1 Boring Old Man

On has to be awed by blogger Neuroskeptic whose scope far exceeds the rest of us combined. Here, he clears up the dilemma I obsessed about recently. When the results of the RAISE study were published a few days ago, the extensive press coverage proclaimed that the NAVIGATE [NAV] patients received a much lower dose of antipsychotics than those with treatment as usual [TAU], yet the paper itself said nothing about the drug doses. That’s a hot issue at the moment. Traditional psychiatric teaching has been that maintenance medication [and plenty of it] was an important ongoing part of treatment to prevent psychotic relapses, whereas an initiative from Mad in America, the British Psychological Society, the studies of Wunderink and Harrow, etc. suggest that maintenance medication interferes with long term functional recovery. And the ideological and guild-driven overlay on this point hangs heavily over any and all opinions on this matter. So the difference between the media hype and the actual papers caught the eye of many [including yours truly – see raising a dilemma…]. Says Neuroskeptic on this point:

Medication for Schizophrenia: Less is More?

Neuroskeptic: Discover Magazine

By Neuroskeptic

October 27, 2015

According to the New York Times [NYT] a week ago, a major new study found that lower doses of antipsychotics are better for the treatment of schizophrenia:

The findings, from by far the most rigorous trial to date conducted in the United States, concluded that schizophrenia patients who received smaller doses of antipsychotic medication and a bigger emphasis on one-on-one talk therapy and family support made greater strides in recovery over the first two years of treatment than patients who got the usual drug-focused care.

The paper, by John M. Kane and colleagues and published in the American Journal of Psychiatry [AJP], is called Comprehensive Versus Usual Community Care for First-Episode Psychosis and it presents the results of the NIMH “RAISE” study. Three days ago the NYT accordingly issued a correction:

An article on Tuesday about a study of the treatment of first-episode schizophrenia referred incorrectly to the conclusions of the study. Though it studied a program intended to reduce medication dosages, the researchers do not yet know for sure if dosages were lowered or by how much. Therefore, the study did not conclude “that schizophrenia patients who received smaller doses of antipsychotic medication and a bigger emphasis on one-on-one talk therapy and family support made greater strides in recovery.”

Which is more like it.

Actually, it’s what I want to hear too. I never didn’t think that a broad intensive focus on the individual and the family with adequate resources [including brief hospitalization when required] along with the careful use of medications was the right approach to these patients. I thought it in the 1970s and in all the years in between. My only recent questions have been whether the RAISE version is the right version and whether it will convince the powers that be to implement some version widely.

The intervention was in fact a complex mix of family and individual support and therapy, supported activities and employment, and a computerized medication management system called COMPASS.

One of the features of COMPASS is that it recommends doctors to use lower doses of antipsychotics than they otherwise might. The COMPASS manual advises that people suffering their first psychotic episode are more sensitive to antipsychotics, and so lower doses will suffice, compared to chronic schizophrenia patients. However, Kane et al. report no information on dosage so we don’t know if the intervention group were actually taking lower doses than the controls.

So where did the focus on medication dosage come from? Possibly from this NIMH press release from 20th October, the same day the NYT story ran, which says that RAISE

Featured a team of specialists who worked with each client to create a personalized treatment plan. The specialists offered recovery-oriented psychotherapy, low doses of antipsychotic medications, family education and support…Featured a team of specialists who worked with each client to create a personalized treatment plan. The specialists offered recovery-oriented psychotherapy, low doses of antipsychotic medications, family education and support…Featured a team of specialists who worked with each client to create a personalized treatment plan. The specialists offered recovery-oriented psychotherapy, low doses of antipsychotic medications, family education and support…

Which is technically true, but a little ambiguous. “Offered low doses” could be read as implying “provided low doses”, and presumably the NYT article was based on such a reading, yet there’s no evidence to suggest that the doses provided were actually lower than in the control group. Even if the doses were lower, we don’t know if the low doses were contributing to the better outcomes in the intervention group, because that group got all kinds of other extra treatments as well [e.g. family therapy, supported education]. Theoretically the lower doses might have been harmful if the harm was outweighed by the other beneficial stuff. Or equally, the lower doses might account for all the benefit. We just don’t know.

Looking over their Manuals [COMPASS, INDIVIDUALIZED RESILIENCY TRAINING] and the NIMH Press Release, I have complaints. The COMPASS Manual is algorithmic and recommends only second generation antipsychotics. I’m not at all sure I agree with that. The metabolic syndrome is not always less ominous than the neurological side effects of the first generation drugs in my hands. And I’m not at all in love with the IRT approach which is not as focused on the Schizophrenic cognitive problems as I would prefer. However, I’m no expert, and there’s plenty of room for iteration in both areas.

But as much as I appreciate Neuroskeptic’s detective work, I don’t buy that "we just don’t know" about the medication doses. I’m suspicious that "we just weren’t told." That data is in some perfectly adequate computer database and there are more than enough statisticians involved in this project to extract it for us. So I’m suspicious that it doesn’t quite show what they want it to show, and  that’s why "we just don’t know." Likewise, that confusing Table 2 in the paper is unnecessarily obtuse. There are a lot more intelligible ways to display the outcome that they didn’t choose. So I smell something fishy, hear something spinning. Time will tell.