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Psychiatric Drugs: Fact or Fiction
- Hugh Mann (9 June 2009)
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Big Brother doesn't always listen
- Zekria Ibrahimi (11 June 2009)
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By changing intracerebral supply/demand.
- Richard G Fiddian-Green (11 June 2009)
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Antipsychotics are mostly antioxidants
- Edmond V O`Flaherty (17 June 2009)
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Altered States: Drugs and Dualism.
- Ian C Reid (28 June 2009)
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Do psychiatric drugs work differently in people with psychiatric diagnoses?
- Michael Albert (2 July 2009)
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What are psychiatric drugs?
- Alistair G. Stewart (2 July 2009)
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Antipsychotics and non specific GLUT blockade
- PRASANNA N. DE SILVA (6 July 2009)
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Explanations to patients about pharmacology should encourage concordance with medication.
- Mark Agius, Sophia Ulhaq. FY1 Doctor , Bedford Hospital MK42 9 DJ (21 July 2009)
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Understanding Psychiatric Drugs as Psychoactive Substances
- J Moncrieff, David Cohen (5 August 2009)
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Hugh Mann, Physician Eagle Rock, MO 65641 USA
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Psychiatric drugs ostensibly help patients by correcting imbalances in neurotransmitters, such as dopamine, serotonin, epinephrine (adrenaline), and norepinephrine (noradrenaline). Unfortunately, this simple and straightforward theory doesn’t translate into practical results. Instead, psychiatric drugs tend to hurt patients by creating new neuropsychiatric problems, which complicate and aggravate pre-existing psychiatric problems. I suggest that the mechanism of action for psychiatric drugs is a folie à deux between doctor and patient, which has been cultivated by Big Pharma, whose economic might exerts enormous control over medical schools, medical societies, medical journals, and the media. Competing interests: None declared |
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Zekria Ibrahimi, psychiatric patient Coombs Library UB1 3EU
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For any psychiatric patient, entering the mental health system can feel as bad as a combination of 1984 and Brave New World. Big Brother is always watching, and now has the Community Treatment Order in addition to the Section 3. And anti- psychotics are indiscriminately doled out like the soma suggested by Aldous Huxley (1). The patient can believe that he or she is just being trampled on. His or her views are not always considered as equal to those of a CPN (Community Psychiatric Nurse) or Consultant. The BMJ article by Cohen and Moncrieff points out sadly that the 'subjective state' induced by anti- depressants or anti- psychotics has not been properly researched (2). The cold emphasis is on seemingly 'objective' rating scales and baffling statistical methods that do not have any essential empathy with the mind of the patient within. How do I experience my own drug, aripiprazole? This is a third generation partial dopamine agonist. I have taken other anti- psychotics, mostly olanzapine. What the average anti- psychotic induces is 'emotional indifference, what David Healy has described as 'a 'Who cares' feeling' (3). David Healy, the same as Joanna Moncrieff, seems to be taking a middle line between the corporate/pharmaceutical/ chemical imbalance model of schizophrenia, and the anti- psychiatrist campaigning stance of a Robert Whitaker (4). It is the 'emotional indifference' onto which, I believe, patients latch when they take anti- psychotics. My drug slows me down and demotivates me. The schizophrenic structure I have constructed for myself no longer becomes so relevant. The anti- psychotic is not curing anything, but is rather establishing an artificial drug- induced condition of its own. My grim experience of schizophrenia is that of being overexcited to the point where I become a danger to myself and others. Everything is an apocalyptic crisis, every comment is directed against me, everyone is the enemy. I talk to myself a lot, and I even shout. I grow so agitated that I long to take that yellow crunchy tablet out of its silver foil. Shockingly, some of the anti- psychotics are turning into drugs of abuse (!). Quetiapine is being pushed by dealers as 'Susie- Q', as a downer after something like cocaine(5). The anti- psychiatric model of the drugs being weapons to put down patients is oversimplistic. Patients can welcome even a depot because they are scared of what they would do without any treatment. They do not want to be so sexually free as they had appeared, they might be reckless with money and fall into terrible debt when they relapse, they neglect themselves, they feel eaten into by guilt and shame. The problem is side- effects. Olanzapine just knocked me out as an excessive sedative. There are four dopamine pathways in the brain- the mesolimbic, the mesocortical, the nigrostriatal, and the tuberoinfundibular (6). A conventional anti- psychotic will block all of these. But only the mesolimbic is associated with the (positive) symptoms of schizophrenia. A dopamine antagonist would theoretically worsen the negative symptoms of schizophrenia, in the