A commenter mentioned some studies, Harrow and Wunderink, and I was snappy. I have acquired snappiness writing this blog from instances where some piece of what I said is questioned and I answer only to find myself being asked to defend forced drugging, commitment laws, ECT, biomedicine, corporate greed, and any number of things that I really have nothing of worth to say anything about. I’ve identified when I feel it [my acquired snappiness]. It’s when I’m being cast in a role as a straw man. One would think I’d be used to it since transference is a central piece of the kind of therapy I did for a career. I think the difference is that being a straw man is just being a target [a narcissistic insensitive biomedical psychiatrist living in a mansion paid for with ill-gotten PHARMA profits]. Being a transference object as a therapist is in the service of learning something useful that might help understand and alter the course of a life. But I snapped at this commenter, perhaps prematurely, because my post was actually opposing the maintenance drug meme. Thinking about it later, as often as I’ve heard "Harrow and Wunderink" held up as a banner, I haven’t read either. So here’s one of them – Wunderink. The oft quoted paper is from 2013, but it’s a follow-up to an earlier study published in 2007:
by Wunderink L, Nienhuis FJ, Sytema S, Slooff CJ, Knegtering R, Wiersma D.Journal of Clinical Psychiatry. 2007 68[5]:654-661.
OBJECTIVE: To compare the consequences of a guided discontinuation strategy and maintenance treatment in remitted first-episode psychosis in terms of relapse rates and functional outcome.METHOD: The study was conducted in 7 mental health care organizations and the Department of Psychiatry of the University Medical Center Groningen in The Netherlands, covering a catchment area of 3.1 million inhabitants. A sample of 131 remitted first-episode patients, aged 18 to 45 years, with a DSM-IV diagnosis of schizophrenia or related psychotic disorder was included [i.e., all patients with a first psychotic episode from October 2001 through December 2002 who were willing to participate]. After 6 months of positive symptom remission, they were randomly and openly assigned to the discontinuation strategy or maintenance treatment. Maintenance treatment was carried out according to American Psychiatric Association guidelines, preferably using low-dose atypical antipsychotics. The discontinuation strategy was carried out by gradual symptom-guided tapering of dosage and discontinuation if feasible. Follow-up was 18 months. Main outcome measures were relapse rates and social and vocational functioning.RESULTS: Twice as many relapses occurred with the discontinuation strategy [43% vs. 21%, p = .011]. Of patients who received the strategy, approximately 20% were successfully discontinued. Recurrent symptoms caused another approximately 30% to restart antipsychotic treatment, while in the remaining patients discontinuation was not feasible at all. There were no advantages of the discontinuation strategy regarding functional outcome.
CONCLUSIONS: Only a limited number of patients can be successfully discontinued. High relapse rates do not allow a discontinuation strategy to be universal practice. However, if relapse risk can be carefully managed by close monitoring, in some remitted first-episode patients a guided discontinuation strategy may offer a feasible alternative to maintenance treatment. Further research is needed to find predictors of successful discontinuation.
by Lex Wunderink, MD, PhD; Roeline M. Nieboer, MA; Durk Wiersma, PhD; Sjoerd Sytema, PhD; Fokko J. Nienhuis, MAJAMA Psychiatry. 2013 70[9]:913-920.
IMPORTANCE: Short-term outcome studies of antipsychotic dose-reduction/discontinuation strategies in patients with remitted first-episode psychosis [FEP] showed higher relapse rates but no other disadvantages compared with maintenance treatment; however, long-term effects on recovery have not been studied before.OBJECTIVE: To compare rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction/discontinuation [DR] vs maintenance treatment [MT] trial.DESIGN: Seven-year follow-up of a 2-year open randomized clinical trial comparing MT and DR.SETTING: One hundred twenty-eight patients participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care services in a 3.2 million–population catchment area. Of these, 111 patients refused to participate and 18 patients did not experience remission.PARTICIPANTS: After 7 years, 103 patients [80.5%] of 128 patients who were included in the original trial were located and consented to follow-up assessment.INTERVENTION: After 6 months of remission, patients were randomly assigned to DR strategy or MT for 18 months. After the trial, treatment was at the discretion of the clinician.MAIN OUTCOMES AND MEASURES: Primary outcomewas rate of recovery, defined as meeting the criteria of symptomatic and functional remission. Determinants of recovery were examined using logistic regression analysis; the treatment strategy [MT or DR] was controlled for baseline parameters.RESULTS: The DR patients experienced twice the recovery rate of the MT patients [40.4%vs 17.6%]. Logistic regression showed an odds ratio of 3.49 [P = .01]. Better DR recovery rates were related to higher functional remission rates in the DR group but were not related to symptomatic remission rates.CONCLUSIONS AND RELEVANCE: Dose reduction/discontinuation of antipsychotics during the early stages of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT. To our knowledge, this is the first study showing long-term gains of an early-course DR strategy in patients with remitted FEP. Additional studies are necessary before these results are incorporated into general practice.
