am referring to here.

If there is a weight/cholesterol/diabetes issue whose onset seems to correlate with the use of an antipsychotic medication, and there are medication options that have not been considered, it is surely worth inquiring about the possibility of using them. Often times, the burden of this communication falls on the loved one, as the person with the problem is not in a cognitive place to be able to do this for himself/herself.

Just know, often times there are options, and it is your right to ask for a discussion about what those options are.

Weiden PJ, Newcomer JW, Loebel AD, Yang R, Lebovitz HE. Long-Term Changes in Weight and Plasma Lipids during Maintenance Treatment with Ziprasidone. Neuropsychopharmacology. 2008 Apr;33(5):985-94

Antipsychotics and cardiac-related sudden death: could selenium be important?

Scientists have started to notice that there is a relationship between the use of antipsychotic (neuroleptic) medications and the development of heart lesions. They have also noticed that these lesions, in other individuals, can be related to selenium levels. So, one research group in France decided to see what was happening to selenium levels in the presence of antipsychotic medications. (This study was done on rabbits.)

Half of the rabbits were given risperidone (Risperdal) and the other half levomepromazine (not available in the US), via intramuscular injection. Another group of rabbits was given a saline injection instead of medication.

Blood samples at the end of 3 months had 20% less selenium than blood samples taken at the beginning of the study. Heart tissue had 50% less selenium at the end of the study. In addition, these rabbits' hearts had disorganization of cardiac fibers, myolysis (dissolved muscle tissue), interstitial and endocardial fibrosis (development of fiber-like tissue), and necrosis (dead tissue) were noted in medication-treated animals, but not in controls.

The next step is logically going to be, whether or not supplemental selenium can help to prevent these negative side effects, and if so, how much is needed.

In the meantime, sounds to me like making sure if you are on an antipsychotic, that you take a supplement including selenium, and that you schedule regular visits with your cardiologist.

It's another reason I feel that eating well when on psychiatric medications is so important. If you're optimizing your diet, you may be able to minimize the amount of medication you need, ultimately reducing the potential for side effects that are at least as troublesome as the problem you're trying to help.

Vaillant F, Turrel F, Bost M, Bricca G, Descotes J, Bui-Xuan B, Tabib A, Manati W, Timour Q. Role of selenium in heart lesions produced by neuroleptics in the rabbit. J Appl Toxicol. 2008 Mar;28(2):212-6.