Placebos Getting More Effective

Wired has an interesting article on how the placebo effect appears to be getting stronger.¹ The placebo effect has been considered by many to be a nuisance variable, which is why many pharmaceutical trials include a placebo wash-out phase. I’ve written on the placebo effect before.

From the article:

MK-869 wasn’t the only highly anticipated medical breakthrough to be undone in recent years by the placebo effect. From 2001 to 2006, the percentage of new products cut from development after Phase II clinical trials, when drugs are first tested against placebo, rose by 20 percent. The failure rate in more extensive Phase III trials increased by 11 percent, mainly due to surprisingly poor showings against placebo. Despite historic levels of industry investment in R&D, the US Food and Drug Administration approved only 19 first-of-their-kind remedies in 2007—the fewest since 1983—and just 24 in 2008. Half of all drugs that fail in late-stage trials drop out of the pipeline due to their inability to beat sugar pills.

The upshot is fewer new medicines available to ailing patients and more financial woes for the beleaguered pharmaceutical industry. Last November, a new type of gene therapy for Parkinson’s disease, championed by the Michael J. Fox Foundation, was abruptly withdrawn from Phase II trials after unexpectedly tanking against placebo. A stem-cell startup called Osiris Therapeutics got a drubbing on Wall Street in March, when it suspended trials of its pill for Crohn’s disease, an intestinal ailment, citing an “unusually high” response to placebo. Two days later, Eli Lilly broke off testing of a much-touted new drug for schizophrenia when volunteers showed double the expected level of placebo response.

It’s not only trials of new drugs that are crossing the futility boundary. Some products that have been on the market for decades, like Prozac, are faltering in more recent follow-up tests. In many cases, these are the compounds that, in the late ’90s, made Big Pharma more profitable than Big Oil. But if these same drugs were vetted now, the FDA might not approve some of them. Two comprehensive analyses of antidepressant trials have uncovered a dramatic increase in placebo response since the 1980s. One estimated that the so-called effect size (a measure of statistical significance) in placebo groups had nearly doubled over that time.

It’s not that the old meds are getting weaker, drug developers say. It’s as if the placebo effect is somehow getting stronger.

The problem is not just that the placebo effect has been growing stronger, but also that it has been systematically eliminated where possible in past studies. The studies are intentionally biased in favor of the active medication.

But, back to the “problem” of the growing placebo effect. There is some speculation in the article that is likely on track.

But why would the placebo effect seem to be getting stronger worldwide? Part of the answer may be found in the drug industry’s own success in marketing its products.

Potential trial volunteers in the US have been deluged with ads for prescription medications since 1997, when the FDA amended its policy on direct-to-consumer advertising. The secret of running an effective campaign, Saatchi & Saatchi’s Jim Joseph told a trade journal last year, is associating a particular brand-name medication with other aspects of life that promote peace of mind: “Is it time with your children? Is it a good book curled up on the couch? Is it your favorite television show? Is it a little purple pill that helps you get rid of acid reflux?” By evoking such uplifting associations, researchers say, the ads set up the kind of expectations that induce a formidable placebo response.

The success of those ads in selling blockbuster drugs like antidepressants and statins also pushed trials offshore as therapeutic virgins—potential volunteers who were not already medicated with one or another drug—became harder to find. The contractors that manage trials for Big Pharma have moved aggressively into Africa, India, China, and the former Soviet Union. In these places, however, cultural dynamics can boost the placebo response in other ways. Doctors in these countries are paid to fill up trial rosters quickly, which may motivate them to recruit patients with milder forms of illness that yield more readily to placebo treatment. Furthermore, a patient’s hope of getting better and expectation of expert care—the primary placebo triggers in the brain—are particularly acute in societies where volunteers are clamoring to gain access to the most basic forms of medicine. “The quality of care that placebo patients get in trials is far superior to the best insurance you get in America,” says psychiatrist Arif Khan, principal investigator in hundreds of trials for companies like Pfizer and Bristol-Myers Squibb. “It’s basically luxury care.”