No relapse occurred in 36 patients [34.9%], 20 of whom were in the DR group [38.5% of all DR patients] and 16 in the MT group [31.4% of all MT patients]. The number of patients with a certain number of relapses in the DR [range, 0-5] and MT [range, 0-8] groups did not differ significantly [Pearson χ2 6 = 4.96; P = 0.55].
Symptoms were assessed with the Positive and Negative Syndrome Scale [PANSS]. The PANSS was used to measure observer-rated severity of symptoms during the preceding week, as well as during the past 6 months.Social functioning was assessed with the Groningen Social Disability Schedule [GSDS], a semistructured investigator based interview measuring disabilities in social functioning in 8 domains [7 of which were included in this study] over the past 4 weeks, as well as during the past 6 months. The 7 domains are self-care, housekeeping, family relationships, partner relationships, relationships with peers, community integration, and vocational functioning. The parenthood domain was omitted because of limited applicability. A disability is rated by the investigator on a 4-point scale: none [0], minimal [1], obvious [2], and serious [3].
Definitions of Recovery, Symptomatic Remission. Relapse, and Functional RemissionCriteria for recovery were met when patients had symptomatic and functional remission for at least 6 months at the 7-year follow-up. Criteria for symptomatic remission were adopted from Andreasen et al. All relevant PANSS item scores have to be 3 [mild] or less on a scale ranging from 1 [not present] to 7 [severe] during an observational period of 6 months. Patients were assessed retrospectively for any symptomatic re- lapse occurring during this period. A symptomatic relapse was defined as an exacerbation of symptoms during at least 1 week with at least 1 relevant PANSS item score above 3 [mild]. Any relapse in symptoms during the 6 months preceding the assessment prevented the individual from being categorized as recovered at the time of the assessment.
According to generally accepted views, functional remission implies proper social functioning in the main domains of everyday life. The 7 domains of the GSDS included in the present study adequately represent these domains. A patient with functional remission should function adequately in all 7 domains with none or only a minimal disability in any of them [not allowing a score of 2 or 3 on any GSDS domain]. Patients were considered to have functional remission if, during an observational period of 6 months before assessment, all functional domain scores remained at 1 or lower.
This is the part that’s hard to follow: What was the difference in medication use/dose between the DR [Dose Reduction/Discontinuation] and MT [Maintenance Treatment] groups? Complicated numbers, complicated analyses, complicated graphs. It’s available for all to read in full. Here’s the take home: During the two years at the end, in the DR Group, 11/52 [21%] were off all medications, and in the MT group, 6/51 [12%] were off all medications. Of those remaining on medications, the [Haldol Equivalent] doses were DR = 2.79 [2.21]mg and MT = 4.08 [4.03]mg with P=0.07 [there’s much more in the paper about this, but it’s not blogger-friendly].
There were some other things of interest. They looked at factors that might predict a good outcome in each of the categories [Recovery, Symptomatic Remission, and Functional Remission]. This is their table trimmed to only show factors with at least one significant correlation [in red; circled values were significant by step-wise logistical regression]:
Mostly, the usual suspects, but was interesting that the solid predictor of Symptomatic Remission was DUP [Days of Untreated Psychosis] – not Arm [DR vs MT]. I’ve had that thought myself – that if a person stays psychotic for a long time without initial treatment, they’re much less likely to respond to medication [as in Dan Markingson who was psychotic for months before his mother could get him home]. My guess is that with prolonged psychosis, paranoid beliefs set in and grow. Elaborate paranoid beliefs are the least treatable of the Schizophrenic symptoms.
I’m not going to paraphrase the author’s conclusions to this study. I think they do a fine job all by themselves, and I’m not interested in getting in their way. Hopefully this summary of their findings will stimulate your curiosity to read their thoughtful remarks. Remember, this paper and topic aren’t about ideology, mental health specialty, or anti-this-or-that. They’re about the best case treatment of First Episode Schizophrenia/Psychosis. For myself, I enjoyed this paper. I think I had felt a little guilty that my own bias in seeking the lowest possible antipsychotic dose [or none] had lead to some un-necessary psychotic breaks. One can always use a little reassurance along the way. I was also comforted that though my own cases were few, their experience was very similar to my own in carrying through with the Dose Reduction/Discontinuation mindset. It may be a goal, but in patient management, the clinical reality is always the compass that leads the way. And you don’t always get what you want…
Of course, only one study indicating advantages of a DR strategy in patients with remitted FEP is not enough evidence in such an important matter. However, these results merit replication by other research groups.
