The National Health Service in the United Kingdom spends over 300 million pounds per year on antidepressants (475 million USD).

Yet in a large study comparing antidepressant drugs with placebos, Irving Kirsch found no significant difference between placebos and ‘active’ drugs except for patients with severe depression.

Last Sunday night the research was discussed in a CBS 60 Minutes report. During her interview, reporter Lesley Stahl challenged Kirsch: "You're saying if (patients taking antidepressants) took a sugar pill, they'd have the same effect?"

Kirsch replied: "They'd have almost as large an effect, and whatever difference it would be, would be clinically insignificant."

Stahl was incredulous. "But people are getting better taking antidepressants, I know them. We all know them."

"People get better when they take the drug, but it's not the chemical ingredients of the drugs that are making them better. It's largely the placebo effect," Kirsch replied.

Kirsch’s research raises many provocative questions. If placebos appear to cure depression, is depression a real disease? How can a sugar pill cure depression? If sugar pills work as well as drugs and have fewer side effects, why not use them?

Nobody doubts that depression can be very serious. (And any patient taking or considering antidepressant medication should consult a qualified practitioner before making treatment decisions.) Instead, it means placebos are particularly good at curing depression. This can be achieved through several mechanisms. The sugar in the pill can influence insulin levels and induce a cascade of physiological effects. Moreover the doctor’s friendly manner, also part of the placebo, has been shown to make mildly depressed patients feel better.

The reason placebos aren’t prescribed is doctors deem them to be unethical. This is because (among other reasons) doctors should only prescribe treatments that are proven to be effective. But effectiveness is often established by demonstrating superiority to placebos; so to prove they are effective, then need to be more effective than themselves, which is impossible. Moreover, as Stahl noted, the ‘real’ drugs have known and serious side effects. So not prescribing placebos might be even less ethical.

Whatever the answers to these difficult questions, surely we can come up with an answer to the placebo ethics dilemma that costs less than 300 million pounds per year. More research, please!

Good practice demands that doctors inform their patients about both known and suspected side effects of any medication they prescribe. (In ethics-speak this is because of the requirement to respect patient autonomy.) On the other hand, the very act of providing information about side effects can produce negative effects (these are called ‘nocebo’ effects)! For example in a trial of a drug for unstable angina, patients were divided into two groups. The first group was given a statement outlining possible gastrointestinal (GI) side effects, and the second was not. Six times as more patients in the first group experienced subjective GI side effects.

How can doctors respect patient autonomy by revealing all information about side effects, yet avoid doing harm by causing the very side effects they describe? One answer is to give the information in the right way. We all know people who give negative feedback in a way that tends to increase anxiety. Others give the same information to evoke positive responses. Good teachers, coaches, and doctors all know how to frame information constructively.

Another solution is to ask patients. Some patients do not want to be burdened with details of all known and suspected side effects (serious side effects do, of course, need to be revealed). In these cases we can respect patient autonomy and withhold some information because the patient requested to be (partially) ignorant. Other patients do want to know about each and every side effect, in which case there may be little choice other than to reveal them, albeit in the right way.

So what’s the take home message? Tell the whole truth that the patient wants to hear and nothing but the truth in a way that will maximize benefit and minimize harm.

It’s been tested in more clinical trials than any other drug in history. Even critics admit it is effective for mild pain, mild depression, and other ailments with subjective outcomes. It has fewer side-effects than most alternatives. And now you can buy a bottle containing 50 pills of it for £3.75 ($5.95).

It’s called Obecalp and it comes in cherry flavor.

Here’s the rub: Obecalp is ‘placebo’ spelled backwards. Their website admits: “Obecalp® is a placebo and is not intended to diagnose, treat, cure or prevent any disease, or illness”. It was designed for parents to please (‘placebo’ means ‘to please’) malingering children. But don’t placebos work because people believe they are ‘real’? If so, I’ve removed the fun – and potential benefit – of Obecalp you. Or have I?

A recent study suggests placebos work even if people know they are placebos. There are two plausible explanations for why this might be the case. The first is classical conditioning. Pavlov’s dogs salivated at the mere expectation of food after having associated the sound with imminent food, and your body might react after popping Obecalp after it has learned (over a lifetime) to associate pill popping with symptom reduction.

Another novel explanation comes from evolutionary psychology. Imagine it is the dawn of human evolution. You feel a flu coming on but a sabre-toothed tiger is attacking your clan. If your body evoked the full immune response there would be less energy for fighting the tiger. Your survival therefore depends on ignoring the flu and increasing circulation to the skeletal muscles required for fighting. (In fact, the ‘fight or flight’ response suppresses the immune system.) Thankfully, you and your fellow tribesmen scare the tiger away, and the fight or flight response subsides. Then an authority figure – an elder or shaman – tells you everything is okay. The message from the trusted figure let you know (perhaps subconsciously) that you won’t need to run or fight for a few days. You are free to lie down and let your body’s immune system get to work.

Today tigers, village elders, and shamans are rare, but people with impressive titles like ‘Doctor’ might play the same role. If an authority figure (either in person or in an advertisement) tells you that you are going to be okay, your body (again perhaps subconsciously) might get the message that it is okay to allow the full immune response to kick in.

So even now that you know what it is, Obecalp still may be better than nothing. In the worst case, nothing is as good.