another thing…

Posted on Sunday 23 June 2013

I think one shouldn’t entitle a post rest my case… because there’s always another thing. In this instance, it’s my own conclusion to seroquel: good to the last drop… and rest my case…. I didn’t get Seroquel® or Seroquel XR®. I had retired from a psychotherapy practice and was comfortably living in the mountains doing not-doctor things. I started volunteering and the patients were on all kinds of medicines – and Seroquel® was among them. I knew nothing about it except that it was an Atypical Antipsychotic. The patients on it weren’t nor never had been psychotic. When I asked them what it was for, they said sleep and to a lesser extent, anxiety. I started reading about it and decided that was a really bad idea, given its side effects. The vast majority had been started on it by Primary Care "country doctors."

When I started trying to get patients off of it, I learned about the withdrawal syndromes pretty fast – from the patients, not the literature. So I started looking into it [series starting with seroquel I: introduction to an “atypical”… and  selling seroquel I: background…], and that’s really where this blog started – that and the Chairman of the Department I had been affiliated with turning out to be busted for being an ethical nightmare [Dr. Nemeroff]. Getting people off of Seroquel®, once I learned to taper it, was easier than getting people off of Benzodiazepines – the main difficulty was sleep problems which kind of cleared after a time. I tried Seroquel® as an antipsychotic and, at least in my hands, it wasn’t very effective. I don’t see a lot of psychotic people, but when the ones I saw couldn’t tolerate the older drugs, I tried Atypicals. The only one that was acceptable to the patients [and me] was Risperdal®.

So time passed, and I was spending a lot of time looking at the psychopharmacology literature, which meant seeing ads – Seroquel XR® was everywhere as an adjuct to antidepressants. Then I ran across the papers claiming it could be used as a monotherapy in depression [Extended release quetiapine fumarate monotherapy for major depressive disorder: results of a double-blind, randomized, placebo-controlled study]. That made no sense to me. Why would an antipsychotic be used in depression? But there were so many other things to chase down, that kind of got put aside. When I saw this recent paper by Dr. Trivedi [or AstraZeneca], it came back up in my mind. Is Seroquel® an antidepressant? an adjunct? So these last two posts were picking up an old thread for me. I actually think that the two papers [Evaluation of the effects of extended release quetiapine fumarate monotherapy on sleep disturbance in patients with major depressive disorder: a pooled analysis of four randomized acute studies. and Quetiapine XR monotherapy in major depressive disorder: a pooled analysis to assess the influence of baseline severity on efficacy] inadvertently made the point that Seroquel XR® is not an antidepressant – it helps the depressed people as a sleep aid whether as monotherapy or augmentation [seroquel: good to the last drop… and rest my case…]. So the question is, "Is it rational to take an anti-psychotic as a sleeping pill?" I  personally think the answer is a very loud "no!" There are plenty of other options, and also a need to look into why the sleep is disturbed [see this comment].

I personally concluded that the first authors on these papers were "guest authors" and that these papers were industry generated. Can’t prove it, but I can sure think it. The Seroquel® and Seroquel XR® story is going to be a chapter in somebody’s book when the definitive history of the psychopharmacology era is written…
    June 23, 2013 | 9:53 AM


    This possibility appears to have also come up before in a much more off the cuff way:

    Some of the postings out there make the point that at 25mg doses Seroquel is essentially a different drug than at the higher doses, that the terms “antipsychotic” isn’t a meaningful guide at these low doses:

    Do you think the idea of 25mg Seroquel primarily being an antihistamine is a fair one? And not necessarily more dangerous than other antihistamines at that dosage is the concept that seems to drive a lot of the primary care use. 1BOM, thoughts?

    June 23, 2013 | 10:06 AM

    Dr Nardo,

    Thank you forexpressing your concerns about Seroquel and for informing readers of the dangers of taking this drug as a sleep aid.


    June 23, 2013 | 10:09 AM

    1BOM, put another way:
    What would benadryl be called if we named it based not on its primary effects at 25mg doses but rather at 400mg? Would parents be giving 12.5 mg/25mg of a drug with that label to their kids to keep them asleep on airplanes?

