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Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics?

  • Robin M. Murray (a1), Diego Quattrone (a1), Sridhar Natesan (a1), Jim van Os (a2), Merete Nordentoft (a3), Oliver Howes (a4), Marta Di Forti (a5) and David Taylor (a5)...
Summary

Patients who recover from an acute episode of psychosis are frequently prescribed prophylactic antipsychotics for many years, especially if they are diagnosed as having schizophrenia. However, there is a dearth of evidence concerning the long-term effectiveness of this practice, and growing concern over the cumulative effects of antipsychotics on physical health and brain structure. Although controversy remains concerning some of the data, the wise psychiatrist should regularly review the benefit to each patient of continuing prophylactic antipsychotics against the risk of side-effects and loss of effectiveness through the development of supersensitivity of the dopamine D2 receptor. Psychiatrists should work with their patients to slowly reduce the antipsychotic to the lowest dose that prevents the return of distressing symptoms. Up to 40% of those whose psychosis remits after a first episode should be able to achieve a good outcome in the long term either with no antipsychotic medication or with a very low dose.

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Corresponding author
Robin M. Murray, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK. Email: robin.murray@kcl.ac.uk
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Declaration of interest

R.M.M. and J.v.O. have received honoraria from Bristol-Myers Squibb, Janssen, Lilly, Roche, Servier and Lundbeck for lectures, and M.D.F. has received honoraria from Janssen and Lundbeck. O.H. has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organised by Astra-Zeneca, Autifony, Bristol-Myers Squibb, Eli Lilly, Heptares, Janssen, Lundbeck, Leyden Delta, Otsuka, Servier, Sunovion, Rand and Roche.

