In some of the countries where these studies of withholding medication were conducted, there are comprehensive health systems that provide organized support for the individual. The USA does not have this type of coordinated
mental health support, even in our large metropolitan areas. Lacking this, it may be unethical to conduct this type of study in this country.View all comments by Jim Botta
It seems bizarre to me to question the ethics of research utilizing non-medication interventions, when medications themselves are responsible for such incredible damage. Whether it's obesity, diabetes, movement disorders, or just general numbing of the mind, "antipsychotic" medications might best be characterized as a poisoned life raft—possibly useful in a pinch, but nothing we should be relying on if we can possibly avoid it. Jim Botta wants to use the lack of psychosocial support in the U.S. as an excuse to not even research alternatives to medication; of course, failing to do the research will only reinforce the continued over-reliance on medications and absence of alternatives. A wiser suggestion would simply be to insure that participants in such research be provided with adequate support. After all, research with good outcomes for people not utilizing medications (such as Soteria) have already been done in the U.S.; why shouldn't there be more such studies?
Long-term studies show that most people who make strong recoveries cease taking medication at some point, though quitting itself is often a difficult process. It makes sense to look for ways to help many people recover without ever getting dependent on medications.
View all comments by Ron Unger
I read with great interest the paper by John R. Bola, which faces a major issue of whether exploratory trials should be conducted on patients at their first psychotic episode. Is it ethically justified to postpone pharmacological antipsychotic treatment for specific research purposes for such patients?
The author used very stringent criteria for inclusion of trials in the meta-analysis that is depicted in table 2 of the paper. Six out of 10 studies included were conducted more than 25 years ago, when ethical criteria were not as stringent as in present years. Only two studies included DSM-IIIR diagnostic criteria, consistent with a modern conceptualization of schizophrenia, and both were conducted in European countries. The time of postponing pharmacological treatment, but not psychosocial intervention, was 6 weeks (including the Mosher study where DSM-II diagnostic criteria were used). In addition, the Finnish study allowed use of low doses of neuroleptic drugs if needed. The limitations of the studies reviewed are wisely and scrupulously summarized by the author.
My major concern is that deriving conclusions about possible long-lasting harm for patients for whom treatment was postponed by analyzing studies that addressed specifically the efficacy of one treatment versus placebo is a very hard task. Due to this core shortcoming, conclusions are indirect and weak. However, the author, with common sense and sensitivity, concludes that until now, no substantive evidence of long-term harm has been demonstrated for patients for whom antipsychotic drugs are postponed.
I believe that the complexity of the research question in the field of schizophrenia, which is a neurodevelopmental disorder, requires a reconsideration of ethical prohibitions. A problem that hasn’t been fully considered is that the disease process of spectrum psychoses begins some years before psychotic symptoms become apparent to close relatives, and that a time spanning from weeks to years may pass before a psychiatric consultation and an appropriate intervention is implemented. It should be noted that such evidence comes also from countries where the healthcare system is public, free of charge, and widely available to the population, and where there are strong commitments to prevention and to treating patients in the community. So the question may be: What kind of patients do we really study when we include them in a first episode trial? Are they really a representative sample of the “true” schizophrenia population?
A related question regards the setting in which we come into contact with patients. If the first contact is due to a hospital admission, is the disease process similar to patients who get in touch with a GP for an “anxiety episode” or for school failure?
Some research questions necessarily require a drug-free or drug-naive state for appropriate testing. In these cases, I believe that the most parsimonious approach is to consider the single experiment thoroughly from ethical, scientific, and clinical perspectives in order to approve the trials (or not).
General rules may hamper the progress of science, but an ethical framework may be useful, and should always be taken into consideration, for refining and designing experiments on humans.
View all comments by Vittorio Di Michele