Showing posts with label antipsychotics. Show all posts
Showing posts with label antipsychotics. Show all posts

Tuesday, September 1, 2026

The Deprescribing Hype...

 


One of the best psychiatrists I know ran a large antipsychotic long-acting injectable (LAI) clinic and the largest clozapine clinic in the state. There was not a side effect he had not seen or addressed related to medications. He also happened to be one of the most well-liked clinicians I have ever known.  Years after he left our clinic his former patients would approach me in the hallways and ask me if I knew how he was doing.

Since I was in acute care, I would occasionally see one of his patients on my inpatient service and call him about that. One day we had a conversation about polypharmacy and all of the guidelines at the time.  Quality assurance guidelines said that monotherapy in any general class of antipsychotics, anxiolytics or mood stabilizers was preferred at the lowest effective dose. We both recalled many patients where that was not true and even slight changes in their medications resulted in significant destabilization.  In some cases the destabilization was so severe it resulted in long term care in a state hospital. 

Both of us had the privilege of practicing in a time when the only atypical antipsychotics were clozapine and later risperidone and olanzapine. But we also saw a lot of people who had been stabilized on first generation antipsychotics that were used for treatment for bipolar disorder, psychotic depression, and schizophrenia.  In those days it was very appealing to consider starting lithium and stopping the antipsychotic, stopping the antipsychotic due to a movement disorder (tardive syndrome or akathisia), stopping the antipsychotic trying to get to antidepressant monotherapy, stopping the antipsychotic to get to antipsychotic monotherapy, stopping the antipsychotic due to more typical side effects, or stopping the antipsychotic just on the general thought that they were bad medicines that should be taken only in desperate situations.

We reviewed a number of clinical scenarios involving polypharmacy.  He told me that some of his patients were taking an embarrassing list of medication.  He used the term because the medication list flew in the face of conventional wisdom at the time about how medications should be prescribed.  He had tried to alter the medications to approach those idealized guidelines but the patients did not do well and he invariably had to go back to the original combination.  Most of these patients had come out of state hospitals where they were observed for months or in some cases years on this medication.  He followed everyone closely, knew their family and social situations, and whether he would admit it or not did supportive psychotherapy. He saw people on a weekly basis during these medication changes.

I shared my same experience with him.  I had been trained by the authors of The Lithium Encyclopedia.  They also ran the Lithium Information Center at the time. My training was that people with bipolar disorder should be treated with lithium. I was seeing people with clear cut bipolar disorder who were stabilized on chlorpromazine – the oldest antipsychotic medication. I knew how to start lithium and gradually taper chlorpromazine so why not do it?  The person I am thinking of had dry mouth as the most significant side effect of chlorpromazine.  When the lithium level was therapeutic for a few weeks, I started the slowly taper of what was considered a low dose of chlorpromazine.  When the uneventful taper was over it took just 2 weeks for the patient to experience a manic episode that required hospitalization and restabilization on chlorpromazine.  

And so, the stories went.  Apparently successful transitions with weeks to months off of a particular medication, nothing that would be considered a discontinuation or withdrawal effect, and then relapse to the primary disorder.  My personal experience was meager compared with what I witnessed as an inpatient doc.  I saw the worst possible outcomes of these medication discontinuations including suicide attempts, homicides, high speed chases and other confrontations with the police including shoot outs, inadequate self care including stopping life saving medications like insulin, and destabilization of living situations and homelessness. I even had to put up with blowback from people I had stabilized. I was criticized by one of my bosses for an aggressive patient on the inpatient unit who was there because an outpatient provider decided to change the medication I had just stabilized the patient on because of concerns about weight gain.  

To be clear, there are many reasons to stop medications or change them.  I am an expert at that.  There is also no assurance that a specific dose of medication will continue to work well forever.  Environmental changes like sleep deprivation can trigger relapse in people who are on effective maintenance medications.  All of the usual lifestyle factors need to be addressed. But it is a clear mistake to think that lifestyle factors or psychological interventions alone are enough to keep people stable in those who need them.  Risk stratification is also important.  I have a review that I co-wrote with Ron Pies, MD coming out next month.  One of the  studies we reviewed looked at all of the antidepressant prescriptions in the country.  Only 3% of that population was ever hospitalized.  It is a good idea to include that risk in any risk/benefit decision on either side of the prescribing equation.    

