A Few More Lost Pieces of the Antidepressant Discussion

 

There was a lengthy article in the New York Times 2 days ago on antidepressants (1).  The main premise of the article is that millions of children and young adults were prescribed antidepressants.  The antidepressants may have been effective for the crisis but now that they continue on them, they have side effects and want to discontinue them because they feel emotionally blunted and disconnected. The chemical imbalance trope was invoked several times.  The author proceeds to extend the argument to suggest that there are millions of people in this predicament, physicians are unwilling or unable to help, and HHS Secretary Robert F Kennedy (RFK) is going to solve the problem largely by reforming psychiatry purportedly by moving into the “rift between patient and doctor” and promising to “free the mental health of Americans from dependence on pills”.

I have addressed this issue in many places on this blog.  That includes my response to RFKs arguments, RFKs comparison of SSRI withdrawal to heroin withdrawal, and strategies to prevent the problem including exposing only those people to antidepressants who need them, using medications with lower withdrawal risk, and generally being aware of the problem. I have also written about how long the problem has existed, when the first review of the problem was written, and that it is a fundamental skill that all physicians should have. 

In the RFK response I was also able to find out that the detailed antidepressant tapering and transition instructions have been in the premier online medical resource UpToDate for at least 18 years. Any practicing physician with access has those details. The facts as they exist show that RFK does not have a rational or even reasonable approach to the problem.  His idea that antidepressants are overprescribed and impossible to stop obfuscates the real problems of undertreatment and both active removal of treatment resources while promoting more high-risk treatment by the Trump administration.  In brief, the RFK approach to mental health has taken a solvable problem of not enough resources and blown it up into another problem.

To be clear, I am not commenting on the anecdote in the New York Times piece.  I have no personal knowledge of the patients or families mentioned.  I think a presentation of any similar situations in medicine should raise the questions: Why is a treatment being continued if it is not at least partially effective for the symptoms?  Why is a treatment not discontinued if the patient or family would prefer, they not take it?  What other treatments were tried before a medication was tried and what other treatments were tried concomitantly?  Invariably that all comes down to the expertise of the physician and knowing that the primary role to give the best advice to the patient and not make up their mind for them.  It is their job whether to take it or not. Almost everybody I encountered in practice had a preference to not take any medications. They either changed their mind about that after a lengthy informed consent discussion or not.  Either answer was fine with me. 

A confounding factor in any longitudinal analysis of medication effects is how people adapt to medications over time.  The first time I discontinued a maintenance antidepressant was in 1986.  That patient was a blue-collar worker who had been on doxepin for many years for migraine headaches and depression.  When I started seeing him his main problems were fatigue and hypersomnia.  I tapered and discontinued the doxepin.  He did well and eventually told me that he did not realize it at the time but he felt like he had the flu while he was on doxepin and that resolved after it was stopped.

Just as people can be unaware of long-term side effects after years on any medication – they can also get habituated to the therapeutic effects. That is the main reason people need close follow up when medications have been discontinued. Those effects go far beyond treating the primary disorder. People will report not feeling as well, not thinking as clearly, and not being as mentally flexible as when they were taking the medication.  In some cases they will experience a recurrence of a secondary disorder that was treated by the antidepressant like migraine headaches or back pain.  None of the symptoms described are due to withdrawal or a clear recurrence of the primary disorder but they would prefer to stay on the medication.

My main concern with the antidepressant controversy is that it is essentially a polarizing political argument at this point.  As far as psychiatry goes, nobody is talking about psychiatry the way I practiced it, how my colleagues practiced it, or how I trained residents to practice it.  The idea that any medication is good or evil is absurd.  The idea that the prescribers of medication are forcing it on clueless unsuspecting patients for the benefit of the pharmaceutical industry is equally absurd.  The most absurd arguments is that RFK or antipsychiatrists are going to save everyone on an antidepressant or psychiatric medication.  How will that happen when all the evidence is ignored and you have the expertise of a political podcaster?

To end this post, I want to include an important part of the antidepressant argument that I have ignored until now and that is how many people stop taking them.  There is a constant drumbeat of how many people take them and inaccurate suggestions that too many take them, so why would I think people stop taking them?  For many years, I worked for a healthcare company and I was on their Pharmacy and Therapeutics (P&T) Committee.  As such we were gatekeepers for medications that would be listed on the health plan formulary and were available to subscribers. We assessed the scientific data on efficacy but also the cost. At some point we also discussed compliance (now referred to as adherence) to the prescribed medications.  We found that a significant number of people never refilled their second prescription for antidepressants. At that point we began sending out reminder letters about the importance of adhering to the medication until there was agreement with their doctor that they should stop.

This occurred in the time frame of about 1995-2005. It was a health plan wide initiative meaning that most of the antidepressants were prescribed by primary care doctors. Stigma and the stigma of psychiatric medications was still hotly debated. There was still active misinformation about psychiatry and psychiatric medications.  There is always a personal bias to not take medications unless they are absolutely necessary. In terms of pure antidepressant prescribing I am sure that in many cases they were prescribed unnecessarily for self-limited crisis situations.  The important information here is that large number of patients stop taking these medications and that is never discussed.  It would be in opposition to the usual political argument of excessive prescribing and an inability to stop.       