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References
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1 Shorter, E. A History of Psychiatry: From the Era of the Asylum to the Age of Prozac. John Wiley & Sons, 1997.
2 Leff, JP, Wing, JK. Trial of maintenance therapy in schizophrenia. BMJ 1971; 3: 599604.
3 Leucht, S, Tardy, M, Komossa, K, Heres, S, Kissling, W, Salanti, G, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 2012; 379: 2063–71.
4 Moncrieff, J. Antipsychotic maintenance treatment: time to rethink? PLoS Med 2015; 12: e1001861.
5 Walker, ER, McGee, RE, Druss, BG. Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis. JAMA Psychiatry 2015; 72: 334–41.
6 Brown, S, Kim, M, Mitchell, C, Inskip, H. Twenty-five year mortality of a community cohort with schizophrenia. Br J Psychiatry 2010; 196: 116–21.
7 Hoang, U, Stewart, R, Goldacre, MJ. Mortality after hospital discharge for people with schizophrenia or bipolar disorder: retrospective study of linked English hospital episode statistics, 1999–2006. BMJ 2011; 343: d5422.
8 Saha, S, Chant, D, McGrath, J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry 2007; 64: 1123–31.
9 Lawrence, D, Kisely, S, Pais, J. The epidemiology of excess mortality in people with mental illness. Can J Psychiatry 2010; 55: 752–60.
10 Laursen, TM, Nordentoft, M, Mortensen, PB. Excess early mortality in schizophrenia. Annu Rev Clin Psychol 2014; 10: 425–48.
11 Frommeyer, G, Eckardt, L. Drug-induced proarrhythmia: risk factors and electrophysiological mechanisms. Nat Rev Cardiol 2016; 13: 3647.
12 Ray, WA, Chung, CP, Murray, KT, Hall, K, Stein, CM. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med 2009; 360: 225–35.
13 Henderson, DC, Vincenzi, B, Andrea, NV, Ulloa, M, Copeland, PM. Pathophysiological mechanisms of increased cardiometabolic risk in people with schizophrenia and other severe mental illnesses. Lancet Psychiatry 2015; 2: 452–64.
14 Stahl, SM, Mignon, L, Meyer, JM. Which comes first: atypical antipsychotic treatment or cardiometabolic risk? Acta Psychiatr Scand 2009; 119: 171–9.
15 De Hert, M, Detraux, J, van Winkel, R, Yu, W, Correll, CU. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol 2012; 8: 114–26.
16 Torniainen, M, Mittendorfer-Rutz, E, Tanskanen, A, Bjorkenstam, C, Suvisaari, J, Alexanderson, K, et al. Antipsychotic treatment and mortality in schizophrenia. Schizophr Bull 2015; 41: 656–63.
17 Mace, S, Dzahini, O, Cornelius, V, Anthony, D, Stewart, R, Taylor, D. Antipsychotic use and unexpected death: a hospital-based case-control study. Acta Psychiatr Scand 2015; 132: 479–88.
18 Murray, RM, Lewis, SW. Is schizophrenia a neurodevelopmental disorder? BMJ (Clin Res Ed) 1987; 295: 681–2.
19 van Haren, NE, Cahn, W, Hulshoff Pol, HE, Kahn, RS. Schizophrenia as a progressive brain disease. Eur Psychiatry 2008; 23: 245–54.
20 Navari, S, Dazzan, P. Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings. Psychol Med 2009; 39: 1763–77.
21 Moncrieff, J, Leo, J. A systematic review of the effects of antipsychotic drugs on brain volume. Psychol Med 2010; 40: 1409–22.
22 Zipursky, RB, Reilly, TJ, Murray, RM. The myth of schizophrenia as a progressive brain disease. Schizophr Bull 2013; 39: 1363–72.
23 Vita, A, De Peri, L, Deste, G, Sacchetti, E. Progressive loss of cortical gray matter in schizophrenia: a meta-analysis and meta-regression of longitudinal MRI studies. Transl Psychiatry 2012; 2: e190.
24 Rais, M, Cahn, W, van Haren, N, Schnack, H, Caspers, E, Hulshoff Pol, H, et al. Excessive brain volume loss over time in cannabis-using first-episode schizophrenia patients. Am J Psychiatry 2008; 165: 490–6.
25 Karama, S, Ducharme, S, Corley, J, Chouinard-Decorte, F, Starr, JM, Wardlaw, JM, et al. Cigarette smoking and thinning of the brain's cortex. Mol Psychiatry 2015; 20: 778–85.
26 Katon, W, Pedersen, HS, Ribe, AR, Fenger-Gron, M, Davydow, D, Waldorff, FB, et al. Effect of depression and diabetes mellitus on the risk for dementia: a national population-based cohort study. JAMA Psychiatry 2015; 72: 612–9.
27 Dorph-Petersen, KA, Pierri, JN, Perel, JM, Sun, Z, Sampson, AR, Lewis, DA. The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys. Neuropsychopharmacology 2005; 30: 1649–61.
28 Vernon, AC, Crum, WR, Lerch, JP, Chege, W, Natesan, S, Modo, M, et al. Reduced cortical volume and elevated astrocyte density in rats chronically treated with antipsychotic drugs – linking magnetic resonance imaging findings to cellular pathology. Biol Psychiatry 2014; 75: 982–90.
