Optimal Use of Neuroleptics, Pt. II; The Monkeys Were Not Psychotic

Sandra Steingard, MD
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I asserted previously that the impression of short term efficacy tends to be inflated.  What I mean by this is that there is a general sense – within my profession and among the general public – that neuroleptic drugs are very effective.  They are after all what allowed us to shutter our state hospitals. The folk narrative (albeit not on MIA) is that the main problem is not that they do not work but that people do not take them reliably so we should therefore put our efforts into getting people to stay on them.

I will review some recent studies that belie that belief.  I have written about most of these before and the links are provided if you want more detail.

Khin et al (Journal of  Clinical Psychiatry 2012; 73(6):856-864)

  • This is a meta-analysis of data from new drug applications submitted to FDA from 1991-2008.
  • The researchers focused on the results of the PANSS (Positive and Negative Symptom Scale). This is a 30 item questionnaire that measures symptoms such as voices and delusions (so called positive symptoms) as well as apathy (so called negative symptoms). Each item is rated on a scale of 1-7 thus the score can be anywhere from 30 to 210 points.
  • At entry into the study, the average score was about 90 points.
  • The average decline in the PANSS in the active treatment group was 15 points and in the placebo group 6.4.
  • The effect size is the difference between these numbers and that is about 8 points.  This was a statistically different effect but it is not one that has a major clinical significance.

Stefan Leucht et al (Mol Psychiatry 2009;14: 429-447)

  • A recent meta-analysis comparing second generation antipsychotic (SGA) drugs to placebo.
  • This includes 38 randomized controlled studies with a total of 7323 subjects.
  • There was an 18% difference in responder rates: 41% SGA versus 24% placebo.
  • The number needed to treat (meaning how many people need to be treated with the drug for there to be a benefit was  6 (CI: 5–7).  This is considered to be a modest effect.

Meltzer et al (American Journal of Psychiatry 2011; 168:857-967)

  • This was sent out to every psychiatrist in America (I received at least three reprints) in support of the new drug lurasidone.
  • This study included over one hundred people in each group and it was conducted at multiple centers.
  • They compared two lurasidone doses to  placebo and olanzapine.
  • The primary measure of efficacy was change in the PANSS.
  • On the PANSS, the lurasidone 40 mg group improved by 25.7 points, 120 mg by 23.6 points, olanzapine by 28.7 points, and placebo by 16 points.
  • These difference are statistically significant but of less clinical significance.
  • The overall difference between the olanzapine group and the placebo group was less than 13 points.
  • On the secondary measure, the CGI (Clinical Global Impression) a 7 point scale, the difference was less than half a point. That difference was statistically significant, but, once again, of questionable clinical impact.

Jin at al (Journal of Clinical Psychiatry 2013;74 (1):10-18)

  • Evaluated the efficacy of the 4 most commonly prescribed antipsychotics in individuals 40 years of age and older.
  • The authors reported , “no significant change in psychopathology with any of the study atypical antipsychotics.

These are four large recent studies published in major psychiatric journals.  The results are at best modest and at worse “sobering”.  I was discussing this one day with a medical student. I told him about the Khin study but before telling him the results, I asked, “What do you think the reduction in the PANSS score would be based on what you have learned so far?”   He guessed that in the active treatment groups there would 50% reduction in symptoms.  He is a bright student and a  50% reduction is not a bad guess given that this would be a reasonable goal for a drug that is effective.  In the Khin study, the reduction of symptoms in the treatment group was less than 20%.

The long term risks associated with these drugs tend to be minimized.

There are risks that are not controversial. This includes tardive dyskinesia, weight gain, and metabolic syndrome. For the sake of time and space, I am not going to review the data on this since I believe this is now accepted by my colleagues (although I continue to believe that it took about 10 years to be fully recognized due to the influence of aggressive and sophisticated marketing).

Robert Whitaker has highlighted other concerns including super sensitivity psychosis and brain atrophy. His most controversial claim is that people who remain on these drugs over time have worse outcomes than those who stop them.  Martin Harrow’s recent article on this topic suggests that even this concept is beginning to be taken seriously within the profession.

