Retrospectacle: A Neuroscience Blog

From the Wall Street Journal:

In the unending quest for a miracle diet pill, Americans are trying an array of prescription drugs approved by the Food and Drug Administration to treat a variety of illnesses. None of them have been approved as diet drugs — but for many, weight loss is a side effect.

The list includes drugs meant to treat attention-deficit hyperactivity disorder (Adderall and Ritalin), depression (Wellbutrin), epilepsy (Topamax and Zonegran), diabetes (Glucophage and Byetta), sleep disorders (Provigil), smoking (Zyban) and even opiate overdoses (Narcan). Often these drugs are used alone, but sometimes they’re taken in combination with each other or with popular weight-loss medications, such as phentermine.

The doctors who prescribe drugs off-label for weight loss believe they fill a void. “Obesity is a chronic disease — diet and exercise aren’t enough for long-term weight loss for most patients,” says Robert Skversky, a bariatric physician in Newport Beach, Calif. “Chronic diseases need drugs to keep them under control.”

Dr. Skversky uses a combination of drugs he adjusts for each patient — a drug cocktail usually consisting of phentermine plus antidepressants such as Prozac, antiseizure drugs such as Topamax or Zonegran, or diabetes drugs such as Glucophage or Byetta. (Ms. Krawczyk, who is one of his patients, takes Adipex, or phentermine; the antidepressants Wellbutrin and Celexa; and Topamax.) A combination of these drugs could cost about $100 to $200 a month or more, says Dr. Skversky.

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Comments

#1 DeanOR
August 29, 2006

The drugs described are a witch’s brew in such combinations, with unknown effects. What some physicians mean by “diet and exercise aren’t enough for long-term weight loss for most patients” is that they give the patient a handout on diet and exercise, and, surprise, that isn’t effective. Or they refer the patient to a weight management class, because they are required to do so, and tell them they only have to attend three of the classes (to show that it doesn’t work for you), “then we’ll get you on the list for (radical bariatric) surgery”.
#2 MattXIV
August 29, 2006

Most of the choices aren’t that suprising. ADHD and narcolepsy drugs tend to be stimulants, which may just be serving as amped up versions of the off-the-shelf caffiene diet pill. Wellbutrin is also perscribed for smoking cessation and ADHD and has CNS stimulant effects.

Narcan is a bit puzzling, since I think it works by blocking the receptors for opiates, as is Prozac (mentioned elsewhere in the article), since it is associated with weight gain.
#3 daksya
August 29, 2006

None of them have been approved as diet drugs

Not as of now, but the amphetamines(Adderall) were prescribed for slimming a few decades ago.

but for many, weight loss is a side effect.

That’s a weird way to phrase it. Generally, you label undesired or unexpected outcomes as side-effects. That’s not the case when they are being used for slimming.
#4 Gerardo Camilo
August 29, 2006

How about take to hours a day in a stairmaster.
Bet it will work a lot better.
#5 darkman
August 29, 2006

narcan is the trade name for naloxone a competitive antagonist of the mu opioid receptor. It’s used when people overdose on heroin and the likes, and is now prescribed as a means of relapse prevention in ex-addicts. It’s been known for a while that animals treated with naloxone don’t eat much, it’s described as a loss of appetite by many researchers and no one yet knows the mechanisms underlying the appetite decrease.
#6 Dennis
August 29, 2006

What? No cocaine?
#7 natural cynic
August 29, 2006

Is Rimonabant now available? This is an endocanabinoid blocker that has been shown to be effective in smoking cessation and weight loss [with the expected side effects of a risk of depression].
#8 Abel Pharmboy
August 30, 2006

Rimonabant was approved in Europe and is already available in the UK. Its launch in Germany has been delayed until 1 Sept.

Derek Lowe at In the Pipeline has some concerns here and here about the potential side effects of this drug due to diffuse distribution of CB-1 endocannabinoid receptors.

Prof Batts, I believe that the WSJ’s Ms Bernstein had her info slightly off regarding Narcan/naloxone. Naloxone has no oral bioavailability and is only useful when given intravenously; perhaps she was thinking of the work on the orally-bioavailable, naltrexone (ReVia), which has been used in the the pharmacotherapy of substance abuse, especially alcoholism.
#9 darius
August 30, 2006

Daksya said:
That’s a weird way to phrase it. Generally, you label undesired or unexpected outcomes as side-effects. That’s not the case when they are being used for slimming.

