1 Boring Old Man

Thanks M.

Jules Angst in Zurich set the bar for maintenance antidepressant use back in the tricyclic days of the 1970s. Mindful of the tendency of melancholic depressive episodes to be recurrent, and of the progressively shortening depression-free intervals between episodes, he concluded from his longitudinal data that we should consider maintenance, preventive antidepressant drug treatment for patients in at least their third lifetime episode, two of which have occurred in the last 5 years.

Any studies done since 1980 (DSM-III) are confounded by high heterogeneity. That applies also to any studies done with the newer antidepressant drugs.

Mickey,

You said, “Avoiding withdrawal may well be the answer” as an explanation as to why people were on Antidepressants for life many times. I couldn’t agree more.

Seems to be another example of covert evil out there in the world of health care.

Its just amazing what’s going on these days, if you’re not aware, the new game in town now is it everybody needs to be on 90 days supplies with meds from the beginning of care. It’s called ” maintenance dosing”, and it’s going to be the death of Psychiatry if its not challenged today!

This post brings up a lot for me.

I don’t want to forget the idea that everyone was batting around in one of the threads several months ago– that SSRI discontinuation symptoms have a different signature from “withdrawal” the way we usually think of it. Many observed that it is usually unaccompanied by craving in the traditional sense, the physical sensations are different, it just kicks in in a completely different way from, say, opiates or benzos, though it can be very powerful– perhaps even deadly.

At the same time, I am reminded of something else– what my rheumatologist told me about Plaquenil for connective tissue disorders: “I absolutely know this drug works. Just ask anyone whose taken it and stops.”

So that was exactly what I did in my online support group. Again and again, people described their experience with the drug in the same way… “Looking back on it, I know it must have helped me, because I really crashed when I stopped taking it.” They never talked about how great they felt when they were actually using Plaquenil– the terrific job they got when their energy returned, fixing the roof, or skiing Mont Tremblant. They only talked about what happened when they stopped.

Obviously, the mode of action for Plaquenil and for SSRIs is very different (though curiously, neither has been adequately explained.) My point here is that this kind of relapse fallacy is a very tempting criteria for efficacy. I’m not discounting greed or deliberate misconduct, just wondering, as I often do, about the wish-fulfillling cognitive error that runs through the SSRI story.

Did you ever see patients who had been prescribed Effexor before they came up with the extended-release version? My roommate in college had been on Prozac (prescribed by her HMO group practice) and was prescribed Effexor at the University Health Services by the head psychiatrist there. She had to take it 4 times a day. If she missed a single dose, she was jonesing. I think she lasted less than a week went back to her HMO, and they put her back on Prozac. At least then, she didn’t have problems when she missed a dose.

The Relapse Trials did not just happen in Yugoslavia. I was in one myself — in Chicago, IL, at Rush Medical Center, in 1994. I think it may have been one of several such trials. Here’s the story:

http://davidhealy.org/lives-touched-by-gsk/

It was years before I heard about the concept of withdrawal. All I knew was, I felt pretty lousy on these pills, as if they weren’t doing me much good at all. But every time I quit, I felt horrible. That just proved I needed them, didn’t it? Like a diabetic needs insulin.

It took another twelve years before I stumbled across the truth. Effexor, however, gave me the beginnings of an education, because the withdrawal was so drop-dead obvious. It was exactly as EastCoaster says — if I was four hours late with the daily dose, I felt like the earth was caving in under me. A very enlightening drug, in that way at least.

All these studies, including before 1980, are confounded by high heterogeneity. Depression has never had reliable biomarkers, and its reliability ratings of 0.2-0.3 in recent DSMs have been awful.

So all these studies are going to be apples and oranges with trends varying depending on how the researcher(s) interpret depression, and who they choose to project or not project the illusory illness of “major depression” into for their particular study.

I’ve never seen convincing evidence that it’s possible to draw a clear line between different categories of “depression”. I don’t think this is possible given all the different life problems and stresses that can lead to different degrees and varieties of depressed feelings.

It’s incredible and tragic that so much investment continues to be wasted on these drugs given that they are frequently no more effective than placebos. But that’s what happens when there are billions of dollars to be made if they are (mis)perceived as effective.