Since these topics are so well covered on this website and in Whitaker’s books, I am not going to review in detail the studies that support these claims.  I do not have much in the way of new information to add.  I also do not believe I have the expertise in neuroscience to adequately address the question of neuroleptic induced super sensitivity  of dopamine receptors.  However, it seems that serious psychiatric neuroscientists consider super sensitivity to be a viable hypothesis.

Howes et al wrote a recent paper in the Archives of General Psychiatry (2012; 69(8): 776-786), “The Nature of Dopamine Dysfunction in Schizophrenia and What This Means for Treatment.”  This was a meta analysis of studies which evaluated the role of dopamine in schizophrenia.  The main assertion of this paper was that pre-synaptic dopamine function is altered in schizophrenia.  However, in their conclusion they write, “It is not surprising that when antipsychotics are stopped, when there is nothing to suppress the dysregulated pre-synaptic system and when there is a potentially supersensitive post synaptic receptor system, then there is a high risk of relapse.” (underline mine)

My point here is that a major research group mentions in passing in a paper published in an academically rigorous psychiatric journal (and I get it that some readers consider that an oxymoron) the possible influence of super sensitivity on increasing the risk of relapse when neuroleptic drugs are stopped.   Yet those of us who raise this as a reason to moderate our use of these drugs are considered biased or scientifically naive.

Another point that I want to address is the issue of brain atrophy associated with long term exposure to neuroleptics. As noted in Anatomy of an Epidemic, Nancy Andreason’s group followed a group of people who came to them early on when they had first developed psychotic symptoms (Ho et al Arch Gen Psych 2011; 68(2):128-137). This was in the early 1990’s when researchers had thought brain atrophy was due to the psychotic condition. The thinking at the time was that early treatment with neuroleptics would arrest the process.

This is what led to the development of a number studies whose goal was to get people into treatment as soon as possible. The initial hypothesis of Andreason’s group was that individuals who remained on neuroleptics would have less brain atrophy but her study results did not support this hypothesis.  They found that the neuroleptics themselves had a direct effect on the extent to which there was brain atrophy.

What is interesting is that this finding has not become as much a part of the mainstream psychiatric narrative as the original hypothesis.  So to those who find it hard to believe that the drugs seem to cause atrophy independent of the psychotic process, I want to point out another study also reported by Whitaker. This is a study by Dolphe-Peterson et al.  (Neuropsychopharm, 2005: 30(9): 1649-1661). This group gave haloperidol to macaque monkeys. They found that the monkeys had and 8-11% decrease in brain tissue after 17-27 months on the neuroleptic drug.  The monkeys were not psychotic.

As noted above, in the early 1990’s there was a hypothesis that if neuroleptic drugs were started early the individual would have a better outcome.  The time between developing psychotic symptoms and starting medications is called the duration of untreated psychosis.  This will be the subject of my next blog.

 

45 COMMENTS

  1. About the long term effects of neuroleptics, I think there are issues that are not easily captured by studies. I’ll give an example from my own life.

    I wasn’t originally psychotic, I don’t think I’ve really ever been. My problems are/were more related to anxiety and depression. In any way, they decided to put me on neuroleptics (Abilify 15 mg and quetiapine 25 mg). I wasn’t even in very bad state in the beginning. The reports read that I sleep 7,5 hours a night and wake up bright. After four months of treatment, the reports say I sleep 14-16 hours night. Despite this amount of sleep, I was continuous tired. I had became very depressed and had developed very severe symptoms which were indistinguishable from the so called negative symptoms of schizophrenia. At this point they had invented that I had psychosis in the beginning and when I told about my problems, they said it’s maybe post-psychotic depression. After maybe eight months I already supposedly had schizophrenia! The drugs were perfectly mimicking the negative and cognitive aspect of schizophrenia. I answered with single sentences and was very passive, and my subjective experience was just like what others describe about the negative symptoms. At this point I started to fight against it, stopped the meds and “recovered”.

    So, one point is that if you start the treatment with high enough doses of neuroleptics and continue it for a long enough time, people won’t usually “recover” because they have their dopamine pathways blocked, so it often does not happen so that doctor and patient agree that hey, now you’re recovered and doing fine, let’s try to quit the neuroleptics. Instead they often start to interpret the effects of the drugs as symptoms of a severe disease and maybe keep adding other drugs to help with symptoms. This is one reason why, in my opinion, it’s often dangerous to even start with neuroleptics.

