Showing posts with label antidepressant discontinuation. Show all posts
Showing posts with label antidepressant discontinuation. Show all posts

Thursday, June 28, 2018

The Problem of Antidepressant Discontinuation



Antidepressant discontinuation is a useful topic to discuss for a number of reasons.  First, it is a legitimate problem for a number of people who want to stop the medication and find that they can't for one reason or another.  Secondly, some of the people are unable to stop because they have discontinuation or withdrawal symptoms from the antidepressants and for some people these symptoms are extremely distressing.  In other cases the people trying to stop get recurrent symptoms of anxiety, insomnia, and depression and have to resume the medication.  Thirdly, the solutions to the problem are poorly defined.  In the US, antidepressants are prescription medications and that should mean that they are prescribed for a clear indication and carefully monitored.  Those safeguards are not clearly present any more and even if they are having the indication and carefully monitoring the medication does not guarantee that the patient will not get severe side effects or problems with discontinuation.  On a population wide basis, prescribing antidepressants for only clear cut indications will mean that the minimum number of people are affected and that an antidepressant will be stopped at the earliest sign of problems.  All of the current trends in screening for depression, encouraging treatment by nonspecialists, and limiting the availability of non-pharmacological methods for treating psychiatric and emotional problems suggests that a major cultural change would be required to reverse those trends.    Fourth, because of these problems - the antidepressant issue is an informed consent issue to patients.  In addition to warnings about the usual side effects they also need to hear about the more serious side effects including serotonin syndrome, cardiovascular side effects, possible drug interactions and withdrawal and discontinuation symptoms.  Finally, it is not clear that liberal antidepressant creates more problems than it solves.  The best example I can think of to illustrate this fact is a paper I posted here in the past showing that there was a clear trend in decreased suicide in the elderly with increased antidepressant prescribing across the entire population of Denmark.  On  clinical basis I have had conversations with hundreds of people about stopping antidepressants and the results of many of those conversations is surprising.  Although the main FDA psychiatric indications for antidepressant prescribing are mood disorders, anxiety disorders, and obsessive compulsive disorder - it is common to find people who are taking them for other reasons. Extreme irritability and anger control is one.  Needing to have a "level mood" is another.  Taking antidepressants for menstrual and menopausal mood symptoms that do not meet diagnostic criteria for major mood and anxiety disorders is another. 

The two main considerations for antidepressant discontinuation are whether the person experiences recurrent symptoms of the primary problem or specific discontinuation or withdrawal symptoms or a combination of both. 

A few addition points about antidepressant withdrawal.  The first case in the medical literature was reported for tricyclic antidepressants in 1959 (1) and the first review in 1993 (2).  The symptoms were also described in the first edition of a major psychopharmacology text (2):

"There is no withdrawal problems with the TCAs of the type seen with narcotics, alcohol, or sedatives.  Instead, abrupt discontinuation of 150-300 mg/day or more of a tricyclic, especially after 3 or more months of treatment can induce autonomic rebound (ie, gastrointestinal disturbances, autonomic symptoms, anxiety, agitation, and disrupted sleep)."  p 276.

Gradual taper rather than abrupt discontinuation was recommended.  The issue of rebound from REM suppression and nightmares or intensification of dreaming was also discussed.

For the sake of brevity, I am going to discuss a recent trial of antidepressant discontinuation (4), what is wrong with that trial, and how to improve the state of affairs in the future.  For some reason, I could not find this study indexed by the National Library of Medicine.  Full text is accessible by the DOI number.

This is a study of an attempt to withdraw patients from antidepressants with success in doing that designed as the primary end point - further defined as no antidepressant use in 6 months and no depression or anxiety by a standard rating at 1 year follow up.  The patients were selected from 45 primary care practices across the Netherlands between February 2010 and March 2013.  The algorithm for patients selection in each stage with the resulting numbers are available in diagram form in the body of the paper.  Anyone not meeting criteria for maintenance anti-depressant or anxiolytic treatment were identified as possible candidates for the study.  Appropriate use of antidepressants for depression and anxiety was defined as a history of recurrent depression [≥3 episodes] and/or a recurrent psychiatric disorder with at least two relapses after antidepressant discontinuation.

