Thursday, December 26, 2013

Pills Don't Save Lives - Psychiatrists Do

I am paraphrasing David Healy from a previous post and I am doing it here to emphasize - it's all about the side effects.  Healy's comment serves as a counterpoint to a highly successful multi-decade advertising campaign by pharmaceutical companies.  It began with the first National Depression Screening Day in 1991.  The emphasis  was on identifying and treating depression with antidepressants.  There was no real discussion of antidepressant side effects or the general problem of side effects with most medications.  Since then antidepressant treatment has been conceptualized as comprehensive treatment wrapped up in a pill or capsule.  That bias continues today as various political forces have shifted depression screening from an annual event to primary care clinics.  Some health care organizations and states consider depression screening and serial ratings of depression to be quality markers of health care services despite the fact that there are definite problems with that idea.  Unless there is a highly specific screening test any screening procedure has the potential to expose more people to the side effects of treatment.  There is no highly specific screening test for depression.

A second factor in considering side effects is the physician's role.  Doctors are trained to identify and treat conditions with surgery or medications.  Psychiatrists have additional training in psychotherapy. When you are in your training, the emphasis in on making the correct diagnosis and selecting the medication that will be the most useful.  Even though medical training is long, the longest you might follow any patient might be for a couple of years.  In medical practice you have the ability to see people for decades rather than months or years and how their medical treatment changes over those years.  You also observe first hand the long term toxicity of many medications when you might have only been exposed to that on a theoretical basis during training.  As a practicing physician you are expected to help people deal with the fact that they have side effects and the medications they are using may not be that useful.  In fact, in many cases they may not be beneficial or may be causing more harm than good.

All of that experience with side effects leads clinicians to develop new practices that they were never trained to do.  Very early in my career, I had the experience of treating a person who had been on an antidepressant for about 6 years.  She had headaches and depression and like many people with chronic depression she was in a stressful situation that she could not remove herself from.  She had chronic depression in the context of a chronic stressor that was not going away.  At some point her headaches resolved and her depression improved.  We decided to taper her off the antidepressant.  She came in 2 weeks later and said: "I feel much better.  All of the years that I was taking that medication I didn't realize it, but I felt like I had the flu.  That has now cleared up."  That early experience led me to modify the ways that I discuss medications with people.

I generally tell people that I don't expect anyone to "get used to" a medication.  I often tell them that people may get used to feeling ill rather than develop a tolerance to medication side effects.  I tell them that if they are experiencing any side effects at all to let me know about it and we will decide what to do about it at that time.  I let them know the range of experiences with medications and what they might expect.  As an example, I might say that "60-80% of people might take this medication and not notice that they are taking anything, but 5-10% of people might not tolerate it at all."  I let them know about all of the FDA contraindications, in some cases I review it with them many times.  I discuss the common side effects and usually provide them with the MedlinePlus handout on the medication.  I think it is more comprehensive than most handouts and it gives the FDA black box warnings (in a red box) on the front of every handout.  I talk with them about rare but potentially serious side effects like drug induced liver disease and arrhythmias and what to look for.  In the case of atypical antipsychotics, I discuss movement disorders and metabolic effects.  I demonstrate what the movements of tardive dyskinesia may look like.  I let people know if the medications they are taking are potentially addictive.  I the case of lithium, I let people know about the unique toxicities and the safest possible way they can take it.  In the case of antidepressants, I let people know that they may be difficult to stop due to discontinuation symptoms.

My side effect discussions with people have taught me valuable lessons.  There are people who are placebo responders and nocebo responders.  The nocebo responders develop problems taking any medication, even medications that are generally well tolerated at low doses.  Some of them are aware of the problem and decline any discussion of side effects.  They might say they don't want the MedlinePlus handout because: "If I read about any side effects I will probably get them."  They would rather be surprised.  Whenever I encounter that attitude, I respect their wishes but advise them to contact me if they have any side effects.  I also recall my Forensic Psychiatry lectures during residency.  The instructor advised us that we "could be sued" if our side effect discussions prevented a patient from taking a useful medication and there was an adverse outcome as a result.  I have realized over the years that basing your decisions on whether you could be sued is generally a bad idea because you can be sued for just about anything.  I think that people need to hear about what really happens with psychiatric medications and consider myself to be a good source of information.

