Wednesday, March 5, 2008

Pills, Pills, Pills

A few studies and media stories that have come out recently may helpt to shed some light on medications and how we use them.

First, the Wall Street Journal , MSNBC and others have reported on an interesting study from MIT published in this week's JAMA that showed a placebo pill was more effective when patients thought it cost more money. Briefly, 82 healthy volunteers were given a placebo pill that they were told was for pain relief. Half were told the pill cost $2.50 and the other half was told the cost was 10 cents. Subjects were (safely) given painful shocks. 85.4% of the participants experienced pain reduction after taking the expensive pill compared to 61.0% of patients taking the cheaper placebo.

Second, and interesting essay in the NY times by Dr. Abigail Zuger on Dr. Jarvik's role in promoting Lipitor ( the story that won't seem to go away) and pharmaceutical marketing in general.

Finally, several sources (Med News Today , Washington Post ) reported on a study that analyzed studies submitted to the FDA on anti-depressants like Prozac, Paxil and Effexor. To determine if these drugs improve depression, studies use a survey called the Hamilton Rating Scale for Depression (HRSD). The HRSD score ranges from 0 to 54. Though on average the medications were better than placebo, with a mean improvement of 9.60 points on the HRSD in the drug groups and 7.80 in the placebo groups, the 1.80 difference in HRSD score while statistically significant, did not reach what is considered to be a real and clinically meaningful change of 3 points, which was found only in the severely depressed patients.

Taken together, these three studies reveal a lot about how medications work and how marketing and cost may even affect medicines ability to work.

The placebo effect is a true phenomenon, and may have about a 30% benefit. Though the MIT study is interesting, it should be noted that both placebos had a substantial improvement. Yet, what we think about a drug may have a huge impact on whether or not it actually works on us. Cost of a drug implies that it is newer, and likely more effective. Thus, if we think we are taking the newest, most expensive drug, it may actually work better. This could imply that having Dr. Jarvik tell us that Lipitor works, may in fact not actually be such a bad thing? (more on that in a moment)

Antibiotics are another example of this. KevinMD's site has a great post from Dr. Rob on the myths of antibiotics. In my experience, patients often want an antibiotic because they think that they have more than just a cold, and that antibiotics are somehow "stronger." I have heard patients say that the only thing that will work on their cold is an antibiotic. Is this also the placebo effect? Though many antibiotics are now generic, use of antibiotics as a placebo is ill advised because of the development of resistant bacteria, which have now become a substantial problem in the community.

Trials submitted to the FDA use placebos to account for this affect. The meta-analysis on anti-depressants was interesting, but one should not infer that we should stop using anti-depressants in depression because the difference between placebo and treatment was on average almost 2 and not 3 points. With the additional real placebo benefit, patients on actual antidepressants had almost a 10 point reduction in HRSD, which is significant and meaningful. We could just start prescribing placebo pills for depressed patients, but I doubt this will ever be considered medically ethical.

Going back to drug advertising, one of my favorite studies on this subject was published in JAMA. Trained actors were sent to doctors offices, half given the role of someone with true depression where a drug would be indicated and the other half given the role of someone who was just sad, but not needing a medication. Both groups were further divided into two groups-half said they saw and ad on television for a drug and they wanted it, the other half did not. Not suprisigly, the patients who mentioned the TV ad were more likely to get the drug, regardless of their condition. What this means is that the TV ad led to increased appropriate prescribing in patients that really needed the drug, but also led to unnecessary prescribing for patients that didn't need the drug. Thus, though there is no question that drug ads on TV increases sales (and cost), the risks and benefits of TV drugs ads are not as clear cut.

Thinking a drug will work is clearly important, and industry can either enhance this effect for patient benefit, or manipulate it for increased profits. Physicians can take advantage of the placebo effect by reinforcing the efficacy of recommended medications with their patients, but must be cautious not to prescribe unnecessary medication just becaue a patient wants something.

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