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 Patients of all categories experience "rebound" symptoms across all classes of meds when they are abruptly withdrawn after long term administration or when doses are lowered too quickly.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.

Supersensitivity Psychosis: Is There Such a Thing, and If There Is Then Why the Hell Haven't We Heard About It Before?

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

In his book, "Anatomy of an Epidemic," Robert Whitaker easily debunked the chemical imbalance myth (see earlier blog piece), which rested on nothing more than some observations in search of an explanation.

The observation: "Certain drugs reduce psychiatric symptoms."

The explanation: "It must be because they correct a chemical imbalance."

The reality: "The brain is not chemical soup."

Whitaker then went on to cite with approval a different set of observations in search of an explanation called "supersensitivity psychosis." Supersensitivity psychosis is central to the whole point of Whitaker's book, which posits that our meds may actually worsen rather than improve the natural course of our illness.

This goes much further than stating that well-known side effects tend to make us feel worse rather than better. Suppose, instead, Whitaker asks, our meds actually amplify the very symptoms they are supposed to remedy? We know, for instance, that indiscriminate use of antidepressants can turn depressives into bipolars and classic bipolars into rapid-cycling bipolars.

What about antipsychotics? Are they really as "anti" as psychiatry makes them out to be, or is there a bit of "pro" to their effect? After all, if these meds truly worked the way Pharma would have us believe, there would be a lot less incidence of mental illness, with a lot less severity, rather than a lot more. Consider this the observation. The explanation may have something to do with many of us being hypersensitive to our meds. But does reality bear this out?

The story begins with the investigations of Guy Chouinard and Barry Jones of McGill University back in the late seventies. We know that antipsychotics knock out psychosis by blocking post-synaptic dopamine D2 receptors. But the brain compensates by, amongst other things, increasing the receptor binding sites on these very same neurons. This has been shown in postmortem brain samples of rats, and more recently in brain scans of humans.

If the antipsychotic (or neuroleptic) is suddenly withdrawn, the brain takes time to readjust, during which all manner of bad things may happen. Down in the nigrostriatal dopamine pathway, neurons are firing too rapidly to maintain full motor control, resulting in facial tics, agitation, and other disturbances. Or, should the patient stay on the med, the morphed neurons may reach a point of no-return. These disturbances may in time manifest as tardive dyskinesia, which is permanent.

So far, so good. But what if, Chouinard and Jones asked, something similar went on in the very dopamine pathway - the mesolimbic pathway - that antipsychotics are supposed to restore to normal? If you suddenly withdrew the antipsychotic, could "rebound" psychosis occur? And could a permanently altered brain turn good prognosis patients into chronic bad prognosis ones? As the authors explained in a 1980 article:

According to this hypothesis, the cessation of maintenance neuroleptic medication induces a relative increase in the mesolimbic dopamine function, leading to psychotic relapse or deterioration in the same manner as tardive dyskinesia can emerge or worsen when medication is stopped or decreased.

In a 1990 paper, Chouinard estimated the likelihood of 43 percent of patients on neuroleptics being affected in this manner. In one of his case studies, he cited "Mrs B," who had five relapses of acute psychosis over the first 22 years of her illness vs six in the last 10, and was no longer responding to increased doses.

"What was psychiatry supposed to do with this information?" asks Whitaker in his book. "It clearly imperiled the field's very foundation." Whitaker then relates how the dean of receptorology, Solomon Snyder of Johns Hopkins, came to psychiatry's rescue by assuring readers in a 1986 book that talk of supersensitivity psychosis was premature. Soon after, the hypothesis was consigned to the "interesting" file and the field breathed a sigh of relief.

Today, Whitaker observes, "the notion that antipsychotics increase the likelihood that a person diagnosed with schizophrenia will become chronically ill seems, on the face of it, absurd." Ask anyone - the top experts, the man on the street - and they "will attest that antipsychotics are essential for treating schizophrenia."

So is psychiatry to be damned for turning its back on us, or is Whitaker reaching too far in his quest for an explanation? Or are there simply a lot more nuances to the issue than he suggests?

Next: We look at the nuances ...   

Previous blog pieces:

Tuning Out the Distractions

Thanks to Stupid Advocacy, Your Life is Worth Just One Penny

The Study Psychiatry Wishes Would Just Go Away - Part II

The Study Psychiatry Wishes Would Just Go Away

Is the Cure Worse Than The Illness?

The Whitaker Controversy: An Irony in Search of Nuance

If Meds Work as Well as Our Psychiatrists Tell Us, Why Do We Have MORE Mental Illness Today Rather Than Less?

RIP: Chemical Imbalance in the Brain