Supersensitivity Psychosis: The Evidence

This is the tenth in my series based on talking points raised by Robert Whitaker's eye-opening "Anatomy of an Epidemic."

We left off with the shocking proposition that our antipsychotics may actually make us more prone rather than less prone to psychosis, thus turning good prognosis patients into chronic bad prognosis ones. The idea was first advanced in 1978 by Guy Chouinard and Barry Jones of McGill University, who coined the term, "supersensitivity psychosis."

We see supersensitivity at work in tardive dyskinesia, when one dopamine pathway (nigrostriatal) is overstimulated after post-synaptic neurons habituate to prolonged antipsychotic exposure. Since we're pretty sure this is true, Chouinard and Jones deduced that it was likely that another dopamine pathway (mesolimbic) was getting overwhelmed, as well. And, of all the crazy things, the particular side effect coming out of this pathway would be psychosis.

That's right - a med administered to treat psychosis with a side effect of psychosis.

This is not as crazy as it sounds. Patients of all categories experience "rebound" symptoms across all classes of meds when they are abruptly withdrawn after long term administration or when doses are lowered too quickly. Usually, the result is temporary, but even a remote prospect of this happening is extremely unsettling. Whitaker states that we may be better off by just saying no to antipsychotics over the long haul, where the best evidence we have indicates that patients fare better by not refilling their prescriptions.

Chouinard and Jones don't go nearly this far, instead restricting their focus to treating supersensitivity psychosis as it occurs and to picking up its early warning signs.

In their 1978 article, Chouinard and Jones referred to a study they conducted on 32 patients. Half the patients were taken off their antipsychotic and given a placebo. The eight patients whose condition deteriorated into psychosis also experienced tardive dyskinesia, lending credence to the  proposition that the two effects were related, induced by the same phenomenon over different pathways.

But here's the catch: How can you tell supersensitivity psychosis from the real thing? After all, if you take a patient off their antipsychotic, it stands to reason the illness will reassert itself. With tardive dyskinesia we know the effect is from the drug rather than the natural course of the illness. But what about psychosis? Chouinard tackled this problem in a 1990 article by proposing diagnostic criteria for "neuroleptic-induced supersensitivity psychosis." His main distinguishing feature was that once the antipsychotic is withdrawn or the dose lowered the psychosis comes on quicker and with greater frequency than illness-related psychosis.

Whitaker doesn't bring this up in his book. Indeed, his whole argument rests on the proposition that you can't tell the two apart, or at least that researchers have not taken the trouble. This is why relapse-prevention studies (which involve taking responding patients off the trial drug) are bogus, according to Whitaker, as the returning psychosis cannot be unequivocally attributed to the illness. As he describes it: "The severe relapse suffered by many patients withdrawn from antipsychotics was not necessarily the result of the 'disease' returning, but rather was drug-related."

Wait. We don't know for sure if it was drug-related. Whitaker has no business saying that. But he does have a point. At the very least, the possibility of supersensitivity psychosis raises "reasonable doubt" in all long-term antipsychotics trials, rendering them null and void.

But the same reasonable doubt exists with Chouinard's studies, as well, meaning that we don't really know the incidence of supersensitivity psychosis (Chouinard claims it may be as high as 43 percent). According to Joanna Moncrieff of University College London in a 2006 review article, "there is the problem of distinguishing the natural history of the underlying disorder from effects related to drug withdrawal," a point that Chouinard acknowledges in a 2008 piece.

Further research would shed light on the situation, but this raises major ethical issues, Moncrieff points out, as "it is difficult to justify experimental studies involving rapid discontinuation of drugs." Whitaker would have no choice but to agree. In the foreword to his book, he mentions clinical trials that came to his attention "that involved withdrawing schizophrenia patients from their antipsychotic medications, which was the unethical thing to do."

So where do we stand? Obviously there is something to the supersensitivity psychosis hypothesis. It may be as serious as Whitaker makes it out to be, but the hard evidence is lacking, and will be for some time to come. It may be as prevalent as Chouinard indicates, but again the hard evidence is lacking. Moreover, Chouinard is quick to add that most of this is reversible, upon the resumption of the antipsychotic. It is worth noting that Chouinard limits his focus to spotting and treating supersensitivity psychosis (often with higher doses and a concomitant mood stabilizer). The wisdom or folly of remaining on an antipsychotic is Whitaker's line of inquiry, not Chouinard's.

Does this mean that Whitaker is off-base? Hardly. His thesis may run far ahead of the evidence, but is nonetheless perfectly in line with the speculative dots he is connecting. We know that antipsychotics are blunt instruments at best. We know that many, if not most, patients on antipsychotics continue to lead miserable lives. Likewise, we know that quite a few patients may be better off not taking antipsychotics. Finally, we know that there is a lot we do not know.

We are already aware that there are many reasons to think twice before taking an antipsychotic, much less remaining on one. Whitaker has given us a few more reasons to be concerned. He may not be right, but someone needs to prove him wrong.