  2. By the way, when people quit neuroleptics and then fall to psychosis which may be more severe than the original one, there may be many other reasons to this besides dopamine super sensitivity, increase in D2High receptors, etc. I have no doubt that neuroleptics can mess up with dopamine issues, long use of most other psychoactive drugs (alcohol, benzos, opium, SSRI, etc) cause the brain to seek for a homeostasis in similar ways, thus the withdrawals.

    But there’s also, for instance, a more system level or neural network level way to look at the brain. The brains constantly create new connections, remove old ones and so on based on our experiences, thoughts, almost anything. For instance, one of the four dopamine pathways that is blocked by neuroleptics leads to our frontal lobes which is part of much of our higher level processing. Andreasen et al say that the use of neuroleptics will cause these networks to atrophy because, essentially, they are not used. This may in essence reduce many important things related to our higher level thinking, maybe control of one’s actions or thoughts, etc. If this atrophy is already well developed and then you take the drugs off and the brain starts to operate without the D2 blocking, maybe with the super sensitivity, then maybe you no longer have the “mental skills” to control that at all. The D2 super sensitivity doesn’t increase continuously over the years, but the system level problems will. Thus, it may be already very hard to quit after 10 years of high dose neuroleptic use. I don’t have any references for this specific case, but that’s in principle how the brain operates.

    You don’t have to even think about it on the brain level at all. Subjectively, if you eat neuroleptics for a long time, you tend to change in the way you behave. Many people who eat neuroleptics life quite simple life often at home, maybe browsing the net, not striving towards much anything, not developing their personality so much. Over time, the person’s habits and personality become transformed because of the drugs. If you then remove the neuroleptic, he maybe doesn’t anymore have the inner capabilities to handle the situation with D2High or lack of D2 blocking, a situation which he maybe could have handled earlier.

    Anyway, these were some thoughts about the long term use of neuroleptics. I haven’t seen much talk about this issue: if someone wants to use neuroleptics for a longer period but not for the rest of the life, then how long should he eat it so that it doesn’t become practically impossible? Three months? Two years? Six years?

    • Hermes, thank you for reminding us, that it’s not all about transmitters and receptors, but also about neural connections. Maybe these neural networks can be retrained and the important pathways strengthened quite fast, I don’t know. But these behavioural changes you describe would also mean that the person might miss important experiences of life in that time. It’s hard to imagine for me taking any 10 years of my life and replace them with 10 years of experiences under the influence of neuroleptic drugs. I think I would be quite a different person now.

    • I think it is important to realize that untreated psychosis may also lead to long lasting plastic changes in neural connections. One theory of the fixed delusions that often accompany chronic psychotic illness involves similar plasticity. Misperceptions of reality in early psychosis if they continue could coalesce into more permanent changes in connectivity underlying delusions. If we assume that both D2 blockade and psychotic illness represent shifts away from a preferred state, they will both result in longer term homeostatic changes in neural circuits.

      Perhaps Sandra will attempt to address this in her next post.

  3. Sandy,

    Yes, I entirely agree and believe that dopamine supersensitivity is one important factor in relapse. The brain and neurons usually try to maintain homeostasis, so when the D2 receptors get blocked, the neurons try to figure out a way around it. Actually, there may be several different ways they do this, such as in changes in dopamine turnover growing more D2 receptors and changing D2 receptors to a D2High state.

    ‘To explore potential mechanisms, we studied presynaptic and postsynaptic elements of the dopamine system and observed that antipsychotic failure was accompanied by opposing changes across the synapse: tolerance to the ability of haloperidol to increase basal dopamine and dopamine turnover on one side, and 20–40% increases in D2 receptor number and 100–160% increases in the proportion of D2 receptors in the high-affinity state for dopamine (D2High) on the other.’

    http://m.jneurosci.org/content/27/11/2979.full

    So, I think this adaptation may in part explain both treatment failure in long term and strong relapse when withdrawing.

  4. I am wondering about the dopamine supersensitivity hypothesis.

    What we are seeing when people withdraw from SSRIs and SNRIs too precipitously — even when they had no withdrawal symptoms while tapering or for months afterwards — is a recognizable supersensitivity to stress, evidenced by unprecedented symptoms described as anxiety surges, panic attacks, and a harsh sleeplessness over days or weeks.

