A sizable number of people leaving the study group is perhaps unavoidable, but only having a quarter of the original group in the final analysis seems enough, to me, to throw all of the conclusions immediately into question.
However, as a layman, I’m obviously underequipped to be confident in that interpretation.
Are these sort of dropout rates typical? Has reliance on studies with similar dropout rates led to (in the main) better clinical outcomes over time? Especially in the case of psychotic disorders, are these rates just something you have to live with, given the decreasing number of long-term care facilities that could ensure more continuous monitoring over an extended period of time?
Unfortunately not that atypical for a psychiatric study like this. Patients can be hard to engage and there is little incentive for them to continue participating over long periods.
I agree with your measured thoughts. My anecdote from the last couple years: I have been the psychiatric provider for an intensive outpatient dual diagnosis program where all of the patients have significant substance use disorders and most of the patients have thought disorders and were recently discharged from the Oregon State Hospital (OSH). I find (especially compared to the population I work with at a secured residential treatment facility that treats mostly patients with schizophrenia who lack the SUD component) that this dual diagnosis population has a lot more success coming off medication than the average patient with schizophrenia. This level of diagnostic nuance will probably never be captured well by these kinds of studies, so I am fully with you on the clinical decision-making and collaboration that goes into this kind of individualized/personalized care.
As an addiction psychiatrist I’m convinced that the over diagnosis of various disorders including psychotic disorders in the SUD folks has caused more harm than good. Though back in the 80s and 90s we all clamored for more recognition of comorbidity, our patients today may have become victims of the success. Of course there is the possibility that these were folks with a vulnerability to psychotic illness and drugs didn’t cause but only precipitate the illness and diagnosis. That would explain your observations. Agree whole heartedly with Aftab that the only approach is a fully personalized one. Sadly most community clinics and non profits don’t make time for this and the average psychiatrist (read NP) at such places has no time or head for this thoughtful measured stance.
For sure. That has always been been a fascinating relationship. Where does substance induced psychosis end and schizophrenia begin? As is this schizophrenia qualitatively different than the schizophrenia not originally induced by substances?
My thoughts are that it's far too heterogenous and the whole thing is such a mess that no conclusions whatsoever can be drawn. I personally haven't seen a single good medium or long term outcome from an antipsychotic ever. It isn't that I don't believe in it, I've been waiting patiently to witness it first hand. I see what antipsychotics do in the short term and I believe Paul Janssen's story about microdosing the coffee with haloperidol but I've just never personally seen anyone get "well" on an antipsychotic and stay "well" in the way I see people get "well" on lithium or from ECT. I see people go home well on lithium every three weeks or so, and to me there is no comparison.
The best bet of what is probably going on underneath all of this is Astrup and Fish (1964).
Astrup, C., & Fish, F. (1964). The response of the different Leonhard subgroups of schizophrenia to psychotropic drugs. Psychiatry and Clinical Neurosciences, 18(2), 133–140. https://doi.org/10.1111/j.1440-1819.1964.tb00018.x
A few quotes from my zettelkasten:
“It had a major impact, but its impact is not comparable to penicillin’s. Penicillin is a causal treatment. It kills the bacteria that causes the disease. Treatment with chlorpromazine is palliative treatment that controls symptoms and optimally keeps patients in remission.”
Thomas Ban on Chlorpromazine Alex Last: BBC Witness History The First Antipsychotic Drug An interview of Thomas Ban
"Moreover therapy is different according to whether the psychosis results in a spontaneous remission or whether there is the risk of a defect developing if appropriate therapy is not provided. Unfortunately these days I see many patients with cycloid psychoses who because of prolonged medication show toxic disabling symptoms, whereas without medication they would be perfectly well. The damage is aggravated by the fact that after prolonged medication, as
ALBERT (1986) has reported, habituation occurs so that even in the case of phasic psychoses discontinuation of medication produces a relapse. In my opinion a patient with a cycloid psychosis should only be treated psychopharmacologically during the acute phase. After the latter has abated the medication should be rapidly discontinued by gradual lowering of the dose so that no habituation may occur. In order to make sure that this was properly done, while I was still directing the department, I saw to it that patients were discharged only after the medication had been discontinued. When this was done no relapses occurred. Habituation occurs in all likelihood because metabolism becomes adjusted to the addition of the medication and after discontinuation of the medication loses the previously acquired equilibrium. In discharging patients only after they were free of medications I went against the modern challenge of early discharge. I did not worry about this, for on the one hand early discharge of patients whose disorders were in phases had no great significance; on the other hand it was important to prevent permanent damage from medical interventions. I was unable to make sure that medication after discharge was discontinued in good time. Such omission produces much damage. Toxic lowering of drive, of affectivity, and the presence of extrapyramidal symptoms represent a severe toxic disorder."
