Do Antipsychotics Help or Harm Psychotic Symptoms?

This is the latest, and perhaps last, of several debates with Bob Whitaker on the role of antipsychotics in treating psychotic symptoms.
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This is the latest, and perhaps last, of several debates with Bob Whitaker on the role of antipsychotics in treating psychotic symptoms. It was triggered by a recent email exchange that clarified our areas of agreement and disagreement. Bob's blog summarizing his views and how he arrived at them can be found here.

Bob and I agree strongly on the following:

1) Antipsychotic medicines are used far too often in people who don't need them.

2) Even when necessary, doses are often too high and polypharmacy too common.

3) Antipsychotics are neither all good, nor all bad. Used selectively, they are necessary and helpful. They are harmful when used carelessly and excessively.

4) The treatment of people with psychosis relies far too much on medication alone, far too little on social engagement, psychotherapy, vocational rehabilitation, and providing adequate housing. We both like the normalizing, recovery models offered by Trieste, Open Dialogue, and Hearing Voices.

5) The care provided for the mentally ill in the U.S. is a disaster that shames our country.

Bob and I disagree strongly on the following:

1) Bob believes that long term use of antipsychotics makes psychotic symptoms worse. He therefore recommends that patients try to avoid antipsychotic medicine altogether or taper off them, whenever possible.

2) Bob believes that psychotic symptoms return when meds are stopped because of medication withdrawal, not relapse of the original disorder that first led to the use of antipsychotics.
3) Bob's views and biases have been shaped by his training as an investigative journalist and his experiences with fairly healthy people who have been harmed by too much medication. My views and biases have been shaped by my training as a clinical and research psychiatrist. Like Bob, I have seen many people harmed by taking too much medication, but unlike Bob, I have also seen many harmed by not having taken enough.

4) Bob's advocacy is ambitious, global, and future oriented- requiring a radical reconception of the US approach to people with psychosis. I am preoccupied more by the desperate, unmet needs of patients living dreadful lives in the current moment. In furthering his long range agenda, I believe Bob is misjudging what is best for severely ill people in the present. His recommended ideal treatment can only have a chance of success in an ideal treatment system. People who might do well with less medicine in his ideal world often get in terrible trouble if they try to stop medicine in our shamefully neglectful real world.

5) Bob acts as if there is an inherent tension between service users and psychiatric providers. I see the current animosity as an unfortunate and idiosyncratic phenemenon, peculiar to the US, and partly contributed to by Bob's own passionate and somewhat misleading rhetoric.

6) Bob is a modest man who wrote: "You are giving me way too much credit in terms of any influence I have related to the state of our country's mental health, and certainly regarding what most consumers think about medication, or relationships between service users vs. providers and families." I see his role differently. Bob is by far the most powerful, articulate, and influential voice advising people with psychotic disorders that taking medicine will make their psychosis worse.

Bob's position that antipsychotics cause more psychosis than they cure is based on his fundamental misreading of the research literature. He makes much of the fact that patients who stay on meds are more symptomatic than patients who stop: "Why were 65% to 75% of the medication, compliant patients psychotic at the fifteen-year followup, and only 25% or so of those who had stopped taking meds by year two and stayed off them."

This is the classic error of confusing correlation with causality. The common sense interpretation of these findings is that the sicker patients have to stay on meds, not that the meds made them sicker. It is a truism throughout medicine that good prognosis patients don't need long term meds; poor prognosis patients do. Bob's contrary causal claim is an extraordinary one that requires extraordinary evidentiary support. He can provide none, because there is simply no proof to back up of his causal claim.

Bob's misreading fails to take into account the fact that psychotic presentations vary greatly in cause, severity, chronicity, prognosis, and appropriate treatment. Many psychotic episodes are transient. Some are stress related- eg a soldier in combat, a college kid or traveller who becomes delusional when away from home. Some are a transient part of mood disorder and remain quiescent if the mood disorder is successfully treated. Some are related to substance intoxication or withdrawal. Some are caused by head trauma or medical illness. And some normal people have hallucinatory experiences that cause no impairment and have no clinical significance. Transient psychotic symptoms in the above situations may require a short course of antipsychotics, but these should be gradually tapered after the episode has resolved. Generally this can be done without much risk of return of psychosis- assuming the stressor, substance problem, mood disorder, or medical problem has resolved. Bob and I would agree on short term or no antipsychotic treatment for such transient psychoses.