    Anxiety surges in the early morning are a common feature, an exaggeration of the diurnal cortisol peak that normally gets us ready to wake up and start our days.

    As SSRIs and SNRIs have only an indirect effect on dopamine, it’s unlikely that dopamine alone is the culprit for these tardive symptoms. Rather, they’re due to a more generalized disruption of autonomic regulatory systems resulting in over-representation of alerting activity.

    These psychiatric drug withdrawal symptoms have a lot in common with endocrine withdrawal symptoms, see

    “….Interestingly, hormones with completely different physiological effects can produce similar withdrawal syndromes, whereas some of the clinical manifestations that are due to the chronic presence of high hormone levels or withdrawal syndromes are also observed with drugs of abuse. This review postulates that changes of the hypothalamic-pituitary-adrenal (HPA) axis and the central opioid peptide, noradrenergic and dopaminergic systems act as shared features in the pathogenesis of several endocrine withdrawal syndromes…..”

    They repeatedly advise slow tapering to avoid such symptoms.

    Although the authors are struggling to associate particular symptoms with putative hormonal mechanisms, which I believe is barking up the wrong tree (the right tree being a more generalized autonomic disruption), the overlap of endocrine withdrawal symptoms with what we know of antidepressant withdrawal syndrome is striking (see Figure 2 in the paper http://edrv.endojournals.org/content/24/4/523/F2.large.jpg ).

    In terms of autonomic disruption, there may be no real distinction between playing with levels of neurohormones and playing with endocrine hormones.

    I suggest that the supersensitivity psychosis seen after even apparently uneventful withdrawal of antipsychotics is parallel to the stress hypersensitivities very frequently seen in SSRI and SNRI post-withdrawal syndromes, but expressed as “psychotic” symptoms reflecting the particular neurological variability of those who came in hearing voices, etc.

  5. Sandy-Thanks for the post.
    Yesterday I attended Frontiers in Neuroscience and heard a presentation by Michael Sutton. He talked about how some mRNAs are translated at the dendrites. Apparently Fragile X is about having a non-functional protein which regulates protein translation at the dendrite. Sutton was talking about responses at a glutamate receptor, but the whole presentation was about how the both the pre-and post-synaptic neurons change in response to receptor blockade. As with most things in physiology, everything is about homeostasis. As I listened to Sutton, I wondered about changes in pre and post synaptic neurons given dopamine blockade. There is good evidence that these phenomena are quite real.

  6. In this case of presynaptic and postsynaptic neurons, we’re talking only of two neurons! There may be kind of a homeostatic thing going on with the growing of receptors and transforming them to D2High on the postsynaptic neuron, and also changing the amount of dopamine released by the presynaptic neuron on the presynaptic side neuron, etc. But this is just between those two neurons, you can’t directly see from it what happens in the human mind. It’s about how easy it is for the presynaptic neuron to ignite an action potential in the postsynaptic neuron. But this doesn’t very directly transform to real world. There’s maybe 10^11 of interconnected neurons in the brain, forming different brain areas and connection between other neurons and brain areas, with different areas working in different ways.

    So, the homeostatis thing that I mentioned referred to just those two neurons, now the whole brain. There are similar things going on with so many other parts of the brain and body, but it’s not the only rule. There are other kinds of rules too, many of which we don’t know yet. How the neurons communicate with each other, what each brain area does, etc.

    Sandra wrote earlier:

    “What puzzles me, however, is that I do not observe many people who need more neuroleptic over time to sustain the same level of “remission”. Now that I look for it, I see it more but there are many others I know who have done fairly well over many years on the same dose. I have worked in the same place for 20 years and I have known a good number of people for that entire time. Believe, me, I am paying attention now.”

