Now the lead author of that paper and his colleagues have found something similar going on in RCT's between 1960 and 2013 of anti-psychotic medications for schizophrenia (the findings were published on line in October in JAMA Psychiatry). Most interestingly, in the 1960's, patients who received the placebo in such studies actually got worse on them. By the 2000's, however, they were getting better on placebo.
Even more striking, the average RCT participant receiving an effective dose of medication in the 1960s improved by 13.8 points on the Brief Psychiatric Rating Scale (BPRS), whereas this difference diminished to 9.7 BPRS points by the 2000's.
Whether these two influences completely cancel each other out is debatable, but I think it is safe to say that many of these possible reasons for a change in placebo response rate advanced by authors have in fact not changed significantly since the 1960's. In fact, if people in the 60's didn't think antidepressants would work, expectancies would have been lower, not only in the placebo group, but in the active treatment group as well.
Because most patients do not understand this, the doctor can usually discriminate a placebo response from a true response by observing when the patient starts to get better combined with the rate at which they improve. Since subjects don't know what to expect, being on this timeline could not be due to the expectancy factor, which in turn is necessary for a having a good placebo response.
I can tell you that a severe, properly diagnosed melancholic depression almost never showed a significant placebo response. The placebo response rate was probably about the same as the placebo response rate to a general anesthetic.
Another thing we observed was that patients with an acute schizophrenic reaction did not seem to get any better at all with such things as additional contact with doctors, which might be expected if a placebo response were taking place. In fact, the more you spoke with them, the more likely it would be that you would hear evidence that patients had a significant thought disorder than if you just had a briefer, casual conversation with them.
A thought disorder is at least as important as delusions and hallucinations in showing that someone is, in fact, someone with schizophrenia. People with a thought disorder see relationships between things that are completely illogical (loose associations). For example, the first patient I ever saw with schizophrenia in medical school believed that everyone who wore oxblood-colored shoes was a descendant of George Washington.
Anyway, back to the question of biasing diagnostic exams. This is particularly easy when diagnosing a clinical depression. It is important to distinguish them from those people who are merely chronically unhappy. People with a clinical major depression, especially with so-called melancholic features, are a very different breed of cat.
The symptoms of both disorders do overlap a bit, so there are some cases in which it is really hard to tell one from the other. However, in the majority of cases it is a fairly easy call. It is, provided you do a complete psychiatric assessment, over several days, to see if a symptom of depression meets the requirement known as the Three P's:
The symptoms need to be pervasive (they do not go away depending on what the patient is doing at a particular time), persistent (lasting almost all day every day for at least two weeks), and pathological (the patients symptoms and functioning differ to a highly significant degree from the patient's usual state). In addition to the three p's, all of the patient's symptoms have to always occur simultaneously.