What would that look like at a national and international level?  A commonly cited statistic is that 50% or persons prescribed antidepressants discontinue them in the first 6 months although many of the studies have lower estimates (see table below).  There are also several studies that estimate population wide use of antidepressants as both a percentage of the population (2-4) and absolute numbers (5).  The 2023 National Health Interview Survey found 11.4% of all adults ≥18 took antidepressant medication. The total population is 269.8M people so that is about 31M people.  Based on the available discontinuation percentages of 22 to 42.9% that means in any given year – 6.82 to 13.2 million people stop taking antidepressants.  Considering that as many as half of the antidepressants starts are for conditions other than depression it is likely that as many people are starting antidepressants as stopping them.   At least some of the survey data indicates that some of the reasons for stopping has to do with negative press and misinformation (fear of dependence)  – a known factor in the nocebo effect.

 

The above estimate is just that.  Four of the 5 studies are surveys.  There is no patient level data on a national scale that looks specifically at the antidepressant discontinuation issue.

There is data that looks at what happens at the treatment level.  That comes from a Danish register study of 66,540 older adults aged 65 or greater treated for depression who received a first-time antidepressant prescription between 2006 and 2016 (7).  Register studies are observational but they have the advantage of detailed information at the individual patient level about interventions when the databases are linked to clinical and pharmacy information for nationwide health plans. In this study, 33.7% of patient stopped antidepressants within 6 months, 26.5% gradually stopped over a period of 2 years, and 39.8% were on antidepressants for the entire 3-year period.  They studied the social determinants of this antidepressant use and also compared use to the recommended guidelines for antidepressant treatment in Denmark. Those guidelines suggest at least 6 months of maintenance treatment after initial remission and 2 years of maintenance for recurrent depression.  One of the social determinants was living in a non-urban area and the authors suggest this may be related to access to mental health specialty care.

The interesting aspect of the information in the Danish study was the detailed information across three general trajectories of antidepressant use.  Those trajectories are commonly seen in psychiatric practice and are far more realistic than what is typically portrayed in the media.  That includes the NYTimes article.       

When you read an article like that one or one of the many I have noted in the past – ask yourself what you really learned.  Like all medications antidepressants have side effects.  In fact, I routinely advised patients was that one person in six or seven would not tolerate them at all either due to initial side effects or withdrawal effects.  In clinical practice or real life - I never met a patient who told me they liked taking medications of any type.  Neither of those factors was a deterrent to trying a medication for most people.  The reason is that they were seeing me was for a severe, life changing problem and they had tried many other interventions. The Danish study (7) showed that only about 3% of that sample was ever hospitalized for severe depression.  Those were the patients I was treating.  

The psychiatric treatment of people over time is a dynamic process. It generally involves more than just medication with close attention to psychological factors and necessary lifestyle interventions. It requires a close collaborative relationship between the patient and the psychiatrist that includes a focus on optimizing therapy, minimizing or eliminating side effects and paying close attention to patient preferences. With that general approach, nobody should regret taking a medication longer than they should.  Nobody should put up with significant side effects.  And nobody should take a medication that is not working.  All of that is open for discussion.

Where I come from there is no rift between the patient and the doctor for RFK to fill.  And if there was – he is the wrong man to fill it.  

      

 George Dawson, MD, DFAPA

 

References:

 

1:  Bromley C.  A Generation on Antidepressants Searches for the Exit.  New York Times.  August 7, 2026.

2: Brody DJ, Gu Q. Antidepressant Use Among Adults: United States, 2015-2018. NCHS Data Brief. 2020 Sep;(377):1-8. PMID: 33054926.

3:  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. PMID: 24345349.

4: Fu G, Li M, Lang X, Luo M, Chen S. Trends in depression and antidepressants use by social determinants of health among adults in the United States: Data from NHANES 2005-2018. J Affect Disord. 2026 Feb 1;394(Pt B):120662. doi: 10.1016/j.jad.2025.120662. Epub 2025 Nov 10. PMID: 41224008.

5:  Chai G, Xu J, Goyal S, et al. Trends in Incident Prescriptions for Behavioral Health Medications in the US, 2018-2022. JAMA Psychiatry. 2024;81(4):396–405. doi:10.1001/jamapsychiatry.2023.5045

6:  Elgaddal N, Weeks JD, Mykyta L. Characteristics of adults age 18 and older who took prescription medication for depression: United States, 2023. NCHS Data Brief. 2025 Apr;(528):1-9. DOI: https://dx.doi.org/10.15620/cdc/174589.

7:  Ishtiak-Ahmed, K., Rohde, C., Köhler-Forsberg, O., Christensen, K.S. and Gasse, C. (2024), Depression Treatment Trajectories and Associated Social Determinants: A Three-Year Follow-Up Study in 66,540 Older Adults Undergoing First-Time Depression Treatment in Denmark. Int J Geriatr Psychiatry, 39: e70006. https://doi.org/10.1002/gps.70006.

 

Supplementary 1: The decision about medications is common in any country with the availability of advanced therapeutics.  I personally take three medications every day that I would prefer not to take. I have to self-monitor for side effects including blood pressure readings every day.  If a doctor tries to give me a temporary antibiotic prescription – I personally do a drug interaction check and let them know if that medication is compatible.  I decide to take the medication not because it makes me feel better every day but because I know the cumulative effects of not taking it are potentially very bad and therefore, I decide to take it.  I have experienced side effects and complications that I had to figure out myself and that doctors missed.  This is all part of what it means to take a prescription medication. 

