Letters to the Editor: Response to “Better Off Without Antipsychotic Drugs?”

August 15, 2014

Are patients with schizophrenia better off without antipsychotics? Here: a point/counterpoint.

Response to Dr Torrey’s Commentary

“Better Off Without Antipsychotic Drugs?”

In a recent Psychiatric Times Commentary,1 Dr E. Fuller Torrey references an article I wrote for The Washington Post.2 I am heartened that Dr Torrey and I have critical areas of agreement, specifically that not everyone who experiences an episode of psychosis will require lifelong drug treatment and that some patients will respond to doses much lower than are commonly prescribed.

Dr Torrey, however, neglected to address some of my core concerns. My article was prompted by a recent study by Wunderink and colleagues.3 This article reported the results of a follow-up study completed several years ago. In the initial study of first-episode psychosis,4 patients were randomized to one of two treatment strategies: maintenance treatment (MT) in which they were maintained on antipsychotics for 2 years, or drug discontinuation (DR) in which the drugs were stopped and restarted if symptoms recurred. In the initial report, they found that the DR group had a higher rate of relapse-no advantages for DR were seen. This study supported the standard practice of recommending that patients remain on antipsychotic therapy continuously.

In the recent report, they followed up with these individuals 7 years later. In the article, 3 categories of recovery are defined:

• Symptomatic remission: few or no psychotic symptoms

• Functional recovery: good function (self-care, relationships, work)

• Full recovery: both symptomatic remission and functional recovery

At 7 years, a clear difference was seen between the MT and DR groups: while both had similar rates of symptomatic remission (approximately 67%), the DR group had a much higher rate of functional recovery (46.2%) and full recovery (40.4%) than the MT group (19.6% and 17.6%, respectively).

The researchers also compared all patients by dose. Those who were receiving no drug or very low doses (less than 1 mg of risperidone equivalents) had a 52.9% rate of recovery compared with 17.4% for those receiving higher doses. This supports Dr Torrey’s point that dose matters. At 7 years, the MT group had the same rate of relapse; it appears that MT postponed but did not reduce the risk of relapse.

There are other studies that support Wunderink’s findings. Johnstone and colleagues5 conducted a somewhat similar study, known as the Northwick Park Study, in the 1980s. They randomly assigned 120 patients who had recovered from a first episode of psychosis to maintenance treatment with drug or placebo and followed them for 2 years. While the placebo group had a higher rate of relapse during this time, they also had an overall higher rate of employment. The authors wrote, “It suggests the disquieting conclusion that the benefits of active neuroleptics in reducing relapse may exact a price in occupational terms.”

More recently, Gleeson and colleagues6 reported on the effects of relapse prevention therapy (RPT), an intervention that was designed to improve adherence to neuroleptic treatment in individuals with first-episode psychosis. Findings indicate that with RPT, more patients continued taking medication, and over the first 12 months, the rate of relapse decreased. But similar to the Wunderink and Johnstone findings, they report that at 30 months, there was no advantage with regard to relapse rate for the experimental group and their vocational outcomes were worse. In other words, drug adherence was associated with worse functional outcome.

Another study also raises questions about the effects of neuroleptics on long-term outcome. For more than 20 years, Harrow has been following a group of individuals who experienced an episode of psychosis. He has found that those who stopped taking neuroleptics had much better outcomes than those who continued taking medication. His study is naturalistic, and one possible explanation for these findings is that those who recovered stopped taking their drugs. However, a recent paper of his raises some doubt about this explanation.7 The presence of psychotic symptoms over the 20 years were examined and compared in 3 groups: those taking drugs at every follow-up visit (group 1), those taking drugs on some but not all visits (group 2), and those not taking drugs at any of the visits starting at the 2-year point (group 3).

At 2 years, 74% of individuals in group 1 had psychotic symptoms, as did 60% of those in group 3. Although these differences are not statistically significant, the lines diverge at year 4.5 and continue to diverge over the next 15 years. At 4.5 years, 86% of group 1 have psychotic symptoms compared with 21% of group 3. By year 20, the difference is 68% compared with 8%.

If the group who stopped taking drugs did so because they were better, one would have expected to see that difference at 2 years, when medications had already stopped being taken. That is, if recovery led to drug discontinuation, then recovery should precede drug discontinuation; however, recovery began a few years after the drugs had been stopped.

This raises troubling questions for psychiatry. Psychosis can be dramatic, frightening, and disruptive. Dr Torrey understandably bemoans the poor outcomes for so many who suffer from psychosis. However, psychiatrists are assigned a powerful role in our society; we can force patients into treatment, and this sometimes includes forcing them to take these drugs. Dr Torrey has been one of the strongest proponents for this. In taking on this task, it seems that psychiatry should be assiduous in assessing risk and utterly transparent in our disclosures. This risk includes not only the failure to treat but also the consequences of our treatments. Yet, this has not been our history. Our profession has been slow to address the limitations of our drugs. We were slow to acknowledge tardive dyskinesia and slow to address the metabolic impacts of the newer antipsychotics. Will we be equally slow in addressing their impact on long-term recovery?

Sandra Steingard, MDMedical Director
HowardCenter; Burlington, Vt

References

1. Torrey EF. Better off without antipsychotic drugs? Psychiatr Times. June 18, 2014. http://www.psychiatrictimes.com/psychopharmacology/better-without-antipsychotic-drugs. Accessed July 17, 2014.

2. Steingard S. A psychiatrist thinks some patients are better off without antipsychotic drugs. Washington Post. December 9, 2013. http://www.washingtonpost.com/national/health-science/a-psychiatrist-thinks-some-patients-are-better-off-without-antipsychotic-drugs/2013/12/06/547f5680-48aa-11e3-a196-3544a03c2351_story.html. Accessed July 17, 2014.