    June 23, 2013 | 10:15 AM

    I was put on 15 mg of Abilify and became a total zombie because of this. When I told my psychiatrist and psychologist that I’m having too much of Abilify, the psychiatrist just looked at me and and assertively said “it’s a good dose”. I told them that I found out that my other drug Paxil may increase the levels of Abilify, the psychiatrist and psychologist looked at each other and the psychologist commented: let’s drop the Paxil since Abilify can also treat depression. Later on they wrote in their papers that “the patient had paranoid thinking concerning his current medication”. I’m now totally out of the system now, but even the latest paper from them claims “patient had paranoid thinking when admitted”. They didn’t at all look at how the drugs were working on me, I got really severe effects and wanted to reduce it, but they said no, maybe they thought they had now reached the ‘target dose’ of the drug for bipolar, psychosis and schizophrenia that they read about in the chart they got from the drug company. They also obviously didn’t understand much about how these drugs work in brain (receptor affinities, etc), they had just read that Abilify also helps in depression, so let’s stop Paxil.

    Here’s incredible commercial about the use of Abilify in depression:

    The funniest part of the commercial is where the doctors pulls down a paper and on the paper there is a clone of him who then describes the possible side effects! Maybe it’s easier for him.

    from Mickey: Here’s that ad he’sreferring to:

    June 23, 2013 | 12:33 PM

    Annonymous, thanks for those links. I like the writings of Last Psychiatrist a lot and it was part of what influenced that other post.

    I don’t think that doctors are generally even looking at what receptors the drugs act on different dosages, etc. They say it’s bio psychiatry or whatever, but they often don’t even understand much of biology and brain function.

    There’s still this general myth of relative safety of newer atypicals which makes doctors give them for all kinds of things. There’s at least one good thing in atypicals such as Seroquel compared to haloperidol, etc: there’s a kind of safety break or training wheels in that you can’t increase the dopamine antagonism to as high amount as is possible with haloperidol no matter how much of Seroquel you give. There are so many studies out there where they give other groups of patients haloperidol at levels where there’s lots of dopamine blocking and other group a new neuroleptic in a dose where there’s relatively small amount of dopamine blocking. Then they pulled out of that all kinds of marvelous effects, such as atypicals reducing brain damage, improving cognition and negative effects, etc. In reality what those studies suggest, in my opinion, is that dopamine blocking, etc, cause all of those.

    June 23, 2013 | 3:32 PM

    “The Seroquel® and Seroquel XR® story is going to be a chapter in somebody’s book when the definitive history of the psychopharmacology era is written…”

    Have you thought about writing such a book? Perhaps not a definitive history, but I’ve often thought that your blog post series on various topics such as Paxil Study 329, Seroquel, KOL’s, etc. would form nice book chapters.

    June 23, 2013 | 4:28 PM

    Dear 1BOM,

    Is there a chance you might Review the CATIE study on your blog?
    I would really enjoy reading that, as the results were extremely controversial.

    The CATIE study was one of 2 federally funded studies to determine the cost-effectiveness/efficacy of treatment with anti-psychotic drugs for schizophrenia . There were 1500 participants.

    Seroquel was one of the drugs used in the study.

    If you’re were curious how effective an antidepressant seroquel was, I think you would be terrified to see how effective anti-psychotics are in treating schizophrenia, the condition they were originally intended to treat.

    Spoiler: there was over a 70% drop-out rate among the 1500 patients.

    June 23, 2013 | 5:03 PM


    I just wrote a long post in response to the question of “low dose” antipsychotics being a different animal. The post disappeared into cyberspace, so I’ll summarize what I said in it. I doubt that I can reproduce it because I was “thinking out loud.”

    In my Internist days, we used low doses of the antipsychotics to treat a lot of things. The idea was that like Benadryl, they acted on the “deep brain,” not the cortex and they weren’t addicting. They worked fine. The last time I did that was in 1973 when I had given a patient 10 mg of Thorazine for anxiety [hospitalized with metastatic cancer]. He got up to go to the bathroom and fainted from orthostatic hypotension. I retought the whole deal and personally stopped the practice. I think that was irrational on my part. He broke his arm [bone metastasis] and I felt really badly about adding to his burden.

