Posted on Monday 21 November 2016

The Bookmobile came every other Saturday. And once the Bookmobile Lady got to know you, she brought wonderful things you didn’t even know existed. Two weeks is a very long time, so there was a shelf with Compton’s Pictured Encyclopedias to fill in the gaps. But neither rivaled the Downtown Library where the selection seemed infinite. When I reached the traveling age, my Saturday Quarter bought either two bus tokens [10¢ each] for a round trip to the Library + a candy bar [5¢], or the Movie Matinee with Serial [10¢] + popcorn [10¢] + a coke [5¢]. Freedom brings some tough choices!

Maybe just an old habit, but I often start with Wikipedia. In this case [Evidence-Based Medicine], it was a good choice, particularly the Limitations and Criticism section. As a simple phrase, what’s not to like about "evidence-based medicine?" What else is there? I’ll not summarize that entry, just recommend it strongly. One thing I learned was that in its modern usage, it had become all the rage in 1987 which is after I left academia proper for practice. So it’s no wonder that I was confused when people began to say "evidence-based medicine" as if it came from some stone tablet delivered from Mount Sinai.
The term "evidence-based medicine", as it is currently used, has two main tributaries. Chronologically, the first is the insistence on explicit evaluation of evidence of effectiveness when issuing clinical practice guidelines and other population-level policies. The second is the introduction of epidemiological methods into medical education and individual patient-level decision-making.
One of the consequences of this paradigm was to promote the Randomized Clinical Trial [RCT] to the level of the "gold standard" for "proof". So third party carriers used it to slash payments for any· and every·thing not backed up by an RCT. On the other hand, it was a "gold mine" for the pharmaceutical companies, a whole industry emerging to conduct [and publish] [and exaggerate] their Clinical Trials. New paradigms, no matter how helpful, can be quickly enlisted by the dark side, and the RCT is  no exception [in a way, that’s what this whole blog is about].

One downside of the evidence-based medicine model for me was the de·emphasis of individual case reports which all but disappeared from our journals – discounted as anecdotes. We had been moved from individuals to groups "…the introduction of epidemiological methods into … individual patient-level decision-making." Of course medicine draws heavily from the data from groups, but we actually see individual human beings with all their variation – the ripples in a stream. And it’s those case studies that have been the key to organizing my own medical learning. Evidence-based medicine and its guidelines tends to bring the patient to the medical group·think rather than vice versa.

And so to the point – akathisia, suicidality, violence, the SSRIs, and the last two posts [anecdote-based medicine… and activation, agitation, akasthisia, agita…]. Back when Prozac arrived, I was in a psychotherapy practice so my prescribing was minimal. But I had patients who had a reaction of sorts. They described agitation, restlessness, anxiety, disturbing thoughts and dreams, a couple said suicidal. While it didn’t happen often, it was enough for me to "ask around" about it. And since all the patients I saw had had previous treatment of some kind, I heard about something similar from others when they were medicated before I saw them – again, not common but notable. This was over the 1990s. I saw patients weekly, and they came back and told me about it. So I began to warn about that possibility [along with the more frequent than advertised decrease in libido]. I heard a couple of patients say, "And so I didn’t go back to see him!" I wondered if my patients came back and told me about it because I saw them frequently and had an ongoing relationship before I prescribed – that maybe the other colleagues I asked didn’t know about it because the patients just moved on.

I retired in 2003, the year before the black-box warning, and stayed away from medicine for about five years. When I started volunteering in a couple of rural charity clinics [adolescent and adult], I was horrified at the medications people were on and started reading – at first to catch·up, but later to catch·on [another, that’s what this whole blog is about]. And then I read about my department chairman’s shady financial connections [Dr. Charles Nemeroff]. Thus, the origins of Shortly after I started, I saw a 17 year old boy who was quite depressed. I prescribed Celexa, discussing the black-box warning I’d read about. Within a day and a half, he had a full blown episode with anxiety, agitation, suicidality, violent outbursts, etc. and his mother called. We stopped the meds and a few days later, when I saw him, he was fine. Not too long afterwards, I read of a 14 year old kid’s suicide in our weekly paper. I’d never seen the patient, but in the months that followed I had the occasion to see his therapist, a parent, his girlfriend, and several classmates. They were all devastated and with no prodding from me said the same thing, "He was different after he started that medicine [an SSRI prescribed by his PCP]."

