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March 25, 2013 by Sandra Steingard, MD

Optimal Use of Neuroleptic Drugs: An Introduction

I have recently put together a talk in which I summarize my current thinking on the optimal use of neuroleptic drugs, primarily focusing on the treatment of individuals who are experiencing psychotic symptoms. In order to foster conversation on this topic, I will be posting the content of this talk in a series of blogs.

First of all, I stipulate two points:

  • These drugs can be very effective for some people in the short term in reducing symptoms of psychosis.
  • Once someone is started on these drugs, the risk of relapse is much higher when they are stopped than when they are continued.

Current treatment standards suggest that:

  • Antipsychotic medications are critical to the treatment of schizophrenia.
  • Antipsychotic medications should be started ASAP.
  • Long term maintenance medication is recommended.

In addition, current treatment practice is:

  • When a person does not respond, dose is increased.
  • Dose is often increased faster than drugs typically work.
  • Additional medications are added fairly often.
  • An enormous amount of resources are devoted to insuring that patients remain on medications.

These are questions that I want to address:

  • When should we begin/what is risk of waiting?
  • How much drug is needed?
  • Should everyone remain on these drugs indefinitely?
  • Is it appropriate to consider relapse as a uniform phenomenon with uniform risks?

This is the argument I will put forth in future blogs:

  • The impression of short term efficacy tends to be inflated.
  • The impression of long term risk tends to be minimized.
  • The impression about the risks of delaying treatment (Duration of Untreated Psychosis) with antipsychotics is inflated.
  • Although antipsychotics are sometimes remarkably effective in reducing psychotic symptoms, this does not mean that they are always required.
  • Compliance is low despite our recommendations so it is almost impossible to comply with recommended guidelines.
  • Relapse does not carry the same risk for all individuals.
  • In the early 1990’s, there was a growing recognition that only minimal D2 blockade was needed to produce optimal results. This concept got lost in the years when the newer antipsychotics were highly promoted but concept remains valid.
  • Joe McEvoy and colleagues (Archives of Gen Psychiatry 48:739-745, 1991) conducted a study in which they determined the minimal dose of haloperidol needed to produce very slight extrapyramidal symptoms, i.e., muscle stiffness. In a carefully controlled study, he found that low doses of haloperidol (on average about 3.5 mg) were just as effective as the higher doses that were commonly used that the time (10-20 mg). Raising the dose above that was only likely to produce more side effects without further clinical improvement.

I come to the following conclusions:

  • Since many people choose to stop, since some may get better without medications, since some may be able discontinue with slow taper, since relapse is not universally a disaster, we should revise our practice standard to try to wait before starting drugs and consider discontinuation in a controlled manner.
  • Since these drugs are not as effective as most people think, we should approach failure to respond with more judicious use of drugs rather than by adding on more drugs.
  • The current practice of recommending that almost all individuals remain on these drugs indefinitely should be challenged.
  • We need to reconsider what we consider informed consent.

In the next blog, I will provide the data that support these assertions. I will provide references for specific articles but at the beginning, I want to cite several books which have had a big impact on my thinking in recent years. Each of them has informed me in important and sometimes profound ways.

Marcia Angel’s The Truth About the Drug Companies. In the 1990′s, I began to notice a disconnect between the published data and the perception of the efficacy of the new drugs. However, I did not have enough data to fully understand this. Dr. Angel who was then the (first female) editor-in-chief of The New England Journal of Medicine began to write about this. She was in a position to understand how profound the influence of Big Pharma was on the practice of medicine and she tracked this story with a directness that took courage given her position at the time.

Irving Kirsch, The Emperor’s New Drugs. Dr. Kirsch is a psychologist who has written extensively about the efficacy of the antidepressant drugs. This book reviews not only his own work but also the larger topic of placebo.

Daniel Kahneman’s, Thinking, fast and slow. Professor Kahneman is a Nobel Laureate in economics. His work is in cognitive psychology. This book elegantly summaries research conducted over the past 50 years and gives us insight into how we think, form opinions, and make decisions. Humans have remarkable abilities of intuition but these abilities can also lead us astray in ways that are surprising and unsettling. It seems critical for anyone who ever has to make a decision to understand what Dr. Kahneman has to tell us about ourselves.

David Healy, Pharmageddon. Dr. Healy is familiar to readers of this website. This work is important in many ways but one critical message in the book is its discussion of the limitations of randomized clinical trials and the ways in which these can be distorted for commercial purposes.

Wendel Potter, Deadly Spin. Mr. Potter was a high level executive for a major health insurance company. Although, his book’s topic is not directly relevant to this discussion, I found it important because it sheds light on the ways that corporations invests huge resources into spinning their message not for the sake of the public good but to advance the financial interests of the corporations.

Robert Whitaker, Anatomy of an Epidemic. This needs no further explanation. This book directly influences this talk and I refer to some of the articles that he cites in his writing and talks. However, I cover some areas not directly addressed in the book, specifically the short term efficacy of these drugs and the question of the impact of not using drugs to treat psychosis.

I look forward to reading your comments.

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