Weight change in Parkinson and Alzheimer patients taking atypical antipsychotic drugs.

As much trouble as I have with indiscriminate use of antipsychotic medications, I do think they have important uses in certain situations, and that we have to be very careful about overgeneralizing their negative aspects.

For example, these medications are increasingly being used to help control side effects in some serious illnesses such as Parkinson's disease and Alzheimer's disease. In some cases, especially when not managing these side effects can make things hard to manage for these individuals' caregivers (who are often family in a home situation), it is important to balance considerations about overall quality of care, caregiver sanity and health, and weight. Each situation is different, and there are no easy answers.

Sixty-one Parkinson's patients on either quetiapine (Seroquel) or clozapine (Clozaril) for at least six months were compared to 28 Alzheimer's patients in similar situations. The weight changes, though small, were statistically significant. Parkinson's patients trended toward weight loss compared to controls, and Alzheimer's patients trended toward weight gain.

It may not be that these medications cause weight changes in one direction or the other...but rather, they foster metabolism moving in a direction that genetic tendency long ago pre-programmed. It is important to not be afraid of a medication that can help ease the life of the caregiver. Of course, judicious use and close monitoring are always the caveats that go with any medication decision. Alzheimer's patients seem to be prone to developing diabetes and that should not be ignored.

I was glad to see this study attempt to parse out exactly what these medications do and why. That's a great use of scientific minds.

Sitburana O, Rountree S, Ondo WG. Weight change in Parkinson and Alzheimer patients taking atypical antipsychotic drugs. J Neurol Sci. 2008 Sep 15;272(1-2):77-82. Epub 2008 Jun 16.

A natural antipsychotic?

l-Stepholidine is a chemical derived from the Chinese herb Stephania. Since it had been found to have dopamine activity similar to that seen in atypical antipsychotics, it was tested and compared to the activity of haloperidol (Haldol) and clozapine (Clozaril). Scientists predicted its activity would more closely resemble clozapine. Indeed, when tested, it did mimic clozapine. The one downside researchers did report was that it was eliminated fairly rapidly from the body, which would make it challenging to use as a long-term therapeutic agent for treating schizophrenia.

What is stepholidine? It is a naturally occurring chemical, extracted from Stephania intermedia, a Chinese herb. I like to find pictures of herbs to share in this blog, but unfortunately, even Google can't pull anything up on this one.

I think this is exciting news, but being that this is very new information, I certainly am not recommending that anyone stop using a prescribed antipsychotic and head for Chinatown! I do promise, if anything new comes up, I'll be sure to share it in this blog along with references.

Natesan S, Reckless GE, Barlow KB, Odontiadis J, Nobrega JN, Baker GB, George SR, Mamo D, Kapur S. The antipsychotic potential of l-stepholidine--a naturally occurring dopamine receptor D1 agonist and D2 antagonist. Psychopharmacology (Berl). 2008 Aug;199(2):275-89.

Life-threatening constipation associated with clozaril

This one is short, and sweet, and there is no need for me to paraphrase what the authors report. The one thing I will point out is that even in combination with a laxative, clozapine was not productive in this case. Persons taking clozaril may not be the best historians or the most assertive regarding medication complications and side effects, so it is important to be thorough from evaluation all the way through treatment in order to prevent problems.

OBJECTIVE: The aim of this paper was to describe the association of clozapine with life-threatening constipation. METHOD: Case report. RESULTS: A 53-year-old man presented to the emergency department with severe abdominal pain and bilious vomiting after being on clozapine for over a year for schizoaffective disorder. Surgery revealed severe faecal impaction in the large and small bowel. Clozapine was ceased. There were significant difficulties in the subsequent psychiatric management. Clozapine was gradually reintroduced with concurrent laxative administration, which resulted in another episode of severe constipation with faecal impaction. CONCLUSIONS: Clozapine can be associated with potentially life-threatening constipation. Psychiatrists, especially consultation liaison psychiatrists, physicians, surgeons and radiologists, should be aware of the seriousness of clozapine-induced constipation and its potentially fatal complications.

Rege S, Lafferty T. Life-threatening constipation associated with clozapine. Australas Psychiatry. 2008 Jun;16(3):216-9.

Mixing old and new to create something better

I've got friends on both sides of the medication issue reading this blog. Some are vehemently anti-medication, while others are suspicious of natural alternatives. My desire is to make this as balanced a blog as possible, and fair to both sides. Maybe that's the Libra in me...maybe it's just that I think there are positive and negative aspects of each approach, and there are safety issues with each approach. It's not so important WHAT treatment is used, as it is WHY and HOW.

I really like this study because it integrates both schools of treatment in a promising way.

Two of the medications I write a lot about, olanzapine (Zyprexa) and clozapine (Clozaril), are notorious for their effects on blood lipids, weight gain, and diabetes risk. I'm not a big fan of either, but I do know because I work with a very skilled psychiatrist in town who completely supports my nutritional and complementary suggestions, that there are simply some people who need the medication in order to be safe to self and others. And because of that, they are simply at risk of metabolic syndrome-related side effects. I am always looking for ways that high-risk-of-side-effects medications can be used in combination with therapies that minimize the actual dose that needs to be used.

Gingko biloba is primarily recognized for its use in preserving memory. However, it was also recently tested on 42 patients with refractory schizophrenia who were maintained on stable doses of clozapine. A dose of 120 mg per day helped to reduce the negative symptoms of schizophrenia. It did not, however, reduce psychopathology symptoms.