Political approaches to complex medical problems never work.  The idea that a government official with no knowledge of the field can start a massive deprescribing program or proclaim that he knows the cause of autism is hopefully the absurd conclusion that medications rather than mental illness is the main problem.  At a more subtle level, deprescribing is has infiltrated the popular culture as a magical solution.  It is widely promoted but has no more legitimacy than the old term that I have used for decades – discontinuation.  Deprescribing carries with it the implicit notion that medications, especially psychiatric medications are overprescribed and either harmful at best or lethal at worst. None of that is consistent with the literature or the experience of clinical psychiatrists.

As I have written many times before - nobody that I ever met inherently wants to take a medication every day.  That includes myself. That decision requires a careful risk/benefit decision. Rational thinking would lead to a decision to keep taking a medication with a favorable risk/benefit/analysis.  That decision is complicated by personal values, personal preferences, cognitive ability, and medication tolerance and efficacy.  It is further complicated by placebo effects, nocebo effects, and habituation to side effects.  As an experienced clinical psychiatrist, I can say unequivocally that it is rare to find a person who needs a medication and cannot tolerate all of the medications in that class.  Notice I said rare, because I am sure those people exist.    

Whether you are a psychiatrist or a patient considering the current deprescribing hype either in social media or the professional literature keep this in mind.  These statements are made with a degree of certainty that does not exist.  Carefully consider the circumstances and err on the side of caution. I don’t anticipate that people advocating deprescribing at a global level will be measuring any outcomes. I hope that some of the experts in observational studies will be able to design outcome studies. The harms of medication discontinuation and deprescribing need to be documented before anyone can truly give informed consent.

 

George Dawson, MD, DFAPA


Supplementary 1:  Galbraith’s concept of conventional wisdom includes the following:

Acceptability over Truth: People associate truth with what is convenient or reassuring. Ideas become "conventional wisdom" because they fit comfortably with existing preferences, self-interest, and social norms.  Creates obvious inertia against any identified out-groups and easily reinforced by rhetoric rather than reality.

Resistance to Change: Because people invest prestige and stability in these accepted ideas, conventional wisdom resists updates even as real-world circumstances shift underneath it.  Antipsychiatry rhetoric is making ideas like the need for deprescribing conventional wisdom and accepted without any critical challenge even though it does not match reality.   

Breakdown via Events, Not Arguments: Galbraith argued that conventional wisdom is rarely overturned by debate or logical argument. Instead, it only breaks down when hit by the unyielding force of events—when real-world circumstances change so drastically that the old ideas can no longer explain reality.  All of the rhetoric against psychiatry has not been able to destroy psychiatry precisely because all of the rhetoric of overprescribing, conflict of interest, social control, etc does not match the reality of the providers of last resort who are actually interested in severe mental problems.  

The conventional wisdom mentioned in the above post were quality assurance guidelines about medication usage that were not empirically derived. 

Note that the third feature of conventional wisdom (if accurate) is why the Trump?MAGA ideology may be unravelling as the events and obvious failures accumulate.


Ref:

Galbraith JK.  The concept of the conventional wisdom.  In:  Galbraith JK.  The Essential Galbraith. Houghton Mifflin, Boston, 2001:  18-30.

 