All of the steps I take to protect myself are the same steps I took with any medication I prescribed for patients.

UpToDate and the Rx Transitions in Mental Health

 

For the nonphysicians reading this UpToDate is a comprehensive online resource for physicians that has essentially replaced internal medicine texts. Before it existed, most physicians who practiced adult clinical medicine could purchase a new internal medicine text every 4 or 5 years for $200-300. UpToDate (UTD) requires an annual subscription that is roughly double that cost. Many large groups of physicians provide access to their medical staff free of charge. In my last years of practice, I had an out-of-pocket subscription but I let it lapse 2 years ago. I renewed it just last week.

My rationale for the subscription comes down to several factors.  First, I need access to the best current information on complex diseases and their treatment.  The counterargument is that you can access it online – but that information is often not balanced or realistic.  UTD is carefully edited by experts in the field who often comment on what they do in their clinics.  There are several levels of editing.  Second, continuing medical education credit is available just from studying what you are interested in.  I can do a deep dive into a subject on UTD and end up with several hours of CME credit that is necessary for licensing.  The free CME credit I can access is often low in quality and requires too much time – like needing to watch an hour-long video to get 1 hour of CME credit. I really have a hard time understanding why anyone would watch or listen to a program when reading is much faster.  The only useful exception is listening while driving.  Third, there is a drug interaction program.  After extensively researching hundreds of polypharmacy combinations – I still like running those analyses.  Fourth, researching my own medical problems.  A colleague pointed out that was one of the main reasons he subscribes.  In today’s world of brief medical appointments, it is good to have some expert backup.  And if any medication is suggested I always do my own drug interaction checks and do not assume the prescribing physician or pharmacists has.  I have suggested modifications of prescriptions to my physicians on that basis.  Fifth, as a reference for my blog.  UTD references are in many of my posts.

When I renewed this time there was an option for Rx Transitions in Mental Health.  I have positively mentioned UTD in the past as a source for physicians on antidepressant tapering and transitions.  Any experienced psychiatrist has done hundreds of these transitions or tapers.  The original UTD chapters were written by senior psychopharmacology experts and they were approaches I had used many times in the past.  It was also a reminder that contrary to some recent discussions about antidepressant withdrawal – psychiatrists have been aware of these issues and have addressed them for decades.

The Rx Transitions interface is sparse. It is explicit about the intent: “to provide clinicians with information about switching antidepressant medications”.   There is a column on the left of antidepressant to be stopped SSRIs (citalopram, escitalopram, fluoxetine, sertraline), SNRIs (duloxetine venlafaxine ER) and DNRIs (bupropion ER).  After selecting the drug and the dose – a drop-down menu appears with a brief list of important information including a link to the drug interaction program.  A more expanded list of antidepressants being started pops up that includes paroxetine, milnacipran and levomilnacipran, mirtazapine, vortioxetine, and vilazodone.  Once that is checked three different schedules are provided for an immediate, rapid or standard switch.  That roughly translates to switches on day 1, week 1 or week 2 respectively.  Several paragraphs of additional information are shown and the entire summary can be printed.

I have included a graphic at the top of this post to illustrate the possible transitions. The possibilities are illustrated for the starting prescription of citalopram and ending the transition with any of the 12 antidepressants on the right side of the diagram.  That is 12 possible transitions x 3 starting doses or 36 possible transitions. If we made similar connections for all the drug and dosages on the left side of the diagram there would be a total of 346.  All would ask about immediate, rapid, or standard switches and all would show additional information about the switch is subsequent windows.

The question is whether this add on would be useful for you in your clinical practice. The first consideration is that UTD has had sections about how to do this in the main resource for years.  They are written by expert psychopharmacologists.  When I have looked at them as a reference, they back up what experienced psychiatrists do in practice.  Secondly, do you treat much depression and should you?  There has been movement in the past 20 years to suggest that antidepressant prescribing should be a function in primary care.  Both the American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) have guidelines about this.  Collaborative care models have been suggested but many if not most primary care MDs have inadequate psychiatric back up. Context is very important since I doubt that getting a prescription in a primary care clinic is the same as seeing a psychiatrist. As an example – if I am discussing an antidepressant transition, I have asked that patient if they have ever stopped the medication and if they have ever had withdrawal symptoms. Some primary care physicians tell me they see minimal withdrawal symptoms because people tend to just stop the medication if they get side effects.  In that case starting a new medication is starting from scratch.

In psychiatric practice it is common to see people on the max doses of antidepressant monotherapy or polypharmacy.  In those cases, I would typically see people much more often until I was sure they had made the transition without side effects or withdrawal.  That might include initial tapering and close monitoring of depressive symptoms.  A final variable is whether the person can be counted upon to self-monitor.  I always told my patients to call me at the earliest sign of a side effect and further that I did not ever expect they would get used to side effects.  That did not prevent many from not reporting side effects until they came in for the follow up visit.  That is another reason for scheduling close follow up during these transitions.

