All Sorts of Realities

Sandra Steingard, MD
23
81

In previous posts in this series, I noted that the standard treatment of conditions labeled as schizophrenia (and related disorders) is to start neuroleptics early and to continue them indefinitely.  This is based on the belief that untreated psychosis is bad for the brain and that relapse is much higher when the drugs are stopped than when they are continued. The rationale for this approach, and my discussion of the limitations of these assertions, were the topics of previous blogs in this series.

In this final post I want to discuss how realistic this paradigm of care is. Many people just do not want to stay on these drugs.  This has resulted in a system of care in which an incredible amount of resources are spent on insuring that people take them.  In much of the discussion on this topic, we tend to focus on people who stop them completely.  But there is another aspect to this story – the impact of missing a few doses.  This happens with most people who are prescribed long term medications not just those who are prescribed medications for psychiatric problems. This happens even when a person’s intention is to take the drug as prescribed.  What are the impacts of these “mild” periods of so-called “non-compliance”? (I have come to appreciate that this is a trigger word that offends some of my readers.  Please understand that it is a failure of my writing skills that I have employed the term used most often in the psychiatric literature.)

A study by Subotnik and colleagues (Am J Psych 2011; 168:286-292) asked this question in a group of 49 individuals who were enrolled in an intensive outpatient program for early episode psychosis.  They define non-compliance as follows in the following chart:

Category

Definition

Participants Meeting Criteria During Follow-Up Assessment (%)

Severe

Compliance with <50% of the prescribed oral risperidone dose for ≥4 consecutive weeks or dropped out

19

Moderate

Compliance with <50% of the prescribed oral risperidone dose for at least 2 but <4 consecutive weeks

16

Mild

Compliance with 50%—75% of the prescribed oral risperidone dose for at least 2 consecutive weeks

33

Adherent

Does not meet any of the above criteria

32

What they find is that there is a 5.8 times risk of relapse with even mild non-compliance and there is no statistical difference between mild, moderate, and severe non-compliance. In a study in which subjects were motivated to participate in an intensive treatment program, close to 70% of individuals had some periods of “non-compliance”.

I participate in a group with other psychiatrists and we sometimes read articles together.  I had raised the question about how long someone should remain on neuroleptics that had been started after a first experience of psychosis. It was suggested that we recommend that they are never stopped because the rate of relapse is so high even with very minor breaks in treatment.

It is interesting how people can respond to the same information in different ways.  The above interpretation, in my opinion, is justified only when “relapse” is viewed as a uniformly disastrous outcome that supersedes all other bad consequences of taking these drugs long term. I just do not see it that way. I have experience tapering these drugs and with some people a recurrence of say, hearing voices, may lead to only to a phone call in which we discuss various options including increasing the dose of a neuroleptic drug.  There is no hospitalization, no disruption in work or social relations, no dangerous behavior.  This is not how it goes with everyone but, thus far, reductions of dose can be handled in an outpatient setting with the majority of my patients.

This brings me to my conclusion.

In my opening post, I made the following assertions:

  • 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 subsequent posts, I presented data to support this:

In several recent large studies published in major journals, neuroleptics were found to be, at  best, moderately effective in the short term.

I pointed out that it is now accepted that long term exposure to these drugs increase the risk of tardive dyskinesia, weight gain, and metabolic syndrome (diabetes, high blood pressure and elevated lipids).  I reiterated the Whitaker argument that while there are not many studies that look at outcome beyond two years, those that have been done suggest long term outcome may be worse for those who remain on these drugs.

Although delay in initiating treatment may lead to worse outcome, treatment does not need to be synonymous with drug treatment.  People who received early psychosocial treatments had better outcomes that was independent of when drugs were started.

Most people choose to not take medications as consistently as recommended and, once started,  even short periods of time off the drugs increases the risk of relapse.

As I put this together, 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, and since relapse is not universally a disaster; we should revise practice standard to try to wait before starting drugs, and (having started them) 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.

The point I am trying to make is that practice is currently guided only to a limited degree by the data.  Yes, these drugs can be dramatically effective in the short term for some people and, yes, there is a higher rate of relapse when they are stopped; but it is also true that the benefits that some people derive from these drugs do not clearly outweigh the risks.