So what's the point of taking it if it didn't reduce the medication need? I have read study after study after study over the years and it is clear, people stop taking medications when they don't like the side effects. If you can help push the balance of effects of a medication over to the positive, you might just increase compliance. And compliance to a medication regime means, potentially, better quality of life.

Who would have thought that beautiful tree with the funny shaped leaves had such a great little secret in its biochemistry?

Doruk A, Uzun O, Ozşahin A. A placebo-controlled study of extract of ginkgo biloba added to clozapine in patients with treatment-resistant schizophrenia. Int Clin Psychopharmacol. 2008 Jul;23(4):223-7.

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

Antipsychotics, weight gain, and beautiful minds

My very first experience in mental health was with a young man with schizophrenia who was also diabetic. It was very challenging to help him with his diet, because he was pretty obsessed with telling me how he'd been recruited away from his professional football career to invent the atomic bomb, and that he'd recently invented the Toyota Corolla. I remember thinking, even as a young intern, that it was sad that someone with so much creative energy was sitting in a locked psychiatric unit instead of focusing his mind in a productive direction.

It turns out, schizophrenia and diabetes are a very common combination. No one really knows why, but my guess is that with time, we'll learn that there is some kind of genetic link between the two problems. What makes this relationship especially important to understand, is that there are medications for schizophrenia that can exacerbate the diabetes, as well as other metabolic syndrome-related problems such as increased triglycerides.

A recent study showed that while rates of metabolic syndrome increased over time in patients prescribed antipsychotics, regardless of the specific type of medication, that the risk of developing metabolic syndrome was three times greater in those individuals using second generation antipsychotics. These people also experienced a greater degree of weight gain. The two medications that appeared to be the most problematic were olanzapine (Zyprexa) and clozapine (Clozaril).

The good news is, that there is also research supporting the fact that behavioral and nutrition "training" with individuals who are on these medications can help to lessen the degree of the negative side effects. I have worked with individuals who have not been able to manage their schizophrenia without using one of these two medications, so I understand their value and necessity for the well-being, productivity, and SAFETY of many people who use them. I just wish that every physician who prescribed them also automatically referred their patient to a nutrition professional who could maximize the benefit of the medication while minimizing the risks these medications pose. And I wish that insurance companies would recognize the importance of utilizing this kind of professional help in mental health, so that reimbursement was available. That would encourage many of these people to actually seek help before problems even started.

Sometimes we assume that when a person has a diagnosis such as schizophrenia, or bipolar disorder, that they aren't a candidate for certain types of services. I've not experienced that at all. In fact, some of my most motivated clients have been individuals with these diagnoses. I love my time with them because they are often highly intelligent and creative. They just need people in their lives who take them seriously, who assume that they're intelligent and treat them as such, and who are willing to show them the ropes as far as being healthy.

I think, if I went through my life being treated as if I was not intelligent, that I'd start to believe it myself. Maybe someday, we won't be so afraid of diagnoses such as schizophrenia, and we'll be as comfortable interacting with people who have mental diagnoses as we are with people who have diabetes or high cholesterol.

Imagine how many potential Vincent Van Goghs and John Forbes Nash Jrs. (A Beautiful Mind) are out there just waiting for us to help them access their potential?

De Hert M, Schreurs V, Sweers K, Van Eyck D, Hanssens L, Sinko S, Wampers M, Scheen A, Peuskens J, van Winkel R. Typical and atypical antipsychotics differentially affect long-term incidence rates of the metabolic syndrome in first-episode patients with schizophrenia: A retrospective chart review. Schizophr Res. 2008 Feb 23 [Epub ahead of print]

Kalarchian MA, Marcus MD, Levine MD, Haas GL, Greeno CG, Weissfeld LA, Qin L. Behavioral treatment of obesity in patients taking antipsychotic medications. J Clin Psychiatry 2005 Aug;66(8):1058-63.

Wu MK, Wang CK, Bai YM, Huang CY, Lee SD. Outcomes of obese, clozapine-treated inpatients with schizophrenia placed on a six-month diet and physical activity program. Psychiatr Serv 2007 Apr;58(4):544-50.

Scocco P, Longo R, Caon F. Weight change in treatment with olanzapine and a psychoeducational approach. Eat Behav 2006 May;7(2):115-24.

Kwon JS, Choi JS, Bahk WM, Yoon Kim C, Hyung Kim C, Chul ShinY, Park BJ, Geun Oh C. Weight management program for treatment-emergent weight gain in olanzapine-treated patients with schizophrenia or schizoaffective disorder: A 12-week randomized controlled clinical trial. J Clin Psychiatry 2006 Apr;67(4):547-53.

Alvarez Jimenez M, Gonzalez Glanch C, Vazquez Barquero JL, Perez Iglesias R, Matinez Garcia O, Perez Pardal T, Ramirez Bonilla ML, Crespo Facorro B. Attenuation of antipsychotic-induced weight gain with early behavioral intervention in drug-naive first-episode psychosis patients: A randomized controlled trial. J Clin Psychiatry 2006 Aug;67(8):1253-60.

Mauri M, Simoncini M, Castrogiovanni S, Iovieno N, Cecconi D, Dell'agnello G, Quadrigli M, Rossi A, Donda P, Fagiolini A, Cassano GB. A Psychoeducational Program for Weight Loss in Patients who have Experienced Weight Gain during Antipsychotic Treatment with Olanzapine. Pharmacopsychiatry. 2008 Jan;41(1):17-23.