Why weight loss experts fail their clients--Part 2

I am a little behind on this post, it's been a busy week!

I wanted to continue with part 2 of a series on why weight loss experts fail their clients. In my first post, just below this one, I described a study looking at brain changes that happen in the presence of depression.

One finding was that the prefrontal cortex, important for memory retention and coordination of complex behaviors, was compromised.

And what are dietitians notorious for doing? Handing over, in a one hour session, a volume of handouts as thick as Tolstoy's War and Peace, full of do's and dont's and calorie counts and exchanges and label reading information. And then they wonder why the client didn't return for a follow up visit.

I will never forget the client who shared with me that he sometimes made two lunches, not because he was hungry for lunch #2, but because he forgot he'd even eaten lunch #1 until he went to put lunch #2's dishes in the sink and encountered remnants from lunch #1.

Yes, it's sometimes that simple. Yet, the dietitian who even takes the time to ask about memory is a rare one.

Reasons for memory issues with depression, in addition to decreased blood flow, include loss of neurons in the hippocampus, another memory center, and low levels of DHA, an omega-3 fatty acid that is an essential component of brain matter.

If those issues are not accounted for and accommodated in a treatment plan, guaranteed your clients are at great risk for dropping out of treatment. Maybe even not remembering appointments they had made, if they actually did want to return.

Another brain center with compromised function with depression is the anterior cingulate, responsible for executive, evaluative, cognitive, and emotional functions, as well as learning and problem solving, error detection, motivation, and emotional modulation.

So if you're a dietitian trying to use the intuitive eating approach and you have a client who can't evaluate how they feel, decide what to do with how they feel, set boundaries in situations that trigger feelings that trigger eating....just how far are you going to get with your approach?

And you know what we do when clients don't do what we think they should? We diagnose them with mental health issues, refer them out, and potentially set them up to be prescribed medication that only exacerbates their metabolic and weight issues.

Just think about it over the weekend. I'll be back next week with a way around this dilemma that may actually help the client to get better and leave the dietitian less frustrated.

Elizabeth Sublette M, Milak MS, Hibbeln JR, Freed PJ, Oquendo MA, Malone KM, Parsey RV, John Mann J. Plasma polyunsaturated fatty acids and regional cerebral glucose metabolism in major depression. Prostaglandins Leukot Essent Fatty Acids. 2009 Jan;80(1):57-64. Epub 2009 Jan 6.

Qnexa--The next frontier in weight management drugs--or is it?

Below my pontificating you will see a press release for a new weight loss medication, Qnexa.

My initial impressions:

1. This looks like the new twist on the old "phen-fen," phentermine being the common ingredient in both, with the problem compound, fenfluramine, being replaced with topiramate (Topamax). Topiramate is a mood stabilizing drug that has been found to have weight loss effects in some people and has been used in an off-label fashion for this purpose.

2. For the record, I've collected a bunch of references on potential side effects reported with topiramate, including: kidney stones, reduced testosterone in males, dry mouth, nausea, reduced sweating, body temperature regulation (which could become an issue if you're following directions and exercising more), cerebellar cognitive affective syndrome, and delusional parasitosis. (That's when you have the creepy feeling that bugs are crawling all over you when none are there.) References are provided below.

3. People aren't overweight because they have phentermine or topiramate deficiencies. Obesity is a huge target for drug research because there's such a huge market--it's a gold mine for anyone who can create and patent a medication that can stay on the market without its negative side effects forcing it to be yanked. My concern is once this med is used in large numbers some of these side effects are going to become huge problems.

4. Just beware if you decide to try this medication when it becomes available. It's not 100% foolproof. Anyone who prescribes you this medication without advising you of these potential problems may not fully understand how this medication works. And that's your red flag of a potential problem. Be informed!

Otoom S, Batieneh H, Hassan Z, Daoud A. Effects of long-term use Topiramate on fertility and growth parameter in adult male rats. Neuro Endocrinol Lett. 2004 Oct;25(5):351-5.

