The placebo “problem”

April 1, 2013March 31, 2013 ~ Jason Schwartz ~ 2 Comments

Prescription placebos used in research and pra... — Prescription placebos used in research and practice (Photo credit: Wikipedia)

It seems that PHARMA’s difficulty in developing drugs with stronger effects than placebo has prompted a creative response to the researching drugs. Kas Thomas at assertTrue(), directs us to a scholarly journal article tackling the “problem”:

But then Fava and his coauthors make the baffling statement: “Thus far, there has been no attempt to develop new study designs aimed at reducing the placebo effect.” They go on to present SPCD as a more or less revolutionary advance in the quest to quelch placebo effect.

Up until this point in science, I don’t think there had ever been any discussion, in a scientific paper, of a need to attack placebo effect as something bothersome, something that interferes with scientific progress, something that needs to be guarded against vigilantly like Swine Flu. The whole idea that placebo effect is getting in the way of producing meaningful results is repugnant, I think, to anyone with scientific training.

What’s even more repugnant, however, is that Fava’s group didn’t stop with a mere paper in Psychotherapy and Psychosomatics. They went on to apply for, and obtain, U.S. patents on SPCD (on behalf of The General Hospital Corporation of Boston). The relevant U.S. patent numbers are 7,647,235; 7,840,419; 7,983,936; 8,145,504; 8,145,505, and 8,219,41, the most recent of which was granted July 2012. You can look them up on Google Patents.

The patents begin with the statement: “A method and system for performing a clinical trial having a reduced placebo effect is disclosed.” Incredibly, the whole point of the invention is to mitigate (if not actually defeat) the placebo effect. I don’t know if anybody else sees this as disturbing. To me it’s repulsive.

Placebos becoming too effective, pharma industry worries (asserttrue.blogspot.co.nz)
New Patents Aim to Reduce Placebo Effect (asserttrue.blogspot.com)

They’ve got hope for something. But, what?

September 23, 2012September 24, 2012 ~ Jason Schwartz

Stimulant maintenance therapy did not work 😦

This study did not find a significant main effect of modafinil on the rate or duration of cocaine use among cocaine-dependent patients.

Now they decide to polish the turd:

Although these results are disappointing, we did find that modafinil-treated patients had nonsignificantly higher odds of attaining abstinence across all of the study time points, and those treated with 400 mg/day had significantly greater odds of attaining abstinence (p = .04) at the end of their 8-week medication trial (Visit 24). There was also a significant difference (p = .02) in the OR for abstinence at the final follow-up visit, suggesting the possibility that modafinil facilitated delayed clinical improvement that was not captured by our 8-week study design.

Back to reality:

Despite its ability to blunt cocaine-induced euphoria in three controlled human laboratory studies ( [Dackis et al., 2003], [Hart et al., 2008] and [Malcolm et al., 2006]), modafinil did not show overall success in this outpatient clinical trial.

Maybe these people are just too tough:

It is important to note that all of the patients in this study tested positive for cocaine at baseline. It is well established that patients who test positive for cocaine at study start have extremely poor clinical outcomes when compared with those who are able to produce a cocaine-negative urine sample ( [Ahmadi et al., 2009],[Kampman et al., 2001], [Patkar et al., 2002] and [Poling et al., 2007]). The reason for this finding is unclear, but it probably stems from greater addiction severity, less motivation for recovery, or both of these clinical features.

There will be evidence, dammit!

Despite our negative study, we believe it is premature to dismiss modafinil as a potential treatment for cocaine dependence.

An exciting time for pharma

June 12, 2012June 12, 2012 ~ Jason Schwartz

money pills by carbonNYC — photo credit: carbonNYC

Ugh!

This Join Together article reads like a ad for pharma:

Many people struggling with alcohol dependence who could benefit from medication are not receiving it, according to an expert who spoke at the recent American Psychiatric Association Annual Meeting.

“Antidepressant prescribing is 100 to 200 times as great as prescriptions for medications approved to treat alcohol dependence, despite the fact that the prevalence of disorders for which antidepressants are prescribed—major and minor depression and anxiety disorders—is only two to three times that of alcohol dependence,” says Henry Kranzler, MD, Professor of Psychiatry at the Treatment Research Center at the University of Pennsylvania and the Philadelphia VA Medical Center.

Perhaps I'm the Wrong Tool by Tall Jerome — Perhaps I’m the Wrong Tool by Tall Jerome

There’s plenty of room for debate about whether high antidepressant prescribing rates represent money well spent or good medicine, but I’ve covered that before. (See below)

He expresses some enthusiasm about Topamax and then touts a new drug coming from Denmark:

Lundbeck, a Danish pharmaceutical company, has submitted an application for approval by the European Medicines Agency of the medication nalmefene to be used on an as-needed basis to reduce heavy drinking, according to Dr. Kranzler. “This is a novel approach and could have an impact on treatment throughout the European Union and possibly the U.S.,” he adds.

Here’s what a disinterested trade publication had to say about the drug [emphasis mine]:

Danish pharmaceutical company H. Lundbeck A/S yesterday unveiled clinical data on its potential blockbuster drug nalmefene at the 2012 European Congress of Psychiatry clinical in Prague. While Lundbeck and its Finnish partner Biotie Therapeutics Corp. from Turku underline an impressive 66% reduction in total alcohol consumption, a closer look at placebo data is disconcerting. In three placebo-controlled Phase III studies, the drug with the trade name Selincro was given to heavy drinkers who also were given medical advice about their drinking habits. Selincro aims at eliminating the brain’s pleasure response to drinking. After six months, numbers of heavy drinking days (total alcohol consumption) in the first study dropped from 19 to 7 (84g to 30g) in the drug arm, and from 20 to 10 (85g to 43g) in the placebo arm. The numbers of the second study were less convincing and – even worse – in the third study the drug arm barely outperformed the placebo. Nevertheless Biotie-CEO Timo Veromaa thinks that “Selincro has the potential to transform the way alcohol dependence is managed by both patients and physicians.”

Too bad the Join Together article didn’t include a commercial interest disclosure statement* and note that he and/or his projects have received money from the manufacturers of Topamax and nalmefene.

I believe that medications may play a helpful role in the future, but I’m underwhelmed by the current stable of drugs and troubled that so much energy gets put into promoting expensive drugs of dubious value.

This is an exciting time in the treatment of alcoholism, because the field of medication treatment for alcohol dependence is expanding into the arena of personalized medicine, he says.

I’d love to see helpful drugs come along and I think a lot of these docs and researchers have good motives, but they have one tool (the prescription pad) and they seem to consistently oversell it.

* The ASAM event disclosure lists that Dr. Kranzler and/or his projects have recieved money from Alkermes, Roche, Pfizer, Lundbeck, Lilly, Eli Lilly, Janssen, Schering Plough, GlaxoSmithKline, Abbott and Johnson & Johnson. ProPublica does not list him at all. Possible explanations are here.