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.

 

Deprescribing - Same Job With A New Spin

During my tenure as an acute care psychiatrist, I had to reconcile a lot of medications. I was doing medication reconciliation before the term was invented for the electronic health record (EHR). The process basically involves trying to figure out what medications the patient was really taking before they were admitted to the hospital. It could be very easy if there were no preadmission medications. On the other hand it could be extremely complicated. There were days when I had to sort through two or three shopping bags full of medications, talk with the patient’s pharmacist, talk with several specialists who were prescribing medications, and talk with the patient’s primary care physician. Even after that long process, I often estimated initial dosages based on the patient's recollection of what they had been taking and how much. I also had to make fairly rapid decisions about whether or not large numbers of medications may have been more harmful to the patient than helpful. Some patients had lists of medications containing 10 to 20 unique medications.

Sometime in the past 10 years the concept of deprescribing medication came up. It is fairly unique term as indicated by the bar graphs below that are drawn based on the references per year to the term. It started out the geriatric literature because elderly people are more sensitive to lower doses of medications and polypharmacy relative to younger and healthier populations. There is actually a list of medications called Beer’s list, that highlights medications that may be more problematic in older adults. It is the intellectual property of the American Geriatrics Society and I can’t reproduce it here. It basically contains classes medications that are known to be problematic in older adults such as anticholinergics and sedative hypnotics. Consistent with that concept - the geriatrics literature has focused on rational pharmacology and the need to reduce the medication burden in some cases the specific pharmacodynamic burden of prescribed medications.  Goal of this post is to look at some of the techniques I typically use to identify polypharmacy - related problems and respond.

In determining whether deprescribing should occur or not I think it is useful to look at hierarchy and I have outlined the following points:

1. In the case of the patient on polypharmacy who is tolerating multiple medications well and they appear to be effective strongly consider doing nothing:

Being an expert in psychopharmacology - doing all the reading and listening to the experts often doesn’t translate into the real world setting very well. There’s no better example than the patient on multiple medications who frequently has a history of numerous or prolonged hospitalizations and who appears to be taking “too many medications”. They could be multiple medications from the same class or different classes. It is easy to take a look at that list of medications and imagine how they came about but with our current fragmented medical record system it would only be an imagining.  It is too high of a risk to stop polypharmacy just based on general principles if the patient is doing well. I am familiar with many cases where changes were made and the patient became markedly destabilized and ended up back in long-term hospitalization. These are the cases that never come to light in the literature where populations rather than outliers are studied.

2. Acute medication side effects: 

In the case of acute side effects changes need to be made based on the urgency involved. Worst-case scenarios would include serotonin syndrome or neuroleptic malignant syndrome where the serotonergic or dopaminergic medications need to be stopped abruptly. That would not occur in typical clinical scenarios but in the emergency setting it is necessary. What clinicians typically face is multiple medications from the same class. When that original guideline was made back in the 1990s classes were a lot more general than they are now. For example, in those days antidepressants were a general class instead of SSRIs, SNRIs, and others.  These days combination antidepressant therapies are relatively common and research articles can be found that look at the addition of bupropion to a standard antidepressant or mirtazapine to a standard antidepressant. Beyond that trazodone might be added to those two antidepressants bring the total to three. This can occur commonly in clinical practice and also can be a source of the patient noted in number 1 above.

Numerous side effects can result from polypharmacy like sedation, headaches, nausea, and cognitive problems that probably indicate the total amount medication needs to be decreased or at least one of the medications could be stopped. The medication I frequently encounter that is prescribed at very high doses resulting in sedation is Venlafaxine ER.  There are areas of the country where very high doses of this medication are prescribed in excess of 350 mg per day - 225 mg per day is considered the FDA recommended max dose. Almost uniformly these patients improve with less venlafaxine and there is less confusion about medication side effects versus depression.

3. Chronic medication side effects:  

Some of the most serious long-term medication side effects include weight gain, metabolic changes including metabolic syndrome, diabetes mellitus, nephrogenic diabetes insipidus, hyperlipidemia, and movement disorders. In many cases the medications being used that lead to the side effects have been the only ones that will that work and even gradual changes may result in destabilization the patient. Some of these transitions between atypical antipsychotics or atypical antipsychotics and mood stabilizers result in a significant medication burden and risk for increasing side effects. It is critical that the transition is actually made to the new set medications.

Any medication side effect on a long term basis is obviously serious. Dry mouth one of the most common side effects can lead to dental caries and mouth soreness. Constipation is often considered a nuisance but it can lead to bowel obstruction and serious medical complications. Sexual side effects are a significant quality of life problem that can impact the most significant relationships in a persons life. Surveying for these side effects is a significant but necessary task for any psychiatrist.  