Tuesday, June 21, 2016

Significantly Lower Mortality With Antipsychotic Use




It is always an interesting phenomenon to see the headline grabbing news about how toxic psychiatric medications are killing people.  At first it was just  cult news, but these days it seems that some people can make a fairly good living at it.  A knowledge of psychiatry or clinical experience is never a prerequisite.  It always requires the reader to suspend their sense of reality and what they know happens in real life.  That reality is that a family member, neighbor, or friend was having some very serious problems - saw a psychiatrist and got better.  It also requires a suspension of belief in the tremendous history of what happens with untreated psychotic disorders both in terms of morbidity and mortality.  Finally it requires suspension of a belief in the usual regulatory mechanisms.  If so many people were dying from treatment - it would be obvious and somebody would be held accountable.  Every state has medical boards that basically solicit complaints against physicians.  Surely any group of physicians prescribing an inordinately toxic medication would come to light.  You have to suspend all of these realities of course because none of it has occurred.  Despite those reality factors there are any number of antipsychiatrists or people claiming to be critics who are basically using the same rhetoric warning people about the toxicities and how many people are killed by these medications each year.  Some of their estimates are astronomical and suggest a clear and biased agenda.  Actual community surveillance reveals an accurate picture and the medications with the highest complication rates are easily recognized by any psychiatrist or primary care physician.

That is not to say that the medications prescribed by psychiatrists are perfectly safe.  As I just posted - no medical decision including one that involves taking a common medication is risk free.  I spend a good deal - if not over half of my time warning people about side effects that will never happen, warning people about severe but rare side effects, managing side effects that do happen, and screening for potential side effects that might go unnoticed by the patient like electrocardiogram abnormalities or blood tests for a specific bodily systems.  In 30 years of practice, I have diagnosed the most severe problems including serotonin syndrome, neuroleptic malignant syndrome, prolonged QTc interval, various degrees of heart block, arrhythmias, myocardial infarctions, strokes, drug-induced liver disease, agranulocytosis, diabetes mellitus, diabetes insipidus, hypo/hyperthyroidism and many other that were either caused by a medication or picked up as a result of my screening for a medical complication or pre-screening for safe use.  But relative to primary care, the number of diagnoses in psychiatric practice for this reason is smaller.  The most significant cause of mortality in psychiatric populations is cigarette smoke.  The most significant number of medical conditions are pre-existing and if the psychiatric disorder is caused by an underlying medical condition - it is not common.

All of the factors in the first two paragraphs led me to read an article on the epidemiology of antipsychotics, antidepressants, and benzodiazepines in a well determined population and the effects on mortality in the June American Journal of Psychiatry.  The authors have a number of studies that appear to use a similar epidemiological approach.  For this study they identified cohort participants from national health care registers of all people 17-65 living in Sweden in 2005.  They identified anyone receiving health care for schizophrenia or psychosis (by ICD-10 codes) and anyone on disability for schizophrenia.  They also  determined all of the antipsychotics, antidepressants and benzodiazepines dispensed from 2006-2010.  They were classified by Anatomical Therapeutic Chemical Codes (ATC codes).  They calculated cumulative exposures using the WHO defined daily dose (DDD) methodology.  The WHO web site has a search engine that will let you search for the defined daily dose of medications.  Examples for antipsychotic medications would include 10 mg for olanzapine and 5 mg for risperidone.  The researchers summed the follow up days minus any hospitalization days and divided this into the sum of the dispensed medication.  That allowed the subjects with schizophrenia to be broken into four DDD groups: 1) no antipsychotics, antidepressants or benzodiazepines during the follow-up, 2) low dose -  small or occasional medications (0-0.5 DDD/day), 3) moderate doses (0.5-1.5 DDD/day, inclusive), and 4) high doses (>1.5 DDD/day).  Using the olanzapine example that would mean a dose range from 0 - >15 mg/day cross all 4 groups.  

A total of 1,591/21,492 or 7.4% of the cohort died in follow-up.  That was 4.8 times higher than a control group of age and gender matched patients.  The commonest causes of death were cardiovascular disease, neoplasms, respiratory diseases, and suicide in that order.  No interactions were noted at the level of demographic variables.  Mortality rates and hazard ratios for antipsychotic, antidepressant, and benzodiazepine use were calculated and the following observations were noted:

1.  Any exposure to antipsychotics or antidepressants was associated with a lower rate of mortality (15-40% lower) compared to no use.          

2.  High exposure to benzodiazepines was associated with a 74% higher risk of death than no exposure.  Benzodiazepine users had the highest mortality, highest risk of suicide, and more frequent visits to health care services.  

3.  In terms of cardiovascular mortality, only high dose antipsychotic use showed an equal mortality to no exposure to antipsychotics with low and moderate dose showing decreased mortality.