Leonhard, K. (1999). Classification of endogenous psychoses and their differentiated etiology (2nd ed., p. 3). Springer.
"What does the term anti-manic mean when applied to a drug like haloperidol or its successors? A favorite clinical pearl from the 1970s at St. Elizabeth’s Hospital in Washington, D.C., concerned a patient arrested by the Secret Service for climbing the White House fence with a personal message for the President. He was transferred to St. E’s where a diagnosis of mania was rendered. After a week on haloperidol, his boisterous overactivity and pressure of speech had subsided. In a ward conference the nurses agreed that he could now be allowed telephone privileges, whereupon he walked calmly to the telephone and dialed the White House! The point of this pearl is that drugs may have only partial effects on a syndrome like mania. The dopamine blocker haloperidol helps to control the impulsivity and overactivity of a manic patient but then it just provides a dopamine brake until the manic thought disorder resolves in due course. But when measured with an operational instrument like the Young Mania Scale, haloperidol can appear to be ‘anti-manic.’"
In response - I'm living the dream - long term remission from both mania and depression with antipsychotics. In someone with a history of severe psychosis. For me, I don't like lithium - polyuria is a deal breaker. And valproate made my hair fall out.
Amisulpride. I've tried close to a dozen antipsychotics, and kept coming back amisulpride as the best tolerated. I do use Risperidone (once in a blue moon now) as my med of choice if acutely symptomatic, as it has the best "settling" effect on acute manic symptoms (it gives me the "stunned mullet" hit on the head with a sledgehammer effect, which I want when experiencing uncomfortable manic overactivity - which amisulpride doesn't - I note that I've never had someone sedate me with antipsychotics against my will (I've was far too manic as an inpatient for meds to have that effect when people may have wanted to sedate me!)). But I don't use it long term as it has an extreme appetite stimulant effect.
A local Professor of Psychiatry at the other medical school in my city states he's never seen psych meds make a dramatic difference to a patient's life - I wonder where he's been, as they've transformed my life; I'm an advocate for euthenasia for psych reasons because without meds (or if my illness was not treatment responsive), my life was not worth living
Yes, it is a strange opinion for a professor. Understandable if they only work in a private clinic but strange given that they would surely see such things during residency at the least. Certainly I have seen antipsychotics dramatically calm people down, and reduce both mania and psychosis significantly. It was stunning the first time I saw it. Over the years though I've become dissatisfied with the effect on the natural history of the disease process. I've never seen people "well" on them, not in the true sense.
On the other hand I've seen people get so well on lithium and ECT that they and their families forget they had ever been ill. I met one family where the time since the last bipolar episode had been so long the aunt had to explain to the adult children what was going on.
I do believe it happens. I'm sure you're aware that Kraepelin reported cases where mania was aborted by potassium bromide, so perhaps antimanic effects are not so rare or unique to lithium.
Valproate isn't so crash hot in my opinion. It's useful, but it doesn't have quality that I'm talking about.
My wife keeps low dose Seroquel in her purse just encase she needs to put herself under for a few days. It's marvellous sleeping through a brief episode.
The question is, how has the course of your illness been altered by the medication? And how does it compare with the natural history of the disease? Obviously there is a great deal of individual variation but I'm very curious to know.
A sizable number of people leaving the study group is perhaps unavoidable, but only having a quarter of the original group in the final analysis seems enough, to me, to throw all of the conclusions immediately into question.
However, as a layman, I’m obviously underequipped to be confident in that interpretation.