I still prescribe SSRIs, but everyone new to the medication gets a full warning – not the mumbly warning on the television ads, but an earnest eye-to-eye warning. Since then, I’ve only used SSRIs in adolescents for OCD or Generalized Anxiety and I follow them like a Hawk. There’s no compelling evidence in the RCTs of efficacy in depresson for this group except some early Prozac RCTs. With adults, I’ve seen more cases of Akathisia – a lot for the infrequency of my practice time. No suicidality but plenty of Agitation [Agita]. I’ve heard about several other suicides that are unquestionably related but I can’t discuss them. These are the kind of anecdotes that I was trying to talk about [anecdote-based medicine…]. It used to be called clinical experience, and I count on it in myself and the doctors that take care of me and my family. So I, for one, liked Peter Gøtzsche‘s meta-analyses [activation, agitation, akasthisia, agita…]. He sees that syndrome I call Agita as a potential harbinger of a more ominous portent, and I do too. I don’t understand why it happens sometimes, and why so infrequently, but my index of suspicious is set on high and will stay there. It comes in a variety of presentations and if you prescribe a lot of these drugs, I’d recommend reading through some of the  SSRIstories just to get oriented to the syndrome. I don’t need a clinical trial for proof, there are enough anecdotes around to calibrate my radar.

Over the years, I’ve followed the campaign to get the black box warning removed  [summarized most recently  in an innovative design…]. Most of the studies are population based, evidence-based-medicine-esque, and clearly start with a conclusion. They preach safety in an area that deserves a gospel of caution. That black box warning slowed the escalation of SSRI sales and I’m glad about that. There was one study along the way about akathisia that I thought was particularly irresponsible [Antidepressant-induced jitteriness/anxiety syndrome: systematic review – 2006]. It denied that what I call Agita even happens. I know it’s off the mark, and I expect PHARMA influenced. Agita doesn’t happen often, but it’s common enough for the busy clinician to see. Just listen for the phrase, "I can’t take that stuff!"
    November 22, 2016 | 3:53 PM

    Thanks so much for this, Dr. N.

    I would argue that any MFT intern or psych assistant is likely to encounter Agita in their first two years of practice, even with only a moderate case load of 10-15 clients.

    In addition to “I can’t take this stuff!” I would add “I can’t stop thinking about knives and I have no idea why.” A quality of perseveration on sharp objects for no reason, at a level where the client is surprised by their own thoughts and is not clear where they come from. I’ve only seen this a few times, but always in people taking SSRIs. Maybe with other folks, they perseverate on other means that have a similar potential level of lethality, but for some reason when I’ve seen it, it’s always been knives or scissors, broken glass, etc. Often client will just be walking through the kitchen and notice a knife in the kitchen sink and be frightened that they cannot stop thinking about it.

    The perseveration has a senseless, compulsive quality that one associates with substance abuse– when folks who drink or use can’t stop thinking about the guy or girl who broke up with them, or something their boss said, why they were passed over for promotion, or the idea that the world is out to get them in one particular way.

    When the substance abuse stops, sure, the idea is still there, but it loses it’s power. Client is then able to use tools provided in tx and the thoughts will become much less distracting and intrusive.

    I could be totally off the mark here; I’ve only been practicing 5 years or so, curious if anyone else has observed this.

    Anyway, thanks so much for this.

    November 22, 2016 | 9:40 PM
    Sounds like a productive five years. I’ve only logged eight years, part-time, in a situation where medications are a regular part of the regimen- so we’re about even.

    I haven’t heard that one, but it sounds right on. You’ve decribed the symptom beautifully, so we’ll know it when we meet it…

    November 22, 2016 | 11:25 PM

    Yes. I have and from when I first started practicing in the mid-90’s. I asked my colleague who I share office space about it and she has too. Not very often, but far more often than say a rash in someone taking lamotrigine.

    I have the suspicion that it is a response to the rapid increase in serotonergic activity which some people are more sensitive too. Kind of like a serotonin syndrome. A lot of people feel more anxious when they start an SSRI, so the people with agita may be much more sensitive to that.

Sorry, the comment form is closed at this time.