Sharief M, Viteri C, Ben-Menachem E, Weber M, Reife R, Pledger G, Karim R. Double-blind, placebo-controlled study of topiramate in patients with refractory partial epilepsy. Epilepsy Res 1996 Nov;25(3): 217-24.

Incecik F, Herguner MO, Altunbasak S. Topiramate associated hypohidrosis and hyperthermia. Indian Pediatr. 2008 Mar;45(3):238-40.

Cerminara C, Seri S, Bombardieri R, Pinci M, Curatolo P. Hypohidrosis during topiramate treatment: a rare and reversible side effect. Pediatr Neurol 2006 May;34(5):392-4.

Baillieux H, Verslegers W, Paquier P, De Deyn PP, Mariën P. Cerebellar cognitive affective syndrome associated with topiramate. Clin Neurol Neurosurg. 2008 May;110(5):496-9.


Fleury V, Wayte J, Kiley M. Topiramate-induced delusional parasitosis. J Clin Neurosci. 2008 May;15(5):597-9.

Vega D, Maalouf NM, Sakhaee K. Increased propensity for calcium phosphate kidney stones with topiramate use. Expert Opin Drug Saf 2007 Sep;6(5):547-57.

Koçer A, Dikici S, Atakay S, Okuyucu E. Serum Uric Acid and Lipid Levels While Taking Topiramate for Migraine. Headache. 2007 Dec 27.

Qnexa Meets Primary Endpoint by Demonstrating Superior Weight Loss over
Components and Placebo in the 28-Week Equate Study (OB-301)

Subjects on Full-Dose Qnexa Attained an Average Weight Loss of 9.2% with
66% Achieving 5% or Greater Weight Loss

MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)--Dec 11, 2008 - VIVUS, Inc.
(NASDAQ: VVUS), a pharmaceutical company dedicated to the development
and commercialization of novel therapeutic products, today announced
positive results from the EQUATE study (OB-301), a 28-week, phase 3
obesity trial conducted at 32 sites with QnexaTM, an investigational
drug. The EQUATE study met the primary endpoint by demonstrating
superior weight loss with both the full-dose and mid-dose of Qnexa, as
compared to the individual components and placebo. Subjects treated with
full-dose and mid-dose Qnexa had an average weight loss of 9.2% and 8.5%
respectively, as compared to weight loss of 1.7% reported in the placebo
group (ITT LOCF p<0.0001). Average weight loss was 19.8 pounds and 18.2
pounds in the treatment arms as compared to 3.3 pounds in the placebo
group. Qnexa was well-tolerated, with no drug-related serious adverse
events in the study.

"The results from the EQUATE trial once again confirmed our belief in
Qnexa. In addition to hitting the primary endpoints of the study with
the full-dose, we were also able to show excellent results with the
mid-dose of Qnexa," commented Leland Wilson, president and chief
executive officer of VIVUS. "The EQUATE study is the first of three
studies in the Qnexa phase 3 obesity program. Data from the EQUIP and
CONQUER studies, which combined enrolled over 3,750 subjects, is
expected in mid-2009."

The EQUATE study included 756 obese subjects (599 females and 157 males)
across 32 centers in the United States. The average baseline BMI of the
study population was 36.3 kg/ m2 and baseline weight was 223 pounds. The
proportion of patients losing 5% or more of their initial body weight
was 66% for full-dose, 62% for mid-dose and 15% for placebo (p<0.0001).
The proportion of patients losing 10% or more of their initial body
weight was 41% for full-dose, 39% for mid-dose and 7% for the placebo
group (p<0.0001).

The most common drug-related adverse events reported for the full-dose,
mid-dose and placebo group were paresthesia (20%, 15%, 3%), dry mouth
(18%, 12%, 0%), altered taste (15%, 8%, 0%) and constipation (11%, 6%,
6%). Reported drug related adverse events for depression and altered
mood were minimal (1.9%, 0.9% and 1.8% respectively) . Moreover,
individual depression assessments for each subject, as measured by
PHQ-9, demonstrated statistically significant improvements (p<0.05) from
baseline for both Qnexa treatment groups. Overall average completion
rate for the Qnexa treatment group was 71%.