I’m kinda irked by the MHRA but, in all honesty, I expected their answer of being ignorant to these trials. Truth is, they can’t say one way or the other that Paxil causes severe withdrawal problems because there is a pending lawsuit in the UK. If they were to agree that ‘some’ people really struggle with Paxil withdrawal then GSK would probably have to settle the action against them.

in any event, why would the MHRA bad mouth an antidepressant when their current CEO, Dr Ian Hudson, was a former World Safety Officer for GSK.

Revolving door syndrome, me thinks.

Edward, biomarkers are not the gold standard for nosology. Your comment above reveals a failure of understanding. The existence of clinically recognized disorders is not predicated on having laboratory tests for them. Biomarkers are developed in response to the clinical recognition of disorders. Biomarkers are the servants of clinical science, not the other way around. Few are pathognomonic and all have to be interpreted in a Bayesian clinical context.

As for pre-1980 reliability of pre-DSM-III depression diagnoses, it was higher than you suggest. In my own program at Michigan around 1980 we had kappa values of 0.80 for melancholia diagnoses versus non-melancholic depressions; for Hamilton severity ratings the intra-class correlation coefficient for multiple raters was 0.74 and the coefficient of variation for these ratings was 10%. CV equals the standard deviation as a proportion of the mean, and 10% is right in line with many laboratory assay measures. We were not atypical in this respect. When you add the advantage of longitudinal familiarity with the patients over years, then the data of Jules Angst that I mentioned cannot be dismissed as you attempted.

You recently claimed that “mental “illnesses” like schizophrenia and bipolar (are) essentially arbitrary, unreliable labels for a variety of loosely related problems arising from severe trauma, abuse, neglect, and overwhelming anxiety…” Have you presented evidence for these assertions and reliability data of your own? For all of my A-list disorders your claim would fail.

Bernard,
Your comment also reveals a failure of understanding. The fact that, despite massive effort, biomarkers continue to fail to appear for the supposed “clinically recognized disorders” points to the inherent lack of reliabliity and validity behind these categories. The categories do “exist” in the minds of researchers who evaluate people; the question is, do they really exist as separable categories within distressed people?

As you know, in science the onus to prove something is on the person making the claim. I have not claimed that depression and schizophrenia exist as illnesses; rather, I am responding to the idea asserted by others that different “mental illnesses” (outside of a few, like dementia) are clearly demarcable conditions.

Unfortunately, insufficient evidence exists to prove that the (variable) “symptom pictures” that are described as “schizophrenia” and “depression” are in fact discrete valid illnesses. One can make it sound fancy by calling certain labels “A List” labels, but that doesn’t mean anything. What you’ve said is essentially “these so-called illnesses exist, because I say so”, which is not evidence. And sure, some researchers say they agree relatively frequently about who has which supposed illness, but that’s also not strong evidence of an actual biological basis or a discrete existence for any of these conditions in “brain malfunction.”

I’m not “against” mental illness labels in any prejudicial sense – if they existed as discrete illlnesses, and if studying them in this way would lead to better treatments, I would be all for that. Also, I think the psychic mental pain people report is very real. Psychotic states of mind and feelings of severe depression do exist (which is different from saying that schizophrenia or depression is a valid illness).

So you see, I’m not trying to be negative for no reason. I just disagree with your viewpoint and find it lacking in evidence and logic. My honest belief is that most severe distress is not separable into clean categories that one can “carve at the joints”, as you seem to believe, but have not given clear evidence for..

A lot of my points are laid out below, by the psychiatrist Sami Timimi, when he argues that “mental illness” diagnoses have done little or nothing to improve mental health outcomes and explain nothing about a person’s problems, as well as explaining why there is no validity behind labels like ADHD. I wonder what you would think of it.

https://www.youtube.com/watch?v=5caitdQA6HY

Until next time.

It’s about here that the topic of Paxil Withdrawal evaporates into the Myth of Mental Illness argument we are all so familiar with. I suppose that’s just the way such things go, but if anyone has something to add about antidepressant withdrawal syndromes, feel free to jump in.

