How little we really know about psychiatric drugs

STI from amazon

In this blog I reflect on what has and has not changed in the field of psychiatric drug treatment in the years between the first and newly published second edition of the Straight Talking Introduction to Psychiatric Drugs.

The second edition of my Straight Talking Introduction to Psychiatric Drugs has just been published 11 years after the first. Some progress has been made in that time. Services for people with early psychosis now routinely prescribe low doses of antipsychotics and frequently support people to come off them.  The UK government funded the RADAR trial that is evaluating a gradual programme of antipsychotic reduction and discontinuation in people with long-term psychotic disorders or ‘schizophrenia’ and several other trials of this sort are going on around the world involving people with a first episode of psychosis. This research is being conducted by psychiatric researchers who recognise that psychiatric drugs can be harmful, and that their use needs to be minimised. From my experience, most psychiatrists are now aware of the evidence that long-term antipsychotic treatment causes brain shrinkage (although many are also enamoured with the misleading studies on antipsychotics and mortality produced by the Finnish group, which have been helpfully deconstructed in this blog by Robert Whitaker). The fact that antidepressants can cause severe and prolonged withdrawal effects has now been widely recognised, although not without the concerted efforts of those who have suffered these problems.   

The drug-centred model of drug action (the idea that psychiatric drugs change normal brain functions and mental states, and that these changes inevitably interact with the ‘symptoms’ of mental disorders) is now established in some circles. It is recommended in the Power Threat Meaning framework and other convention-challenging texts and textbooks. I know many psychiatrists who feel that, as well as making sense of the evidence, it provides a useful guide for a cautious and collaborative approach to the use of psychiatric drugs. Yet mainstream psychiatry has ignored it and presses on with business as usual. Prescriptions for antidepressants continue to rise and money is still poured into research trying to locate the specific brain abnormality that produces disorder X or Y. Despite the failure of this research to provide any conclusive findings, clinicians and much of the general public remain bedazzled by the disease-centred model of drug action – the idea that drugs work by tweaking some underlying brain abnormality, sometimes specified as an imbalance or ‘dysregulation’ of particular brain chemicals.  

The few psychiatrists who have engaged with ideas about models of drug action take different positions. As I discussed in a previous blog, some leading academic psychiatrists have re-asserted the disease-centred view (though sometimes denying that this is what they are doing). Others argue that most psychiatrists have an ‘outcome-based’ understanding of drug action. This means they prescribe drugs because research has shown that they can be helpful, with no commitment to an explanation of why that might be. We do not ingest a drug or recommend others do so without having beliefs about what it might do, however, and if psychiatrists provide no other explanation, then they are implicitly endorsing the disease-centred model of drug action. This is how they are generally understood nowadays, at any rate.

The drug-centred model obviously touches a nerve among mainstream psychiatrists. This is because it suggests that the way drugs ‘work’ when prescribed for mental health problems is different from what drugs are doing in other areas of medicine. Those who oppose it are keen to defend the medical identity of psychiatry. It is ironic that the drug-centred model demands a much fuller understanding of the action of drugs on every aspect of physical functioning, mental states and behaviour, compared to the blinkered approach of the disease-centred model that focuses primarily on the site of the presumed disease or abnormality. The drug-centred model is, therefore, a much better basis for a properly scientific, medical training.

Some important research has been published since I wrote the first edition. Further follow-up studies show that people who take long-term antipsychotic treatment for psychotic episodes have worse outcomes than those who do not (e.g. Moilanen et al 2016; Wils et al, 2017). Most importantly the follow-up of participants in the Dutch randomised trial confirmed that this is not simply a reflection of the more severe profile of those who end up on long-term treatment, but likely to be due to the drugs themselves (Wunderink et al, 2013). More recently, a small, but well-conducted study from Australia showed that antipsychotics had no advantage over placebo in people experiencing a first episode of psychosis who were receiving high quality psychosocial support (Francey et al, 2020). These studies fundamentally change the way we should approach the use of antipsychotics. Combined with the mounting evidence that these drugs cause serious effects on the brain and other body systems, they underline the need to use antipsychotics as sparingly as possible, and to try to help people come off them where possible. Certainly some psychiatrists have taken this on board.

I have learnt a lot in the last 11 years – much of it from people who have had the courage to share their experiences of using psychiatric drugs and thereby publicise effects that official research has barely tried to address. Perhaps most importantly I have come to appreciate how little we really know and understand about what psychiatric drugs do, especially in the long-term, and the terrible consequences this ignorance can have.

