What does sham treatment tell us?

A few years ago, there was a report from the US Veterans' Administration (VA) on using transcranial magnetic stimulation (TCMS) for "treatment resistant major depression" in veterans [1]. This study was a pretty big deal, with a great deal of work coordinating studies across different hospitals, preliminary reports, etc. However, they didn't follow the normal procedure of comparing the treatment group with another group on antidepressants, where the drugs are taken as "effective and safe." Instead, they used a control group who were treated exactly the same as the treatment group except their treatment was sham, meaning they didn't get the magnetic blast to the brain. Presumably, they were fed a recording of active TCMS as some of the machines are noisy.

They are also expensive. A clinic in Sydney called "TMS Erina - Clear your mind," charges A$400 for the first session and $200 for the rest (normally about 20 mins). As their website says a normal course is 35 sessions, that's a nifty $7,200 for which the Medicare rebate is a bit under $5000, so customers are about $2,300 out of pocket. However, that's for out-patients; for people in hospital, the sky is the limit. But back to the veterans' study.

They had 164 patients who were "treatment resistant," meaning two drugs had failed to lift them out of depression but, by grubbing through the paper, we find that 76% of them were unemployed and over half of them had a diagnosis of substance abuse. As a group, they were white (75%), older (mean age 55yrs) and not very well educated. Being an older unemployed veteran in the US is definitely a mental health hazard so that may have had something to do with why tablets didn't make them bounce around cheerfully. Anyway, after up to 30 sessions, the results were quite clear: 40% of the treated veterans had recovered while, of the sham group who did not get "the treatment," 40% of them had also recovered. No difference. A further follow-up at 24 weeks gave much the same result. Amazing.

I suspect this was a shock to the researchers who had put a great deal of time (and government money) into this study. Their earlier papers made it quite clear that they expected TCMS to be far better than no treatment. They couldn't explain the result but suggested that "non-specific" factors were important. For example, patients were interviewed regularly and had lots of contact with hospital staff and the researchers: "These findings may reflect the importance of close clinical surveillance, rigorous monitoring of concomitant medication, and regular interaction with clinic staff in bringing about significant improvement in this treatment-resistant population." At the end of their paper, they suggested that the results were encouraging and needed more research:

Future work with (TCMS) may show an enhanced effect when newer coil models, better stimulus targeting, biological markers of response, higher frequency rates of stimulation, and longer duration of treatment are implemented.

That is, they wanted more and better TCMS machines, not research into why no treatment was as effective as treatment. This was interesting because, long before TCMS became the latest hot treatment in mental disorder, even before ECT, there was insulin treatment. This goes back about a hundred years, to when insulin was isolated in 1922. It was quickly found that overdose with insulin produced very low blood sugar levels, resulting in seizures, so this had to be avoided during treatment of diabetes. A few years later, a pathologist in Hungary, Laszlo Meduna, was studying the brains of patients who had died either of epilepsy or with schizophrenia. It was thought that epilepsy somehow protected against schizophrenia, and he found what he thought was the reason. Compared with those with schizophrenia, the brains of people who suffered epilepsy showed widespread, minor damage. Meduna wondered whether losing neurons was the protective factor, as in "too many neurons for their own good," so he had the idea of inducing seizures in people with schizophrenia to cause diffuse brain damage in the hope of improving their condition. He started experimenting with a camphor product to cause convulsions and it wasn't long before insulin was pulled in to do the same job.

Over the next thirty years, mental hospitals in many parts of the world set up specialised units to administer insulin to patients to induce seizures. These were expensive to run and soaked up a large part of the hospital's budget but it was felt that anything that could get people back home had to be used. In 1939, a paper by an influential British psychiatrist, Ian Skottowe, in the prestigious journal, Proceedings of the Royal Society of Medicine [2],suggested that the problem in schizophrenia is that brain cells are short of sugar, so reducing the blood level shocks them into getting better. Or something, it makes no sense at all but it was widely quoted and everybody was happy with it. ECT had just been developed but there was competition between psychiatrists who thought insulin coma treatment was better and those who favoured ECT, because it was quicker, cheaper and didn't require so much specialised nursing.