29 Konopaske, GT, Dorph-Petersen, KA, Pierri, JN, Wu, Q, Sampson, AR, Lewis, DA. Effect of chronic exposure to antipsychotic medication on cell numbers in the parietal cortex of macaque monkeys. Neuropsychopharmacology 2007; 32: 1216–23.
30 Vita, A, De Peri, L, Deste, G, Barlati, S, Sacchetti, E. The effect of antipsychotic treatment on cortical gray matter changes in schizophrenia: does the class matter? A meta-analysis and meta-regression of longitudinal magnetic resonance imaging studies. Biol Psychiatry 2015; 78: 403–12.
31 Boonstra, G, van Haren, NE, Schnack, HG, Cahn, W, Burger, H, Boersma, M, et al. Brain volume changes after withdrawal of atypical antipsychotics in patients with first-episode schizophrenia. J Clin Psychopharmacol 2011; 31: 146–53.
32 Vernon, AC, Natesan, S, Crum, WR, Cooper, JD, Modo, M, Williams, SC, et al. Contrasting effects of haloperidol and lithium on rodent brain structure: a magnetic resonance imaging study with postmortem confirmation. Biol Psychiatry 2012; 71: 855–63.
33 AV, Terry Jr, Gearhart, DA, Warner, SE, Zhang, G, Bartlett, MG, Middlemore, ML, et al. Oral haloperidol or risperidone treatment in rats: temporal effects on nerve growth factor receptors, cholinergic neurons, and memory performance. Neuroscience 2007; 146: 1316–32.
34 Terry, AV Jr, Hill, WD, Parikh, V, Evans, DR, Waller, JL, Mahadik, SP. Differential effects of chronic haloperidol and olanzapine exposure on brain cholinergic markers and spatial learning in rats. Psychopharmacology 2002; 164: 360–8.
35 Gur, RE, Turetsky, BI, Bilker, WB, Gur, RC. Reduced gray matter volume in schizophrenia. Arch Gen Psychiatry 1999; 56: 905–11.
36 Taylor, M, Cavanagh, J, Hodgson, R, Tiihonen, J. Examining the effectiveness of antipsychotic medication in first-episode psychosis. J Psychopharmacol 2012; 26: 2732.
37 Leucht, S, Tardy, M, Komossa, K, Heres, S, Kissling, W, Davis, JM. Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2012; 5: CD008016.
38 Harrow, M, Jobe, TH, Faull, RN. Does treatment of schizophrenia with antipsychotic medications eliminate or reduce psychosis? A 20-year multi-follow-up study. Psychol Med 2014; 44: 3007–16.
39 Moilanen, J, Haapea, M, Miettunen, J, Jaaskelainen, E, Veijola, J, Isohanni, M, et al. Characteristics of subjects with schizophrenia spectrum disorder with and without antipsychotic medication – a 10-year follow-up of the Northern Finland 1966 Birth Cohort study. Eur Psychiatry 2013; 28: 53–8.
40 Morgan, C, Lappin, J, Heslin, M, Donoghue, K, Lomas, B, Reininghaus, U, et al. Reappraising the long-term course and outcome of psychotic disorders: the ÆSOP-10 study. Psychol Med 2014; 44: 2713–26.
41 Wunderink, L, Nienhuis, FJ, Sytema, S, Slooff, CJ, Knegtering, R, Wiersma, D. Guided discontinuation versus maintenance treatment in remitted first-episode psychosis: relapse rates and functional outcome. J Clin Psychiatry 2007; 68: 654–61.
42 Wunderink, L, Nieboer, RM, Wiersma, D, Sytema, S, Nienhuis, FJ. Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial. JAMA Psychiatry 2013; 70: 913–20.
43 McGorry, P, Alvarez-Jimenez, M, Killackey, E. Antipsychotic medication during the critical period following remission from first-episode psychosis: less is more. JAMA Psychiatry 2013; 70: 898900.
44 Howes, OD, Murray, RM. Schizophrenia: an integrated sociodevelopmental-cognitive model. Lancet 2014; 383: 1677–87.
45 Smith, RC, Davis, JM. Behavioral evidence for supersensitivity after chronic administration of haloperidol, clozapine, and thioridazine. Life Sci 1976; 19: 725–31.
46 Grace, AA. Dopamine system dysregulation and the pathophysiology of schizophrenia: insights from the methylazoxymethanol acetate model. Biol Psychiatry 2015; doi:10.1016/j.biopsych.2015.11.007.
47 Samaha, AN, Seeman, P, Stewart, J, Rajabi, H, Kapur, S. “Breakthrough” dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time. J Neurosci 2007; 27: 2979–86.
48 Ginovart, N, Wilson, AA, Hussey, D, Houle, S, Kapur, S. D2-receptor upregulation is dependent upon temporal course of D2-occupancy: a longitudinal 11Craclopride PET study in cats. Neuropsychopharmacology 2009; 34: 662–71.
49 Zakzanis, KK, Hansen, KT. Dopamine D2 densities and the schizophrenic brain. Schizophr Res 1998; 32: 201–6.
50 Howes, OD, Kambeitz, J, Kim, E, Stahl, D, Slifstein, M, Abi-Dargham, A, et al. The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch Gen Psychiatry 2012; 69: 776–86.
51 Silvestri, S, Seeman, MV, Negrete, JC, Houle, S, Shammi, CM, Remington, GJ, et al. Increased dopamine D2 receptor binding after long-term treatment with antipsychotics in humans: a clinical PET study. Psychopharmacology 2000; 152: 174–80.