I’ll add that East Coaster’s point was sure true. It sometimes happaens even with the extended release version. Effexor is the one drug that I’ve seen people who simply cannot get off of. Paxil is hard, but people seem to get free of it. Effexor is, at least in my world of anecdotes, the hardest of all [if not sometimes, seeming to be impossible]…

Only this – the most obvious way to avoid Paxil withdrawal is to not prescribe it. I have not prescribed it since the second patient I prescribed it to described the symptoms. The only reason it is not on my no prescribe list is that there are still some people who insist on taking it because it has worked for them in the past. That is the only reason it is not there next to chlorpromazine.

I will never recommend Paxil for any patient I see who has never taken an antidepressant and needs one.

Edward, not at all. If we followed your version of nosology, then Parkinson’s disease did not exist before 1962 because there was no biomarker for it. Your argument fails because Parkinson’s disease was diagnosed on clinical grounds for 145 years before that happened. Actually, the shaking palsy was recognized as far back as AD 175 or even earlier. With newer knowledge the nosology of Parkinsonian conditions has been elaborated, but don’t lose sight of the forest for the trees.

To repeat an example I have used before, you should try going before the magistrate at a commitment hearing for a gentleman who loudly commandeered a commercial airliner at the departure gate, prevented the scheduled passengers from boarding, expressed the grandiose delusion that he was the new owner of the airline, announced that he intended to fly his entire extended family to London to give advice to Margaret Thatcher, and became obstreperous with security personnel when they tried to redirect him. Oh, and he had a history of repeated manic episodes with hospitalizations going back decades. By all means tell the magistrate that the psychiatrist who states the man’s diagnosis is a classical psychiatric disorder called mania with psychosis must be wrong because he has not presented a laboratory test result to the court. See how far that gets you! That was a real case of mine, by the way.

To this very day, doctors routinely misdiagnose withdrawal syndrome as “relapse” and convince patients they need the drug to prevent recurrence of illness (even if the “illness” was a long-ago divorce or other transitory distress).

Failure to properly discontinue unnecessary psychoactive medication is endemic. The methods of tapering most often used are too fast, resulting in “relapse.”

I believe this is why, according to the CDC, http://www.cdc.gov/nchs/data/databriefs/db76.htm “More than 60% of Americans taking antidepressant medication have taken it for 2 years or longer, with 14% having taken the medication for 10 years or more.”

The excessive tenure is not because these people suffer from capital-D “Depression.” The CDC found that 2/3 of “persons with severe depressive symptoms” do NOT take antidepressants.

According to my calculations (based on NIMH claims that the rate of MDD is 6.7%), more that 80% of those taking antidepressants never had capital-D “Depression” — although they may have had more than one unsuccessful discontinuation due to withdrawal syndrome, which can cause dramatic escalation in psychiatric diagnoses.

If you’d like to be able to differentiate psychiatric drug withdrawal syndrome from “relapse,” please see more than 2,000 case histories of withdrawal syndrome here http://survivingantidepressants.org/index.php?/forum/3-introductions-and-updates/

Bernard,
I hope that psychiatrists have better luck finding the biomarkers for schizophrenia and major depression in the next 100 years than in the last 100. My guess is that in the year 2115 they’ll still be searching.

As for your example about Parkinson’s… the point is that evidence does not YET exist that most of your supposed “A List” illnesses are discrete, valid conditions based upon biology/brain chemistry. Perhaps such knowledge will one day be found. But speaking about labels like schizophrenia or major depression as if they were demarcable illnesses caused by malfunctioning brain chemistry is not yet backed up by today’s evidence. What I’m saying is not to jump the gun when the understanding is not there yet, to have a little less certainty.

As for the magistrate example, whether someone does or does not convince some legal official in a hypothetical scenario doesn’t prove or disprove anything related to this debate.

I sense we are not going to be able to agree and that is ok. We have both made our points. My point in relation to the original article is that the study was based on an unreliable label; that is why I think there is so much variation and confusion around different studies of these supposed illnesses, because unlike physical illnesses “they” (mental illness labels) mean different things to different researchers. In other words, applying a medical or disease model to emotional-developmental problems is not (yet) working very well for scientific study.