Rx Transitions in Mental Health may be useful for physicians who have not had a lot of experience making these transitions.  It is an outline for what is possible in both the time domain and end results based on the list of medications that are used.  I think the choices could be further simplified.  For example, I do not see the utility for transitioning to paroxetine – an antidepressant with the highest withdrawal and drug interaction risk from any other medication in the diagram.  Similarly, I do not see the utility in including both citalopram and escitalopram as antidepressants to transition to, especially now that they are both generic drugs. Escitalopram is preferred because it has a lower effective dosage and better side effect profile. Using this program assumes a knowledge of antidepressants in general.  There are still many prescribed for other indications like sleep, headaches, and chronic pain.  Depression specialty clinics still prescribe tricyclic antidepressants and monoamine oxidase inhibitors that require special considerations.  There are also augmenting therapies (aripiprazole brexpiprazole, buspirone) that factor into the transitions. For the basic cases listed and with all the qualifications posted in the software – many will find the suggestions useful.

An easy thought experiment is possible to assist in the decision to get Rx Transitions.  Just look at the above diagram and think about each transition listed.  If you have done it many times before without any complications and are aware of all the considerations and precautions - you probably don't need it.  

The written chapter in UpToDate (2) is more comprehensive than the antidepressant switching tool.  It discusses concepts like antidepressant equivalent doses, pharmacokinetics, antidepressant withdrawal/discontinuation, and has links to specific classes of antidepressants, general approaches to treating depression, and treatment resistant depression.   Even at that level – psychiatric training should provide the clinical psychiatrist with what they need.  If you are a psychiatrist, I would encourage you to read this chapter first if you are considering subscribing to UTD for the psychiatric content only.  I hope that you know all this information cold including how to set up the medication transitions and monitor them.  As previously stated, there are many other reasons for psychiatrists to subscribe to UTD.

Primary care physicians will probably find this chapter to be very useful – especially if you have been nominated in your group to treat anxiety and depression.  I would recommend reading the chapter (2) first.  If your group provides access, they might also consider the switching tool but I would not consider it a necessity. If you have been using UTD for years you are probably aware of this chapter.     

 

George Dawson, MD, DFAPA      

 

Supplementary:

I have had UpToDate staff comment on this blog before.  If you are an UTD staff member please post a reference to the very first chapter on antidepressants transitions in UTD.  I think the original chapter was written by Ross J. Baldessarini, MD.  I would appreciate knowing how long that content has been in UTD.  

References:

1:  Rx Transitions for Mental Health: Antidepressant switching tool. In: UpToDate, Connor RF (Ed), Wolters Kluwer. (Accessed on October 2, 2025.)

2:  Hirsch N, Birnbaum RJ.  Switching antidepressant medications in adults.  In: UpToDate, Connor RF (Ed), Wolters Kluwer. (Accessed on October 2, 2025.)

Are Medication Trials For Depression Too Long In Duration?

Depression is a significant cause of disability in the world.  That is complicated by the fact that there are not enough resources to treat people with depression, access is rationed in many areas including the United States, there is a high rate of attrition during treatment, and depression is often associated with significant medical and neurological disability further restricting access to adequate care. 

Over the past 30 years, strategies for treating depression have increased considerably since antidepressants medications are not uniformly effective and they have side effects that may not be well tolerated.  Antidepressants have evolved over the years from monoamine oxidase inhibitors to tricyclic antidepressants to selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) and norepinephrine dopamine reuptake inhibitors (NDRI).  The suggested pharmacology of more modern antidepressants is even more complex and the initial classifications may mean a lot less than what was initially hypothesized.

Although antidepressant monotherapy is the preferred treatment path – failure of one or two rounds of antidepressants can result in combinations of augmenting agents designed to improve treatment response.  Early augmenting agents included triiodothyronine, thyroxine, and lithium.  More recent augmenting therapies include additional antidepressants (typically bupropion), aripiprazole or brexpiprazole, or buspirone.  There are several additional agents that are used in lower frequencies.  Context is important in considering the origins of the augmenting therapies. When thyroid hormones were added, there was an active research focus on neuroendocrinology including the impact of physical illnesses on thyroid function. Later focus on treatment resistant depression assumed that all depression was treatable - it was just a question of finding the correct treatment. Both hypotheses have had low yields. 

The relative advantage of these approaches is that they are potentially cost effective (most antidepressant medications are generic and prescribed by non-psychiatrists), they are readily available, and they are more culturally accepted than they used to be.  The disadvantages include side effects most commonly nausea, vomiting, diarrhea, sexual side effects, and dry mouth. Patients need close monitoring initially to prevent side effects and assure that the medication is working. The physicians doing that monitoring also have to be aware of rare serious side effects that require emergency treatment – like serotonin syndrome, neuroleptic malignant syndrome, and acute neurological side effects.  A good knowledge of general medicine is also required to avoid treating people with chronic illnesses where there are contraindications. 

Another disadvantage is treatment non-response.  What happens if two different prescriptions are tried for adequate amounts of time and there is no response. Where does the treating physician go from there?  Seeing thousands of patients well into a course of treatment for depression and/or anxiety this is a very common problem – often complicated by additional problems including insomnia and substance use disorder.

Before anyone suggests addition exercise or psychotherapy at that point – practically all patients seeing psychiatrists have already done that.  Most of the people I treated had seen more than one therapist and these days they are branded therapists (CBT, DBT, IPT, etc).  The only non-pharmacological modality that was rarely used was bright light therapy and I typically discussed that as an add on to antidepressants. That therapy requires purchasing a device and using it for set periods of time each day. 