But I disagree strongly when Bob nonselectively applies the same recommendation to psychotic symptoms that are severe and impairing. My research and clinical experiences have repeatedly taught me the painful lesson that going off meds for people who have been stabilized on them is an extremely risky gamble that most patients eventually lose.

I began my career in psychiatry in the mid 1960s, just when antipsychotics were first being used widely. The new meds dramatically improved psychotic symptoms, but equally dramatically produced dreadful side effects, especially in the ridiculously high doses then being tried.

Troubled by this, I was one of the principal investigators on a multisite NIMH funded study testing the feasibility of two new approaches to reducing medication burden. The first was very low dose treatment; the second was expectant treatment, with meds used intermittently only when patients needed them. Patients were randomly assigned to 3 conditions: 1) standard dose injectible med; 2) one-fifth standard dose injectible med; 3) placebo injection with oral meds added as needed. All three groups also received intense individual and family therapy and social support, often done in the home. Many patients in the low dose and expectant groups did well, but the catastrophes were sometimes catastrophic and irreversible. I became convinced that the risks of going off meds for people with chronic psychosis usually overwhelm the benefits. It is the patients' decision to make, but my advice has been not to rock the boat when chronic psychotic symptoms are responding to meds. Stay on the lowest possible dose, but stay on it over time. When psychosis has been chronic, the risks of discontinuing medication usually far outweigh the benefits.

The caution that came from research experience was reinforced many times over by my clinical work in emergency rooms and hospital inpatient units. By far the most common cause of relapse in chronically psychotic patients is their stopping medication. I have seen many hundreds of patients get into serious legal trouble, lose jobs, lose families, or become homeless as a consequence of stopping meds.

I have suggested to Bob on several occasions that his statements depicting antipsychotics as mostly harmful may have the unintended consequence of promoting relapse in patients who are scared off the meds they desperately need. Bob's response is questionable and off point. "I think there is abundant evidence to support a conclusion that part of what you see upon the cessation of antipsychotics is a withdrawal syndrome, and yet is chalked up to the disorder."

Bob's emphasis on withdrawal over relapse is theory based and unsupported by empirical evidence. It resides on the speculative assumption that antipsychotics cause receptor hypersensitivity that accounts for return of symptoms. Perhaps such hypothesized withdrawal may someday turn out to be a partial causal factor in the return of symptoms in some people, but certainly it is neither necessary nor sufficient. The returning symptoms are generally identical to the pre-existing ones that initiated med use and are not at all like the withdrawal syndromes that are a huge problem with benzos, opioids, and SSRI's. The psychosis usually returns unpredictably months after the meds are stopped, not in any defined withdrawal period. If meds are tapered slowly, the possibility of withdrawal symptoms is further minimized or avoided, and any emerging psychotic symptoms can be even more confidently attributed to relapse off meds. Bob has confused the acute pharmacology of drug withdrawal with relapses of the primary disorder occurring a much later point in time.

There is no real evidence that hypersensitivity is related to the return of symptons. It is just Bob's unproven and in a way irrelevant theory For any given patient, it matters little why psychotic symptoms return when the meds are stopped. The harm is already done. And the special tragedy is that often psychotic symptoms that were kept under good control for years by medication maintenance will no longer respond nearly so well in treating an accute recurrence triggered by medication discontinuation. When things turn south once meds are withdrawn, they often stay south- not only in terms of symptom severity and duration but also the corollary consequences of family and job loss, jail, homelessness, suicide, violence, and accident.

Bob's stubborn insistence on blaming meds for causing psychosis also flies in the face of history and everyday common sense experience. Severe mental illness was part of the human condition well before antipsychotics were ever invented to serve as their cause. And we have an ongoing natural experiment in the many people who have untreated psychotic symptoms because they have refused meds or had no access to them. They manage to stay chronically psychotic and have poor outcomes, even though there are no meds to shoulder the blame.

