Thanks for this excellent review. Also, I appreciate you raising questions about the Harrow findings, which one would expect if patients stop taking their antipsychotics when their psychosis goes into remission (rather than patients experiencing remission as a result of discontinuing antipsychotics).
As the parent of an adult with an early-onset psychotic disorder, I have noted changes of opinion over the past 20 years that often seem as driven by popular psychology as tied to strong evidence. Should antipsychotics be prescribed in the prodromal stages as a hypothetical preventative, or does that risk putting patients who may never develop a psychotic disorder on unnecessary medication? Claims about the effects of antipsychotics have varied from them needing to be taken lifelong (as already noted and critiqued in this article); to being necessary as an intervention against kindling of brain pathways (while some articles have found patient response to antipsychotics is not much worse among patients with longstanding untreated psychosis when compared to those who received early intervention); to being neuroprotective or even stimulating growth of grey matter; to disagreements about whether brain shrinkage is related to antipsychotic use or is a symptoms of the disease and even whether the amount of brain shrinkage is clinically significant (since patients with much more brain missing due to developmental variation or injury are doing just fine). Authors of journal articles reach different conclusions based on investigations of patients naive to antipsychotics, those using antipsychotics for a short time, and those with a history of longterm antipsychotic use. One article a number of years ago found higher-than-recommended doses of olanzapine to be similar in efficacy to clozapine. And a recent comparison of long-acting injectables found some to be statistically as efficacious as clozapine, making me wonder if the required monitoring of clozapine use is a partial explanation for its higher efficacy. Earlier this year, an article in the UK raised concerns about the elevated risk of sudden death associated with clozapine. If suicidal ideation is not an issue for a particular patient, if they have a strong family history of heart disease, and they are able to function despite the positive symptoms of psychosis, does that mean clozapine is counter-indicated due to its elevated risk of iatrogenic harm? It's a rhetorical question.
Similarly there have been disagreements about the pros and cons of mood stabilizers including lithium, carbamazepine, and oxcarbazepine with arguments that some are more effective than others, some may be neuroprotective, one or more may reduce suicidal ideation, and maybe some are more suitable for adults or children. Twenty years ago, popular thinking seemed to be that lithium was ineffective in children and carbamazepine must be used. A local residential treatment center was so enamored with oxcarbazepine a decade ago that they used it exclusively in their patients and often at doses much higher than manufacturer recommendations (which may be somewhat arbitrary). Similarly, while lithium has often been called the gold standard for mood stabilization, that position has been challenged by papers that disagree on whether it reduces suicidal thoughts, whether it is neuroprotective, and whether it causes kidney damage over time. Who should one believe?
Parents like me rub their heads and wonder how they are supposed to make an educated choice for the care of a family member--they can get a different opinion from each doctor they visit. Novice advocates and journalists read this stuff, choose their favorite journal article, and use it to make the policy arguments they prefer. This is one reason why it is impossible to agree on mental healthcare policy: We have advocates for medication, therapy, social supports, and so forth with academicians who hold terminal degrees in their fields disagreeing with one another. Anti-psychiatry activists including the Church of Scientology use these disagreements to malign the medical model and attack the entire medical speciality. The biggest losers are patients with the more serious and intractable psychiatric illnesses who are homeless on our streets and in our prison cells.
b) personalized care, and take patient input seriously.
It would be great if we knew more, but we can AT LEAST abstain from a one-size-fits-all method where all patients with the same diagnosis are supposed to get the same kind of treatment, regardless of whether it helps this specific individual or not.
Also, we really should have drug-free OPTIONS (like they've recently instituted in Norway). I think lots of psychiatrists who are in the enthusiastic pro-medication camp are quite disconnected from reality, to be frank. They talk as if an alternative where all psychosis patients take their meds and then all the patients are helped by them EXISTS. No, sorry. That alternative does not exist outside of your dreams.
They talk about all the risks of discontinuation, sure, but then often bring up cautionary tales of people who suddenly quit ON THEIR OWN, had dramatic relapses, sometimes tried to self-medicate with street drugs instead, committed suicide or violence to others, etc. Sure, that's horrible, but we'll likely see FEWER of these cases if people could get support for quitting within the care system.