For the people with severe treatment resistant depression, more complicated interventions including electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and ketamine (intranasal, IV, IM) are on the horizon but difficult to find in one place.  As an acute care psychiatrist, I had very easy access to ECT.  As an outpatient psychiatrist there was essentially no access, even when I called the facility where I previously worked. Because of the current systems problems, my patients needing ECT had better access if they presented to emergency departments where they knew ECT was an option and got admitted to that hospital. The same barriers seemed to preclude any contact with me as an outpatient psychiatrist.  No calls for a collegial discussion and in many cases no discharge records from the treating facility.  Siloed care these days is a major impediment to care.

Last weekend, I was exposed to a modern approach that concentrated all the advanced treatment modalities in the same clinic that happened to be staffed by researchers interested in treatment resistant depression. Before I get to their approach – I designed the slide at the top of this post to illustrate the standard approach to moderate to severe depression over the course of my career starting in 1984.  I remind readers that psychiatrists are seeing a highly selected group of patients who have probably already failed several antidepressants and psychotherapies.  As time goes by and the number of non-psychiatric prescribers continues to increase greatly – that selection process will greatly intensify.

Looking at the general scheme of antidepressant approaches to only depressive disorders (DSM major depression and persistent depressive disorder) – there has been a clear progression of newer medications designated by older class names like tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), and monoamine oxidase inhibitors (MAOI). These general class names have significant limitations – not the least of which being reuptake blockade by of specific transporters is probably only part of the mechanism of action and some class designations depend more on chemical structure than physiology. If anyone would like a second explanatory slide with all of the current FDA approved antidepressants and more modern nomenclatures – let me know and I will make the slide.

In treating significant depressions – psychiatry added adequate dosing and duration and therapeutic drug monitoring (TDM) to determine adequate trials of antidepressants therapy.  There were active debates and research suggesting 6 weeks might be adequate on the lower end and 16 weeks as adequate duration on the high end. Pharmacokinetic factors came into play with some antidepressants with longer or shorter half-lives. If an adequate trial of medication was completed there was the question of “What’s next?”  The next issue was either changing the antidepressant or adding an augmenting therapy (adjunctive therapy per the FDA).   As noted in the graphic thyroid hormones (Triiodothyronine or T3 and tetraiodothyronine or T4/thyroxine) were both used early on in doses that were typically much lower than physiological doses (25 – 50 mcg) as well as stimulant medications (amphetamines). As time went by additional adjunctive strategies were added.  The first study of adding lithium to tricyclic antidepressants occurred in 1981 (1).  Adjunctive medications started to take off in the early part of the century with pharmaceutical companies getting that indication for newer antipsychotic medications that also had bipolar disorder indications (see specific dates of approval).   

The upside to these strategies was that antidepressant effects could be improved often to the point that depression remitted. The potential downsides were twofold – the burden of taking a second medication that could introduce new side effects or synergistic side effects with the current therapy and the prospect of endless medication trials.  Now there was the additional time of seeing whether any of several adjunctive therapies worked in addition to the antidepressant monotherapy trials. Although I did not indicate it on the diagram – several antidepressant combinations were also suggested and some patients were taking 3 or 4 antidepressants at once.  That was a significant departure from quality metrics used in the late 20^th century where antidepressant monotherapy was the rule.

The concept of treatment resistant depression – generally defined as a failure of a specified course of pharmacotherapy was often stimulus for these trials. The application in clinical practice was not as clearcut because of the number of choices and how individual patient factors affected those choices. Acuity, disability, and access were the usual limiting factors leading to cessation of pharmacotherapy trials and a trial of neurostimulation like electroconvulsive therapy (ECT).

Last week, I saw a unique solution to this bottleneck problem presented by C. Sophia Albott, MD, MA entitled  “Next Generation Treatments for Resistant Depression: The UMN Interventional Psychiatry Approach.”  She described a well-staffed clinic with a stimulating practice environment that offered ECT, transcranial magnetic stimulation (TMS), ketamine (intranasal, IM, and IV), Vagal Nerve Stimulation (VNS), and Behavioral Activation Therapy provided to all the patients in their clinic.  Their general hierarchy was to start with TMS and if that was not effective to branch out into other specific therapies. The overall description of the clinic and some of their early successes suggests to me that this is potentially a good approach.  The idea of these therapies all being concentrated in one place, taking over treatment of the patient until they are in remission, and additional support is what is lacking in most systems of care.

I am sure that some would wax philosophical about similar clinics being the future of the field – but there still needs to be psychiatrists out in the community providing acute care and consultation to primary care physicians. A subspeciality clinic could function well as back-up those psychiatrists who often lack a referral resource for neuromodulation and other advanced techniques.  The largest potential benefit would be to patients who are being maintained in long term medication trials longer than they should be. This approach may be the best way to shorten the period of disability and suffering from difficult to treat depression as well as the adverse effects of polypharmacy.

George Dawson, MD, DFAPA

 

References:

1:  Dé Montigny C, Grunberg F, Mayer A, Deschenes JP. Lithium induces rapid relief of depression in tricyclic antidepressant drug non-responders. Br J Psychiatry. 1981 Mar;138:252-6. doi: 10.1192/bjp.138.3.252. PMID: 7272619.