6442 long-term antidepressant users were identified in these primary care settings.  2411 (37%) were eligible with that determination made by their primary care MD. 358/2411 (15%) consented to participate and 146 were included in this study.

The specific intervention is hard to get at in the description given.  For the intervention group a patient specific letter was sent to the general practitioner with the recommendation to taper the antidepressant. Antidepressant tapering instructions, antidepressant discontinuation symptoms, and the recommendation for slow tapering were all included.  The GP discussed this with the patient and then sent a response to the research team on whether or not the patient would comply with the recommendation.  Reasons for not complying were requested.  For the control group, patients continued their usual care and their GPs were unaware of their participation in the study.  In US studies this would be the treatment as usual group.

34/70 rejected the intervention citing fear of relapse or recurrence as the primary reason.  That is interesting giving the inclusion criteria.  Is it possible that disorder severity or anxiety or depressive subtypes were perceived as more severe by the patient than the recorded primary care diagnosis? None of those patients cited antidepressant discontinuation symptoms as a reason.

Only 4 (6%) patients in the intervention group and 6 (8%) patients in the control group were able to successfully stop antidepressants.  There was a slightly higher relapse rate in the intervention (18/70)   versus the control group (10/76).  No other variables other than duration of antidepressant (5.7 years versus 9.6 years) were significant in who could discontinue the antidepressant and who could not.

In their discussion the authors comment on a higher relapse rate in the intervention group that was not associated with antidepressant discontinuation.  They attribute it to anxiety about wanting to comply with the recommendation but not being motivated to do it.  I think that any anxiety about the recommendation is more likely due to the fact that the recommendation is coming from a source that is not their primary care physician.  Most people in primary care with longstanding relationships with their physicians are there for a reason.  Taking a recommendation in opposition to their GP would be highly problematic for many.  They cite several other reasons among them a poorly done meta-analysis of antidepressant trials suggesting a large placebo effect.  In fact, all of these meta-analyses are significantly flawed based on the included studies.  But more on how to sort that out below.   

I am going to avoid constructing my own antidepressant discontinuation checklist but plan on that in the next several days.  My extensive clinical experience and the literature lead me to the following conclusions:

1.  Expose only the subpopulation who needs antidepressants to them:

This is easier said than done because of the literature on under diagnosis of depression in primary care settings, the literature (and lack of evidence supported guidelines) on screening everyone for depression, the new collaborative care initiative encouraging the use of a checklist to diagnose and treat depression, and the massive bureaucratic interventions to encourage screening and treatment with medication.  Like opioids - primary care physicians were scapegoated for not recognizing and treating depression.  Now both of the primary care professional organizations have their own depression treatment guidelines and these physicians are criticized for overprescribing antidepressants.  Things might go a lot better if the politics was wrung out of medicine.

2.  Recognize that some patients have severe discontinuation effects: 

There is 60 years of literature on this topic, we have all seen it, and it should be a given.  It should be addressed even if there is not perfect research on how to help these people.  I have said it in the past and will say again - I have treated people with severe discontinuation symptoms and helped them stop the medication.  Some syndromes are much more complicated than others - like SSRI withdrawal that has an anticholinergic component.  As I have said in the past - I just don't prescribe some of these medications (paroxetine) and have not in decades.  I would never have prescribed venlafaxine again if they had not invented an extended release version and found it was very useful for people who can't tolerate any SSRIs - but that does not mean that there aren't people out there who don't get severe discontinuation symptoms because of venlafaxine XR.  All of this is an informed consent issue and you can't have that discussion seeing people very 10 minutes and handing them a prescription.