So I gravitated to psychiatry. And just after I had finished my training, Psychiatry and Managed Care decided I shouldn’t take the time to do that anymore. Now they even want me to do Collaborative Care and not even see the patients. I said and say no thanks to all of that – and I’m glad I made that decision. In regard to the topic of this paper – First Episode Schizophrenia is a mega-big-deal in the life of a person and a family. These patients don’t just need Guidelines, they need a person to go along on the ride. It helps a lot if that person is not otherwise connected with their life and knows a whole lot about their illness. I had no interest in having some watchdog telling me what to do based on an accounting program, or some KOL premetabolizing medical information. So I never dealt directly with Insurance companies, and I adjusted my fees to fit the patient if I could. I dropped out of the APA from lack of interest [and relevance].
I think there’s a lot more to following a patient with Schizophrenia than just the medication prescription, more than something like CBT, or psychoanalysis, or anything that can be put down as a procedure. Whatever this condition is, it’s a hard way to be alive and the patients deserve whatever consistent ongoing benevolent interpersonal help they can rely on [and tolerate]. And it sometimes needs to be without an ending.
What is amazing to me is that they would go to all that effort, only using drugs. No teaching at all about circadian rhythm maintenance, self-treatment for stress, no evaluation of trauma, etc. etc. This was also my experience as a patient. I have had to figure it all out on my own…the sleep apnea, food allergies, etc. I won’t be able to cite studies because SZ isn’t my thing, but supposedly 20% of SZ is caused by parasites and 5% by celiac disease. My nephew spent 11 days in involuntary hospitalization because he had steroid-induced psychosis and five doctors (2 psychiatrists, an internist, an allergist, and the urgent care doc who started the ball rolling by mistaking mono for a sinus infection) were 100% sure the meds he’s been taking combined with mono-induced liver impairment couldn’t be the cause. Sent home on Seroquel. My vote is for n=1, each patient treated as an individual whose mind and body are inextricably connected, versus “evidence-based” treatment.
For those who are interested in going deeper into this topic, I have found two previous studies that essentially found the same thing: that those who stay on the drugs have worse functional outcomes (on average!) than those who stop).
One is from Timothy Crow’s group in the 1980’s:
http://www.ncbi.nlm.nih.gov/pubmed/2224368
And the other is from Patrick McGorry’s group in the 2000’s:
http://europepmc.org/abstract/MED/19323964/reload=0;jsessionid=tsUVKzggW2V5YUcwS7GW.12
And someone just sent me a link to this paper which showed that most clinicians are not persuaded by expert guidelines to continue the drugs indefinitely:
http://www.ncbi.nlm.nih.gov/m/pubmed/25962446/?i=12&from=%28psychosis%29%20AND%20%28%222015/04/10%22%5BDate%20-%20Entrez%5D%20:%20%223000%22%5BDate%20-%20Entrez%5D
It makes me think that the only people who believe the expert guidelines are those who spend a lot less time with the people who are actually taking the drugs and a lot more time with people who are selling them.
I’m with you on that, RKP — and I think Wunderlink might be too, actually. Getting off antipsychotics after a psychotic episode isn’t easy. People determined to do it would be hungrier for some alternate approaches to emotional distress, and more motivated to use them, than people who were content with their meds or afraid to stop. Inviting them to taper off meds in the context of a program with all kinds of moral support and practical training would make perfect sense.
The reason Wunderlink didn’t offer such a program, I think, wasn’t his own preference. Rather, it was because he was doing a Randomized Controlled Trial, in which both groups had to be treated exactly the same, EXCEPT for the drug use strategy. And why? Perhaps not because he really felt that was the only route to the truth, but because it was the only “respectable” route, and the only way to avoid having his findings totally dismissed by the Establishment.
Funny about that “gold standard” route to the truth. It turns out all these company doctors who pledge allegiance to the sacred RTC when it tells them what they want to hear, turn into big-time skeptics when it does not. For example: A large “meta-analysis” of randomized controlled trials published last year found no advantage for monthly injections over daily pills for preventing “relapse” in schizophrenia.