2:  Trivedi MH, Rush AJ, Crismon ML, et al. Clinical Results for Patients With Major Depressive Disorder in the Texas Medication Algorithm Project. Arch Gen Psychiatry. 2004;61(7):669–680. doi:10.1001/archpsyc.61.7.669

3:  Sonmez AI, Wilson S, Olsen S, Sullivan C, Herman A, Widge A, Nahas Z, Albott CS. Outcomes from University of Minnesota Clinical rTMS Clinic for resistant depression: naturalistic data on suicidal ideation. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation. 2021 Nov 1;14(6):1652.

4:  Papakostas, G.I., Trivedi, M.H., Shelton, R.C. et al. Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02468-x

Antidepressants Are Not Miracle Drugs - They Are Also Not Tools Of The Devil

I decided to end the year on a less intense but serious note about antidepressants. I am currently working on some posts on biological psychiatry most notably on the hypothalamus. When you see that posted it will hopefully contain some licensed graphics, numerous worthwhile references, and it will be the first post on this blog where copy-paste function will be blocked.  I have seen the results of not blocking my blog content and many people pointed out that it is just copied to another site and not referenced.  In what had to be a worst case scenario, I was at a conference where an academic used my custom graphics in his PowerPoint presentation without referencing that they were from this blog.  Hopefully those days are over.

But in the meantime a few comments about the war on antidepressants which is really a war on psychiatry. There are numerous posts on this blog refuting some of the published material but I want to speak about what happens at the clinical level without all of the academic references and articles. I decided to post this because antidepressants have been heavily politicized over the years. The initial rhetoric was that psychiatrists were prescribing them because they were being corrupted by pharmaceutical companies. The next step was to suggest that antidepressants were highly toxic medications for one reason or another. When both those criticisms were obviously not valid, the next step was to suggest that antidepressants simply don’t work at all.  In social media this takes on a tone that discourages people from treatment.  Psychiatrists are shamed for prescribing these medications and patients are shamed for taking them. Why would a rational person take a medication that did not work?

There have been slight modifications along the way. A good example would be the “chemical imbalance” theory that has been heavily criticized and attributed to psychiatry despite the fact that no psychopharmacology books contain this reference and the discovery that the term is an advertising meme from the late 20^th century. Some of the critics like the “critical psychiatry” movement came out with an actual position paper that proposed medications basically work because of side effects rather than any primary therapeutic effect. That is an incredible position to maintain and that may be why nobody pays attention to it. The critics of antidepressants and psychiatry are very vocal and if they are not complaining about psychiatric expertise or medications they are complaining about criticism they might receive. But the overall tone of their arguments illustrates that they have nothing positive to offer.  Many of these critics have the luxury of not treating people with severe psychiatric disorders.  In some cases that extends to denying that these disorders exist.

One of the critics complained about being “gaslighted” for some of criticisms. This is more than a little ironic for several reasons.  The standard positions of most antipsychiatrists is the very definition of gaslighting.  That position is to basically create a hostile environment that denies the legitimacy of psychiatry and psychiatric practice and treatments.  I have received hundreds of posts to this blog that never see the light of day. Some say (in many posts) that I am a hack who should not be treating patients. They claim I am an agent of the pharmaceutical industry (search all of the databases and you will see that I have not accepted as much as a nickel). They tell me that my research is poor and I have very little understanding of the literature. Some have suggested that they would like to see me physically assaulted.  One of them went so far as to hide the fact that he was a writer for a major anti-psychiatry blog until the last possible moment. I think he was really expecting that I was going to publish his post and name so that everyone on that website could have a good laugh at my expense. These critics seem to have a very thin skin and can’t take the slightest criticism for what are typically outrageous positions. 

I could quote all the evidence to the contrary hundred times but it would not do any good.  The dynamic is very similar to other antiscience arguments, like the arguments against vaccines.  The average person with a realistic concern about antidepressants should just be aware of the process at this point. There are a group of people who are out to discredit psychiatric care and medications that psychiatrists use strictly based on political agenda that has nothing to do with whether or not medications or psychiatry works.  The lesson of politics is that "the narrative" becomes the truth - particularly if one side "wins." Demonizing a perceived opponent is a common political strategy that may be amplified by social media.  This process focused on demonizing psychiatrists and the medications they prescribe can be observed in social media on a daily basis. 

There’s no better evidence that psychiatry works than the fact that we all go to work and see hundreds of thousands of people every day. Those people come back to see us because they are satisfied both with the relationship they have, the advice they get, and the fact that their treatment is effective. That includes treatment with antidepressants.  People don't take time out of their day, endure the problem of finding a psychiatrist who can see them and hassles with their insurance company, and follow treatment recommendations if the treatment is not effective.  

As I noted in the title - antidepressants are certainly not miracle drugs. About one person out of seven or eight that I see cannot tolerate selective serotonin reuptake inhibitors (SSRIs). About one person out of 15 cannot tolerate any antidepressant from any class. That fact alone points out one of the limitations of antidepressants. Additional patients will get more isolated side effects that create physical effects or affect their lifestyle and they have to make tough decisions especially if the medication is effective. They have to decide whether they want to keep taking it or not. But the clinical truth that you don't hear among the critics is that the majority of people can take an antidepressant and not get any side effects.  I know this because, I ask that specific question to every person I see who is taking a medication - every time I see them.