mesocortical route. Obstructing the nigrostriatal and tuberoinfundibular pathways provokes extrapyramidal symptoms (EPS) and hyperprolactinemia, respectively. So, even under the dopamine theory of schizophrenia, a conventional anti- psychotic would do harm in three out of four of the available pathways. And there are potential autonomic adverse effects throughout the nervous system. It would appear that anti- psychotics have evolved from a multi- receptor drug, Chlorpromazine, the initial anti- psychotic, to a 'selective conventional' drug like haloperidol, then to a second generation serotonin and dopamine antagonist atypical, to a partial dopamine agonist such as aripiprazole. The older drugs (particularly haloperidol) produced movement disorders, worst of all, tardive dyskinesia; the newer ones have metabolic difficulties. My opinion, which is far from expert, is that the conundrum of hitting so many dopamine pathways in the brain cannot be solved without a partial agonist approach. But a drawback with aripiprazole is akathisia. The dilemma for psychiatric patients is the Big Brother syndrome. They are always under gnawing surveillance, they must accept the not always kindly paternalism of the psychiatrists, they have imposed on them drugs about which their own views are not sufficiently considered. There is Big Brother, grey- haired and overbearing, ordering us about as though we are brainless infants! Big Brother doesn't always listen. REFERENCES: (1)Doctor's Orders. Liz Miller. Mental Health Today. April 2009. Pg. 34. (2)How do psychiatric drugs work? Joanna Moncrieff. David Cohen. BMJ 2009;338:b1963. (3)Psychiatric Drugs Explained. David Healy. Pg. 12. (4)The case against antipsychotic drugs: a 50- year record of doing more harm than good. Robert Whitaker. Medical Hypotheses (2004) 62, 5-13. (5)Liz Miller. Op. cit. (6)Stahl's Essential Psychopharmacology. S.M.Stahl. Cambridge. Third Edition. 2008. Pg. 330-337. Competing interests: None declared |
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Richard G Fiddian-Green, FRCS, FACS None
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Alen J. Salerian, Nansen G. Saleri, and Justin Salerian "reviewed the studies on core body and brain temperature’s influence on mood, mood disorders and their treatment. Our review suggests the majority of therapeutic strategies [pharmaceuticals] against mania are hypothermic while thermogenic strategies are used to combat depressive disorders"(1). The differences in mood and behaviour associated with the menstrual cycle in women and between patients that are hypothyroid and those that are hyperthyroid are consistent with this hypothesis. Temperature is a measure of metabolic rate and hence of ATP utilization. The inference is that therapeutic stategies that are hypothermic reduce metabolic rate and those that are thermogenic increase it. There is, however, another variable to consider the pH which has related biochemical effects. In so far as this might be a reflection of the balance between ATP utilization and synthesis drugs that are thermogenic might either increase or decrease the availability of ATP if the rate of utilization begins to exceed the rate of synthesis. The converse applies to hypothermic strategies. Particularly important might be the cyclical changes in brain temperature and pH. Hence the suggestion that mood and behavioural disturbances might be more effectively managed by monitoring and even changing and pacing changes in intracerebral temperature and pH by sterotactic means (2). 1. Brain temperature may influence mood: A hypothesis Medical Hypotheses (2008) 70, 497-500 By Alen J. Salerian, MD, Nansen G. Saleri, PhD, Justin Salerian. 2. Richard G Fiddian-Green Stereotactic modulation of intracerbral energetics. http://www.jnnp.com/cgi/eletters/75/7/1019#180, 21 Jun 2004. Competing interests: None declared |
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Edmond V O`Flaherty, GP Gleneagle Clinic,Greygates,Mount Merrion,Co Dublin
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Most antipsychotics are antioxidants, with the notable exception of Geodon (Ziprasidone). However many natural substances are antioxidants too and in my experience if they also are used patients need far less antipsychotics in the long term. This makes them much more alert and less prone to diabetes and the numerous other side effects of these drugs.If you were to analyse the biochemistry of a paranoid schizophrenic you would expect to find high serum copper and low plasma zinc for example.If you give zinc- typically about 50mg- lower intake of copper from the gut results. As copper is used in the body in the process of converting dopamine to noradrenaline this will reduce this production and in turn this will give the patient less adrenaline. Used in association with niacinamide or niacin at about 1.5g bd,B12,folic acid plus antioxidants such as vit C and E you can expect these patients to see a reduction in depression by months 3-6 and anxiety by months 7-8. By 12 months they are often quite well with the paranoia and voices gone.I enjoy psychiatry much more now that so many of my patients are getting better. Two other points I would like to make. About 4% of those with a history of psychosis have coeliac disease and if treated by a gluten-free diet they get well. I noticed that the antipsychotic quetiapine (Seroquel) made many of my patients quite drowsy. I found out that that is because it has a strong affinity for the histamine receptors and if they take 120mg fexofinadine (Telfast) the drowsiness is much improved to the point of being able to work. Competing interests: None declared |