So what did the authors do–accept their own findings? Hell no. They rattled on about how RCT’s were “less representative of real-world patients” than naturalistic studies. The oral-meds group might have contained too many patients whose motivation to cooperate was above average. The study’s organizers might even have (OMG!) excluded patients “expected to have poor adherence.” Turns out the only side they were loyal to in the great “RCT vs. clinical practice” debate was whichever side their bread was buttered on.
What I’ve taken away from Mickey’s last few columns is that responsible medical care, psychiatry especially, will always demand treating each patient as an individual. It’s OK to violate that to some extent for the sake of a research study – but only as long as you have a Rescue Plan for people who are clearly suffering and/or getting worse in the controlled experiment. And only as long as the experiences of those distressed dropouts are taken into account when you write up the study.
These company-sponsored “experts” who advocate maintenance drugging for everyone refuse to treat either research subjects or “real-world” patients as individuals. They end up abusing the research subjects, the better to abuse the rest of us after the tainted research is published.
Thanks, Mickey, for once again laboring through both good and bad studies and then insightfully summarizing the results for me.
The work of Wunderrink et al is largely consistent with my experience, though my patients differ in major ways from those studied in the Netherlands. In the last 3-4 decades I have rarely seen a patient with a Dx as simple or as singular as schizophrenia. Instead, they come to me pre-Dx’ed as Schizoaffective; Bipolar; Major Depressive Disorder NOS; and Borderline Personality Disorder. It in not unusual for there also to be co-morbid ADHD, while Trauma is rarely if ever mentioned. Very often a given patient is said to have each of these Dx’s, all at the same time. And their prescriptions are not limited to one antipsychotic. These patients often are on cocktails of one or two 2nd generation antipsychotics; one or two mood stabilizers, a stimulant for ADHD or to correct for over sedation; one or two benzos for anxiety; an antidepressant and trazadone for sleep. The good news about all this lies in my being told by several colleagues in Australia and the UK that this style of over Dx’ing and over Rx’ing is still largely an American phenomenon.
Having developed somewhat of a niche market in doing 2nd opinion evaluations, I have polished up on how to take patients and their families through the evaluation process. And then, if indicated if and everyone is in agreement, I take the patient through cautions tapering trials. A consistent result is that the overwhelming number of such patients do just as well or better on lower doses or no medications at all. Admittedly, an important part of all this is the patient being in a solid and effective working relationship either with me or the therapist of record, who likely referred the patient to me.
Ed,
That’s also how I spend much of my time in a rural charity clinic. I long for the patients having “therapists of record,” but we do the best we can. I now visibly cringe when I see the word “co-morbid” because it so often means the kind of dx/rx soup you describe. Keep up the good work…
Ed, I would very much like to be able to refer patients to you for tapering off these unholy cocktails. Please write me at survivingads at comcast/net.
(I run a peer support site for tapering off psychiatric drugs. I have almost 2,000 case reports here http://tinyurl.com/42ewlrl).
Wunderink, 2007 specifies “The discontinuation strategy was carried out by gradual symptom-guided tapering of dosage and discontinuation if feasible.” (The synopsis of the way it should be done, in my opinion.) I don’t have access to the full text, does anyone know the details of the tapering methods?
Sandra Steingard mentioned an early confirmatory study from Eve Johnstone and Tim Crow. She said it “essentially found the same thing: that those who stay on the drugs have worse functional outcomes (on average!) than those who stop.” That statement from Dr. Steingard is a serious misstatement of what was reported. The study found that better functional outcome was associated with dose reduction only in a subgroup of the patients – those with an untreated duration of illness less than 1 year (p < 0.05). Moreover, the effect did not hold up in the authors’ multivariate analysis.
At the same time, other factors measured at baseline had far stronger predictive significance for functional outcome – factors such as unemployed status, lack of positive interpersonal assets, and inability to complete an examination for neurological soft signs (all p < 0.001). Additional factors indicative of baseline negative symptoms also strongly predicted poor outcome (p < 0.01). None of these were mentioned by Dr. Steingard. There was nothing more than the whiff of a hint in the data to support Dr. Steingard’s blithe overstatement that I quoted above. Besides, as the original authors obliquely acknowledged, even this weak finding would not have survived Bonferroni correction for multiple comparisons.
My old friend George Winokur liked to joke that the scientific literature is like the Bible: people can find in it whatever they are looking for. ’Nuff said. Wishful thinking does not move the ball down the field, and erroneous strong opinions based on blithe misreadings of the scientific literature do not advance our purpose in these discussions.