The placebo effect, in my opinion, takes advantage of the same mechanism as does hypnosis. Irving Kirsch, has speculated much the same.²

Many psychological problems are maintained, in part, by dysfunctional response expectancies, and changing those expectations is an essential part of treatment. Hypnotic inductions alter response expectancies and have been shown empirically to substantially enhance the effects of psychotherapy. Therefore, hypnosis can be used therapeutically as a nondeceptive placebo. Expectancy plays a major role in hypnotic inductions and their effects. …

References
1. Silberman, S. Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why. 8/24/09. Wired.com
2. Kirsch, I. Clinical hypnosis as a nondeceptive placebo: empirically derived techniques. Am J Clin Hypn. 1994 Oct;37(2):95-106.

Anger and Responsibility

Be ye angry, and sin not (Ephisians 4:26).

If you do not wish to be prone to anger, do not feed the habit; give it nothing which may tend to its increase (Epictetus).

If you are patient in one moment of anger, you will escape a hundred days of sorrow (Chinese Proverb).

We have our emotions for a reason. They tell us things. They help us understand what we like and what we don’t like. They help motivate us to make changes in our lives and environments. They help us form and maintain relationships, and motivate us to address problems in those relationships.

Anger, like the rest of our emotions, is part of life. You can’t rid yourself of anger. You might think that you would like to, but without it you’d be missing out on an important signal and motivator. However, many people have problems with how they respond when angry, or have anger that is too intense to the point of rage. Anyway, your stuck with feelings of anger, but what you do when you are angry is a choice. This is difficult to understand for some people who have for so long thought that they have no control over their anger and what they do when they are angry. But it is the truth.

Some people view their anger as something they are born with. While there may be some support for a genetic component to the range or intensity of emotions that people feel, how you respond when angry is learned. For many men, they learned how to express their anger during childhood, from family members or other important people in their life. For men, if dad is angry and abusive, they sometimes learn that this is the way that men respond when angry. Others in the same circumstances learn to fear and suppress their anger, which can come out as anxiety or indirectly (such as the silent treatment). For many women, they learn not to express their anger, and again, this can come out in a variety of ways.

So there are two major problems with anger that people develop. They either can become violent, abusive, destroy things, yell and scream, or they can bury their anger and seethe on the inside or to the point that they are not consciously aware they are even angry. Both of these patterns are problematic.

The most important thing to know about anger and emotions in general is that they are temporary. They will subside on their own whether you do anything about them or not. So, if you have a problem with what you do when you are angry, you need to plan to isolate yourself when you have those intense feelings so that they have time to dissipate. One of the best descriptions of emotions that I have heard is that they are like waves breaking on a beach. The wave comes in to the shore, and then it goes back out again. This is true of anger. So, plan to remove yourself from the situation when you find your anger becoming overly intense. If you are in a relationship, you need to make it clear to your significant other ahead of time that you have a problem with anger and that there may be times when you need to be alone to “cool off.” Be sure to work this out ahead of time, because not doing so can lead to misunderstandings and further arguments.

Now, one of the most significant aspects of what determines how angry we get about something is what we think about something. It’s not true to say that someone else made you angry, such as “My boss made me angry.” The truth of the matter is that your boss may have done something, and you perceived it in a certain way. The way you perceived it determined how angry you became over it. For example, if you think, “My boss is such a jerk. All he ever does is put me down. I’d like to knock him in the head.” Now, if you think about it that way, you’re going to become very angry, and depending on your history, you may or may not do something you regret as a result of those thoughts. If you perceived things in a different way, such as, “My boss is disrespectful to me and I don’t appreciate that. I need to either discuss this with him or start looking for another job.” When you think about it this way, you may also feel some anger, but it will not be as intense as the first way of thinking. It also makes it more likely that your actions as a result of your anger will be constructive and beneficial.