When I learned that Paroxetine had the highest affinity for serotinergic receptors, that bothered me a bit, and then when it was obvious there was weight gain risks with it that were minimized by the reps, well, I bowed out as a provider. The discontinuation syndrome issue, yes, worst with Paxil and Effexor, but the high dosing of SSRIs in general, well, think about this:

this attitude of doubling dose with SSRIs in general, what is the rationale to that?? Paxil should have been started at 10 and increased as tolerated and responded by 10mg at a time, Zoloft in increments of 12.5-25 at most, Prozac also in 10mg increments, and this lame agenda these days with Lexapro, what the hell are people thinking you go from 10 to 20 to 30 or more mg??? Wait for it, we will see the same consequences with lexapro as we saw with Paxil, what with over 80% of Lexapro started and jumped to 20mg by non psychiatrists.

Any opinions to this Brintellix, I include this for any readers who are new to this alleged new addition to the list.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296590/

I guess we go back to the debate above about nosology and statistical figures that allegedly prove points…

Edward, the point to grasp concerns the construct of convergent validity. If it looks like a duck and walks like a duck and talks like a duck and flies like a duck then it is a duck until proven otherwise. Diseases like Parkinson’s disease were valid diagnoses before biomarkers were discovered. Discerning clinical scientists recognized them by their characteristic signs and symptoms, manner of onset, course of illness, responses to treatments, and genetic associations. The new biomarkers then were the icing on the cake. The classical A-list conditions of psychiatry are pretty much unmistakeable, especially with a longitudinal view of the patient, just as classical Parkinson’s disease was pretty much unmistakeable even before 1962.

These classical A-list examples are important anchors in clinical psychiatry: the closer an individual patient’s presentation and course are to the classical forms then the more confident the diagnosis can be. Some people, yourself included, become distracted by the existence of fuzzy boundaries, to the point where you lose sight of the signals in the noise. That is even more true when you inject etiological claims without evidence. We are still waiting for you to back up your claim that the A-list diagnoses like schizophrenia and bipolar disorder are nothing more than “emotional-developmental problems” that arise “from severe trauma, abuse, neglect, and overwhelming anxiety…”

Bernard,
We are still waiting for you to back up your claim that A-list diagnoses are reliable, valid illnesses. Other readers can judge for themselves whether you have presented actual evidence, or mere opinion and anecdotes.

Sincerely,
Edward

After you, Alphonse…

^{“It’s about here that the topic of Paxil Withdrawal evaporates into the Myth of Mental Illness argument we are all so familiar with.”}

Actually, the stated topic here was Paxil Withdrawal, and it may have something to do with the discussion of “disease.” I, for example, am one of those people who believes that the major depressive syndromes like Melancholia fit the “disease” metaphor in a biomedical way and may well turn out to have an underlying physical “cause.” Tons of reasons for thinking that – but nothing close to solid proof. On the other hand, I think that the majority of people I see complaining of “depression” have a symptom with multiple causes that have their roots in unique life situations and personal biography. So I don’t think of the latter as “disease” in the same way. In the first instance, I call Dr. Carroll or someone with experience and resources to deliver what’s needed and make a referral. In the second instance, I start listening and talking. In a few of those latter cases, I might try an SSRI [that doesn’t start with “P”]. Which cases? I’ve found them useful in those patients who are “too depressed to think” and those who spend their time “ruminating.” They often help get people over the hump, and those patients usually stop them as soon as they begin to see a “patch of blue.” My point here is that using a symptomatic medication doesn’t require a biological underlying cause. And I don’t personally think this second group has a physical problem.

Presume for the moment that I had given Paxil to a patient with a depressive symptom related to his-or-her life. And when he-or-she started to get clear of the grip of their “illness,” he-or-she stopped the medication – then showed up in my office with the very misery we’re meant to be talking about here. I think that’s a biological phenomenon [in fact, I’m sure of it].

