What I Have Changed My Mind About: There is No Science in Psychiatric Clinical Trials

Patient Expert

Last month, I took a look at an Edge question from a bipolar perspective. Each year, Edge - which bills itself as on online salon - poses one question to more than 150 of the deepest thinkers in the world, then publishes their answers as a book.

In my first piece, I addressed "What Scientific Concept Would Improve Everybody's Cognitive Toolkit?" My answer was the restorative power of sleep. You can click the link to check out my reasons.

OK, this month's question: "What Have You Changed Your Mind About? Why?"

Since first writing about depression and bipolar back in 1999, I have changed my mind about many things. The one that literally jumps out of my brain is the so-called scientific validity of clinical drug trials.

Basically,   although there are many clinical drug trials for psychiatric conditions,, we have no true "evidence-based medicine."

I first entered the field with a far more accepting frame of mind. Over the course of about six years, my attitude shifted from mildly skeptical to having serious reservations to contemptuously dismissive. I can cite more reasons than all the quarters in all the coin-operated washing machines in all the world. I will focus on two:

1 No evidence base for long-term treatment.

2 The one-size-fits-all nature of testing psychiatric meds.

We can get through the first one in a jiffy. Clinical drug trials for psychiatric conditions typically last four to eight weeks. They test patients in the crisis phase of their illness, using very high doses.

Needless to say, what may get us out of crisis and what may be useful for maintaining long-term wellness are two totally different concepts. Unfortunately, credible long-term trials do not exist. If you find this hard to believe, check out any psychiatric medications treatment guideline for convincing citations. (See my HealthCentral post here.)

Translation: Your doctor is treating your long-term condition based on short-term evidence.

As for the second: "Depression" and "mania" and "psychosis" and "anxiety" do not describe what is biologically taking place in the brain. At best, they are umbrella terms to describe visible symptoms, equivalent to "pain" and "fever" and "runny nose."

So ... What if your real condition is a rare gene copy variant that results in a failure of a certain enzyme to degrade glycine? Funny you should ask.

In his latest Director's Blog post, Thomas Insel, head of the NIMH, mentions the case of Jessie Close, sister of the actress Glenn, and her nephew, Calen Pick. Jessie has been diagnosed with bipolar, Calen with schizophrenia.

Recently, a research team at McLean Hospital outside Boston discovered that both Jessie and Calen possessed the same rare glycine copy gene variant. When the doctors administered glycine under controlled double-blind conditions, "their psychiatric symptoms largely resolved."

Dr Insel first notes that a single condition may underlie two different diagnoses. Think about that for a second. Maybe their real illness is "glycine failure disease." Maybe if researchers were to conduct large-scale clinical trials of glycine on people with "glycine failure disease," they would get spectacular results.

But not everyone with bipolar or schizophrenia may have this glycine condition. Thus, the absurdity of testing a specific med on an "umbrella" population. Indeed, Dr Insel mentions this is exactly what happened - a glycine med tested on patients with "schizophrenia." Surprise, surprise - no evidence of efficacy.

Dr Insel asks us to imagine giving antibiotics to everyone with "fever." The antibiotic, of course, is bound to fail on all those whose fever is the result of a viral infection.

Let's focus on "depression." A successful antidepressant trial results in at least 50 percent of patients showing at least 50 percent improvement. Trial results are typically only slightly better than the placebo. Sometimes, the placebo actually beats the antidepressant.

What we can infer from these trials is that an antidepressant works very well for some, merely OK for others, not at all for still others, and is a total disaster for a good many.

Who are these people? We don't know, other than they have "depression." The same can be said for mood stabilizers for "bipolar."

Does this sound totally ridiculous to you? Maybe now you can see why I changed my mind about the scientific validity of clinical trials. There is no science.

Please do not interpret the above as advice to go off your meds. The science may be lacking in that it fails to predict which meds will work for certain groups of people. We are all unique. But through personal trial-and-error we may find the right meds at the right doses. This is not exactly science, but through persistence we can often arrive at a satisfactory result.

But do maintain a healthy skepticism. Do challenge your doctor. Do take the lead in your own treatment and recovery.

Please feel free to give us your own answer to the question, "What Have You Changed Your Mind About? Why?"

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