So, one of the first tasks is becoming aware of the situations that trigger your anger, and then examining how you think about those situations. You need to work on changing how you think about those situations in order to experience less anger and to avoid negative consequences that would occur if you express your anger inappropriately. It can be difficult work to change the way you think, and you may need the help of a psychotherapist to help you in this process. The reason is that we often have blind spots, things that we are unaware of, and need another person to be able to help us discover those blind spots. In a nutshell, the type of thinking that leads to inappropriate anger has been called “distorted thinking.” It is thinking that ignores, magnifies, minimizes, or in some way filters information about the situation in a way that distorts the reality of the situation. You can do a Google search on distorted thinking if you would like to learn more about the various types of distorted thinking.

Another fallacy about anger is that doing something like hitting a punching bag, pillow, or breaking something of little importance will help to diminish your anger. The fact is, that these actions actually increase your anger, and are a form of ‘anger practice.’ In other words, you are practicing responding to your anger with aggression. The more you do this, the more it becomes automatic and begins to feel more comfortable. Also, many many people think that yelling and screaming is a good way to “release” their anger. The truth is, that the louder your voice becomes, the angrier you become. Most people think this is the other way around. “The angrier I am, the louder I yell.” But the truth is, that yelling and screaming increases anger. You want to pay attention to how loud your voice is becoming and lower the volume of your voice if you want to become less angry. It really does work! So, don’t hit pillows, and don’t yell and scream to release your anger. If you feel like you are losing control, immediately remove yourself from the situation (count to 10, go to another room, take a walk). Then you can return to the discussion when you are in a calmer state of mind.

And as you begin to become more aware of when you are becoming angry, you can use your thoughts to help yourself become less angry. One way I have heard this described is “using cool thoughts.” Some examples are to think to yourself, “This is not that big of a deal, I just need to calm down. I am blowing this out of proportion. I don’t need to get bent out of shape about this. I just need to chill out.” Now, you’ll probably have your own thoughts that may help you to reduce your anger, and what I provided is just an example. The example may not be the ideal thing to use for everyone.

Another aspect of anger are the physical and non-verbal aspects. You want to begin to pay attention to these things when you become angry. You might notice that your fists are clenched, your jaw is clenched and your muscles are tense. When you notice these things, you’ll want to unclench your jaw, open your fists, and focus on relaxing your muscles. Some people find progressive muscle relaxation techniques to be helpful here. You can also do a search on that to learn more. The point is, by changing this physical response in your body, you will become less angry. Pay attention to your non-verbal behavior such as intense angry stares, or your body posture. When you notice you are staring aggressively, breaking this stare will help you to become less angry. There are also aggressive body postures, which can be handled by changing your posture, or leaning up against a wall, putting your hand of a chair, etc…

It’s good to establish some ground rules for yourself.

Some that I would suggest are:
1. Never hit anyone, break anything, throw anything, or hit anything when angry.
2. Do nothing at all. The feeling will pass with time. One of my patients described this as “riding the wave.”
3. Do not yell or scream.
4. Do not curse when angry (this actually increases the intensity of your anger).
5. Immediately remove yourself from the situation when you feel your anger is too intense.
6. Do not make any big decisions when extremely angry.
7. Develop some strong personal beliefs about anger, “Whatever is happening, it’s never worth getting bent out of shape over.”

Above all, plan to practice responding appropriately to your anger. After something happens and you become angry, think back about what happened and try to figure out how you could have responded differently or thought about the situation differently. The most important thing to remember, is that you will require a great deal of practice in learning to respond more appropriately when you are angry. And don’t hesitate to seek professional help if you find yourself having a significant anger problem that you have struggled with for many years. If the psychotherapist tells you to hit a pillow, fire him or her, and find a psychotherapist with more experience and knowledge about anger.

I plan to post more in the future on the other side of this equation, anger that is suppressed or repressed, and finds it’s outlets in unconscious ways.