Take the example of benzodiazepines. We understand the mechanism of action of benzodiazepines better than most drugs. They produce their relaxing effects through modifying the actions of the natural neurotransmitter known as GABA. But we do not know exactly how they affect the GABA system, nor how these or other actions produce the range of disabling withdrawal effects that can occur. We also do not understand the mechanisms underlying the cognitive impairment that benzodiazepines appear to cause both during and after withdrawal from long-term use (Crowe & Stranks, 2017). Most worryingly, as I highlighted in a previous blog, we have known since at least the early 1990s that some people develop new medical conditions or symptoms while coming off the drugs (including tinnitus and restless legs, for example). These can last for months afterwards, possibly longer, suggesting the drugs have permanently altered the brain in some way. Yet we have no idea what benzodiazepines are doing to the brain that might result in these persistent and often disabling symptoms.

Unfortunately, neither this data, nor the evidence that antipsychotics can cause permanent neurological damage (tardive dyskinesia), seem to have made us any more wary of launching new drugs without good data on their long-term effects.

The SSRI ‘antidepressants’ flooded onto the market in the 1990s. At first they seemed relatively innocuous. They are certainly safer in overdose and far less sedating than their predecessors, the tricyclic antidepressants. But then, as I described in my previous blog, withdrawal effects started to come to light, and more recently persistent sexual dysfunction.  These effects suggest these drugs too are changing the brain in significant ways that we do not understand, and that may take a long time to normalise when the drugs are stopped.

Esketamine is one of the latest chemicals to be aimed at people who are looking for relief from chronic misery. The story of how esketamine was licenced illustrates why we have so much propaganda and so little data on the safety of psychiatric drugs. The FDA and other drug regulatory agencies were easily persuaded by Janssen to relax their criteria for establishing efficacy and did not express particular concern about the natural deaths, driving accidents and suicides that occurred during or shortly after treatment. They had little curiosity about withdrawal effects and other long-term complications.  

If drug regulatory agencies are not interested in data on immediate and long-term safety, then clearly there is no incentive for drug companies to produce it. Government funding agencies are also focused primarily on establishing the effectiveness of interventions, rather than exploring their harmful effects. Hence it is left to users themselves to highlight the adverse effects of drugs – some of which will only come to light after years of use and after thousands, maybe millions, of people have been exposed.

I am not opposed, in principle, to the use of psychiatric drugs. I believe, as I say in the book, that ‘some psychiatric drugs do help some people in some situations’. Having said this, I think it is likely that the vast majority of people who take psychiatric drugs derive little or no benefit from them, and yet are susceptible to all the harms they can induce. It is people’s right to know how little we really know about these drugs. People should be informed that the story they have been told, implicitly or explicitly, about having an underlying chemical imbalance that drugs can correct is just that – a story – with very little evidence to back it up. They need to know that these drugs are doing things to the brain that we do not understand properly, and people should be aware how little research there has been into the long-term effects of the drugs, and the difficulties of coming off them. I hope the second edition of a Straight Talking Introduction to Psychiatric Drugs will enable people to make better informed decisions about whether to start or continue these sort of drugs.

15 thoughts on “How little we really know about psychiatric drugs

  1. I have taken many antidepressants, plus lithium. Dr. Moncrief, research shows that lithium stokes the immune system against the virus. I was on full dose lithium for 30 years, didn’t get flu shots, didn’t get viruses. Then my kidneys got weak. But I’m back on 300 mg.

    I take a small dose of venlafaxine daily, but what with my CBD intake, I doubt that I need an additional antidepressant.

    Retired neuropsychologist, 18 years of looking over the shoulders of psychiatrists.

  2. Thank you for the blog It confirms what I have seen for many years. In aasddition I will add that often the diagnosis, at least here in Norway, do not meet the ICD10 criteria for the diagnosis schizofrenia. This means that may be many patients with the diagnosis are not schizofrenic at all. Beeing treated with ‘antipsycotic’ drugs they often become both dizzy and withdrawn, often diagnosed as schizofrenic symptoms. This means MORE DRUGS.