    Yeah, I think that study told about people needing to go up in neuroleptics. In practice there may be some increases needed to the dose but then people find a steady dose (which they often keep on taking indefinitely). In this particular case, for instance, we’re talking about those two two neurons and there’s natural limits about how much they can change their functioning. They can grow only a certain amount of new D2 receptors, etc. When the neuroleptics block enough of D2, there’s just no more that the two neurons can do between each other. And often it’s not useful to look at just the two neurons, and especially it’s not useful to just think about the brains in the “brain in a soup of neurotransmitters” kind of a way. 🙂

    Sometimes a better way to think about the action of neuroleptics is on a more systemic level. Here’s “What Doctors May Not Tell You About Psychiatric Drugs” by Grace E. Jackson:

    http://www.whale.to/drugs/Jackson.pdf

    See Appendix E. That’s part of one of the dopamine pathways (neuroleptics block all four). The more there’s D2 blocking by neuroleptics, the less effective these pathways will work. Those arrows go towards the frontal cortex, etc. Neuroleptics will dampen the traffic in these pathways, in a way. The neurons in the dopamine pathways just cannot propagate the action potentials anymore, at least not as easily, depending on the dose.

  7. Hi Sandy. Thank you for the references to studies that don’t receive the publicity that they should. The information is critical even if the conclusions will not come as a surprise to followers of MIA. I’d like to know how this information affects your personal practice. Though not as effective as hyped, is the use of neuroleptics justified at all? If the use is justified, under what circumstances? Peter Breggin, Phil Thomas, Joanna Moncrieff have made public their views on how psychiatry should be practiced and they are specific on their views of neuroleptic use. You should too. You did give some indications in your previous articles on MIA. The title of this series led me to expect you would give a synopsis of the concrete consequences of your evolving point of view and of some elaboration on the rationale of whatever changes your are making.

    In a comment of mine in your previous article, I stated that you “supress” information. I regret having written that; I was wrong and I wish to take it back. I do believe there is a bias in how long-term brain atrophy of subjects using neuroleptics is being reported, however. In particular you refer to it as a risk. From my reading of the literature, I believe that the brain degeneration of diagnosed schizophrenics on such neuroleptic regimes is virtually certain as much as it is for Alzheimer’s disease. In Alzheimer’s disease, brain degeneration is not called a risk; it is a characteristic. Calling it a risk of long term neuroleptic use is a dangerous mischaracterization. Whether the cause is drugs or the inherent physiology of the cohort studied may not yet be determined beyond doubt but, as you note, the fate of monkeys is a good clue.

  8. I believe disruption of homeostasis, whatever the mechanism, is the key to how psychiatric drugs “work” (if they can be said to work). Some people interpret the disruption as beneficial, others adverse, and others don’t feel it.

    Disruption of nervous system homeostasis often has unintended consequences far from the therapy target, e.g. sexual disfunction.

    Once the entire organism accommodates to an artificial hormonal elevation, whether by psychiatric drugs or steroids, a second homeostasis is created that depends on continued application of the drug.

    As Hochberg, et al, say in Endocrine Withdrawal Syndromes http://edrv.endojournals.org/content/24/4/523.long#ref-166
    “Long-term adaptations to hormones may involve relatively persistent changes in molecular switches, including common intracellular signaling systems, from membrane receptors to transcription factors.”

    (The authors believe, erroneously, that rather than throwing another wrench into the works, antidepressants will ease the withdrawal transition. Why can’t they figure out these represent another excessive hormonal therapy?)

    Removal of the artificial hormonal elevation by drug withdrawal requires re-adaptation to yet another homeostasis tending toward normal functioning. As medicine is largely willfully ignorant of these iatrogenic effects, how long that might take — or how complete it might be — is a mystery.

    This is true in adult and neonatal psychiatric drug withdrawal syndromes. Depending on the discipline, that iatrogenic state of autonomic dysregulation is variously described as post-acute withdrawal syndrome, supersensitivity psychosis, kindling, and HPA axis dysregulation.

    What that final post-drug homeostasis might feel like probably varies among individuals. Given the influence of the drugs and the passage of time, it is unlikely that the nervous system reverts to factory settings. You can’t step in the same river twice, especially if it’s been flooded with artificial hormones.

    What this argues if, if drug intervention is required, the absolute minimum effective dosage be used to minimize disruption to the original nervous system homeostasis. The usual dosages in psychiatry are more like bludgeons to the nervous system rather than subtle corrections.

    • Yes, I agree pretty much. Brain and body is full of different types homeostatic systems which try to do their best to adapt.

      “What that final post-drug homeostasis might feel like probably varies among individuals. Given the influence of the drugs and the passage of time, it is unlikely that the nervous system reverts to factory settings. You can’t step in the same river twice, especially if it’s been flooded with artificial hormones.”