Dr. Carroll,
I made a quick reference to the study and offered a link. My comment above was not intended to be a thorough discussion of the study but merely to alert anyone reading of its existence so that they, like you, could review it in more detail. I am well aware that the duration of psychosis prior to entering the study had a huge impact on outcome. But in my reading, even among those who had symptoms for less than a year, the group who was randomize to placebo after one month on antipsychotic drug had worse outcomes with regard to occupational functioning. This was true even though relapse had a negative impact on occupational outcome and the group on placebo had a higher rate of relapse. What I found interesting in this study is that the rate of relapse in the group on placebo seemed to plateau after one year whereas the group on drug were continuing to have increasing relapse when the study ended (and I am referring here to the group who had been symptomatic for less than one year).
This suggestion that drug postpones rather than reduces risk of relapse is what is also suggested in the Wunderink study and I found that to be of interest.
Yes, Dr. Carroll, as Dr. Nardo has made abundantly clear in his wonderful blog, people can find what they want in the scientific literature. On that we are in agreement.
Dr. Steingard, are you not being disingenuous? You gave the article an unqualified endorsement. Now you acknowledge caveats and limitations after I called you on it. But you still don’t accept that there is no positive finding that meets acceptable standards of analysis and statistical significance. The whiff of a hint of a positive finding disappeared in the multivariate analysis. I am reminded of the prospectors who catch a glint of fool’s gold and proceed to act like they found the mother lode.
A gentle suggestion here that when people comment on a blog they may be doing so in haste and between handling numerous other tasks.
I think it is important to give a person the opportunity to retract or qualify what they stated in a comment. If not then the comment section may easily take on the same tone as a court case making polite discourse and dialogue well nigh impossible.
Thanks
Dr. Steingard also cited a second paper, this one from the McGorry group. Once again, she said it “essentially found the same thing: that those who stay on the drugs have worse functional outcomes (on average!) than those who stop.” Now she must be called out again for seriously misrepresenting this second article she referenced. Coming from a physician, these misrepresentations cannot go unremarked, because a good many readers here understandably assume that she knows what she is talking about. She doesn’t. That’s what her two examples today tell us.
There is no kind way to say this to Dr. Steingard: the McGorry article did not even address the issue of stopping antipsychotic drugs! The focus was on whether intensive individual and family CBT delivered as a Relapse Prevention Treatment (RPT) added to Treatment as Usual (TAU) was more effective than TAU alone in preventing relapse over 7 months after an average 30-week stabilization and remission period in patients with a first episode psychosis. There was no significant difference in antipsychotic drug use between the RPT and TAU groups. The authors found a weakly significant difference in relapse rate favoring RPT at 7 months (p = 0.042) but that disappeared by 8 months. Meanwhile, there was absolutely no difference favoring RPT on any functional measure (adherence to medication, psychosocial functioning and quality of life) or on any ratings of psychopathology. Thus, in no way can the McGorry report be represented as essentially finding the same thing as Wunderink reported. Recall that functional recovery was the main focus of the Wunderink study and that the McGorry study found no functional advantage for their intervention.
One could find much to criticize in the McGorry report, but I will not digress on those issues here. The important point for this thread is that people who make authoritative-sounding pronouncements here with references to the medical literature should please get their facts straight – if they want to be taken seriously. That applies especially to physicians. To do otherwise is a disservice to this fine blog and to the blogmeister. It’s not a matter of authority or of power or of gender, as some here have complained – it’s a matter of competence and rigorousness.
Yes, Dr. Carroll. There is much to criticize in the reports from Patrick McGorry and his followers in more places than Australia. They are out to prove the efficacy of early intervention in psychosis by way of psychosocial therapy and usual drug treatment, without discussing the implications and hazards of the brain-damaging, potentially lethal drugs they even prescribe to “prepsychotic” youngsters, whatever that is.They avoid the ethical and iatrogenic issues. They avoid highlighting their own finding that no psychiatric intervention may be the better option for so-called at-risk-kids.
No, Dr Carroll. There are kinder ways than yours to put things right. I’m mad as hell about con games presenting as medical science to keep heaps of money coming in. But I know from shared experience that an angry woman is judged differently than angry males – by most. And there is more false authority in medicine and psychiatry than I could have imagined, when I was naively trusting the guild of “experts”.
Yes, Dr. Carroll, to competence, rigorousness – and humility. We are barely scratching the surface of knowledge about ourselves and the miraculous human brainbody. We have much to gain from listening to each other – about one self also.
It’s not that angry males or females are judged any differently, it’s that critical thought and not suffering foolishness is now judged by an increasingly oversensitive public to be a manifestation of “anger”. Diligence does not equal anger. Skepticism, which I regard highly in the spirit of Spinoza and Popper, has become a dirty word. Look at how AGW skeptics are treated by the media and politicians.