Subjects in the EQUATE study had a 4-week dose titration period followed
by 24 weeks of treatment. The study was a randomized, double-blind,
placebo-controlled, 7-arm, prospective trial with subjects randomized to
receive once-a-day treatment with mid-dose Qnexa (7.5 mg phentermine/ 46
mg topiramate CR), full-dose Qnexa (15 mg phentermine/ 92 mg topiramate
CR), the respective phentermine and topiramate constituents, or placebo.
Subjects were asked to follow a hypocaloric diet representing a
500-calorie/ day deficit and advised to implement a simple lifestyle
modification program.

About the Qnexa Phase 3 Obesity Program

In addition to the EQUATE study, the phase 3 Qnexa program includes two
pivotal, double-blind, placebo-controlled, multi-center studies that
will compare the efficacy and safety of Qnexa to placebo during a
56-week treatment period. The first year long study, known as EQUIP
(OB-302), has enrolled approximately 1,250 morbidly obese adult subjects
with a Body Mass Index (BMI) of 35 or greater with or without controlled
co-morbidities. The second trial, known as CONQUER (OB-303), has
enrolled overweight and obese adult subjects with BMIs from 27 to 45 and
at least two co-morbid conditions, such as hypertension, dyslipidemia
and type 2 diabetes. The co-primary endpoints for these studies are the
mean percent weight loss and the percentage of subjects achieving a
weight loss of five percent or more. Results from these studies are
expected mid-2009. In total the phase 3 program has enrolled
approximately 4,500 subjects.

VIVUS R&D Day December 12, 2008

As previously announced, VIVUS will host a Research and Development Day
Event on Friday, December 12, 2008 at 8:00 a.m. ET in New York City.
Additional details on the data released today will be presented.

To access the webcast of this event, please visit:
http://phx.corporat e-ir.net/ phoenix.zhtml? p=irol-eventDeta ils&c=79161& ev
entID=2046581 or VIVUS' Investors site at http://www.vivus. com. Replay
will also be available on demand from the website at the conclusion of
the program and will run through December 31, 2008.

If you are interested in attending, please contact Brian Korb at The
Trout Group at 646 378 2923 or bkorb@troutgroup. com.

About VIVUS

VIVUS, Inc. is a pharmaceutical company dedicated to the development and
commercialization of novel therapeutic products. The current portfolio
includes investigational product candidates addressing obesity, diabetes
and sexual health. The investigational pipeline includes: QnexaTM, which
is in phase 3, for the treatment of obesity and has completed a phase 2
study for the treatment of type 2 diabetes; avanafil, for which a phase
2 study has been completed for the treatment of erectile dysfunction
("ED") and LuramistTM (Testosterone MDTS(r)), for which a phase 2 study
has been completed for the treatment of Hypoactive Sexual Desire
Disorder ("HSDD"). MUSE(r) is approved and currently on the market for
the treatment of ED. For more information on clinical trials and
products, please visit the company's web site at http://www.vivus. com/.

Certain statements in this press release are forward-looking within the
meaning of the Private Securities Litigation Reform Act of 1995. These
statements may be identified by the use of forward-looking words such as
"anticipate, " "believe," "forecast," "estimated" and "intend," among
others. These forward-looking statements are based on VIVUS' current
expectations and actual results could differ materially. There are a
number of factors that could cause actual events to differ materially
from those indicated by such forward-looking statements. These factors
include, but are not limited to, substantial competition; uncertainties
of patent protection and litigation; uncertainties of government or
third party payer reimbursement; reliance on sole source suppliers;
limited sales and marketing efforts and dependence upon third parties;
risks related to the development of innovative products; and risks
related to failure to obtain FDA clearances or approvals and
noncompliance with FDA regulations. As with any pharmaceutical under
development, there are significant risks in the development, regulatory
approval and commercialization of new products. There are no guarantees
that future clinical studies discussed in this press release will be
completed or successful or that any product will receive regulatory
approval for any indication or prove to be commercially successful.
VIVUS does not undertake an obligation to update or revise any
forward-looking statement. Investors should read the risk factors set
forth in VIVUS' Form 10-K for the year ended December 31, 2007 and
periodic reports filed with the Securities and Exchange Commission.