It's no use wishing for an impossible situation in which all psychosis patients take their prescribed meds and then everyone is helped by them. For some, they just don't work, and for some, the side effects are intolerable on any effective dosage. When people experience intolerable suffering, they're usually gonna do something about it. And if all they hear from the mental health care system is that they MUST take their meds, no matter how much they suffer from it they MUST, they're gonna drop out and quit on their own, often in dangerous ways.
Sometimes things would go badly even if medication-free options existed within the mental health care system, but I'm certain that NOT offering such alternatives is WORSE.
Thank you for the thorough, balanced, and nuanced review, Awais!
For those of us who spent the bulk of our professional careers caring for severely ill patients with chronic schizophrenia [1], your conclusion is entirely on the mark; i.e.,
"If you go off antipsychotics that were effective for you, and they caused minimal side effects and you tolerated them well, and if you have a recurrent or chronic form of psychotic illness, then you are at a higher risk of experiencing future episodes/exacerbations of psychosis, and your functioning is likely negatively affected by discontinuation (i.e. the net effect of antipsychotics on your functioning is positive)."
Patients fitting this description should be encouraged to continue their antipsychotic medication, with careful attention paid to managing side effects; e.g., using the lowest effective dose of medication. I would also note the need for greater use of clozapine, which is known to reduce suicidality in schizophrenia and--in my experience--can vastly improve quality of life. Psychosocial treatments are also an important component of care, for patients with chronic schizophrenia.
One important study to consider is that of Beasley and colleagues. This 52-week, double-blind, relapse prevention trial tested whether stable patients with schizophrenia who were taken off active drug treatment would experience greater improvements in long-term quality of life than those who were continued on antipsychotic treatment. The study found that, on average, Heinrichs-Carpenter Quality-of-Life Scale total scores improved by 4.3 ± 10.6 points during treatment with olanzapine (10 to 20 mg/d; n = 212), but decreased by 7.1 ± 14.6 points during treatment with placebo (n = 92; P < .001). The researchers also found that “. . . stable patients with schizophrenia who were taken off active drug treatment experienced no greater improvements in long-term quality of life than those who were continued on antipsychotic treatment, even in the absence of psychotic symptoms.” [2]
All that said, we need many more randomized, long-term studies of antipsychotic medication before reaching any confident conclusions of their long-term risks and benefits.
2. Beasley CM Jr, Sutton VK, Taylor CC, et al. Is quality of life among minimally symptomatic patients with schizophrenia better following withdrawal or continuation of antipsychotic treatment? J Clin Psychopharmacol. 2006;26:40-44.
If a significant number of practitioners are unable to provide best treatment (personalization) for either personal or systemic reasons, then arguably it is rational for the patient who can access only lesser and possibly harmful treatment to refuse treatment. If some clinicians are misleading patients, scaring them, shaming them and so forth, then isn’t that in itself a reason to be anti-psychiatry? After all, we don’t know what the quality of our clinician will be, we don’t know enough when we’re young and naive to be able to evaluate a clinician and go elsewhere. If we’re hurt, then we’re hurt, and then we have to recover from our clinicians.
I think this is a good point. I'm not saying that it's always better not to seek treatment. It depends on how terrible a state you're in, it might depend on what you know about the psych unit where you're gonna seek help (you might have heard either good or bad from other patients), depend on a bunch of things.
But I really try to stress to people that there are LOTS of important reasons for not seeking help, or for dropping out of psychiatry, beyond "too crazy to understand their own good". The idea that it's ALWAYS rational to seek psychiatric help and ALWAYS irrational not to does SO much harm.
"or they are folks with chronic symptoms who have the psychological and social resources to manage symptoms without antipsychotic medications."
Raises hand! Though I haven't always been in this group. Not back when my life was more stressful - back then I couldn't manage without, making me extremely grateful for the fact that some necessary changes happened not too long after Haldol stopped working as well as it used to do (simultaneously less positive effects and more bad side effects).
I always try to stress BOTH these things: Yep I'm super privileged in many ways, obvs the fact that I managed to quit all my pills doesn't mean everyone is better off without, BUT ALSO it's still interesting that I can manage without, since all psychosis disorders and schizo-spectrum stuff in particular is often talked about in these very biological terms, as if all that matters is what goes on with your neurotransmitters and synapses (perhaps with some small addition of "it's better to meet people and do something during the day than to be wholly isolated and passive").