There is no reason in the world that a psychiatrist who is sensitive and empathic in a clinic cannot be rigorous and exacting in case conference. For the same reason one can be kind and gentle to one’s children and a shrewd negotiator on one’s lease renewal. 100% mensch all the time is a huge mistake and maladaptive. And it hurts science. Too many doctors feel they have to be soft in all situations or be labeled a meanie.
I recently had a debate with a pain management doctor on Psych Times about the genesis of the opioid epidemic, and I was particularly critical of a chart review that many used as the foundation of mass prescribing. Notice that my first post was actually complimentary so I wasn’t looking for an argument:
http://www.psychiatrictimes.com/addiction/prescribing-opioid-analgesics-are-we-going-right-direction
But then he didn’t like my use of the term junk science, and chose to defend an obviously defective study.
His conclusion was that less than 1% get addicted, my conclusion was that opioid addiction is not identified or charted well by physicians or at least that was the case in 1980. And he felt that chart review was a good method of ruling out addiction, when I begged to differ. I don’t think you have to be a statistical genius to see how flawed the Porter and Jick study was. A lot of physicians don’t like being challenged at all, and double down when their logic falls apart.
RPT was a therapy intended to improve adherence to drug. It was effective in that more subjects in the RPT group were adherent. However, at end point the adherent group had worse functional outcomes. This was an unexpected finding. That was the portion of this study that I thought – and think- is consistent with Wunderink’s findings.
Yes, competence, rigorousness and humility go together. When humility is lacking, the duty to be accountable for the accuracy and balance in what we say is dismissed. Then the forum is fouled by erroneous, misleading and nutty opinions, sometimes paraded with an arrogance that can be breathtaking.
Just a quick note re the three studies (Johnstone’s, Wunderink’s, and McGorry’s.
A) Johnstone. Yes, it was in the subgroup of patients who had been ill less than a year that the placebo group had better occupational outcomes at the end of two years. I don’t know about the multivariate analysis, but here is what the researchers wrote in their conclusion:
“The present finding may be considered as a stronger indication [than even an earlier study] of the possible social cost of maintenance neuroleptic medication.”
I would say that is a finding similar to what Wunderink found, which goes to the question of the effect of neuroleptics on long-term vocational functioning, and thus the need to adopt protocols that will help at least some patients diagnosed with psychotic disorders get down to low doses or off altogether.
b) At a recent conference, Wunderink gave a talk on his seven-year results, and I also interviewed him for a MIA continuing education course. Although patients were randomized to a drug-reduction arm, there was no protocol for the drug reduction—the doctors just said they would give it a try, and many apparently were resistant to the idea, Wunderink told me. So these were results in a drug tapering strategy of a most modest sort.
At the end of seven years, there is also another way to group the patients. Some in the group randomized to regular drug maintenance nevertheless got off or down to a very low dose on their own. Here is the grouping of outcomes at end of seven years based on medication use (regardless of randomization). For those who ended up off neuroleptics or on a low dose, 56% were in functional recovery at end of seven years, versus 22% of those on regular maintenance therapy, and as for full recovery, the difference was 53% vs. 17%.
This data, in my opinion, furthers the finding that it would be good to have protocols that maximize the percentage of patients who can get off neuroleptics long term, or down to very low doses.
c) As for the McGorry study, the idea was that those randomized to the special care would have increased medication adherence (which, it was hypothesized, would be a good thing). Sandy linked to the 7-month data, but the relevant link is to the 30-month data, which was published in 2013. The protocol did work in the sense that specialized care did increase medication adherence. But, at the end of 30 months,the researchers wrote, increase in medication adherence was associated with “decreases in psychosocial functioning and increases in negative symptoms.”
Moreover, the researchers then looked back at the Johnstone/crowe study, and noted the congruency of these findings:
“This is consistent with previous research showing an association between better vocational functioning at 2-year followup and placebo treatment compared with antipsychotic medication in a first-episode schizophrenia sample.”
Here is the citation for the 30-month results: J. Gleeson. “A randomized controlled trial of relapse prevention therapy for first-episode psychosis patients.” Schizophrenia Bulletin 39 (2013):436-48.
Thus, I think Sandy’s comments do point to a consistent finding, which is that those patients who can get off neuroleptics, or down to low doses, as a group have better vocational functioning.
um, I’m a bit perplexed to the issue here. I come from training that antipsychotic drugs, if not treating profound psychotic disorders, should not be continued for long periods of time, especially with affective disorders.