One of my very first experiences with chronic medication side effects was a patient who had been taking an old antidepressant - doxepin for about 5 years.  I started seeing him in that 5th year and he was no longer sure that he was depressed but he did notice he was chronically fatigued.  Because he had been on the medication for 5 years, I suggested that we taper him off of it.  He came back to see me and said he had not felt as well in a long time.  Not only had his fatigue resolved, but he no longer had chronic headaches.  In retrospect, he said he felt like he "had the flu" for the last 5 years. That experience led me to never suggest that people "get used to the medication" if they are having side effects.  I know that does happen in some cases, but I also know that most people just get used to feeling ill.

4. Rare but serious medication side effects: 

Looking at both neuroleptic malignant syndrome and serotonin syndrome, the literature frequently states that these acute life-threatening disorders occur around times of medication transitions. Trying to keep the load on both serotonergic and dopaminergic systems low during these transitions is one of my goals but I can’t really find any scientific literature to back it up. Literature out there tends to be case reports and that includes literature suggesting that medication transitions are associated with the acute disorders.

5. Interrupted medication transitions: 

I frequently see people who are on full doses of two and often three antidepressants. When I take their history there was a plan to add the new antidepressant and then taper and discontinue the old one but for some reason the old medication was not stopped.  This often happens in the outpatient setting and many times it is due to the patient not knowing that the old medication should be stopped or not getting a specific schedule to taper and discontinue it.

6. Polypharmacy: 

Polypharmacy can be highly problematic. It happens in just about every class of psychiatric medications. As an example, Adderall XR is designed to produce a concentration curve that is equivalent to Adderall immediate release dosed twice a day and yet I commonly see people taking Adderall XR either more than once a day or combined with an afternoon dose of Adderall immediate release. There are similar combinations of antidepressants, antipsychotics, mood stabilizers, and benzodiazepines. In a controlled setting where I practice I can make the necessary medication changes and follow-up the patient frequently. If that occurs in the outpatient setting there needs to be a plan in place for frequent follow-ups as well as active collaboration with the patient and the family.

7. Pharmacokinetic problems: 

The most common pharmacokinetic problem I encounter is people who abruptly stop Lamotrigine and resume the full dose.  Since lamotrigine began its psychiatric applications I have been in touch with the manufacturer many times and was advised that if the patient stops the medications for more than three or four days, the standard titration of lamotrigine needs to occur. It is fairly common for me to hear from people that they go off lamotrigine for a week or two and then resume the full 200 or 400 mg dose. I often see them after they have been on that resumed dose for one week.

The prototypical pharmacokinetic polypharmacy problem was SSRIs that were CYP2D6 inhibitors combined with tricyclic antidepressants (CYP2D6 substrates). The original reports of severe arrhythmias in some cases death from tricyclic antidepressant toxicity was the initial impetus for psychiatric interest in pharmacokinetics and drug interactions. I still see people today who are getting amitriptyline or nortriptyline in combination with fluoxetine or paroxetine and there has been no clear concern about those potential interactions.

8. New medical problems that impact prescription patterns:  

Acute renal and hepatic problems can directly impact the patient’s drug metabolism and dosing requirements or ability to take a specific drug.. One of the best examples I can think of is a case of 40 year old man who was taking gabapentin for anxiety and chronic pain. He was seen by an internist and started on a statin for dyslipidemia. Four days later when I saw the patient he was delirious and completely disoriented. He also had the significant ataxia and sedation. He was evaluated immediately and blood tests showed that he had acute renal failure that was believed to be secondary to the statin. The statin and the gabapentin were discontinued and within days he was back to his baseline.  If he had been on any other medications with primary renal clearance those would have been discontinued at same time.

9.  Correcting the medical side of things:

If the psychiatric medications are being taken incorrectly, there is a good chance  that the polypharmacy for heart disease, hypertension, diabetes mellitus, and asthma/COPD are also being taken incorrectly if they have been taken at all. It is problematic when a person has a disabling mental illness and they are left to take several doses of medication at different times of the day by themselves. When I started out in psychiatry, I could make a public health nursing referral at any time by sending in a form to the appropriate agency.  The next day, an RN would be at the patient's apartment setting up their medications, taking their blood pressure and pulse, and assisting them with managing their medications for the psychiatric disorder as well as all of their chronic medical problems.  That service ended with the rationing of all services to people with severe psychiatric disorders, making it much more likely that these medical conditions will not be as stable as they should be when they see their psychiatrists.  The is both a problem for the patient and the psychiatrist but also an opportunity to correct things.  

These are a few examples of the hierarchy of problems that occur with polypharmacy and in some cases standard pharmacy and how they can be approached. There apparently some groups out there at this time were trying to establish a hierarchy of how medications can be discontinued and when they should be discontinued. Like most cases in medicine in the extreme it is obvious but anything less than that is more difficult and it takes a lot of time to figure out. One thing that might be useful would be to consider drug combinations that are commonly prescribed as a baseline and look for polypharmacy being defined as anything beyond that.

One thing is for sure - the old rule about never prescribing two drugs from the same class - no longer applies.

George Dawson, MD, DFAPA