Thanks for this excellent review. Also, I appreciate you raising questions about the Harrow findings, which one would expect if patients stop taking their antipsychotics when their psychosis goes into remission (rather than patients experiencing remission as a result of discontinuing antipsychotics).
As the parent of an adult with an early-onset psychotic disorder, I have noted changes of opinion over the past 20 years that often seem as driven by popular psychology as tied to strong evidence. Should antipsychotics be prescribed in the prodromal stages as a hypothetical preventative, or does that risk putting patients who may never develop a psychotic disorder on unnecessary medication? Claims about the effects of antipsychotics have varied from them needing to be taken lifelong (as already noted and critiqued in this article); to being necessary as an intervention against kindling of brain pathways (while some articles have found patient response to antipsychotics is not much worse among patients with longstanding untreated psychosis when compared to those who received early intervention); to being neuroprotective or even stimulating growth of grey matter; to disagreements about whether brain shrinkage is related to antipsychotic use or is a symptoms of the disease and even whether the amount of brain shrinkage is clinically significant (since patients with much more brain missing due to developmental variation or injury are doing just fine). Authors of journal articles reach different conclusions based on investigations of patients naive to antipsychotics, those using antipsychotics for a short time, and those with a history of longterm antipsychotic use. One article a number of years ago found higher-than-recommended doses of olanzapine to be similar in efficacy to clozapine. And a recent comparison of long-acting injectables found some to be statistically as efficacious as clozapine, making me wonder if the required monitoring of clozapine use is a partial explanation for its higher efficacy. Earlier this year, an article in the UK raised concerns about the elevated risk of sudden death associated with clozapine. If suicidal ideation is not an issue for a particular patient, if they have a strong family history of heart disease, and they are able to function despite the positive symptoms of psychosis, does that mean clozapine is counter-indicated due to its elevated risk of iatrogenic harm? It's a rhetorical question.
Similarly there have been disagreements about the pros and cons of mood stabilizers including lithium, carbamazepine, and oxcarbazepine with arguments that some are more effective than others, some may be neuroprotective, one or more may reduce suicidal ideation, and maybe some are more suitable for adults or children. Twenty years ago, popular thinking seemed to be that lithium was ineffective in children and carbamazepine must be used. A local residential treatment center was so enamored with oxcarbazepine a decade ago that they used it exclusively in their patients and often at doses much higher than manufacturer recommendations (which may be somewhat arbitrary). Similarly, while lithium has often been called the gold standard for mood stabilization, that position has been challenged by papers that disagree on whether it reduces suicidal thoughts, whether it is neuroprotective, and whether it causes kidney damage over time. Who should one believe?
Parents like me rub their heads and wonder how they are supposed to make an educated choice for the care of a family member--they can get a different opinion from each doctor they visit. Novice advocates and journalists read this stuff, choose their favorite journal article, and use it to make the policy arguments they prefer. This is one reason why it is impossible to agree on mental healthcare policy: We have advocates for medication, therapy, social supports, and so forth with academicians who hold terminal degrees in their fields disagreeing with one another. Anti-psychiatry activists including the Church of Scientology use these disagreements to malign the medical model and attack the entire medical speciality. The biggest losers are patients with the more serious and intractable psychiatric illnesses who are homeless on our streets and in our prison cells.
I think the best we can do is
a) admit how little we know for sure, and
b) personalized care, and take patient input seriously.
It would be great if we knew more, but we can AT LEAST abstain from a one-size-fits-all method where all patients with the same diagnosis are supposed to get the same kind of treatment, regardless of whether it helps this specific individual or not.
Also, we really should have drug-free OPTIONS (like they've recently instituted in Norway). I think lots of psychiatrists who are in the enthusiastic pro-medication camp are quite disconnected from reality, to be frank. They talk as if an alternative where all psychosis patients take their meds and then all the patients are helped by them EXISTS. No, sorry. That alternative does not exist outside of your dreams.
They talk about all the risks of discontinuation, sure, but then often bring up cautionary tales of people who suddenly quit ON THEIR OWN, had dramatic relapses, sometimes tried to self-medicate with street drugs instead, committed suicide or violence to others, etc. Sure, that's horrible, but we'll likely see FEWER of these cases if people could get support for quitting within the care system.