If I had the code book that I needed, I would’ve coded my initial contact as something like neurotic depression to borrow a term we don’t say [but many still think]. And I would code the later visit as SSRI withdrawal syndrome. It doesn’t matter what I think is different between them in terms of cause – they both cause “dis ease.” If I decided to head for Xanadu the next day and was never heard from again, when Dr. Carroll took over my practice after my disappearance, he would look at those two codes or diagnoses and instantly know what I was thinking, so he could pick up the ball [even though he might shake his head thinking, “Neurotic Depression? That went out with bell-bottom leisure suits“].

That’s why you have trouble engaging a lot of physicians in your myth-of-mental-illness/no-biomarker-ergo-no-disease argument. Causality isn’t the only thing in the front of our minds when we think about diagnosis. It’s often the many other useful things that are gained by classification – including passing on information. If on the other hand, you and I are both at a lecture where Dr. Nemeroff says [as he does every chance he can get], “Major Depressive Disorder is a well-recognized, proven, biologically-determined disease…” I’ll get up and move to your side of the room, and later join you chanting on the picket-line.

When Dr. Spitzer wrote the introduction to the DSM-III, and in it he said …

Undoubtedly, with time, some of the disorders of unknown etiology will be found to have specific biological etiologies, others to have specific psychological causes, and still others to result mainly from a particular interplay of psychological, social, and biological factors…

… but nobody paid much attention to that. A pity.

Making some proven biological causality a precondition for “disease” was the creation of Dr. Szasz, or at least that’s the first place I ever heard anyone say it [in either a career in internal medicine or psychiatry]. The term comes to us from antiquity, and to me, it means what it says – “dis ease.” In fact, that’s similar to most of our words like that – eg “dis ease” or “ill ness” or “sick ness.” The classification of “diseases” came centuries before we had much of a clue about biological etiology. Medicine started with empiric symptomatic treatment.

I’m not trying to change your mind, just trying to explain why you are unlikely to change any minds yourself with your argument. If you want to be effective, you can work on making sure that the down sides of diagnosis is something all physicians are clear on – the stigma of labeling, making categorical errors, gaining a false security, the inertia of mistakes, depersonalization or dehumanization, “recipe medicine“, etc. etc. There’s always a down side…

Well put Mickey.

There are of course the time proven measures of validity originally espoused by Syndenham and that fact that psychiatrists basically accumulate these measures of validity in order to make a diagnosis (and reject in incorrect one). But the myth of mental illness folks have to adhere to a single measure of validity that by no means is applied to all or most medical or surgical diagnoses.

Just another reason why Szasz had nothing to offer.

Mickey,
Thanks for explaining your thinking, and I agree with most of it. I’m aware that many psychiatrists don’t think about diagnosis rigidly/concretely, and do a lot to help people by understanding their life problems, being empathic, and using medications in limited targeted ways for symptoms. It is curious to me, however, that while most of your clinical work focused on talking to and understanding people as individuals, that proportionally of your blog focuses on debates over medication. But I imagine you are responding to a lot of what is going in present day psychiatry, which is different than how you practiced.

Bernard,

My earlier point stands that the side first asserting existence of an illness category is the one with the burden to prove it is valid and evidenced… a basic tenet of science is that the burden of proof falls first on the claimant, not the critic. In other words it is up to the proponents of the theory that a label like schizophrenia represents a valid illness to prove that this is so, not up to a critic to prove that it is not.

If the converse were true, a researcher could claim any set of behaviors represented a brain-based illness and say it was valid because critics hadn’t disproved their unproven theory. This is essentially what you have attempted to do.

I expect that you’ll avoid or deny this point, as before, which would be smart on your part since there isn’t yet strong evidence for the separable existence of most supposed mental illness diagnoses.

Edward,

The reason for my late life focus on medication is not pro or con medication as treatment. It’s the shame I felt when I caught on to how much corruption had crept into psychopharmacology. I have nothing but respect for the biological psychiatrists who have spent their lives working on remedies for sick people that are effective and have been honest about the down side. But, as we know, commercial bias found its way into psychiatry, and that’s what this blog is about. I use medication in what I hope is a rational way. But I write this blog because what needs blogging about is the corruption – which has no justifiable place in Medicine…

Edward,

Dr. Carroll gave you his kappa numbers, where are your kappa numbers for developmental issues and major mental disorders? If your response is to badger him for more data while failing to provide your own, the debate ends by TKO.