3. Wunderink L, Nieboer RM, Wiersma D, et al. Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial. JAMA Psychiatry. 2013;70:913-920.

4. Wunderink L, Nienhuis FJ, Sytema S, et al. Guided discontinuation versus maintenance treatment in remitted first-episode psychosis: relapse rates and functional outcome. J Clin Psychiatry. 2007;68:654-661.

5. Johnstone EC, Macmillan JF, Frith CD, et al. Further investigation of the predictors of outcome following first schizophrenic episodes. Br J Psychiatry. 1990;157:182-189.

6. Gleeson JF, Cotton SM, Alvarez-Jimenez M, et al. A randomized controlled trial of relapse prevention therapy for first-episode psychosis patients. J Clin Psychiatry. 2009;70:477-486.

7. Harrow M, Jobe TH, Faull, RN. Does treatment of schizophrenia with antipsychotic medications eliminate or reduce psychosis? A 20-year multi-follow-up study. Psychol Med. 2014. http://www.mentalhealthexcellence.org/wp-content/uploads/2013/08/HarrowJobePsychMedMarch2014.pdf. Accessed July 17, 2014.

Dr Torrey Responds

Dr Steingard is correct that we agree that a subset of patients with schizophrenia will recover without antipsychotic medication, as has been noted for over a century. And we agree that many others can be maintained on “doses much lower than are commonly prescribed.” Conversely, for the same reason cited in my original article, a few patients need to be maintained on doses much higher than are commonly prescribed.1

Dr Steingard says I failed to address some of her “core concerns,” although she does not explicitly say what those are. Rather, she cites studies in which individuals who did not continue maintenance antipsychotic medication appeared to have a better long-term functional recovery than those who did. The most interesting of these is the Dutch study by Wunderink and colleagues.2,3 One major problem with this study is that the results are based on a select sample of patients; half (129/257) of the patients recruited for the study refused to participate, were lost to follow-up, or never recovered. Another major problem is that the study took place in the Netherlands, which has excellent mental health services, including rehabilitation services, far superior to those available in the US. Thus, it suggests that select, motivated patients who are not too sick may achieve a better functional recovery with minimum antipsychotics if intense rehabilitation services are available, although this study needs to be replicated.

The other studies cited by Dr Steingard have even greater limitations. For example, the naturalistic study by Harrow and colleagues,4 which did not include a control group, simply illustrates the fact that individuals with schizophrenia who are doing well tend to lower their dose or discontinue their medication. Similarly, the study by Gleeson and colleagues5 can also be interpreted as demonstrating that patients who are doing well are less likely to continue taking their medication. Dr Steingard suggests that this means that “adhering to drugs was associated with a worse functional outcome.”

In contrast to these small studies of nontreatment, I would remind Dr Steingard that the ultimate study of nontreatment has been going on for 50 years and is called deinstitutionalization. Currently, 2.6 million individuals with schizophrenia have more or less randomized themselves to antipsychotic treatment or nontreatment. Among the latter group, approximately 200,000 are homeless and at least that many are incarcerated in jails and prisons, mostly for crimes committed because of their untreated disease. The latter group is also victimized much more commonly. The difference between the two groups on virtually any measure of well-being is highly statistically significant.

It is also important to remember that the patients/consumers who blog on antipsychotic medication Web sites are a select group. They do not include my two former patients with schizophrenia who were told by social workers that antipsychotic drugs are dangerous; both stopped their medication and subsequently jumped off bridges. And they don’t include my former patient who did very well while taking antipsychotics but said he preferred his voices to the sexual adverse effects of the medication. He was subsequently stabbed to death by a woman he inappropriately approached and who became terrified by his bizarre behavior. These individuals are no longer alive to blog about the pluses and minuses of antipsychotics.

So yes, let’s agree that the antipsychotic, mood-stabilizing, and antidepressant medications we have available are far from perfect and should always be used with regard to weighing possible benefits against possible risks. But let’s also agree that schizophrenia, bipolar disorder, and severe depression are not merely “behavioral health problems,” as the Substance Abuse and Mental Health Services Administration calls them, but rather vicious brain diseases that can destroy lives and families. These medications have helped millions of people affected by these diseases lead better lives, and we should regard them as an important and integral tool in our armamentarium to help such individuals recover.

E. Fuller Torrey, MDAssociate Director
Stanley Medical Research Institute
Chevy Chase, Md

References

1. Torrey EF. Better off without antipsychotic drugs? Psychiatr Times. June 18, 2014. http://www.psychiatrictimes.com/psychopharmacology/better-without-antipsychotic-drugs. Accessed July 21, 2014.

2. Steingard S. A psychiatrist thinks some patients are better off without antipsychotic drugs. Washington Post. December 9, 2013. http://www.washingtonpost.com/national/health-science/a-psychiatrist-thinks-some-patients-are-better-off-without-antipsychotic-drugs/2013/12/06/547f5680-48aa-11e3-a196-3544a03c2351_story.html. Accessed July 21, 2014.

3. Wunderink L, Nieboer RM, Wiersma D, et al. Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial. JAMA Psychiatry. 2013;70:913-920.

4. Harrow M, Jobe TH, Faull RN. Does treatment of schizophrenia with antipsychotic medications eliminate or reduce psychosis? A 20-year multi-follow-up study. Psychol Med. 2014. http://www.mentalhealthexcellence.org/wp-content/uploads/2013/08/HarrowJobePsychMedMarch2014.pdf. Accessed July 21, 2014.

5. Gleeson JF, Cotton SM, Alvarez-Jimenez M, et al. A randomized controlled trial of relapse prevention therapy for first-episode psychosis patients. J Clin Psychiatry. 2009;70:477-486.