      The huge neural network of brain, consisting of maybe 10^11 neurons (give or take some), each connected to other neurons, is the core of what the brain does and how mind operates. The neurons communicate with each other by sending downstream connected neurons signals with the mechanism of action potential (neuron will “launch” in certain different biochemical settings). The signal may or may not cause a new signal in the downstream neuron. The neurons also constantly change their connections to other neurons, new connections may grow according to new stimulus and old connections may die because they have not been used, etc.

      For instance, neuroleptics do not regulate the general amount of dopamine in the brain. It’s not like a thermostat, it’s not a brain in a soup of neurotransmitters.

      The molecules of neuroleptics go between two neurons, part of this network, and prevent the signal going from one neuron to the downstream neurons. Such connections of neurons are part of important dopamine pathways in the brain, one of which goes to the frontal lobes (the same frontal lobes that they used to cut or destroy with lobotomy), related to a “higher” level of functioning. Another pathway goes to the limbic regions, a more “emotional” part of the brain. (Note that gave those adjectives as a general guidelines, it’s not simple like in saying that emotions reside here, etc. But you probably knew that already.) There are also other pathways, blocking of one which causes men to grow tits. But I digress. Some have said that it’s the blocking of the “frontal lobe pathway” which helps in psychosis, others claim it’s the “limbic pathway” which helps. In any way, you can see that it blocks many dopamine pathways, which are actually a huge number of neurone connected to each other and sending signals to each other.

      When you insert the molecules of a neuroleptic into the brain, they will go between the neurons in these pathways and prevent the neurons from signalling to each other. The brain atrophy thing is basically because when the connections/neurons won’t be used for a long time, they will die away. If there is such a thing as a homeostasis for the whole neural network (or mind?) as a whole, it will have to get used to the new reality where the dopamine pathways are not so easily used. With time and living in this new depleted state, the neurons in the brain will grow others kinds of connections (paralleled by a new kind of a “slower lifestyle”, etc).

      If the neuroleptic is given for a long time in a sufficiently large state, taking the drug away will not cause the neural network to return to its original state automatically. Actually every experience changes the network and you can’t ever return to the previous network (that’s how the life is), but with neuroleptics especially the change can be pretty drastic. The old connections and neurons are dead and they have been replaced by some new connections. Taking he drug away will not grow back the old connections or neurons nor will the new connections go away.

  9. People, including doctors and psychiatrists, seem to concentrate only on how antipsychotic medication affects dopamine supply in the brain. They totally ignore the noctious effect they have on histamine and adrenaline receptors in the brain. Because they disrupt histamine supply, people get sleep problems as well as metabollic problems and suffer from constant hunger. Histamines regulate appetite and play a role in sleep cycles. Antipsychotics also disrupt adrenaline supply, hence all the cardiovascular problems and insulin problems. The patients get blaimed for all these. I think doctors who prescribe antipsychotics should go back to their endocrinology books. I did just that and was surprised.

  10. Hi Sandra,

    Thanks for the great review on neuroleptics. In one your future blogs, I’d be curious to hear your opinion on the use of anti-epileptics and other drug classes (as well as supplements like N-acetyl cysteine and omega-3 fatty acids) as tools for relapse prevention. There has been quite a bit coming out in the last few years on the role of the stress cascade, HPA axis dysfunction, hippocampal atrophy and their resulting rises in glutamate as the biochemical precursors to acute psychosis. This is currently being looked at in the context of ‘prevention of conversion to psychosis in the prodromal stage of the first episode’ but I have wondered recently if these same mechanisms are involved in relapse and could provide some insight into alternatives to the current paradigm of ‘maintenance with neuroleptics.’

    Alexa

    • I think that the things that you listed (HPA axis, hippocampus, glutamate, etc) are often important factors in depression, psychosis and so on. Prolonged stress, etc, can lead to psychosis on some people. The thing is that neuroleptics don’t generally help even in getting the stress cascade or HPA axis in control, it just shuts down, for instance, the frontal lobes. It shuts down the “end results” but not the factor which caused them in the first place. So people are left inside their mind in great anxiety/depression/negative symptoms, they just took away the outward signs of aggression, etc, and perhaps many parts of the higher human mind.