Are these sort of dropout rates typical? Has reliance on studies with similar dropout rates led to (in the main) better clinical outcomes over time? Especially in the case of psychotic disorders, are these rates just something you have to live with, given the decreasing number of long-term care facilities that could ensure more continuous monitoring over an extended period of time?
Unfortunately not that atypical for a psychiatric study like this. Patients can be hard to engage and there is little incentive for them to continue participating over long periods.
I agree with your measured thoughts. My anecdote from the last couple years: I have been the psychiatric provider for an intensive outpatient dual diagnosis program where all of the patients have significant substance use disorders and most of the patients have thought disorders and were recently discharged from the Oregon State Hospital (OSH). I find (especially compared to the population I work with at a secured residential treatment facility that treats mostly patients with schizophrenia who lack the SUD component) that this dual diagnosis population has a lot more success coming off medication than the average patient with schizophrenia. This level of diagnostic nuance will probably never be captured well by these kinds of studies, so I am fully with you on the clinical decision-making and collaboration that goes into this kind of individualized/personalized care.
As an addiction psychiatrist I’m convinced that the over diagnosis of various disorders including psychotic disorders in the SUD folks has caused more harm than good. Though back in the 80s and 90s we all clamored for more recognition of comorbidity, our patients today may have become victims of the success. Of course there is the possibility that these were folks with a vulnerability to psychotic illness and drugs didn’t cause but only precipitate the illness and diagnosis. That would explain your observations. Agree whole heartedly with Aftab that the only approach is a fully personalized one. Sadly most community clinics and non profits don’t make time for this and the average psychiatrist (read NP) at such places has no time or head for this thoughtful measured stance.
Interesting observation! Makes one wonder about the role the substances were playing in maintaining the psychotic state.
For sure. That has always been been a fascinating relationship. Where does substance induced psychosis end and schizophrenia begin? As is this schizophrenia qualitatively different than the schizophrenia not originally induced by substances?
Yeah, I doubt there is a clean way to disentangle these things.
My thoughts are that it's far too heterogenous and the whole thing is such a mess that no conclusions whatsoever can be drawn. I personally haven't seen a single good medium or long term outcome from an antipsychotic ever. It isn't that I don't believe in it, I've been waiting patiently to witness it first hand. I see what antipsychotics do in the short term and I believe Paul Janssen's story about microdosing the coffee with haloperidol but I've just never personally seen anyone get "well" on an antipsychotic and stay "well" in the way I see people get "well" on lithium or from ECT. I see people go home well on lithium every three weeks or so, and to me there is no comparison.
Here is the Janssen interview:
https://inhn.org/inhn-projects/archives/paul-janssen-from-haloperidol-to-risperidone-david-healys-interview
The best bet of what is probably going on underneath all of this is Astrup and Fish (1964).
Astrup, C., & Fish, F. (1964). The response of the different Leonhard subgroups of schizophrenia to psychotropic drugs. Psychiatry and Clinical Neurosciences, 18(2), 133–140. https://doi.org/10.1111/j.1440-1819.1964.tb00018.x
A few quotes from my zettelkasten:
“It had a major impact, but its impact is not comparable to penicillin’s. Penicillin is a causal treatment. It kills the bacteria that causes the disease. Treatment with chlorpromazine is palliative treatment that controls symptoms and optimally keeps patients in remission.”
Thomas Ban on Chlorpromazine Alex Last: BBC Witness History The First Antipsychotic Drug An interview of Thomas Ban
"Moreover therapy is different according to whether the psychosis results in a spontaneous remission or whether there is the risk of a defect developing if appropriate therapy is not provided. Unfortunately these days I see many patients with cycloid psychoses who because of prolonged medication show toxic disabling symptoms, whereas without medication they would be perfectly well. The damage is aggravated by the fact that after prolonged medication, as
ALBERT (1986) has reported, habituation occurs so that even in the case of phasic psychoses discontinuation of medication produces a relapse. In my opinion a patient with a cycloid psychosis should only be treated psychopharmacologically during the acute phase. After the latter has abated the medication should be rapidly discontinued by gradual lowering of the dose so that no habituation may occur. In order to make sure that this was properly done, while I was still directing the department, I saw to it that patients were discharged only after the medication had been discontinued. When this was done no relapses occurred. Habituation occurs in all likelihood because metabolism becomes adjusted to the addition of the medication and after discontinuation of the medication loses the previously acquired equilibrium. In discharging patients only after they were free of medications I went against the modern challenge of early discharge. I did not worry about this, for on the one hand early discharge of patients whose disorders were in phases had no great significance; on the other hand it was important to prevent permanent damage from medical interventions. I was unable to make sure that medication after discharge was discontinued in good time. Such omission produces much damage. Toxic lowering of drive, of affectivity, and the presence of extrapyramidal symptoms represent a severe toxic disorder."