52 Konig, P, Benzer, MK, Fritzche, H. SPECT technique for visualization of cerebral dopamine D2 receptors. Am J Psychiatry 1991; 148: 1607–8.
53 Mizrahi, R, Agid, O, Borlido, C, Suridjan, I, Rusjan, P, Houle, S, et al. Effects of antipsychotics on D3 receptors: a clinical PET study in first episode antipsychotic naive patients with schizophrenia using [11C]-(+)-PHNO. Schizophr Res 2011; 131: 63–8.
54 Chouinard, G, Jones, BD, Annable, L. Neuroleptic-induced supersensitivity psychosis. Am J Psychiatry 1978; 135: 1409–10.
55 Chouinard, G, Chouinard, VA. Atypical antipsychotics: CATIE study, drug-induced movement disorder and resulting iatrogenic psychiatric-like symptoms, supersensitivity rebound psychosis and withdrawal discontinuation syndromes. Psychother Psychosom 2008; 77: 6977.
56 Chouinard, G, Annable, L, Ross-Chouinard, A. Supersensitivity psychosis and tardive dyskinesia: a survey in schizophrenic outpatients. Psychopharmacol Bull 1986; 22: 891–6.
57 Tenback, DE, van Harten, PN, Slooff, CJ, van Os, J. Worsening of psychosis in schizophrenia is longitudinally associated with tardive dyskinesia in the European Schizophrenia Outpatient Health Outcomes study. Compr Psychiatry 2007; 48: 436–40.
58 Carpenter, WT, McGlashan, TH, Strauss, JS. The treatment of acute schizophrenia without drugs: an investigation of some current assumptions. Am J Psychiatry 1977; 134: 1420.
59 Moncrieff, J. Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse. Acta Psychiatr Scand 2006; 114: 313.
60 Roy-Desruisseaux, J, Landry, J, Bocti, C, Tessier, D, Hottin, P, Trudel, JF. Domperidone-induced tardive dyskinesia and withdrawal psychosis in an elderly woman with dementia. Ann Pharmacother 2011; 45: e51.
61 Lu, ML, Pan, JJ, Teng, HW, Su, KP, Shen, WW. Metoclopramide-induced supersensitivity psychosis. Ann Pharmacother 2002; 36: 1387–90.
62 Seeman, P. Yes, Breast is best but taper domperidone when stopping (e-letter). Br J Gen Pract 2014; January 15.
63 Joyce, JN. D2 but not D3 receptors are elevated after 9 or 11 months chronic haloperidol treatment: influence of withdrawal period. Synapse 2001; 40: 137–44.
64 Quinn, R. Comparing rat's to human's age: how old is my rat in people years? Nutrition 2005; 21: 775–7.
65 Corstens, D, Longden, E, McCarthy-Jones, S, Waddingham, R, Thomas, N. Emerging perspectives from the hearing voices movement: implications for research and practice. Schizophr Bull 2014; 40: S28594.
66 Corstens, D, Longden, E, Rydinger, B, Bentall, R, van Os, J. Treatment of hallucinations: a comment. Psychosis 2013; 5: 98102.
67 Tadokoro, S, Okamura, N, Sekine, Y, Kanahara, N, Hashimoto, K, Iyo, M. Chronic treatment with aripiprazole prevents development of dopamine supersensitivity and potentially supersensitivity psychosis. Schizophr Bull 2012; 38: 1012–20.
68 Takaesu, Y, Kishimoto, T, Murakoshi, A, Takahashi, N, Inoue, Y. Factors associated with discontinuation of aripiprazole treatment after switching from other antipsychotics in patients with chronic schizophrenia: a prospective observational study. Psychiatry Res 2016; 236: 71–4.
69 Demjaha, A, Egerton, A, Murray, RM, Kapur, S, Howes, OD, Stone, JM, et al. Antipsychotic treatment resistance in schizophrenia associated with elevated glutamate levels but normal dopamine function. Biol Psychiatry 2014; 75: e113.
70 Demjaha, A, Murray, RM, McGuire, PK, Kapur, S, Howes, OD. Dopamine synthesis capacity in patients with treatment-resistant schizophrenia. Am J Psychiatry 2012; 169: 1203–10.
71 Suzuki, T, Kanahara, N, Yamanaka, H, Takase, M, Kimura, H, Watanabe, H, et al. Dopamine supersensitivity psychosis as a pivotal factor in treatment-resistant schizophrenia. Psychiatry Res 2015; 227: 278–82.
72 Oda, Y, Kanahara, N, Iyo, M. Alterations of dopamine D2 receptors and related receptor-interacting proteins in schizophrenia: the pivotal position of dopamine supersensitivity psychosis in treatment-resistant schizophrenia. Int J Mol Sci 2015; 16: 30144–63.
73 Girgis, RR, Phillips, MR, Li, X, Li, K, Jiang, H, Wu, C, et al. Clozapine v. chlorpromazine in treatment-naive, first-episode schizophrenia: 9-year outcomes of a randomised clinical trial. Br J Psychiatry 2011; 199: 281–8.
74 Howes, OD, Egerton, A, Allan, V, McGuire, P, Stokes, P, Kapur, S. Mechanisms underlying psychosis and antipsychotic treatment response in schizophrenia: insights from PET and SPECT imaging. Curr Pharm Des 2009; 15: 2550–9.
75 Schizophrenia Commission. The Abandoned Illness. Rethink, 2012.
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Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics?