Antipsychotics have many grave disadvantages that make them a last resort. They suppress symptoms, rather than curing them. They can cause unpleasant side effects and dangerous medical complications. They contribute to shortened life expectancy. And they are subject to wide overuse even when their is no indication. We should be extremely cautious and selective in their use quite independent of Bob's tenuous claim that they worsen psychosis.

This debate does have serious real world consequences.There is no more momentous decision in the life of someone who has had psychotic symptoms than whether ot not to stop meds- and it always comes up in the treatment, often repeatedly. If the person's symptoms have been brief and not life threatening, I fully encourage a decision to gradually taper and then stop. It is, under these circumstance, definitely worth the fairly minor risk of relapse to avoid the major risk of medication side effects and complications. Many of Bob's most enthusiastic followers are in this category- harmed by prolonged overtreatment for transient problems

Even among those who previously had chronic psychotic symptoms, perhaps 20-30% will have improved enough over time that medication is no longer necessary. But we have no way to predict in advance who belongs to the smaller group who will do well vs the majority who will do poorly off meds. When symptoms have been chronic and severe, the risk/benefit ratio shifts dramatically in favor of staying on the meds. Some may choose to make the risky bet, but they and families must first understand how risky it is. And the benefit of going off meds should be understood as reduction of side effects and complications. There should be no illusory promise that discontinuation will reduce psychotic symptoms. Bob's doctrinaire, ideological, and one sided warnings of medicine's harms can lead to reckless risk-taking.

My hope is that Bob will present a more balanced and objective view in his future writings and talks. Rather than emphasizing just one side of the equation, he should give due weight to both sides. He should openly admit uncertainty and recognize the possible dire consequences of people making life changing decisions based on unproven hypotheses. Scaring people who need them off meds on shaky evidence can lead to disastrous outcomes.

Bob is so definite in his position because it is frequently reinforced by emails like this from one of his enthusiastic followers: "Just an update: My son has been off Zyprexa and Abilify for almost six months now and he is doing very well, no more psychotic breaks or suicidal compulsions. And during his last hospital stay in March the doctor said we were 'killing' and 'torturing' him by trying to take him off the medication. It was your books that gave us the courage to disagree."

I have had many similar happy experiences tapering people off meds and am a great fan of 'deprescribing'- something that is much harder to do than prescribing. I have often seen miraculous effects reducing medication in people who previously had been overmedicated.

But I can match Bob's happy story with many hundreds of tragic endings when meds were stopped inappropriately. Here's one example: Bill had a teenage onset of chronic delusions and hallucinations that occasioned four hospitalizations before he was twenty. Fortunately, he was then stabilized enough on medication and psychotherapy to graduate from a community college, get a job, have a girlfriend, and avoid hospitalization for the next eleven years. Delusions remained in muted form, with some exacerbations under stress that responded to short-term increases in medication and increased frequency of psychotherapy visits. After reading Bob's book and against doctor's advice, Bill decided to try stopping his meds. All went well for three months, but then his voices returned for the first time in a decade, his delusions worsened, he became agitated, and couldn't sleep. Bill broke off relations with his family and girlfriend, drove cross country, ran out of money, was homeless for a week, and finally was caught stealing food from a grocery store. When a cop arrived to arrest him, Bill (who had never been violent before in his life) wrestled him to the ground causing a back injury. Bill is in jail and faces a ten year prison sentence.

The prisons and streets are filled with people whose lives are wrecked because they had no access to meds they needed or stopped taking them. The US has 350,000 mentally ill in prison for crimes that mostly could have been avoided if they had been provided with adequate treatment, decent housing, and an inclusive social environment. And 250,000 people with severe mental illness are homeless.

Bob and I have both fought against the massive and inappropriate overuse of antipsychotic medication. I hope he will now feel a responsibility to join me in also making clear that meds are essential for some and that stopping them entails severe risks. Bob's constituency should include not just those who can do better without meds, but also those who suffer greatly without them. They are without voice, shamefully neglected, and subjected to degrading life circumstances. Bob's could be a powerful voice to help bring the severely ill back into the human circle.

Allen Frances is a professor emeritus at Duke University and was the chairman of the DSM-IV task force.

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