Now some can claim that the first generation or typical antipsychotics warrant a different attitude, but, having been practicing for 15 plus years with the 2nd generation / atypical antipsychotics, I don’t see any difference with side effect risks, therefore the issue of tapering meds, especially antipsychotics, should be addressed with patients who do not have a primary psychotic disorder. In fact, I think that the ongoing prescribing of antidepressants for years borders on inexcusable. When patients are stable, such meds should always be considered tapered at least to a lower dose.
Frankly, I found it nothing less than total b******* that Psychiatrists telling their patients they need to be on meds the rest of their lives. I look forward to reading about some idiot in our field being sued for selling that message when consequences play out when they refused to lower high dose psychotropics.!
Too bad we won’t be hearing from Dr. Steingard any more. She’s been having success carefully tapering psychosis patients to the lowest effective dosage, some to zero.
I admire her tremendously for her courage, ingenuity, and commitment to her patients.
I inadvertently linked to the wrong Gleeson study. There is a 30 month outcome study here:
http://www.ncbi.nlm.nih.gov/pubmed/22130905
This is where they report that those who were more adherent had worse functional outcomes.
Sorry for the confusion.
Dr. Steingard and Robert Whitaker now introduce a third publication and they misrepresent it just as seriously as they misrepresented the first two. The 30-month follow-up report from McGorry’s group just… doesn’t… say… what they claim it says.
In an earlier comment I used the metaphor of prospectors acting with irrational exuberance on glimpsing fool’s gold. A further aspect of cognitive style here is the suppression of attention to clear evidence that contradicts a desired narrative. In Johnstone/Crow, the overwhelming evidence pointed to baseline negative and organic features as the major predictors of poor functional outcome. In McGorry II, neither of the primary outcome measures was significant. Plus, the authors engaged in determined p-hacking, running at least 63 secondary and tertiary analyses of 21 measures. Then they went out of their way to speculate for their narrative on the basis of very slim evidence – not to mention the lack of corrections for multiple comparisons. If we saw this in a clinical drug trial report we would hold our noses.
But at least McGorry and company acknowledged that several speculative possibilities might apply – including that the imputed effect of increased medication compliance on functional impairment and negative symptoms could be a spurious finding. It is important here to note that the finding of increased medication adherence in the RPT group which occasioned so much hand waving – actually, it was a group by time interaction – was pitifully weak, with P = 0.045, and that it did not have a snowflake’s chance in hell of surviving Bonferroni correction.
Mr. Whitaker recognized none of these nuances. As a matter of fact, McGorry’s group never did positively link increased medication adherence with functional/psychosocial impairment. All they did was to find in a tertiary analysis that the significant group by time interaction for social functioning and for attention became nonsignificant when medication adherence was added as a further covariate. What Mr. Whitaker failed to mention was that the corresponding significant interactions remained significant in these same tertiary analyses for the negative features of SANS alogia and SANS summary scores, with the RPT group still doing worse than the TAU group.
The humorous irony here, of course, is that the p-hacking and tertiary analyses were done in an effort to “unfind” an inconvenient result, namely the worse functional outcome of the RPT group at 30 months. Such is the nugatory basis for Mr. Whitaker’s statement that “… those patients who can get off neuroleptics, or down to low doses, as a group have better vocational functioning.” Meanwhile, Dr. Steingard went one better with her statement that “… those who were more adherent had worse functional outcomes.” Once again, there is no kind way to say this to Dr. Steingard: they never made any such analysis! Adherence was no different between RPT and TAU groups.
I come back to an earlier point: if people want to use the scientific literature to further their narratives or to grind their axes then they have a duty at least to get their facts straight. That didn’t happen three times here. I call that a strikeout.
I am wondering if anyone could help me with the ‘big picture’ of this debate. I have issues regarding ‘informed’ consent for serious mental illness, as I have not received thorough evidence-based answers to my questions from mainstream psychiatrists in my area. I do not say this to offend anyone, simply as an explanation as to why I come to this site to try and gain information.
Although it seems there are guidelines in place to use neuroleptic medications for long term maintenance, my understanding is that there are currently no long term studies that support this? It would seem from this blog post that the Wunderlink study is solid, and may indicate that using neuroleptics in the long term is detrimental. I think that Dr. Carroll is saying something along the lines (and please forgive my layman way of expressing it) that the findings of the two additional studies are not scientifically significant enough to be considered support for Wunderlink’s study. I am thinking, and please correct me if I am wrong, that Dr. Carroll is NOT saying that these two studies in any way support the idea that maintenance neuroleptics is beneficial?