I will say that the majority of people that all psychiatrists treat routinely go on and off antidepressants without problems.  It is so commonplace that many health care companies have systems that send the physician a letter if the patient has not picked up their antidepressant prescription.  That is very common and typically because patients have reservations about starting the medication or how the appointment went.

3.  Study the problem in a realistic setting: 

The study I discussed above was destined to fail. A more realistic study should reflect the clinical reality that every psychiatrist knows.  Instead of an intervention telling people when to stop, the intervention could look at all episodes of antidepressant discontinuation in a health care system.  Various strategies could be used and data on the reason for stopping and any discontinuation symptoms could be gathered in a systematic way.  There are several statistical models that can be applied to multiple episodes across fewer patients.

I would suggest that the intervention not be conducted by the physician who prescribed the original treatment because of the aforementioned conflict of interest.

As in antidepressant trials, the nocebo effect is significant and needs to be studied in discontinuation.  In other words, if a person is told that the antidepressant is being discontinued and they are given the exact same dose of the same antidepressant will they develop symptoms of discontinuation?

There is also a lot to be said for an unblinded study of people who are motivated to just get off the antidepressants with a standard protocol. I would not mind conducting that study myself and also adding a component to see, if the success of people who are highly motivated to stop could be predicted.

4.  Despite the evidence-based crowd, the experts need to be heard: 

Like many other psychiatrists, I have seen severe antidepressant discontinuation symptoms, but have been able to get the patient off of the antidepressant.  The idea that there are people who cannot get off these medications and they need evidence to get off the medications is a circular argument.  The evidence is out there, and the experts should write a consensus statement.  That should be the basis for further trials and those trials should employ psychiatrists who know how to do this.  If there are that many people with the problem - it should be easy for any University department to recruit them and study them in detail in the hope that they can successfully get off the medication.

5.  The issue is important in everyday clinical practice:

The best illustration is changing antidepressants.  There are three methods, abrupt discontinuation and starting the new one, gradual taper and start, or taper with cross titration.  The majority of people I see can tell me if they have ever had discontinuation symptoms when they stopped or ran out of the antidepressant that we are changing. That turns out to be a good predictor of who can just stop the antidepressant and start a new one the next day.

That concludes my brief discussion of the problem and what I think can be done about it.  One thing is for sure - political discussions of this issue fail to advance getting the best care to the maximum number of people - whether that is a bitter discussion of how antidepressants are poison and nobody should take them to how they should be casually prescribed as part of a screening process.



George Dawson, MD, DFAPA



References:

1: Mann AM, MacPherson AS. Clinical experience with imipramine (G22355) in the treatment of depression. Can Psychiatr Assoc J. 1959 Jan;4(1):38-47. PubMed PMID: 13629473.

2:  Garner EM, Kelly MW, Thompson DF. Tricyclic antidepressant withdrawal syndrome. Ann Pharmacother. 1993 Sep;27(9):1068-72. Review. PubMed PMID: 8219442.

3:  Philip G. Janicak, John M. Davis, Sheldon H. Preskorn, Frank J. Ayd.  Principles and Practice of Psychopharmacotherapy.  Williams and Wilkens, Baltimore Maryland, 1993.

4:  Eveleigh R, Muskens E, Lucassen P, Verhaak P, Spijker J,  van Weel C,  Voshaar RO, Speckens A.   Withdrawal of unnecessary antidepressant medication: a randomised controlled trial in primary care.  BJGP Open 2018; 1 (4): bjgpopen17X101265.  DOI: 10.3399/bjgpopen17X10126


Supplementary:

Reviews of antidepressant discontinuation syndrome. Link


Polling Question:

I thought I would add a polling question to this post for any physicians out there treating depression.  One of the commonest encounters that I have had due to this blog have been people who claim:

1.  Severe antidepressant discontinuation/withdrawal.
2.  Associated long term conditions with withdrawal.
3.  A complete inability to stop antidepressants.
4.  Extraordinary measures needed to stop antidepressants - like breaking the capsule or grinding up the tablet and reducing the dose by 1 mg amounts.

