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Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial

BMJ 2012; 344 doi: (Published 05 April 2012) Cite this as: BMJ 2012;344:e2233

Re: Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial

I appreciate the hard work of Professor Morrison and colleagues in developing their study design and data interpretation (1). This is the largest trial to date looking at a population at risk for psychosis. And it is good when solid study methodology and a good sample size lead to conclusions that contradict prior pessimistic formulations. In this case it would be great news to report that the conversion rate to psychosis in at-risk population is lower than what’s been previously reported. The 8% conversion rate of Morrison et al. study is much better that rates of up to 38% conversion in untreated at risk samples (2). But is this truly the case?

Unfortunately to confidently draw this conclusion one would need much better clarity with regards to the subjects' antipsychotic medication history. Instead we are summarily told that 14 subjects in the cognitive therapy arm and 13 subjects in the monitoring arm were prescribed antipsychotics. However we do not know if these were the subjects that eventually converted; if this were the case, this would indeed greatly strengthen the conclusion that perhaps the rate of conversion might have been overestimated in prior studies. However if it turns out that the antipsychotics were prescribed for a completely different group of patients (than the patients who ended up converting) this would indicate that the antipsychotics were in fact the causa proxima for the relatively low rate of conversion. If this were to be the case the logical conclusion would be that we are only looking at a conversion rate lowered by the antipsychotic protective effect.

The authors appropriately address the potentially confounding effect of ”active monitoring” which might have resulted in more of an active intervention than just plain monitoring. I actually find the term “monitoring” a bit misleading. As in fact we are looking at “an enhancement over routine care” including non-judgmental, empathic listening and psychosocial services, factors that have all been reported to be therapeutically effective. To make matters even more complicated the active group were offered CBT on top of active monitoring, rather than as a parallel intervention. As a result, we are looking at controls who have received a lot of services, or active subjects who have received not only a lot of services but also additional therapy.

Then the fact that the subjects in this study did better than prior samples might simply be an effect of an active intervention across study groups. Not a true lower conversion rate but a treatment effect.

Finally the study design and findings raise questions about which was the active intervention. And the evidence seems to indicate that we are looking at an "active monitoring" effect that plateaus and could not be further improved by the addition of CBT.

In a way Professor Morrison’s study leads to a somewhat paradoxical conclusion: in lack of a clear additional gain, the recommendation would be against CBT (the "active" intervention) and in favor of active monitoring (the "control" intervention), which turns out to be the true active intervention, for a population at risk for psychosis.

Adrian Preda, Health Sciences Associate Professor of Psychiatry,


1. Morrison AP, French P, Stewart SLK, Birchwood M, Fowler D, Gumley AI, Jones PB, Bentall RP, Lewis SW, Murray GK, Patterson P, Brunet K, Conroy J, Parker S, Reilly T, Byrne R, Davies LM, Dunn G. Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial. BMJ 2012; 344: e2233 doi: 10.1136/bmj.e2233.

2. McGlashan TH, Zipursky RB, Perkins D, Addington J, Miller T, Woods SW, Hawkins KA, Hoffman RE, Preda A, Epstein I, Addington D, Lindborg S, Trzaskoma Q, Tohen M, Breier A.Am J Psychiatry. Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis.2006 May;163(5):790-9.

Competing interests: No competing interests
04 May 2012
Adrian Preda
Health Sciences Associate Professor of Psychiatry
University of California Irvine
101 The City Drive S Orange CA 92868
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