Topamax and kidneys...these two will probably never be BFF's

I've noticed in looking at my blog statistics that a previous entry on kidney stones resulting from topiramate (Topamax) use continues to be one of my most visited pages on this blog. So when I found more information about this medication and its effect on kidneys I wanted to be sure to share it.

Within 5 days of starting topiramate, the six subjects in this study experienced an average drop of calcium in their urine of about 31% and of citrate by about 40%. When calcium and citrate are not showing up in the urine, it's likely because it's accumulating elsewhere. Like in kidney stones.

Interestingly, increasing the topiramate dose seemed to improve calcium readings and to worsen citrate readings. Meaning you might get less of one kind of kidney stone and more of another.

The authors of this study said that the degree of reduction of urinary citrate was profound enough to be compared to the clinical presentation of renal tubular acidosis. This is a condition in which the body's pH is shifted to an unhealthy level, promoting important changes such as bone demineralization. And THIS will cause rickets in children and osteomalacia in adults. These are not things you will see or feel in those first few days. You need to measure them clinically.

I would strongly recommend, if you and your physician have concluded that the absolute only way to manage your bipolar disorder, your migraine, or your epilepsy, is with topiramate, that you closely monitor your urinary metabolites to be sure you're not doing more harm than good.

And if you're one of those souls who's been convinced that it might be nice to try topiramate to see if it helps you lose weight, consider that you might not just be
losing fat, you might also be losing bone. What's the point of being thin if you have to be sick when you get there?

The only way to know is to monitor. Please don't stick your head in the sand and hope it's not happening to you.

Warner BW, LaGrange CA, Tucker T, Bensalem-Owen M, Pais VM Jr. Induction of progressive profound hypocitraturia with increasing doses of topiramate. Urology. 2008 Jul;72(1):29-32; discussion 32-3.



I found a photo of a kidney stone on the 'net. Imagine trying how it feels to pass something this big through an opening about as big as a piece of cooked pasta. Now you know why I'm trying to get your attention!

Your blood pressure will rise over this one

I don't have to tell you that it's important to keep your blood pressure under control. And if you're intelligent enough to have interest in reading this blog, then you also know that if you're overweight, and your blood pressure is high, it is likely to drop if you take the steps to lose the weight.

Well, some scientists got a little muddled about why it's important to lose weight in the first place. And they developed this medication, sibutramine (Meridia), that is supposed to be a weight loss aid.

The only problem is, sibutramine doesn't help reduce blood pressure. In fact, in enough people so that it routinely shows up in the research literature, sibutramine has been observed to raise blood pressure. I've got twelve references about this in my drug book (listed below for your reference). In addition to raising blood pressure, elevated heart rate, insomnia, and agitation were also reported side effects.

MY blood pressure started to rise as I reviewed these references. Because I couldn't help but wonder if sibutramine would even be allowed on the market if it were a drug for cancer, or ulcers, or arthritis, and it caused hypertension, arrhythmia, and/or agitation? You can bet not.

But there is such a race to see who can create the magic weight loss pill that scientists seem to have forgotten why we even want people to lose weight. I can just see these Dr./patient interactions behind closed doors everywhere..."Well, Mr. Smith, the bad news is you can't sleep, your heart's racing, you're on the verge of a stroke, and you've annoyed the hell out of your family, friends, and coworkers with your new Type A personality. But hey, guess what? (Drum roll..........) You're THIN!!!"










HUH?!?!?

Your blood pressure isn't high because you have a Meridia deficiency. It's high because you have an activity and good food deficiency.

Is it just me, or is this a little bit like a scientific "Who's On First?"