I don't doubt #1 at all because I have seen it and treated it.  In the case of #2, the only medication I have seen this occur with was beta blockers - metoprolol  specifically.  In that case the patient was taking the medication for blood pressure control and developed severe panic attacks and associated tachycardia and insomnia trying to taper and discontinue the medication.  There was no previous history of anxiety.

I am interested in what physicians have directly observed in these areas.




Tuesday, April 10, 2018

Sensational Antidepressant Article from the New York Times





Take some quotes taken out of context, the suggestion that doctors know less about the problem than the New York Times does, and the suggestion that you may be "addicted to antidepressants" and what do you have - the latest article on antidepressants by the New York Times.  Although the New York Times has never been an impressive resource of psychiatric advice they continue to play one and the latest article  Many People Taking Antidepressants Discover They Cannot Quit is a great example.

The reader is presented with numbers that seem to make the case "Some 15.5 million Americans have been taking the medications for at least five years. The rate has almost doubled since 2010, and more than tripled since 2000." and "Nearly 25 million adults, like Ms. Toline, have been on antidepressants for at least two years, a 60 percent increase since 2010."  Guaranteed to shock the average reader, especially in a culture that systematically discriminates against the treatment of mental illness.

Adding just a little perspective those figures translates to 15.5M/254M = 6.1% and 25M/254M = 10% of the adult population in the US.  Looking at the most recent epidemiological estimates of depression in the US 1990 - 2003 shows one year prevalences of 3.4 - 10.3% of the adult population.  The lifetime prevalences from some of those studies 9.9-17.1%.  It seems that the claims of antidepressant utilization may be overblown relative to the epidemiology of depression and the number of people disabled by it.  The authors go on to quote a study on the overutilization of antidepressants on data obtained from the National Health and Nutrition Examination Survey (NHANES) study.  These same authors have quoted an increase of antidepressant use of 10.4%.  This same study estimated a lifetime prevalence of depression of 9.5%.

Depression alone is not the sole indication for antidepressants. Anxiety disorders is another FDA approved indication.  Anxiety disorders can add an additional 3% 1 year prevalence and 5-6% lifetime prevalence.  About 16.5% of the population has headaches and antidepressants are used to treat headaches.  Another 6.9-10% of the population have painful neuropathies that are also an indication for antidepressant treatment.  Over a hundred million Americans have chronic back pain another indication for a specific antidepressant.  The main reference points to a study (3) that suggests only about 7.5% of antidepressants are prescribed for nonpsychiatric conditions.  Only 65.3% of the prescriptions were for "mood disorders. A study looking at antidepressant drug prescribing in primary care settings in Quebec Canada (5) provides specific data and concludes that  29.4% of all antidepressant prescriptions were not for depression or anxiety but for insomnia, pain, migraine, menopause, attention-deficit/ hyperactivity disorder, and digestive system disorders. Those same authors go on in a subsequent paper to provide a detailed analysis of the off-label use of those antidepressants.

The number of antidepressant prescriptions is far less drastic when taken in that context.  I am not arguing that every person with an eligible condition should be on antidepressants.  I am definitely saying that given the large numbers of people who will potentially benefit - the number of antidepressant prescriptions is not as outrageous as portrayed in the article.

What follows is a brief descriptions of antidepressant discontinuation symptoms and the fact that the medical profession doesn't know what to do about it.  This is certainly not the case in any setting where I have practiced. Discontinuation symptoms are well know to occur with SSRI and SNRI medications.  I routinely describe them and their varying intensity as part of the informed consent procedure when I prescribe these medications. The reality is that 20% of people will stop taking antidepressants in the first month after getting a prescription. Many will just get the prescription and never start.  An additional 20-30% will stop in the next 3-4 months.  Stopping antidepressants without medical guidance is so common that I routinely ask patients if they have abruptly stopped at any point when I am making any changes in their medications.  The majority have stopped without getting any of the discontinuation symptoms.  I qualify that by the fact that I have not prescribed paroxetine in 30 years because I considered it to be a problematic medication and I have a very low threshold for stopping antidepressants if I don't believe they are tolerated.  Even in their referenced study (2) the authors state: "In one national study, for example, only about one-quarter of adults initiating antidepressants for new episodes of depression continued to take their medications for 90 days...".  Does that sound like it is a medication that is difficult to stop?