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Ian C Reid, Psychiatrist University of Aberdeen AB25 2ZH
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The notion of a “drug centred model” is hardly novel. But it demands a rather naive dualism to focus exclusively on drug treatments in psychiatry. Consider instead an “intervention centred-model” and apply it to all ‘medical’ treatments in the context of general physiology: the ‘model’ transfers happily to the effects of interventions as diverse as beta-blockers, aspirin, surgical procedures and cognitive therapy. All set up complex physiological states, some of which map to ‘known’ pathological mechanisms, some of which clearly do not, and some which are presently unfathomed (including those Rumsfeldian things we don’t know that we don’t know about). The authors are quite right to highlight the shortcomings of some of the early theories surrounding the aetiology of psychiatric disorders, such as the monoamine hypothesis of depression - but this is something of a 'straw man' argument: the hypothesis has long been superseded. In any event, it does not follow that current psychiatric drug therapies cannot, in principle, interact with pathological processes. It is one thing to exercise circumspection about how psychoactive drugs ‘work’ – quite another to imply that they can’t, simply because aetiopathological accounts are incomplete. Unless, of course, one harbours a blanket antipathy to the notion that physiological accounts of mental states can be coherent – but that is another issue, hiding with a few other trojans inside the article. Competing interests: Has worked both as paid and unpaid consultant to government; mental health charities; NHS; pharmaceutical industry; voluntary organisations. |
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Michael Albert, 2nd year medical student Nottingham University Medical School, Queen's Medical Centre, Nottingham NG7 2UH
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Moncrieff and Cohen’s view of ‘How do psychiatric drugs work?’ was amusing. Out of the 20 references, 8 are by the authors themselves, of which one is a book and the other is a book chapter. I wonder whether this is a very scientific way of doing things. They cite two articles published in 1960 to argue about the mechanism of action of psychotropic drugs. This was within a few years of the first psychotropic drugs and the first neurotransmitters were identified i.e. when psychopharmacology was a very newborn speciality. When telephone was invented, it was claimed that every American city needs a telephone. It will be inappropriate to use this statement to restrict the use of phones. The authors argue that psychotropic drugs act by causing sedation, activation, psychomotor slowing and altered sense perception. Valproate and carbamazepine are used to treat bipolar disorder as well as epilepsy and migraine. Duloxetine is used to treat depression as well as neuropathic pain and stress incontinence. Propranolol is used to treat anxiety as well as hypertension. I wonder if the authors consider all therapeutic effects of these drugs to be due to sedation or stimulation, or they act differently in people who have psychiatric diagnoses. I found it a very interesting exercise to identify the number of occasions the different cognitive distortions e.g. selective abstraction and overgeneralization are manifest in this article. Reference Moncrieff J, Cohen D. How do psychiatric drugs work? BMJ 2009; 338:b1963 (27 June) Competing interests: None declared |
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Alistair G. Stewart, Consultant psychiatrist Royal Oldham Hospital OL1 2JH
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Moncrieff and Cohen have delivered a very timely corrective to the way we often think about drug treatments, although they focus too narrowly on psychiatry and on the roles of the pharmaceutical industry and the biological model of mental illness, influential though these are. They also overlook the fact that an important, even though currently not dominant, aspect of the medical tradition is scepticism and a critical attitude to the effects of proposed treatments. All patients, all people, all of us hope to find a cure for our ills and illnesses which will not be too distressing or painful itself. Drug companies are driven overwhelmingly by the search for profit, so their sales pitch will always be that they can give people what they want (that is the proportion of the world’s population who have the means to pay for it). Doctors’ motivations are complex. We want to do what our patients are seeking from us. It helps our self-esteem if we feel we are doing this. At the same time our education and experience, if reflected on, tell us that things are not so simple and that relief from illness and disability comes at a cost, in terms of the unwanted effects of treatment. We try hard, and with some success to improve treatment so that they are both more effective and less harmful, but much of the time this is an aspiration, not a reality. We need to maintain a separation between the process of diagnosis, which itself is always approximate, from the choice of treatments, which are even more approximate. Otherwise we continue to fall into the trap of thinking that all diagnoses point specifically to particular “targeted” treatment, or even, with encouragement from the drug companies, into the