I have also found that there is a hearty group of people who decide on their own that they will try to tolerate side effects and not let me know about it despite our discussion.  When I see them in the follow up appointment they will say: "Well you know doc, I had a pretty good headache the first three days on the medications, but I decided to keep taking it to see if it would go away and sure enough on day 4 the headache was gone."  They tell me that even though I advised them to not tolerate side effects and to call me if they had any side effects.  These patients are almost always men with a history of avoiding doctors and not taking care of themselves.  I guess their experience confirms that some people develop a tolerance to side effects but why would you want to?  I was at a large conference on the treatment of anxiety disorders and listened to a renowned psychopharmacologist talk about his technique for treating anxiety disorders with SSRI and SNRI type antidepressants.  His approach was to keep titrating the medication "to the point of toxicity" and then back off to the lower dose.  My experience has taught me that the best approach in non acute situations is to use the lowest possible dose.  That is usually the dose recommended for anxiety disorders and titrate it to the exact point where the symptoms are in remission.  I am never  compelled to increase a medication by a multiple based on the pill size or a drug level based on the aggregate experience of a cohort of people in a drug trial.

I obsess about the hypothetical.  Physicians in practice are aware of trends in the medications that are prescribed and psychiatry is no exception.  Drug interactions have been an area of focus in psychiatry since it was first learned that fluoxetine could inhibit the hepatic metabolism of tricyclic antidepressants and that could lead to antidepressant toxicity.  I treat people who are often on a mind boggling combination of medications for their chronic illnesses and psychiatric disorders.  I routinely run those lists through one or more computerized drug interaction software packages.  The software is inconsistent and I often have to look up the case report or study that suggest a specific interaction or problem.  I have to make the decision to accept or reject what the software is telling me.  The QTc interval or the interval on the electrocardiogram that corresponds with the total time of ventricular contraction and relaxation has been a major concern since the approval of ziprasidone.  It has been complicated lately by the FDA concern that citalopram may prolong the QTc interval in some people to a significant extent.  I screen people with electrocardiograms if it appears that their clinical status or total medication burden may lead to prolongation of the QTc interval.          

In some cases a concern for the hypothetical requires some inductive reasoning.  Current textbooks, literature, and standard prescribing references create the illusion at times that everything is known about a medication, it is just a matter of finding it.  There are plenty of examples where that is not true or where there is a lot of uncertainty about when a medication can be safely and effectively prescribed.  To illustrate, consider a hypothetical situation of patient with bipolar disorder who may benefit from taking lithium.  For a time during my residency training the renal toxicity of lithium was openly debated.  Nephrologists at the time certainly believed it was nephrotoxic but there were large series of patients who were described with minimal signs of renal toxicity.  Clinical practice treating patients with severe bipolar disorder has lead me into situations where I have treated patients on, during and after dialysis and kidney transplantation.  The estimation of glomerular filtration rate (GFR) by 24 hour urine collections was also problematic.  That has been greatly improved by the practice of using calculated GFRs.   I have no doubt at all that taking lithium for a period of time can lead to renal failure in a portion of patients taking it.  Anyone prescribing lithium needs to be aware of this fact and take all measures necessary to minimize episodes of lithium toxicity and exposure to other nephrotoxins.  In some cases like NSAIDs, the toxins are well known.  In other cases like tenofovir, the interactions are not known and in fact you can scan an entire FDA approved package insert and might find no references to lithium.   Making that decision may take hours or a weekend of study to figure out the best course of action.

I hope that I have made the case for psychiatric medications needing a careful analysis of side effects before they can be initiated and continued.  The decision to take medications is a serious one.  In 29 years of practice I have not met a single person who told me that they liked to take medications.  The decision to take medications often comes down to having tried everything else and realizing that a major change is necessary to get back to where you want to be.  A recent reply to my previous blog post described medications as "tools" rather than a panacea and I think that until perfectly safe and effective medications are invented that is true.  Healy's point is that the advertising notion of "Take an antidepressant and get better" is false.  Psychiatrists are trained to help you navigate the complicated process of recovery from depression and side effects and the potential for side effects is generally the most complicated aspect.

George Dawson, MD, DFAPA

Additional Clinical Note 1:  Another blogger sent me an e-mail earlier this week asking me to send a list of psychiatrists who I thought were competent to taper people off of SSRI/SNRI type antidepressants.  The intention of the e-mail was to have a ready list of people who could help people with that particular problem.  I think that all psychiatric residents should be taught about medication discontinuation effects and how to resolve them, but apparently that is not the experience of some people who end up taking these medications.  As an instructor in a psychopharmacology course, I can verify that the residents I taught were all aware of this problem and how to deal with it.  They also had the very good back up reference of the ASCP psychopharmacology course PowerPoints and lecture materials on this problem.  I realize that this blog is not widely read, but I would appreciate any posts from instructors or professors about the issue of side effect recognition and treatment in general and SSRI discontinuation symptoms in particular and the approach to teaching these topics in your program.  I would also appreciate hearing your thoughts on this problem about SSRI/SNRI discontinuation symptoms and the variable experiences of people trying to get the problem diagnosed and treated.