They don't stop there.  After making it seem like we are in the midst of an antidepressant epidemic and that people are unable to stop antidepressants they make an even more absurd argument - doctors are unable to help patients get off antidepressants.  Before I go into their details consider this.  I work at a facility where we routinely detox people off high doses of the most addictive drugs in the world.  If we are able to do that, why would a doctor not be able to figure out how to discontinue a non-addictive antidepressant?  This specific statement really had me rolling my eyes:

"Yet the medical profession has no good answer for people struggling to stop taking the drugs — no scientifically backed guidelines, no means to determine who’s at highest risk, no way to tailor appropriate strategies to individuals."

Do I really need a study to do something that I have been doing successfully for 30 years?  Tapering people off of medications is something that every physician has to do.  Successfully using antidepressants means being able to taper and discontinue one and start another or taper and discontinue one while starting another or starting another and eventually tapering and discontinuing the original antidepressant.  That is not innovation - that is standard psychiatric practice.

I can only hope that the quotes from family physicians that follow were totally out of context.  Statements about "parking people on these drugs for convenience sake." and that the "state of the science is absolutely inadequate" are ludicrous.  I would say if you have to park somebody on a psychiatric drug or have questions about how it is used - it is time to send that patient to see a psychiatrist.  Nobody should ever be "parked" on a drug.

These physicians seem to have lost sight of the fact that they do not have similar problems prescribing equal amounts of antihypertensive medications and leaving people on them indefinitely.  There is no rhetoric about "parking" somebody on an antihypertensive medication or a cholesterol lowering drug or a medication for diabetes.  The fact that depression is the leading cause of disability in the world seems to be ignored.  The fact that up to 15% of people with depression die by suicide is not mentioned.  The suggestion is that this disabling and potentially fatal condition should not be addressed as rigorously as other chronic illnesses.

In the midst of all of the confusion created in this article, the authors fail to point out the likely cause of increased antidepressant prescriptions but they quote one psychiatrist who comes close.  He points out that the increase in antidepressants is due to primary care physicians prescribing them after brief appointments and (probably) not being able to follow the patient up as closely as a psychiatrist.  This was one of the main findings in the paper by Mojtabi and Olfson (2).  The specific quote "...the increase in long-term use (of antidepressants) was most evident among patients treated by general medical providers."

What is really going on here?  This blog has repeatedly pointed out that mental health care and treatment by psychiatrists has been rationed for about 30 years.  The result of that rationing is that there are few reasonable resources to treat all kinds of mental illnesses.  With that end result, the argument is now being made that we really don't have to build the infrastructure back up - we just need to shift the burden to primary care clinics.  In order to make it more simple for them we can just screen people with a rating scale for depression (PHQ-9) or anxiety (GAD-7) and treat either symptoms with a medication.  That way we can not only ration psychiatrists, but we can also ration psychologists and social workers who could possibly treat many of these patients with psychotherapy alone and no medication. For that matter, we could treat a lot of these patients with computerized psychotherapy - but managed care organizations will not.  State governments and managed care organizations will screen people, make a diagnosis based on a rating scale, and put that person on an antidepressant medication as fast as possible.

That is a recipe for high volume and very low quality work.  A significant number of those patients will not benefit from a medication because they do not have a compatible diagnosis.  A significant number will not benefit from the medication because it is not correctly prescribed.  In order to compensate for that inadequacy, a model of collaborative care exists that provides a psychiatric consultant to the primary care clinic.  That psychiatrist never has to directly see the patient.  The collaborative care model depends on putting patients on antidepressants as soon as possible and even more classes of psychiatric medication.