4.  A sensitivity analysis of first episode patients showed that there was a decreased risk of mortality with exposure to low and moderate exposure to antipsychotics and increased mortality with exposure to moderate to high dose benzodiazepines.  More striking is the fact that during the follow up period this was a cohort of 1,230 patients and 45 (4%) of them died.  Most of the patients with first episode psychosis who I treated were otherwise healthy 20 year olds, illustrating the significance of this problem.

This is an excellent study from a number of perspectives.  It looks at well defined data across a population that is generally possible only in Scandinavian populations.  By contrast studies done in the US typically look at either incomplete retail pharmacy data designed originally for pharmaceutical sales or detailed health interview data that is based entirely on self report using long and detailed questionnaires.  The study uses WHO methodology suggested for pharmacoepidemiological research.  The follow-up period is during a times when most atypical antipsychotic medications are widely available.  These are the drugs that are suggested as a source of higher cardiovascular mortality in psychiatric patients.  The authors findings are discussed in light of several other studies that show similar effects.

 The finding of this study will come as no surprise to acute care psychiatrists across the US.  It is the reason why psychiatrists cover these settings despite the hardships involved.  They know they are treating very difficult problems with very little assistance and that even in the absence of a continuum of care they can be successful.  These psychiatrists are also aware of the medication toxicity and more importantly as this article points out - they can identify high risk patients and safely treat them.  Despite the concerns about the metabolic effects of atypical antipsychotic medication there is an implication that other factors (like smoking) may be more significant in the development of cardiovascular disease (3).  The risk of antidepressant and antipsychotic medication can be seen in an appropriate context in this study and that is lowering mortality rather than causing it.

The study also provides very useful guidance on benzodiazepine use.  In my opinion, benzodiazepines should be used only briefly for the treatment of catatonia and acute agitation in patients with psychotic disorders.  They should not be used on a long terms basis.  I agree with the authors' idea that tolerance is a problem.  When dose escalation fails or results in withdrawal and panic attacks or protracted insomnia, the risk for impulsive behavior and increasing depression is much greater.  More frequent primary care visits can also occur due to tolerance and the need for dose escalation and more discussions of appropriate use.  Treating this population in the United States is problematic because at a certain point, people can be safely detoxified from benzodiazepines only in an inpatient unit, and those services are widely unavailable.   This study is a blueprint for quality assurance projects using the same methodology on electronic health records (EHR) across the country.   Every clinical population should be examined using the authors' techniques and followed for outcomes and active interventions.

The reference provides an opportunity to see the realistic risk and benefits of treatment in people with high risk psychiatric illness.  It also presents an opportunity to use this methodology to provide better treatment to people with the same illness and prescription profiles everywhere.  Instead of using the EHR to catalogue useless full text information and track physicians, the authors methods can be used with much finer tracking of details like BMI, blood pressure, smoking status and other relevant lifestyle factors.  Apart from the aspects of polypharmacy, the overall difference in mortality due to a diagnosis of a psychotic disorder needs to be addressed, and it needs the level of detail available in an EHR.  Psychiatrists in major health plans using large databases could get active feedback in a very similar manner.  The EHR could finally be used the way they advertised it a decade ago.         



George Dawson, MD, DFAPA


1: Tiihonen J, Mittendorfer-Rutz E, Torniainen M, Alexanderson K, Tanskanen A. Mortality and Cumulative Exposure to Antipsychotics, Antidepressants, and Benzodiazepines in Patients With Schizophrenia: An Observational Follow-Up Study. Am J Psychiatry. 2016 Jun 1;173(6):600-6. doi: 10.1176/appi.ajp.2015.15050618. Epub 2015 Dec 7. PubMed PMID: 26651392.

2: Robinson DG. Early Mortality Among People With Schizophrenia. Am J Psychiatry.2016 Jun 1;173(6):554-5. doi: 10.1176/appi.ajp.2016.16030334. PubMed PMID: 27245185.

3:  Newcomer JW, Hennekens CH. Severe mental illness and risk of cardiovascular disease. JAMA. 2007 Oct 17;298(15):1794-6. PubMed PMID: 17940236.