      I have found a system of almost daily heavy walking in the woods, zen meditation, healthy diet, and other similar practices to be helpful for me, but I can’t generalise my practices for other people. Omega-3 may help but it may not if you otherwise don’t eat in an healthy way (see inflammation, etc).

      Even the traditional Chinese/Taoist treatment, though they didn’t have any science, had a better general idea. They incorporated body, mind, food, exercise, meditation, chi kung and basically everything between Yin and Yang to their system. Now we’re trying to nuke down some specific receptors and see what comes out.

      • Hi Hermes,

        That’s a great explanation of it. Elevated dopamine is the end result of a cascade. If you want to do prevention/maintenance of psychosis, the focus has to be on the problems upstream, not on beating down dopamine levels continuously.

        The cornerstone to my approach to relapse prevention is stress reduction, as the first step in the domino effect that leads to active psychosis is elevated glucocorticoids (particularly avoiding the worst stress culprit ‘expressed emotions!’). I also integrate NAC and Omega 3’s which have shown to have some level of protective factors against transitioning into active psychosis. I use a dietary approach as well that focuses on supplementation of key minerals, stabilization of blood sugar levels, and anti-inflammatory foods. Plus a whole lot of insight meditation/positive thinking/self-awareness practice.
        Take any one of the ingredients out, and I start to unravel, take two or three out and I am gone in a matter of weeks. Of course I try to explain this to my doctors, and they think this is all a bunch of new age rubbish (“the reason your symptoms are coming back is because you are not taking your anti-psychotics!”) Then I typically ask them how many of their ‘medication compliant’ SZ patients have been continually full time employed, law abiding and tax paying citizens, and are in great physical condition? There is no way to run a multi-year double blind placebo trial of this, so they will never believe it. The proof is in the pudding, or so they say!

        Alexa

  11. Thanks for posting all of this and for “translating” and summarizing all this research. You have offered a great resource for people in practice and those who occasionally need to reference the formal literature in their efforts to encourage conscientious care. I’m glad that people in the field are beginning to realize that the standard treatment protocols may actually be quite harmful.

    I am going to bookmark this! Thank you!

    (It really is a big experiment, isn’t it? The research certainly indicates that.)

  12. One more thing. Note that I’m not trying to argue, merely trying to find some new ways to look at this issue.

    The Jin et al study found no significant change in psychopathology with the four atypicals (compared to what?). I suppose this is the same study that I read before. In any case, the people in that study were 40 or older. The first psychosis often comes with a young age. The experience and the life leading to that event and the hospitalisation was perhaps quite traumatic.

    Joanna Moncrieff gives some typical examples of experiences from a website in her slides. You can see the same kind of reasoning everywhere. The person had some distressing experiences at a young age and neuroleptics took the worst edge off. They often admit the meds are giving them problems and they live a very passive life, don’t work, can’t concentrate, etc. But they still believe the drug is keeping their “beast” in chains. So they take it for the rest of their lives, combined with maybe two other drugs.

    • “it makes me feel like a veggie, but that was better than what I was going through and it kept me out of the hospital” (olanzapine)
    • “Although I felt very well, I felt as if I had absolutely nothing to talk about. I kept wondering about whatever [it] was that had been so interesting during most of my life that I had suddenly lost… But I was very much in contact with reality and for that I was thankful” (haloperidol)

    They themselves think that they need to eat the drug, or else! and they’ll keep on taking the drug for the rest of their lives, never really improving but living some kind of a stabilised life. They often have had some strong experiences at an early point in their life and they’ll absolutely take the drug that they think will prevent it happening again indefinitely, even though it makes them feel like shit and gives other problems. And I’m not saying they should taper down, I’ve seen many people like that and I don’t know if it would be a good idea to try to taper them down anymore if they don’t want it. ?

    The official guides in Finland say that after psychosis, the patient should be treated for 2-6 years and if the patient has “recovered”, then the medications can be stopped. But the patients never “recover” because their dopamine pathways and other receptors are chronically altered, and at that point they already have at least two other drugs in their system and no one wants to change the drug induced homeostasis. So they’ll go like that to the rest of their shortened life. People are constantly told that neuroleptics or other drugs will be taken away if they recover, but that never happens in practice. The only times people practically get off neuroleptics is when they themselves for some reason or another decide to do it , and it’s sometimes done with help from officials, sometimes not.