Lechin F, van der Dijs B, Hernandez G, Orozco B, Rodriguez S, Baez S. Neurochemical, neuroautonomic and neuropharmacological acute effects of sibutramine in healthy subjects. Neurotoxicology 2006 Mar;27(2):184-91.

Avenell A, Brown TJ, McGee MA, Campbell MK, Grant AM, Broom J, Jung RT, Smith WC. What interventions should we add to weight reducing diets in adults with obesity? A systematic review of randomized controlled trials of adding drug therapy, exercise, behaviour therapy or combinations of these interventions. J Hum Nutr Diet. 2004 Aug;17(4):293-316.

Rucker D, Padwal R, Li SK, Curioni C, Lau DC. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ 2007 Dec 8;335(7631):1194-9.

Di Francesco V, Sacco T, Zamboni M, Bissoli L, Zoico E, Mazzali G, Minniti A, Salanitri T, Cancelli F, Bosello O. Weight loss and quality of life improvement in obese subjects treated with sibutramine: a double-blind randomized multicenter study. Ann Nutr Metab 2007;51(1):75-81.

Hanotin C, Thomas F, Jones SP, Leutenegger E, Drouin P. Efficacy and tolerability of sibutramine in obese patients: a dose-ranging study. Int J Obes Relat Metab Disord 1998 Jan;22(1): 32-8.

Dunican KC, Desilets AR, Montalbano JK. Pharmacotherapeutic options for overweight adolescents. Ann Pharmacother 2007 Sep;41(9):1445-55.

Elliott WJ. Drug interactions and drugs that affect blood pressure. J Clin Hypertens (Greenwich). 2006 Oct;8(10):731-7.

Porter JA, Raebel MA, Conner DA, Lanty FA, Vogel EA, Gay EC, Merenich JA. The Long-term Outcomes of Sibutramine Effectiveness on Weight (LOSE Weight) study: evaluating the role of drug therapy within a weight management program in a group-model health maintenance organization. Am J Manag Care. 2004 Jun;10(6):369-76.

Faria AN, Ribeiro Filho FF, Kohlmann NE, Gouvea Ferreira SR, Zanella MT. Effects of sibutramine on abdominal fat mass, insulin resistance and blood pressure in obese hypertensive patients. Diabetes Obes Metab. 2005 May;7(3):246-53.

Perrio MJ, Wilton LC, Shakir SA. The safety profiles of orlistat and sibutramine: results of prescription-event monitoring studies in England. Obesity (Silver Spring). 2007 Nov;15(11):2712-22.

Berube Parent S, Prud’homme D, St. Pierre S, Doucet E, Tremblay A. Obesity treatment with a progressive clinical tri-therapy combining sibutramine and a supervised diet-exercise intervention. Int J Obes Relat Metab Disord 2001 Aug;25(8): 1144-53.

McMahon FG, Fujioka K, Singh BN, Mendel CM, Rowe E, Rolston K, Johnson F, Mooradian AD. Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1-year double-blind, placebo-controlled, multicenter trial. Arch Intern Med 2000 Jul 24;160(14): 2185-91.

Weintraub M, Rubio A, Golik A, Byrne L, Scheinbaum ML. Sibutramine in weight control: a dose-ranging, efficacy study. Clin Pharmacol Ther 1991 Sep;50(3): 330-7.

Van Gaal LF, Wauters MA, Peiffer FW, De Leeuw IH. Sibutramine and fat distribution: is there a role for pharmacotherapy in abdominal/visceral fat reduction? Int J Obes Relat Metab Disord 1998 Aug; 22 Suppl 1:S38-40; discussion S41-2.

Hanotin C, Thomas F, Jones SP, Leutenegger E, Drouin P. A comparison of sibutramine and dexfenfluramine in the treatment of obesity. Obes Res 1998 Jul;6(4): 285-91.

Fanghanel G, Cortinas L, Sanchez-Reyes L, Berber A. A clinical trial of the use of sibutramine for the treatment of patients suffering essential obesity. Int J Obes Relat Metab Disord 2000 Feb; 24(2): 144-50.