That was the whole point of the article. The drugs are generally meant to have other effects, such as diabetes control, ADHD control, etc. Weight loss is a side effect. So instead of using the drugs for the primary purpose, they are using them for the side effect.

It’s a side effect because it’s not what the drug is developed and/or marketed for, not because it is “good” or “bad”. Also, weight loss is not good for everyone; people exist who are already at or below their proper weight.
#10 romunov
August 30, 2006

There’s no fat people in Africa. It’s very hot there. Looks like the capitalists are trying to warm the entire globe to make Americans slim. It’s the only logical explanation…
#11 Paul Atreides
August 30, 2006

Actually 2 hours a day on a stairmaster just made my legs stronger, it didn’t make me lose any weight…but thanks for the amazing advice Gerardo, I’m sure the millions who suffer from obesity didn’t think of that.
#12 Doc Bushwell
August 30, 2006

Is Rimonabant now available? This is an endocanabinoid blocker that has been shown to be effective in smoking cessation and weight loss [with the expected side effects of a risk of depression].

It has been launched in Europe, but FDA approval for the US market is pending. I posted a screed on rimonabant and anti-obesity drugs under development in the Refuge a while back. Personally, it’s not my favorite therapeutic area.

“Obesity is a chronic disease — diet and exercise aren’t enough for long-term weight loss for most patients,” says Robert Skversky, a bariatric physician in Newport Beach, Calif. “Chronic diseases need drugs to keep them under control.”

By Jove’s jiggling white adipose tissue, this takes the buttercream-frosted cake for most self-serving remark.
#13 daksya
August 30, 2006

darius, weight loss is a side-effect for Adderall patients taking it for ADHD, but not for those taking it for weight-loss. There’s no divine list of intended effects and side-effects. There’s only effects, which fall into those the patient wants, doesn’t want, and doesn’t care about.
#14 Shelley Batts
August 30, 2006

Prescribing a drug for something other that its “primary indication” is common—thats off-label prescribing. Its not illegal, and in fact many doctors are “educated” by the pharma companies as to what the possible off-label uses could be in order to widen their market. This is not necessarily a bad thing, as almost every drug prescribed to children is techinically “off-label” due to the fact that drugs are not usually tested on children (some are). Its gets tricky though when you are prescribing a drug off-label to benefit from one of its side-effects. You cannot avoid the whole host of “primary effects,” as the drug was not meant to treat obesity you’re essentially getting your non-existent depression or substance abuse problem (and the pathways targeted) treated as well. Whether that is worth it for the pounds shed, who knows?
#15 kemibe
August 31, 2006

While some of these drugs are comparatively new, the practice of using prescription as well as non-prescription substances to lose weight is not. People (notably health professionals) have been using thyroxine for this purpose for a long time. Many women admittedly owe the maintenance of a smoking habit primarily to the slimming effects of nictotine; ditto cocaine and even narcotics (I’ve heard more than one recovering opiate addict say that one of the main factors keeping her* from trying to “kick” was the weight loss that accompanied long-term use).

*I realize that this is not strictly a gender issue
#16 Dan R.
September 1, 2006

One other thing — there are more than a few studies that show that people with Syndrome X (metabolic syndrome) who take Glucophage lower their risk of contracting Diabetes II.

That maybe reason enough to take it regardless of weight loss.
#17 knight in dragonland
September 10, 2006

As a pediatrician, I am very familiar with weight loss as a side effect of the methylphenidate derivatives (Ritalin, Concerta & others) and the amphetamine salts (Adderall & others). They can also inhibit growth (? by augmenting the inhibitory dopaminergic inputs into the pituitary decrease growth hormone output – just my speculation), although the effect is minimal.

I don’t know if any studies have been done looking at using these drugs in obese adolescents except for dextroamphetamine sulfate being used in kids that were s/p craniopharyngioma resection (hyperphagia and obesity are big problems in those kids).

Topiramate (Topamax) has been used in kids with Prader-Wili who also have problems with hyperphagia.

Some small studies have been done with metformin (Glucophage) in adolescents with (1) obesity and insulin resistance and (2) polycystic ovarian syndrome with some positive results. It’s all still very preliminary.
#18 onehotnanna
April 25, 2007

Anyone remember Anna Nicole and her “drug combinations”. I think she was on a mission to lose weight, keep her energy level up,but try to sleep at night. Thus a deadly drug combo. Just my thoughts.