trap of creating new diagnoses to fit already existing treatments. A distressingly common bad practice, especially in psychiatry, is that of reading off a diagnosis from the drugs which someone has had prescribed for them. The term “side effects” should be abandoned. Drugs simply have desirable effects and undesirable effects. The British National Formulary is a very useful tool, but it perpetuates the idea that drugs can be classified by a particular selection of their effects, either clinical or physiological, when it might be better to classify them by their chemical structure. Just as it is erroneous to lump certain drugs together as “antidepressant” and other as “antipsychotic”, so it is misleading to talk about “psychiatric drugs”. Amitriptyline, sodium valproate, benzodiazepines and propranolol all have uses in the treatment of mental disorders and in the treatment of other common non-psychiatric conditions. Moncrieff and Cohen over-simplify by saying that psychiatric drugs have been developed deliberately to “fit” particular diagnoses. In fact the prototypes of what became known as “antipsychotics”, “antidepressants” and “mood stabilisers” in particular chlorpromazine, isoniazid and lithium, were all discovered serendipitously and began to be used and developed further because they were found to have beneficial effects on some of the symptoms suffered by people with mental disorders. Therapeutics remains, as it has always been, the judicious use of poisons. We try to increase the judiciousness, and sometimes we succeed in this. Patients are frequently ready to put up with unpleasant or unwanted effects of drug treatments because they feel these are outweighed by the beneficial effects. In general, the more serious the illness, the more discomfort we are willing to accept as part of the treatment. Many mental disorders have very serious consequences if left untreated. This does not even mean that treatment should necessarily include any drugs, simply that both we and our patients should always acknowledge that there is always a risk benefit equation. Competing interests: None declared |
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PRASANNA N. DE SILVA, CONSULTANT PSYCHIATRIST Whitby Hospital (Tees, Esk and Wear Valleys NHS Foundation Trust), Springhill, Whitby YO21 1 D
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Further to the article by Moncrieff and Cohen, it is perhaps worth noting that most anti psychotic agents (both typical and atypical) produce blockade of cell membrane bound Glucose transporter (GLUT) proteins -in the brain (GLUT 1 and 3) and peripherally (GLUT 4). The stronger GLUT blockers (Clozepine, followed by Olanzepine, Quetiapine and Risperidone) are also the drugs deemed most effective clinically. Peripherally, it is likely that GLUT 4 blockade contributes to systemic hyperglycaemia and weight gain (see Dwyer and Donohoe). Furthermore, GLUT blockers probably reduce the metabolism of brain ‘hot spots’ by reducing glucose uptake, for example those associated with hallucinations (Hoffman et. al.). Therefore, anti psychotics works in a similar manner to some chemotherapy drugs, non-specifically reducing areas of high activity. Unfortunately in the brain, areas which need to function at a high level for us to remain active in our complex social environment will face similar deprivation, resulting in apathy and psychomotor retardation. Perhaps patients, carers and non specialist referrers need to be aware of this area of research, to make informed choices on duration of treatment with antipsychotics. References 1.Joanna Moncrieff and David Cohen. How do psychiatric drugs work? BMJ 2009;338:b1963 2.Dwyer, D.S., and Donohoe, D.Induction of hyperglycemia in mice with atypical antipsychotic drugs that inhibit glucose uptake. Pharmacology, Biochemistry and Behaviour.2003 Vol. 75(2): pp 255-260 3.Hoffman,R.E., Anderson, A.W. et al. Time course of regional brain activation associated with onset of auditory/verbal hallucinations 2008 The British Journal of Psychiatry Vol 193: pp 424-425 Competing interests: None declared |
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Mark Agius, Associate Specialist Bedfordshire and Luton Partnership Trust Weller Wing Bedford Hospital MK42 9 DJ, Sophia Ulhaq. FY1 Doctor , Bedford Hospital MK42 9 DJ
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Moncrieff and Cohen’s discussion about how psychiatric drugs work suggests that a disease centred model “ will enable patients to be the ultimate arbiters of what drug regime suits them best.” However they raise one important problem. They suggest that after recovery from an acute episode, “some people may decide that the cost of continued drug treatment is not outweighed by the reduction in the risk of relapse that long term treatment may produce.” Thus according to the drug centred model non-compliance may be a rational response to the effects of the drugs which needs to be accommodated and understood by the prescriber. “In this way the drug centred model provides a rationale for periodic rather then continued drug use”. Unfortunately such a model of periodic use of medication has not been shown to cause a reduction in the risk of relapse and the taking of long term medication to prevent relapse remains a key strategy in the management of psychotic illness [1]. In the study by one of us on the effectiveness of an early intervention service for psychosis, it appeared clear that the ongoing use of medication was linked to a reduction in admission due to relapse and