    • There’s schizophrenia, schizoaffective disorder, and bipolar disorder. Bipolar disorder is sometimes accompanied by psychotic symptoms. However, having participated in diagnosis of hundreds of patients in my hospital practice, I did not have difficulty distinguishing the three conditions. Schizophrenic patients are often somewhat depressed, but do not show marked mood swings. Schizoaffective patients do show mood swings. Schizophrenic patients, even paranoid schizophrenics, show characteristic cognitive deficits. They may show prodromal symptoms even in early childhood. Bipolar and schizoaffective conditions never start in early childhood. I saw three cases that started after age 7. And by the way, schizophrenia does not begin after about age 32. Look for another diagnosis. Organic psychosis, as used to be the case with untreated syphilis. Huntington’s disease. And schizoaffective.

      Big Pharma is often recommending new antipsychotics for unstable bipolars, and these can have nasty side effects. Cannabidiol (CBD) is worth adding before trying antipsychotics.

  3. Thank you for your excellent work in this area. The drug-centered model of drug action is an important piece in understanding what has gone wrong in psychiatry. Yes, people have been fed a story, and but it has become an ideological fact. The question for me (psychiatrist since 1989) is how these ideas have gained and maintained such a hold on the profession and the public. We need to understand how these drugs ‘work’ in a societal sense even when they are actually not very effective.

    • I don’t think it’s much of a mystery why the model took hold of the profession ($$$, prestige), but the public generally follows the lead of societal “experts”, for better or worse.

      • Leave off the pseudo religious criticisms. Has anyone noticed the recent article showing that lithium stokes the immune system against viruses? I’m not surprised. On full dose for depression for 30 years, I never got colds or flu. A little lithium has many other benefits, as does a little CBD. The latter can protect the lungs during a covid19 attack.

  4. Thank you for your excellent work in this area. The drug-centered model of drug action is an important piece in understanding what has gone wrong in psychiatry. Yes, people have been fed a story, and but it has become an ideological fact. The question for me (psychiatrist since 1989) is how these ideas have gained and maintained such a hold on the profession and the public. We need to understand how these drugs ‘work’ in a societal sense even when they are actually not very effective.

  5. I think another cultural force involved is latent Calvinism-Puritanism; Anglo-American societies don’t like to admit that people need to feel good to some extent, so they need to invent disease categories to justify a “medical” intervention (instead of just admitting people need relief).

  6. Yes, you are correct. I was first diagnosed MDD at 19. I took medicine for about 2 to 3 months. But my parents threw it away coz I tried to OD myself with the meds. And then I basically force myself to function and finish my degree due to guilt I felt for my parents and support from my uni friends. At then at age 26, again MDD. Took medicine for about 2-3mths. Then I was depressed for a year then force myself to work. Found my hubby I guess he was my support friend. Only when I was 33, they diagnosed me with Bipolar as they caught me on during my mania episode. Took medicine for 3 years, then I decided to quit medicine fought with my hubby, psychiatrist then at age 36 I was in major episodes again. Forced to be hospitalised. Now I’m off medicine for about 5 years. I am in normal neutral episode. I notice I always face major epi every 7 years when Im off medicine. But when I was full on medicine it relapsed within 3 years. I also know what triggering factors that caused me to experience these 4 major episodes. I notice that I can function well without the medication, only with my support system family and friends. Why cant psychiatrist focus on more therapy, support group, listen to your trigerring factors, change of lifestyle. No substance abuse, more scheduled routine and gradually make these people off the medicine.

    • Low dose lithium and cannabidiol. A little lithium potentiates antidepressants and boosts the immune system against viruses. Cannabidiol is cheap, antidepressant, anti-inflammatory, and strongly fights some cancers. You can get low dose lithium from Amazon as lithium orotate, and CBD every where. Google!

      • The things is why I need lithium when my mood is stable? And why do I need cannabidiol when Im not depressed? Yes, medication helps during those major episodes, but when I am in normal human being and functional. Why I need the medication? Off meds for 5 years, (2 years on and off,mostly off. 3 years fully stop )relationship improved significantly within this 5 years. The underlying was I never confront my childhood trauma, stress factors, and all this major episodes occured during I was on substance abuse. Not going to elaborate what kind of substance abuse. The things was, I wasn’t even like using substance everyday. At 19, after trying like 4 to 5 times. At 26, after trying 2 times. At 33 only trying one time during holiday. And at 36, due to the medicine I took which I dont remember the name. All this happened with substance abuse and underlying issues like typical stress factors during those age. Of course, as someone with Bipolar, i have to be responsible too. Thats why I said managing my symptom with changing lifestyle, therapy and support system. Why stay on meds, when can function without one?

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