That is the real reason for increased antidepressant prescriptions and people taking them.  It is not because nobody knows how to prescribe them or stop them.  It is not because they are "addictive". It is because there is a lack of quality in the approach to diagnosing and treating depression in primary care settings and that is a direct result of federal and state governments and managed care organizations.


To be perfectly clear I will add a series of rules that will not question the current business and political rationing of mental health resources but will address the problem of antidepressant over prescribing and antidepressant discontinuation:

1.  Stop screening everyone in primary care clinics with rating scales - there is no evidence at a public health level that this approach is effective and it clearly exposes too many people to antidepressants and other medications.  I am actually more concerned about the addition of atypical antipsychotics to antidepressants for augmentation purposes when nobody is certain of the diagnosis or reason for an apparent lack of response and nobody knows how to diagnose the side effects of these medications.

2.  Provide any prospective antidepressant candidate with detailed information on antidepressant discontinuation syndrome - including the worse possible symptoms. While you are at it give them another sheet on serotonin syndrome as another complication of antidepressants.  It is called informed consent.  I encourage the New York Times not to write another article about serotonin syndrome.

3.  Triage depressed and anxious patients with therapists rather than rating scales - brief, focused counseling, CBTi for insomnia, and computerized psychotherapy all have demonstrated efficacy in addressing crisis situations and adjustment reactions that do not require medical treatment.

4.  Refer the difficult cases of discontinuation symptoms to psychiatrists who are used to treating it.

5.  Don't prescribe paroxetine or immediate release venlafaxine - both medications are well know to cause discontinuation symptoms and they are no longer necessary.

6.  Every physician who starts an antidepressant needs to have a plan to discontinue it - the idea that a patient needs to be on a medication "for the rest of their life" in a primary care setting is unrealistic.  If that determination is to be made - it should be made by an expert in maintenance antidepressant medications and not in a primary care clinic.

7.  Every patient should be encouraged to ask to see an expert if either their medication prescribing or treatment of depression is not satisfactory.  The standard for treating depression is complete remission of symptoms - not taking an antidepressant.  If you are still depressed - tell the primary care clinic that you want to see an expert.

In an ideal world, people with severe depression would be seen in specialty clinics for mood disorders, by psychiatric experts who could address every aspect of what they need.  That used to happen not so long ago.  It still happens in every other field of medicine.

But quality care like that is no longer an option if you have depression.


George Dawson, MD, DFAPA


References:

1: Carey B, Gebeloff R. Many People Taking Antidepressants Discover They Cannot Quit. New York Times April 7, 2018.

2: Mojtabai R, Olfson M. National trends in long-term use of antidepressant medications: results from the U.S. National Health and Nutrition Examination Survey. J Clin Psychiatry. 2014 Feb;75(2):169-77. doi: 10.4088/JCP.13m08443. PubMed PMID: 24345349.

3: Mark TL. For what diagnoses are psychotropic medications being prescribed?: a nationally representative survey of physicians. CNS Drugs. 2010 Apr;24(4):319-26. doi: 10.2165/11533120-000000000-00000. PubMed PMID: 20297856.

4: van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014 Apr;155(4):654-62. doi: 10.1016/j.pain.2013.11.013. Epub 2013 Nov 26. Review. Erratum in: Pain. 2014 Sep;155(9):1907. PubMed PMID: 24291734.

5: Wong J, Motulsky A, Eguale T, Buckeridge DL, Abrahamowicz M, Tamblyn R.Treatment Indications for Antidepressants Prescribed in Primary Care in Quebec, Canada, 2006-2015. JAMA. 2016 May 24-31;315(20):2230-2. doi: 10.1001/jama.2016.3445. PubMed PMID: 27218634.

6: Wong J, Motulsky A, Abrahamowicz M, Eguale T, Buckeridge DL, Tamblyn R.Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system. BMJ. 2017 Feb 21;356:j603. doi: 10.1136/bmj.j603. PubMed PMID: 28228380.