I mentioned Daniel Kahneman’s book, Thinking, Fast and Slow in my introductory post. He writes about the great power of intuition but he also discusses its limitations.  He points out that intelligence does not protect one from the limitations of our cognitive systems and I suspect that those of us who have had years of education and training may be more prone to overvalue our intuitive capabilities than others.

If you graduate from medical school and complete 4 years of post graduate training and through that entire time you have been told how powerful the neuroleptic drugs are – they helped close down the state hospitals, after all – then you may be inclined to remember more vividly the patient who had a dramatic improvement after taking a drug and dismiss as an exception the one who showed no improvement.  You might explain the poor outcome in a person who has been taking neuroleptics for years as a reflection of the progression of the underlying disorder and view the story of the person who stopped taking drugs and did well as a reflection of that small minority who we always knew could do well.

A disproportionate amount of psychiatric residency training is on inpatient units where people are not at their best.  There is scant opportunity to work with individuals who are coming off drugs or doing well – why would they be in our offices or inpatient units, if they were doing so well?  All of this lays down a framework for thinking about psychosis that influences people for many years into the future.

The whole issue of “relapse” is fraught with value judgments.  If the goal is to minimize any and all psychotic symptoms no matter the extent to which they interfere with a person’s ability to live a full and satisfying life, then perhaps one could justify a practice standard that has everyone start these drugs early and remain on them for life.  I talk frequently with individuals whose symptoms are serious and sometimes frightening. They get into legal trouble or they put themselves in harm’s way. Their families plead for help not out of a sense of control but a sense of desperation for their loved one.  At the same time, I also talk to individuals who are miserable when taking these drugs. All of these people deserve an ongoing discussion of the risks and benefits of these drugs including what we know and do not know; not only about these drugs but also about the conditions we are trying to treat.

There are all sorts of realities here and it seems that the available data supports being flexible.

Thank you for reading and for sharing with me your stories, information, links, and insights.

23 COMMENTS

  1. Sandy, this is a great post (and a great series of posts.) I only wish it could be a series that would be published in a place where it would be read by psychiatric residents and those who prescribe the medications today, and that it could provoke a widespread discussion about best practices. But this is a really important exploration of the use of neuroleptics you have written, and I am so proud that it appeared on Mad in America.

  2. Sandra, again i want you to know i SO much appreciate your thoughtful, honest, realistic approach to this issue as reflected in this series of articles. I especially appreciate your balanced approach as one working “in the trenches” to help people in very real and difficult situations. As sad and angry as i’ve been about the terrible “treatment” my family member has endured and the devastating effects i believe neuroleptic medications (and other psych meds have had on her, the “just say no to drugs” approach is not the answer for her. Can she be safely tapered? She encountered a terrible setback while attempting to do so in the past, but the alternative (to stay on them and “lock into” the diminished life that has resulted)is unacceptable. So she’s back in the process of tapering the one that seems most problematic at present (with success, to date). Kudos to you for your courage and willingness to dialogue with us here on MIA, even though i know you’ll take some heat from those who think you’re still too much a part of the establishment! Please keep us posted.

  3. I have some skepticism about the Subotnik study.

    First, it was only 2 to 4 weeks between the withdrawal and the follow up assessment. That’s not long and I suspect rebound psychosis was a factor.

    Second, how was compliance measured? Were there blood tests? If it was just patients’ accounts, that’s a problem. Many people who are well (and I’m one of them) lie to their doctors and say they’re compliant in order to avoid coercion and forced treatment.

  4. The NICE guidance for Schizophrenia makes a similar point about not taking medication. “If psychotic episodes are brief and psycho-social functioning is not affected then not prescribing medication should be considered” (roughly from memory)

    I was quite surprised when I read this guidance….

    http://www.nice.org.uk/nicemedia/pdf/CG82FullGuideline.pdf

    Far to much emphasis is placed on “relapse and symptoms” at the expenses of the rest of peoples lives. Even florid psychotic episodes don’t have to be turned into the crisis they are by mental health services.

    Thats how I see it…

    As a side note compliance is the accurate word because it accurately reflects how most people practice. It would be nice if concordance was the word that appeared in the literature…

    • I like the word, “Concordance,” thanks for that.