A more challenging clinical situation occurs when a patient asks me to start an antidepressant that they are certain has worked for them in the past and now they develop a symptom that may be a side effect that they did not have in the past. We need to figure out what is happening and what the best plan will be. The more common scenario is the person for whom the antidepressant does not work completely and we need to figure out how to get rid of their depression or anxiety.

All the negative talk about antidepressants is designed to take psychiatrists out of the equation. Nobody talks about the psychiatrist who is in the room with the patient actively working on and solving all of these problems. The problems that need to be solved from a medical and psychiatric standpoint can often make up a long list. Pre-existing medical conditions, 5-10 medications that are being taken for those conditions, drug interactions with any pre-existing conditions or medications, medication side effects, unstable medications, ECG abnormalities, medical causes of the psychiatric symptoms, neurological problems, significant renal or hepatic disease, and alcohol and substance use problems are all in that room and all need to be acted on by the psychiatrist and the patient in the room.  If somebody suggests that psychiatrists are doing less than that - take a look at the way psychiatrists are actually trained.  The ask yourself why you are not getting the whole story.

And even before we get to that point, there has to be some clarification of a diagnosis indicating that medication might be useful. There has to be a diagnostic formulation looking at how that diagnosis fits into that person’s life and conscious state. The prescription of a medication can’t be a formula based on a checklist. There are many times when a prescription medication is not the right answer. Don’t expect to hear that level of discrimination from somebody who tells you that antidepressants or psychiatrists are either generally bad or all bad.  When you hear that opinion - drill down and figure out what their conflict of interest is.  

In my current capacity, a significant number of people I see have suicidal ideation and many have attempted suicide or are actively contemplating suicide. Some have survived highly lethal suicide attempts. Most of them have depression and substance use disorders. I have to figure out the most likely diagnosis out of about 40 possibilities. In proceeding with treatment, my job is to help the person get well, recover from depression, and recover from suicidal thinking. That is a complex process and it is not just a question of prescribing medication. What is said and done in that process is not the same for any two people. I have to make sure the person is getting well and making necessary changes along the way to recover. There are many people along that path to confirm that the treatment is proceeding in a positive direction. This process is one of many leading to the demand for psychiatrists across the country. Psychiatrists have the clinical expertise to solve these problems and we are often consulted at the last possible moment after all of the other attempts have failed. 

With any luck it will be a better year ahead. I don’t expect the anti-psychiatry gaslighters to go away. I do want to reassure people that psychiatrists are result oriented and we are trained to work intensely with people to help them get better. If you see suggestions contrary to that fact - consider the source. If you see someone suggesting that they are being “gaslighted” by psychiatrists remember what I said about the posts I get here on this blog. And remember, antidepressants are just like any other medication. They don't work for everybody, but most people who can tolerate them notice a difference.  For some people the difference is life changing and it allows them to function the way they used to function. Like practically all medications, the decision to take antidepressants is a highly individual one and a decision that is not made lightly.  Most people making that decision are not making it based on what is on social media.

As professionals we take a safe recovery from mental disorders and substance use problems very seriously. 

Happy New Year!

George Dawson, MD, DFAPA

Graphics Credit:

Color gradient during the sunset in Antarctica. Vernadsky Station. Antarctic Peninsula 2008.

By Maksym Deliyergiyev from Shutterstock per their standard user agreement.

Supplementary:

Academic gaslighting?  Of course, it exists.  I realize that it is a vague and non-specific term A few examples follow from this blog.  Unfortunately, journal editors either don’t seem to get it or they are too desperate for content to care.

The Identity Crisis Card: https://real-psychiatry.blogspot.com/2019/11/there-is-no-identity-crisis-in.html

The Diagnostic Heterogeneity Card: https://real-psychiatry.blogspot.com/2019/09/recent-opinion-about-diagnostic.html

The Epistemic Injustice Card: https://real-psychiatry.blogspot.com/2019/07/some-of-greatest-minds-in-psychiatry.html

The Chemical Imbalance Card: https://real-psychiatry.blogspot.com/2019/05/chemical-imbalance-as-advertising-meme.html

The Critical Psychiatry Card: https://real-psychiatry.blogspot.com/2019/05/chemical-imbalance-as-advertising-meme.html

The Antipsychiatry Card: https://real-psychiatry.blogspot.com/2018/08/why-antipsychiatrists-have-it-all-wrong.html

The Antidepressants Are Toxic Card: https://real-psychiatry.blogspot.com/2018/04/sensational-antidepressant-piece-from.html and this recent review.

The Physicians Are Corrupted by Big Pharma Card:  https://real-psychiatry.blogspot.com/2017/05/wait-minute-is-psychiatry-less-unhinged.html

The Too Much Neuroscience Card: https://real-psychiatry.blogspot.com/2016/10/the-balanced-rhetoric-against.html

The Psychiatrist Shortage Card: https://real-psychiatry.blogspot.com/2016/08/a-better-analysis-of-psychiatrist.html

The Reductionism Card: https://real-psychiatry.blogspot.com/2015/11/reductionism-is-not-dirty-word.html

The Monolithic Psychiatry Card: https://real-psychiatry.blogspot.com/2015/06/the-myth-of-monolithic-psychiatry.html

The Philosophy Card - written by an expert on Foucault: https://real-psychiatry.blogspot.com/2013/02/moralizing-about-psychiatry-and-limits.html

This Supplementary section was added on 1/2/2020 at 0200.  The body of the original post is unchanged.