Additional Clinical Note 2:  The processes that I am describing in the above post take time.  In many cases the equivalent amount of time required to do psychotherapy and longer.  I do have people telling me that their physicians (all types) seem to be poised over a prescription pad.  They tell me nobody has ever informed them of the risks or potential side effects of a medication.  I don't think the problem has been investigated and it would be difficult to do.  The idea that "medication management" in psychiatry, internal medicine or any other field is a brief uncomplicated encounter that takes little thinking on the part of a physician is largely an invention of business interests seeking to reimburse physicians at the lowest possible rate.  If you are a consumer of medical services, consider my approach in the above post and ask yourself if you have had the discussions that I describe.


  1. Brintellix was approved in October and every psychiatrist I talked to knows nothing about it. This has to be the most subdued release of an antidepressant I can recall I wonder if the pendulum has swung too far the other way.

    1. You may be right. Schatzberg mentioned it in his presentation on treating mood disorders at the UW conference last fall by generic name only (vortioxetine). At that time (early October) he said the FDA review was underway and that it potentially had positive cognitive effects. The receptor/reuptake effects were listed as all serotonergic. I think we will start seeing journal ads soon. In order to get some success against the generics, I think newer drugs will either need head to head comparisons or unique additional indications like duloxetine.

  2. I wrote this:
    about Brintellix, back in October. From what I can tell, it's no better than anything already out there, and probably not as good, and its big claim to fame seems to be that it doesn't impair driving.

    As a resident, I was never formally taught about how to gently get someone off an SSRI, or SNRI, other than to tell them that they can expect withdrawal symptoms. What do you tell your residents?

    1. I would be shocked if Brintellix was any better than anything else but I have been pleasantly surprised by one relatively new drug that just turned generic.

      I review the available literature, including the descriptions of the syndrome and how much it can vary from person to person and strategies to treat it. I generally advise them that it is an informed consent issue when starting, stopping or cross over tapering SSRIs and SNRIs. I was never formally taught myself as a resident but that was before the days that there were SSRIs.

  3. Of the 5 psychiatrists I have met after I started treatment as a teenager for 'situational depression', I think I would be another to say "nobody has ever informed me of the risks or potential side effects". Aside from a gastroenterologist, no other doctor has done so either. He was rather blunt though, he said the 'medical devices come and go, none work" and referring to an old acid reflux drug, he said "killed people". An older Indian-born doctor, he came across as very patient and wise.

    For the 8 or so years I was treated, I was not able to find a psychiatrist or other physician that was knowledgeable of discontinuing psychotropic drugs (or about drug dependence). As a result, I eventually chose to adopt a tapering schedule I found 'somewhere on the internet' and got off a Benzodiazepine I had been taking for 5 years with only a single followup appointment half-way through a year long taper. The experience was then, and continues to be, somewhat excruciating. I suffered a withdrawal syndrome that has persisted for 2 and a half years now after I stopped the drug. The sum of the experience was rather negative, and I don't think I would be willing to see a psychiatrist again, or encourage anyone else to do so for any reason. The chances of finding a good one who was as knowledgeable as the author of this blog seemed too low to take the risk, and the risk was sometimes extreme. One of my friends wound up on 2 anti-psychotics simultaneously to augment an antidepressant. That could just as easily have been me..

    Although my story is more complicated, overall 9 years of treatment ultimately caused me 5 years of drug dependence/withdrawal induced disability. Mostly concerning the issues discussed here. I think the approach described could have prevented much of that.

    Dr. Sandra Steingard, MD, a psychiatrist, more recently wrote an interesting article on tapering patients off anti-psychotic drugs for the website ''.
    Of the few psychiatrists experienced in withdrawing patients from drugs, I think she might be a valuable resource in that area. She sometimes write guest articles for, which is run by a retired psychiatrist, Dr. Mickey Nardo.

    This is an excellent article, thanks.

    1. I remember the reflux drug very well - cisapride or Propulsid.

      I frequently hear that the addictive properties of medications are rarely explained and I think it is a critical part of informed consent. I am glad you brought up the issue of antidepressant augmentation. I think that anytime there are a number of what appear to be equivalent strategies, it makes sense to review them in terms of relative side effect risk. I generally advise people that the atypical antipsychotic route in the high risk strategy, but that there are risks with the others as well.

  4. this post is very informative....thanks....i value your blog and read it regularly....something about this post....your topic...your thinking....your writing...cannot point to anything in particular....but this post was a highlight of my experiences in my reading your blog

  5. FYI I just got an email today from Takeda on the Brintellix rollout, so maybe they are starting to ramp it up.