the early increase in the dose of preventative medication together with reduction in stress was correlated with the possibility of rapidly treating relapse without admission to hospital [2]. We therefore would tend to favour the proper use of the drug centred model of action, but we would raise one issue. Rather than concentrating on the issue of the modification of neurotransmitter action, it would be more accurate and indeed acceptable to describe the action of such drugs as antidepressants (and to some extent antipsychotics) as modifying the proportions of trophic factors (such as brain-derived neurotrophic factor – BDNF) versus atrophic factors within neurons and thus affecting the promotion of neurogenesis and neuroplasticity [3]. This, besides being now more scientifically accurate, would give patients a better understanding of the need for effective and ongoing medication to adequately treat mental illness. References [1] Agius M, Oakham H, Biocina SM, Murphy S.The use of card sort exercises in the prevention of relapse in serious mental illness.Psychiatr Danub. 2006 ;18(1-2):61-73. [2] Agius M, Shah S, Ramkisson R, Murphy S, Zaman Three year outcomes of an early intervention for psychosis service as compared with treatment as usual for first psychotic episodes in a standard community mental health team - final results..Psychiatr Danub. 2007 ;19(3):130-8. [3] Santarelli L, Saxe M, Gross C, et al. . "Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants". Science 2003 ;301 (5634): 805–9. Competing interests: None declared |
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J Moncrieff, Senior Lecturer University College london, David Cohen
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We are glad that our paper on the actions of psychiatric drugs provoked a good discussion. Some of the correspondents, and others who contacted us, clearly felt that our account concurred with their experience of taking or prescribing these drugs. Ibrahimi (1) highlighted the benefits of the drug-induced state produced by antipsychotics for suppressing psychotic symptoms and emotional reactions. He also expressed the dilemna posed by the global nature of these effects. Although he was prepared to tolerate the effects because his relapses were so severe in nature, it is not clear that this is always the case. We argue, in contrast to Agius and Ulhaq (2), that for some patients, the adverse effects of ongoing drug treatment may outweigh the benefits of a reduced risk of relapse. This position is strenghtened by the fact that maintenance trials have failed to consider the adverse effects of drug withdrawal in the placebo group, and may therefore have overstated the benefits of ongoing drug treatment (3). Reid (4) suggested that there was no justification for singling out psychiatric drugs in our critque. We disagree. Some medical drugs certainly have psychoactive effects, like beta-blockers. However, in general, they do not exert their therapeutic action through these effects, but by targetting the specific physiological processes involved in producing symptoms of various diseases. Even modern painkillers work according to a disease-centred model, by acting on the physiological mechanisms that produce pain and some, like paracetamol and NSAIs, do not produce any significant psychoactive effects. Opiates, in contrast, do produce psychoactive effects, and may have a dual action on pain. They directly effect pain pathways, but they also induce an altered state characterised by emotional indifference, which reduces the emotional impact of pain. We agree with Reid (4) that we have not shown that psychiatric drug treatments cannot work in a disease specific way. What our paper points out is that there is no evidence that current drug treatments do act in this way. Neither are we suggesting that all biological theories of mental disorders are incorrect or unproven. We are merely showing that the biochemical theories of mental disorders which have been used to justify the disease-centred view of drug action cannot be used for this purpose. We support Stewart’s (5) emphasis on the importance of scepticsm and his encouragement to acknowledge the risk-benefit equation involved in taking any sort of medical treatment. What we have tried to highlight is that unless we have a better understanding of psychiatric drugs as psychoactive substances, which induce significant global mental and physiological effects, we are not able to evaluate them in a properly informed way. References 1) Ibrahimi Z. Big Brother doesn’t always listen. BMJ 2009; www.bmj.com/cgi/eletters/338/may29_1/b1963 2) Agius M, Ulhaq S. Explanations to patients about pharmacology should encourage concordance with medication. BMJ 2009; www.bmj.com/cgi/eletters/338/may29_1/b1963 3) Baldessarini RJ, Viguera AC. Neuroleptic withdrawal in schizophrenic patients. Arch Gen Psych 1995; 52: 189-92. 4) Reid I C. Altered states: Drugs and dualism. BMJ 2009; www.bmj.com/cgi/eletters/338/may29_1/b1963 5) Stewart AG. What are psychiatric drugs? BMJ 2009; www.bmj.com/cgi/eletters/338/may29_1/b1963 Competing interests: JM is the co-chair person of the Critical Psychiatry Network and a member of the International Centre for the Study of Psychology and Psychiatry. DC is currently funded by the National Institute of Mental Health, the State Attorneys General Consumer and Prescriber Grant program for the CriticalThinkRx project and is a board member of the Alliance for Human Research Protection. |
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