It's no use wishing for an impossible situation in which all psychosis patients take their prescribed meds and then everyone is helped by them. For some, they just don't work, and for some, the side effects are intolerable on any effective dosage. When people experience intolerable suffering, they're usually gonna do something about it. And if all they hear from the mental health care system is that they MUST take their meds, no matter how much they suffer from it they MUST, they're gonna drop out and quit on their own, often in dangerous ways.
Sometimes things would go badly even if medication-free options existed within the mental health care system, but I'm certain that NOT offering such alternatives is WORSE.
Thank you for the thorough, balanced, and nuanced review, Awais!
For those of us who spent the bulk of our professional careers caring for severely ill patients with chronic schizophrenia [1], your conclusion is entirely on the mark; i.e.,
"If you go off antipsychotics that were effective for you, and they caused minimal side effects and you tolerated them well, and if you have a recurrent or chronic form of psychotic illness, then you are at a higher risk of experiencing future episodes/exacerbations of psychosis, and your functioning is likely negatively affected by discontinuation (i.e. the net effect of antipsychotics on your functioning is positive)."
Patients fitting this description should be encouraged to continue their antipsychotic medication, with careful attention paid to managing side effects; e.g., using the lowest effective dose of medication. I would also note the need for greater use of clozapine, which is known to reduce suicidality in schizophrenia and--in my experience--can vastly improve quality of life. Psychosocial treatments are also an important component of care, for patients with chronic schizophrenia.
One important study to consider is that of Beasley and colleagues. This 52-week, double-blind, relapse prevention trial tested whether stable patients with schizophrenia who were taken off active drug treatment would experience greater improvements in long-term quality of life than those who were continued on antipsychotic treatment. The study found that, on average, Heinrichs-Carpenter Quality-of-Life Scale total scores improved by 4.3 ± 10.6 points during treatment with olanzapine (10 to 20 mg/d; n = 212), but decreased by 7.1 ± 14.6 points during treatment with placebo (n = 92; P < .001). The researchers also found that “. . . stable patients with schizophrenia who were taken off active drug treatment experienced no greater improvements in long-term quality of life than those who were continued on antipsychotic treatment, even in the absence of psychotic symptoms.” [2]
All that said, we need many more randomized, long-term studies of antipsychotic medication before reaching any confident conclusions of their long-term risks and benefits.
Ronald W. Pies, MD
1. https://www.psychiatrictimes.com/view/quality-life-and-case-antipsychotics
2. Beasley CM Jr, Sutton VK, Taylor CC, et al. Is quality of life among minimally symptomatic patients with schizophrenia better following withdrawal or continuation of antipsychotic treatment? J Clin Psychopharmacol. 2006;26:40-44.
If a significant number of practitioners are unable to provide best treatment (personalization) for either personal or systemic reasons, then arguably it is rational for the patient who can access only lesser and possibly harmful treatment to refuse treatment. If some clinicians are misleading patients, scaring them, shaming them and so forth, then isn’t that in itself a reason to be anti-psychiatry? After all, we don’t know what the quality of our clinician will be, we don’t know enough when we’re young and naive to be able to evaluate a clinician and go elsewhere. If we’re hurt, then we’re hurt, and then we have to recover from our clinicians.
I think this is a good point. I'm not saying that it's always better not to seek treatment. It depends on how terrible a state you're in, it might depend on what you know about the psych unit where you're gonna seek help (you might have heard either good or bad from other patients), depend on a bunch of things.
But I really try to stress to people that there are LOTS of important reasons for not seeking help, or for dropping out of psychiatry, beyond "too crazy to understand their own good". The idea that it's ALWAYS rational to seek psychiatric help and ALWAYS irrational not to does SO much harm.
"or they are folks with chronic symptoms who have the psychological and social resources to manage symptoms without antipsychotic medications."
Raises hand! Though I haven't always been in this group. Not back when my life was more stressful - back then I couldn't manage without, making me extremely grateful for the fact that some necessary changes happened not too long after Haldol stopped working as well as it used to do (simultaneously less positive effects and more bad side effects).
I always try to stress BOTH these things: Yep I'm super privileged in many ways, obvs the fact that I managed to quit all my pills doesn't mean everyone is better off without, BUT ALSO it's still interesting that I can manage without, since all psychosis disorders and schizo-spectrum stuff in particular is often talked about in these very biological terms, as if all that matters is what goes on with your neurotransmitters and synapses (perhaps with some small addition of "it's better to meet people and do something during the day than to be wholly isolated and passive").