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.

More on Benzodiazepines (Like Xanax).

The topic of benzodiazepines will just not go away.  At the top and bottom of this post - I include a number of book covers from my library on the topic from the last 30 years.  The publication dates are 1983, 1985, and 1990.  I wrote a brief review for the Psychiatric Times and included my unedited version  on this blog from earlier this year.  My overall message was that benzodiazepines as a group are great for very specific indications.  In fact for some indication like detoxification from alcohol or sedative hypnotic drugs and catatonia they are life saving.  The majority of benzodiazepines are not prescribed for those indications.  They are prescribed primarily as add on medications for anxiety and insomnia.  Their use is limited by tolerance and addictive properties that are expected from a medication that reinforces its own use.  It is also problematic to prescribe them to any population of patients where alcohol use is prevalent and not expect significant drug interactions or abuse.

I really wanted to include a graphic from the paper listed below (1) from JAMA Psychiatry on the prescribing rates of benzodiazepines in patients being treated for depression.  I will post it if I get permission.  That graph illustrates the growth in benzodiazepine prescribing from 2001 to 2104.  During that time the fraction of patients taking a benzodiazepine in addition  to an antidepressant rose from 6% to 12.5% of the depression treated patients.  Subgroups were analyzed and psychiatry came across as a the top prescriber of benzodiazepines across all years.  Other practitioners and specialists came in under the curve prescribed by psychiatrists. 

 A recent anxiety disorder diagnosis was a strong predictor of concurrent use of benzodiazepine use with 24.1% of patients with a recent unspecified anxiety disorder diagnosis and 39.1% or patients with a panic disorder diagnosis taking both the benzodiazepine and antidepressant.  At 6 months 45.6% of the antidepressant + benzodiazepine and 48.1% of the antidepressant monotherapy were still taking an antidepressant.  After initial adjustments 12.3% of the simultaneous benzodiazepine and antidepressant users received long term benzodiazepines with 5.7% taking them for one year.  The prescribed benzodiazepines were almost all high potency including alprazolam (43.9%), lorazepam (26.3%), and clonazepam (21.8%).  About a tenth (13.5%) of the patients got a limited supply of for only 1-7 days).

The authors generally conclude that benzodiazepine prescribing seems to be consistent with current guidelines.  These suggest that a Cochrane report that concomitant benzodiazepine use with antidepressants increased the short term antidepressant response and decreased the drop out rate attributable to antidepressant side effects.  I would think that would be offset at least as much by guidelines suggesting limited use.

The overall strength of this report is that it is a study of a very large insurance database population of 684,100 new antidepressant users and 81,020 simultaneous antidepressant and benzodiazepine users. They give a breakdown of antidepressant classes (overwhelmingly SSRIs).  Only 12.7% and 16.5% (respectively) of the patients in each class were treated by psychiatrists.  Interestingly 77.4% and 80% of each class had not received any form of psychotherapy, although it is conceivable that at least some patients were being seen by therapists outside of the database.  As noted psychiatrists were more likely to prescribe combination therapy.  The authors speculate that may be due to referral patterns and psychiatrists seeing patients with more severe anxiety and depression, training patterns in psychiatry, or more familiarity with benzodiazepine pharmacology.  I think a more likely factor is chronicity and the fact that psychiatrists tend to see more patients with chronic anxiety and temperamental forms of anxiety that are not taken into account in DSM-5 nosology.

Despite the large N, there are many drawbacks to database studies like this one.  I think it is useful in terms of the basic pharmacoepidemiology of prescriptions but it doesn't say anything about symptoms severity and many of the practical issues involved with benzodiazepine prescribing (like substance used disorders) are eliminated by the study protocol.  The authors do a good job of describing the downsides (use disorders, falls/fractures, motor vehicle accidents) of benzodiazepines in their discussion.  I would have included cognitive problems and tolerance. It also does not address the optimal way to address combined anxiety and depressive disorders. My biggest concern is the current "evidence based" fad of diagnosing anxiety and depressive disorders using symptom rating scales like the PHQ-9 (Patient Health Questionnaire-9) and the GAD-7 (Generalized Anxiety Disorder 7-item).  In a primary care setting they pass for a diagnosis.  In a psychiatric setting they short circuit any analysis of the etiological factors of anxiety or depression.  Instead these disorders are conceptualized as disorders that that require a basic medical treatment and they resolve.  That is a gross oversimplification.     

But the main limitation should be evident - we do not have a specific enough diagnostic system with reliable objective markers.  In that context a large N doesn't mean as much unless we know how many subtypes there are and the associated treatment parameters.

George Dawson, MD, DFAPA

References:

1:  Bushnell GA, Stürmer T, Gaynes BN, Pate V, Miller M. Simultaneous Antidepressant and Benzodiazepine New Use and Subsequent Long-term Benzodiazepine Use in Adults With Depression, United States, 2001-2014. JAMA Psychiatry. 2017;74(7):747–755. doi:10.1001/jamapsychiatry.2017.1273