To paraphrase Dean Wormer, hippie Rousseauist utopianism is no way to go through life, son.

For those still reading this thread who are perplexed by Edward’s posture, he already has his answer, could he but see it. I already gave the template for converging on valid constructs of psychiatric disease. Discerning clinical scientists recognized the A-list disorders by their characteristic signs and symptoms, manner of onset, course of illness, responses to treatments, and genetic associations. The new biomarkers then would be the icing on the cake. Independently of biomarkers, the classical A-list conditions of psychiatry are pretty much unmistakeable, especially with a longitudinal view of the patient. Edward didn’t grasp that. Now he wants chapter and verse on the convergent validators for each of the A-list conditions. Those are widely available in standard textbooks of psychiatry. For Edward to claim there is no valid entity like classical mania or melancholia is like saying there was no valid entity called Parkinson’s disease before 1962, which is preposterous.

The ball is in his court, as James just remarked. We are agog.

Given the inherent wonder and complexity of neurodevelopment (I still marvel at how differentiation and apoptosis proceeds in such an orderly fashion), it’s a wonder that most people turn out pretty normal and not psychotic, not cognitively impaired, not depressed with full motor and sensory faculties intact. The idea that nature creates this perfect tabula rasa that is occasionally damaged by the environment or an uncool culture is a very sixties notion, but it doesn’t really jibe with common sense. Nature sometimes screws up, and sometimes very badly. And it doesn’t really take much. Narcolepsy is though to be due to developmental failure of a comparative few orexin producing cells. By the way, narcolepsy existed before sleep labs existed, to further Dr. Carroll’s point. And so did Rett’s Disorder (a statistically genetically small but phenotypically devastating defect) before the genetic test was recently developed.

This blog’s comment section is rapidly becoming a monoculture of ideas and intolerant of alternative viewpoints… My suggestion is that anyone who doesn’t agree with Bernard head for greener pastures. While Dr. Nardo’s content is terrific as asual the debate here is really a lost cause. Dominating, categorical and ad hominem comments have been made by many, but only those made by white, male psychiatrists are consistently tolerated… The writing is on the wall for those who don’t belong to the club, but I say, their ship has set sail and their wind is fading so let them cling to what they must.

The problem is, you have nice guys like Dr. Nardo who try to be completely civil and respectful, and then you have people like me. I’ve been practicing 23 years now, & I have no problem calling it the way it is. A lot of Psychiatry ,even if it is under 50 percent, is composed of whores and cowards. And that’s what is a shame, because too many physicians who adhere to this fraternity mindset, can’t call their colleagues on what they really are.

So, you can debate this paxil issue and other failef studies, and Big Pharma agendas per alleged studies that are just out to make a buck, but, it’s important to pay attention to the fact that psychiatric illness is a biopsychosocial phenomenon.

What should bother people, that bothers me greatly, stop paying attention to the few idiots who will take advantage of the public as all these cretins want to do is make a buck and/or glorify their name eternally, but, pay attention to these moronic defenders and apologists who seem to be much greater in number, who want to just further this disgusting cause of selling drugs!

As I’ve been staying here and elsewhere to some level, its not that we have Hillary Clinton and Donald Trump as candidates, but, we haven’t entrenched 20 to 30 percent of the public on either side of this polarized equation of politics that support these narcissistic / antisocial cretins.

The analogy here is, we have the polarized people of anti Psychiatry against pure biological driven psychiatry supporting each other’s causes to the ends of the earth.

So, you as readers, if you really are concerned about the welfare of this country and the healthcare system, need to stop trying to make sense of these selfish idiots who are just out to screw everybody else for the needs of the few. And, I don’t care how harsh or inappropriate this comment is, I find the moronic and disgusting lack of attention to concern and details to what the public welfare should be gets lost in all these, in my opinion, trivial and off base debates.

That’s the point I keep trying to make and yet we all want to get lost on nosology, statistical values, and other distractions that take away from the viewpoint that it’s about getting rid of these bad people and not trying to at least come up with inadvertent ways to make sense of them! or even worse, coming up with creative ways to tolerate them!?

Just my imperfect opinion…