Bailey DG, Dresser GK. Interactions between grapefruit juice and cardiovascular drugs. Am J Cardiovasc Drugs. 2004;4(5):281-97

Xu J, Chen JD. Peripheral mechanisms of sibutramine involving proximal gastric motility in dogs. Obesity (Silver Spring). 2006 Aug;14(8):1363-70.

Connoley IP, Liu YL, Frost I, Reckless IP, Heal DJ, Stock MJ. Thermogenic effects of sibutramine and its metabolites. Br J Pharmacol 1999 Mar,126(6): 1487-95.

Derosa G, Cicero AF, Murdolo G, Ciccarelli L, Fogari R. Comparison of metabolic effects of orlistat and sibutramine treatment in Type 2 diabetic obese patients. Diabetes Nutr Metab. 2004 Aug;17(4):222-9.

Gokcel A, Karakose H, Ertorer EM, Tanaci N, Tutuncu NB, Guvener N. Effects of sibutramine in obese female subjects with type 2 diabetes and poor blood glucose control. Diabetes Care 2001 Nov; 24(11): 1957-60.

Hauner H, Meier M, Wendland G, Kurscheid T, Lauterbach K, Study Group SA; SAT Study. Weight reduction by sibutramine in obese subjects in primary care medicine: the SAT Study. Exp Clin Endocrinol Diabetes. 2004 Apr;112(4):201-7.

McNeely W, Goa KL. Sibutramine. A review of its contribution to the management of obesity. Drugs 1998 Dec;56(6): 1093-24.

Fanghanel G, Cortinas L, Sanchez Reyes L, Berber A. Second phase of a double blind study clinical trial on sibutramine for the treatment of patients suffering essential obesity: 6 months after treatment cross-over. Int J Obes Relat Metab Disord 2001 May;25(5): 741-7.

Norris SL, Zhang X, Avenell A, Gregg E, Schmid CH, Lau J. Pharmacotherapy for weight loss in adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD004096.

Padwal R, Li SK, Lau DC. Long-term pharmacotherapy for obesity and overweight. Cochrane Database Syst Rev. 2004;(3):CD004094.

Fanghanel G, Cortinas L, Sanchez Reyes L, Berber A. Second phase of a double blind study clinical trial on sibutramine for the treatment of patients suffering essential obesity: 6 months after treatment cross-over. Int J Obes Relat Metab Disord 2001 May;25(5): 741-7.

Stimac D, Ruzic A, Majanovic SK. Croatian experience with sibutramine in the treatment of obesity--multicenter prospective study. Coll Antropol. 2004 Jun;28(1):215-21.

Appolinario JC, Godoy Matos A, Fontenelle LF, Carraro L, Cabral M, Vieira A, Coutinho W. An open-label trial of sibutramine in obese patients with binge-eating disorder. J Clin Psychiatry 2002 Jan;63(1): 28-30.

Horvath K, Jeitler K, Siering U, Stich AK, Skipka G, Gratzer TW, Siebenhofer A. Long-term effects of weight-reducing interventions in hypertensive patients: systematic review and meta-analysis. Arch Intern Med. 2008 Mar 24;168(6):571-80.

Antidepressants and weight gain

If you're coming directly to this blog instead of linking through my website, you may be interested in a chart I have posted on that website, listing references referring to antidepressants and their potential for causing weight change (gain or loss). This particular chart ONLY covers antidepressants, but it is a very popular page and I wanted to let you all know about it.

The medications included to date are: Celexa/citalopram, Cymbalta/duloxetine, Effexor/venlafaxine, Elavil/amitryptyline, Ludiomil/maprotiline, Nardil/phenelzine, Norpramin/desipramine, Parnate/tranylcypromine, Paxil/paroxetine, Prozac/fluoxetine, Remeron/mirtazapine, Doxepin/sinequan, Tofranil/imipramine, Wellbutrin/bupropion, and Zoloft/sertraline.

The link to this chart is http://afterthediet.com/antidepressant_medications.htm