    In the studies reported above, it wasn’t lost on me the that 50mg of Seroquel® was as good as 300mg. I’ll bet 25mg would’ve worked too. I think I agree with the premise that low dose antipsychotics are a different animal. The thing that would worry me is what happened at the VAH with the PTSD cases. Seroquel® became the VAH’s biggest expense, drug-wise, and the dose escalation was rampant with some deaths.

    I think I still have the soul of an old Internists because we used those old drugs [Chloral Hydrate & Paraldehyde] back in the day for refractory cases of PTSD sleeplessness [and TCAs to suppress REM sleep]. It worked. I’ve never seen PTSD helped with antipsychotics, unless the patients became grossly psychotic.

    I’m always a bit confused internally when asked questions like yours. I think I know why. I’m wary about saying that the use of these drugs, any of them, is a good idea in the hypothetical even though I myself have used them in the actual, the specific. Where people get in trouble with our drugs is when their use becomes “routine.” I think that I feel like using antipsychotics shouldn’t become routine for anything. That may be idiosyncratic to me. I feel the same way about steroids and some other drugs. For me, each case with either antipsychotics or steroids is a new day because the troubles I’ve seen are when people have done otherwise, myself included.

    It’s one of the reasons I light up when I see an article by Dr. Trivedi or Dr. Rush. I have developed a reflex high alert whenever treatment algorithms or treatment guidelines are on the table. I’m sure my head is as filled with algorithms as any doctor, but I’m suspicious of them coming from the outside. They can be a way to “push” drugs for one thing. But they also can make people careless. I feel the same way about ECT. Never routine in my lexicon. There are cases where it has seemed right as rain, so I can’t get with the people who think it should be banned. I’m equally uncomfortable with people who “push” it. I avoid general discussions about it because I don’t know what I think without a case. If practicing medicine is following recipes, then I’m not interested. I hate to sound corny about this, but every intervention is a new experiment deserving close attention. I made sure to guide my career such that I could always follow that rule.

    So what would I do if I were a VAH clinician with a huge case load of very ill veterans and couldn’t give them personal care? Quit. What if I were a GP with an overly filled schedule? Go back and do a residency. What if I were a psychiatrist being paid by insurance companies to do brief med checks? Retire. Get an ER job. Work at McDonalds. Write a blog. I know you didn’t ask about that, but it’s part of my answer. You’re a thoughtful person, and I expect I’m preaching to the choir. But others read these public things we do. So I think that low dose antipsychotics might be a safe alternative to other ways of treating sleep problems or anxiety in some people, but I don’t like it as a routine because unwatched, it can lead to trouble. It’s that “do no harm” thing again.

    June 23, 2013 | 6:23 PM


    That’s a nice thing to say, but I’m not the book type. Writing a book, you are locked into a place in time. I see this current business with psychiatry as a moving thing right now. Maybe there will come a “look back on” time or an issue that needs lingering on, but right now isn’t either for me. I see the current task as applying what we’ve learned from the foibles of the past to what’s happening right now, or tomorrow. If I started a book, tomorrow’s Pharmalot would grab me, or RIAT, or AllTrials.

    June 23, 2013 | 6:26 PM

    Dear Dr. Mickey — Just caught up with this post and your earlier “good to the last drop” story about Seroquel. I’ve been trying to get someone who knows this f** ed up territory to write about Seroquel dependence, and problems kicking it, for RxISK. Would you consider maybe writing up your experiences with this in the free clinic? David Healy & friends would be thrilled to have it I’m sure. I know I would be.

    I think it would be awesome because 1) you know what you are seeing and 2) you actually listen to the people. Among those who need to hear this are our Iraq vets, the folks in the pain clinics with their failed back surgeries, and those who treat them. We are developing a street market in Seroquel now, and I think it’s not so much because it gives anyone a lovely high but because they got hooked on it in the army or in prison (another key A-Z market). And you can’t find a doctor who knows doodly-squat!

    June 23, 2013 | 7:18 PM

    1BOM, thank you for your response. It is very much appreciated.


    June 25, 2013 | 8:42 PM

    I believe there’s evidence that even at the low dose of 25mg, Seroquel causes disturbances in glucose metabolism. It is not harmless at low doses.

    June 25, 2013 | 8:47 PM

    As long as we’re pointing to The Last Psychiatrist, here’s his typically obscure take on how psychiatry has been the victim of a scam

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