Leonhard, K. (1999). Classification of endogenous psychoses and their differentiated etiology (2nd ed., p. 3). Springer.
"What does the term anti-manic mean when applied to a drug like haloperidol or its successors? A favorite clinical pearl from the 1970s at St. Elizabeth’s Hospital in Washington, D.C., concerned a patient arrested by the Secret Service for climbing the White House fence with a personal message for the President. He was transferred to St. E’s where a diagnosis of mania was rendered. After a week on haloperidol, his boisterous overactivity and pressure of speech had subsided. In a ward conference the nurses agreed that he could now be allowed telephone privileges, whereupon he walked calmly to the telephone and dialed the White House! The point of this pearl is that drugs may have only partial effects on a syndrome like mania. The dopamine blocker haloperidol helps to control the impulsivity and overactivity of a manic patient but then it just provides a dopamine brake until the manic thought disorder resolves in due course. But when measured with an operational instrument like the Young Mania Scale, haloperidol can appear to be ‘anti-manic.’"
Bernard Carroll, 2013, The Neurocritic
In response - I'm living the dream - long term remission from both mania and depression with antipsychotics. In someone with a history of severe psychosis. For me, I don't like lithium - polyuria is a deal breaker. And valproate made my hair fall out.
It's always interesting to hear these stories, so far I only ever hear about them online. Which antipsychotic?
Amisulpride. I've tried close to a dozen antipsychotics, and kept coming back amisulpride as the best tolerated. I do use Risperidone (once in a blue moon now) as my med of choice if acutely symptomatic, as it has the best "settling" effect on acute manic symptoms (it gives me the "stunned mullet" hit on the head with a sledgehammer effect, which I want when experiencing uncomfortable manic overactivity - which amisulpride doesn't - I note that I've never had someone sedate me with antipsychotics against my will (I've was far too manic as an inpatient for meds to have that effect when people may have wanted to sedate me!)). But I don't use it long term as it has an extreme appetite stimulant effect.
A local Professor of Psychiatry at the other medical school in my city states he's never seen psych meds make a dramatic difference to a patient's life - I wonder where he's been, as they've transformed my life; I'm an advocate for euthenasia for psych reasons because without meds (or if my illness was not treatment responsive), my life was not worth living
Yes, it is a strange opinion for a professor. Understandable if they only work in a private clinic but strange given that they would surely see such things during residency at the least. Certainly I have seen antipsychotics dramatically calm people down, and reduce both mania and psychosis significantly. It was stunning the first time I saw it. Over the years though I've become dissatisfied with the effect on the natural history of the disease process. I've never seen people "well" on them, not in the true sense.
On the other hand I've seen people get so well on lithium and ECT that they and their families forget they had ever been ill. I met one family where the time since the last bipolar episode had been so long the aunt had to explain to the adult children what was going on.
I do believe it happens. I'm sure you're aware that Kraepelin reported cases where mania was aborted by potassium bromide, so perhaps antimanic effects are not so rare or unique to lithium.
Valproate isn't so crash hot in my opinion. It's useful, but it doesn't have quality that I'm talking about.
My wife keeps low dose Seroquel in her purse just encase she needs to put herself under for a few days. It's marvellous sleeping through a brief episode.
The question is, how has the course of your illness been altered by the medication? And how does it compare with the natural history of the disease? Obviously there is a great deal of individual variation but I'm very curious to know.