      I have inhalable steroids for asthma, they like me to take a standard dose twice a day. I’m not always compliant (no great harm done). Concordant with the Dr’s recommendations is a much nicer term, it implies choice by the patient.

  5. Another excellent article, thank you, Sandy.

    Once someone has been on any of these drugs for longer than a few weeks, withdrawal symptoms should be suspected whenever doses are skipped.

    Could you tell me what protocols in those studies were in place to distinguish “relapse” from withdrawal symptoms?

    From what I’ve seen, any type of distress is called relapse, and withdrawal symptoms can cause a lot of distress.

    • There probably wasn’t any protocols to measure that kind of thing, they just measured what they did and at max made some observations (I haven’t read this particular study that the table is based on). The uber non-compliants were without drugs for four weeks or more or dropped out of study.

  6. Thanks Sandra. I wish that in these studies they would always publish the raw data they’ve used (at what time point the interviews were made, what the exact results were, etc) instead of just publishing the papers, so that the data could be interpreted in different ways by different parties. But I digress. 🙂

  7. Yeah, I read though it here. Subotnik seemsto be pushing the idea how important it is to prevent even slight nonadherence of Risperdal.

    http://ajp.psychiatryonline.org/article.aspx?articleid=106744

    When the atypical neuroleptics were pushed to the market, there were lots of studies which seemed to suggest that they improve cognition, work better and so on compared to the old neuroleptics. They’re not doing those studies anymore so much. Why? The patents have dropped. I’m afraid that we’ll see more studies done on the importance of the atypical depot neuroleptics (such as Risperdal Consta) which of course may cause better adherence.

    Here Robinson comments on this same study and hpromotes the use long acting neuroleptics.

    http://ajp.psychiatryonline.org/article.aspx?articleid=106821

    ‘Another potential intervention to maintain adherence is the use of long-acting formulations of antipsychotics with recent-onset patients early in the course of treatment before nonadherence becomes established. Long-acting formulations eliminate the covert nonadherence that can occur with oral formulations. Knowing that patients are nonadherent allows for discussions between patients and their families and clinicians about the patient’s choice to suspend medication treatment and about making appropriate plans. Long-acting formulations have advantages that may be especially relevant with recent-onset patients. Young patients frequently do not wish to have their peers know that they are receiving medication and may live in situations, such as dormitories, that limit the ability to comply with oral medications without detection. Injectable medications can enhance confidentiality, since they only have to be taken within a health facility. Because recent-onset patients tend to be responsive to monotherapy with antipsychotics, they are more likely than multiepisode patients to only require injections, without supplementation with oral medications. Of specific interest in light of the data from the Subotnik et al. study, patients who accept injections are fully adherent in contrast with the partial adherence common with oral formulations. Preliminary data for long-acting formulations of newer antipsychotics suggest promise with these strategies. Two studies (5, 6) have demonstrated that agreement to injections can be obtained with a substantial percent of recent-onset patients. Weiden et al. (6) found that medication adherence, measured by time to a 2-week medication gap, was significantly longer in subjects who were randomly assigned to receive and also accepted long-acting risperidone treatment compared with subjects receiving oral maintenance medication. However, the number of recent-onset subjects studied with long-acting antipsychotic strategies remains relatively small, and further study is clearly indicated.’

    Here’s a reply from Green and Gordon, I think it’s much more in line with the opinions of people here.

    http://ajp.psychiatryonline.org/article.aspx?articleid=116576

  8. This may have been mentioned already Sandy, but your conclusions are very consistent with the Medication Optimization principles established in Oregon a couple years ago:
    http://www.femhc.org/Portals/2/Foundation%20Documents/Medication_optimization_in_the_service_of_recovery.pdf

    For me, the constant refrain when trying to work with prescribers is, what can they do instead? If not drugs, than what? Advocating with physicians without a well thought out alternative strategy, ends in frustration all around. I believe many physicians are eager to hear about alternatives because they aren’t comfortable prescribing these drugs, but what are they? An effective/immediate referral process for these alternatives from the physicians offices to something else is typically required to get “buy in.”

    D

LEAVE A REPLY