This little cat fight continued until 1953, when a trainee in psychiatry in London published a paper in Lancet with the provocative title of The Insulin Myth [3]. Harold Bourne was then aged thirty but he had had extensive experience in some of the huge mental hospitals in England and had been involved in insulin treatment at close hand. By a careful analysis of all the figures available (not many), he concluded that the insulin treatment itself was essentially worthless. The factors that counted were the fact that patients were highly selected toward those with a good prognosis; they were given intense treatment in what was seen as an elite unit by staff who firmly believed the treatment was a godsend; and they were given extra diets and privileges as part of their treatment. They were special patients in every respect.

The reaction of the Establishment was immediate and bitter. Many of the most senior psychiatrists in the country had built their reputations on using insulin coma treatment. They were infuriated by the idea that a young nobody could come along and, using figures alone, argue that the treatment they believed in was a waste of time (and money). Effectively, he was saying that their "clinical experience," in which they had an almost delusional belief, was valueless. In smaller hospitals, insulin treatment soon fell into disuse but the chiefs of psychiatry persisted with it. For example, the future president of the Royal College of Psychiatrists, Sir Martin Roth, continued using it until the early 1960s and praised it in his textbook. Dr Bourne was not able to get a job in the UK so he went to Otago University in New Zealand, where he was very popular. When he went back to the UK in 1974, he worked in child psychiatry until he retired at age 65, after which he moved to Rome where he worked as psychotherapist to the expatriate community. In 2014, he moved back to London because of ill health and died in 2018.

The point here is that the "effective therapeutic factors" of insulin treatment, described just on 70 years ago, are essentially the same as those described in the paper on TCMS. If you treat mentally troubled people nicely, a lot of them will actually get better. Truly amazing. I have emailed a courteous letter to the VA group pointing out the similarity between their conclusions and those by Dr Bourne so long ago, asking them if they can offer any suggestions as to why psychological management is so effective in what they believe is a biological disease of the brain. I don't expect an answer because, as we all know, their belief in their "treatment" is stronger than their belief in the evidence.

So back to the question in the title? "What does sham treatment tell us?" It should tell us whether a form of treatment is effective, and what are the effective components of the treatment program. In fact, what it normally tells us is that psychiatrists are wedded to their doctrinaire belief that all mental disorder is biological in nature, and we don't need to look at all that tender-hearted stuff like (erk) feelings. So much for the notion that modern psychiatry is "evidence-based."

Talking of "evidence base," in my post on February 21st, I described the drama over getting a copy of a lecture on ECT given to the members of the Qld Mental Health Tribunal. After various appeals, the decision from the Information Commissioner is I can't have it, it's secret because they say it is and that's that. When I get the energy, I'll send a firmly worded letter to the president of the Tribunal arguing that it is her moral duty to release the information. I have never met a lawyer who was swayed by moral arguments but we'll see. My (expensive) application for information relating to the refusal of the Qld to allow the UN Committee for the Prevention of Torture to access institutions here is awaiting action, as they say.

PS I have been able to correct the payment system so it is now in AUD, which is a lot cheaper. If you wish to donate (to help pay for the FOI applications and so on), you will need to correct from USD. Thank you.

References:

1. Yesavage JA et al (2018). Effect of Repetitive Transcranial Magnetic Stimulation on Treatment-Resistant Major Depression in US Veterans. JAMA Psychiatry. 2018 Sep; 75(9): 884–893.

Published online 2018 Jun 27. doi: 10.1001/jamapsychiatry.2018.1483

2. Skottowe I (1939). Shock Therapy: A Plea for Proportion in Psychiatry. Proceedings of the Royal Society of Medicine . Vol XXXII, pp843-852.

3. Bourne H (1953). The Insulin Myth. The Lancet. Nov 7th 1953, pp964-968.