Dr. Carroll, when you say things like ‘looking for fool’s gold’ , ‘furthering narratives’ and ‘grinding axes’, it makes me think that you think the ‘narrative’ of which the Wunderlink study is a piece, is a faulty narrative. If this is the case, then I would appreciate so much if you would explain why. If, on the other hand, you think the Wunderlink study is solid and might have something significantly different to say then the current mainstream ‘narrative’, I would implore you to use what seems to be deep scientific knowledge to try and unravel the big picture. (e.g. critical analysis of studies leads to finding out the truth whereas trying to belittle those who have shed light on the shortcomings of the current ‘narrative’ , is not going to help us get to the truth)
Finally, Dr. Carroll says that the Johnstone/Crow sudy shows that ‘the overwhelming evidence pointed to baseline negative and organic features as the major predictors of poor functional outcome’. I am curious (again for personal information) whether neuroleptic medication is thought to improve negative symptoms, and what is usually included under the definition of ‘organic features’ ? Can anyone help me out with this information?
Sally,
If you want to discuss this further with me, feel free to email me at sandys@howardcenter.org
Sally, thank you for bringing the conversation back to the big picture and to the Wunderink study. I will not comment on Wunderink for now because Dr. Mickey has signaled that he has a Part II in the works. Also, I need to get up to speed on the corpus of Wunderink’s publications and that will take a little time, as my primary field is not psychosis studies. I will be glad to come back to these issues after Dr. Mickey shares his next instalment.
Dr. Carroll states that three times I failed to get my facts straight. So here are the facts:
a) Did the Johnstone group find that in those patients who had been ill less than a year,the placebo group had better occupational outcomes at the end of two years? Yes. And did the researchers comment on it as a possible indication of the negative impact of neuroleptics? Yes.
b) I have no idea what Dr. Carroll is saying was wrong with what I wrote about Wunderink.But did Wunderink report higher recovery rates for the group randomized to a tapering protocol, yes. And if you group all patients by medication use (as I reported above), do you find much higher recovery rates in the low dose/off med group? Yes.
c) As for the McGorry study, here is what the researchers wrote: “It is notable that the relative timing of changes in medication adherence and psychosocial functioning in the RPT group as depicted in figure 3 show that increases
in adherence (18–24 months) preceded decreases in psychosocial
functioning and increases in negative symptoms
(24–30 months) in the RPT group.” And contrary to what Dr. Carroll says, if you look at the scores for medication adherence, the RPT group (which is the experimental group) had greater adherence to medication in the last 12 months of this study (when their outcomes deteriorated.)
So did the McGorry group make note of this (and call it “notable”? Yes. Did this difference in outcomes show up during a period when there was a difference in medication adherence? Yes. And did the researchers themselves then note this was consistent with the finding in the Johnstone study? Yes.
And those are the “facts” of what I wrote, in a brief comment to a blog.
Mr. Whitaker has responded as a journalist in what is essentially a scientific debate.
As to Johnstone/Crow, the article is clear that there was no significant association of treatment group (active drugs/placebo) with functional outcome in the full sample (Table 1). At best there was a weak primary level association (p<0.05) in the subgroup with short duration of untreated psychosis (DUP) before multivariate correction for confounders, and even that would never have survived the Bonferroni correction that the authors finessed. The authors were silent on whether this association held up after multivariate analysis in the subgroup with a short DUP. That silence is pregnant… did they find a negative result and didn’t want to talk about it? What the researchers themselves said about their weak finding was just gilding the lily for their own desired narrative, and that is what Mr. Whitaker copied and pasted. At least the authors emphasized that other factors were far more salient determinants of functional outcome, something that Mr. Whitaker continues to overlook. That is like splashing in the waves while ignoring the tides.
Mr. Whitaker’s second point is inoperative because I said nothing about the Wunderink study. Here he is just throwing chaff into the debate. I refrained from comment on the new information he had related from Wunderink because it is not publicly available.
As to McGorry I and II, Mr. Whitaker again copies and pastes selectively from the authors’ passages in which they put lipstick on their own pig. I gave a more nuanced, scientific analysis in my earlier comment. To repeat, McGorry’s group never did positively link increased medication adherence with functional/psychosocial impairment. Yes, they said what Mr. Whitaker copied and pasted, but their optimism was not rigorously supported by their data. There is the difference between journalism and scientific analysis. No offence intended to Mr. Whitaker – he is widely regarded as a journalist, but it would be best if he refrained from getting in the weeds on complicated scientific reports.
I just cannot resist saying thank goodness Mr. Whitaker “got in the weeds on complicated scientific reports”. It was only through his study of the scientific literature that attention was drawn to this very,very important issue.