  • Robin M. Murray (a1), Diego Quattrone (a1), Sridhar Natesan (a1), Jim van Os (a2), Merete Nordentoft (a3), Oliver Howes (a4), Marta Di Forti (a5) and David Taylor (a5)...
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eLetters

Should psychiatrists prescribe ' long term antipsychotics ' for relapse prevention of schizophrenia ?

K.A.L.A. Kuruppuarachchi, Senior Professor of Psychiatry, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka
24 January 2017

The editorial on Should psychiatrists be more cautious about the long- term prophylactic use of antipsychotics? (Murray RM et al. 2016) has been read with much interest as it is thought provoking and has a global relevance.

As correctly highlighted in the article the common practice is to continue the antipsychotics for a considerable period of time after the remission. This is a universal perception and many clinicians adhere to this practice all over the world at present.

The views of schizophrenia have been changed over the last few decades after focusing on organic factors in the aetiology. On the other hand in the first episode of psychosis, even though there is some evidence to suggest that the duration of untreated psychosis may contribute to neurotoxicity it is still not very clear those structural changes are permanent or reversed by antipsychotics(Anderson 2014).

The other important aspect note worthy is many other psycho-social factors influence the prognosis of schizophrenia. The people who continue to take antipsychotics may be more motivated , having other good prognostic factors such as good psycho- social support etc. These compounding variables may add to the course of the illness. On the other hand patients with other poor prognostic factors may not adhere to long term medication. In such situations we may erroneously believe/interpret that the poor outcome is a result of non compliance of antipsychotic medication.

A recent study done in China demonstrated that the outcomes of the never treated patients with schizophrenia were poor compared to the treated group( Ran et al. 2015). It has also been mentioned that the outcome may be better with long term antipsychotics. Also incorporating psychosocial interventions such as family psychoeducation, social skill training, cognitive behavior therapy in addition to pharmacotherapy is beneficial in preventing relapses and recovery process (Schooler NR 2006).

It has also been shown that the new generation antipsychotics help to prevent relapses in schizophrenia (Leucht et al. 2003).

As medical teachers we continue to teach postgraduates as well as undergraduates that patients with schizophrenia particularly relapses need long term medication in addition to psychosocial interventions. Hence the general perception among them is also that those patients need long term antipsychotics to prevent relapses and enhance recovery process.

It is interesting to note that the necessity to maintain the patients on minimal effective dose after careful assessment which was highlighted in the article. However the general assumption/practice is to continue with the same antipsychotic dose after full recovery unless there are other adverse consequences. As clinicians we have an inherent fear of reduction of antipsychotic dosage believing that the patient may end up with having a relapse. On the other hand many believe that the therapeutic response is poor with relapses. An earlier review has shown that the stable patients with schizophrenia who developed relapses when the neuroleptics were withdrawn may come across difficulties in returning to the previous level of functioning (Wyatt 1991). We still tend to prescribe high doses as well as seek polypharmacy when the response is poor even though there is poor scientific evidence. Particularly in developing countries clinicians appear to rely on medication more often, may be due to scarcity of resources and time constraints. On the other hand there is a possibility of delaying clozapine therapy due to problems with monitoring etc as well as reservations among clinicians. It appears that there is a reluctance of initiating clozapine across the globe (Cetin 2014).



Obviously socio-cultural factors as well as genetic factors will interfere with the long term outcome. Therapeutic response , drug metabolism etc. are influenced by the genetic variability.

We need to do more cross-culturally appropriate research work in order to unravel the mysteries of this fascinating area.

References;

Murray RM, et al. Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics? British Journal of Psychiatry 2016; 209: 361-365.

Anderson KK, Voineskos A, Mulsant BH, George TP, McKenzie KJ. The role of untreated psychosis in neurodegeneration: A review of hypothesized mechanisms of neurotoxicity in first-episode psychosis. Can J Psychiatry 2014; 59(10): 513-517.

Ran MS, et al. Different outcomes of never-treated and treated patients with schizophrenia: 14 -year follow- up study in rural China. British Journal of Psychiatry 2015; 207: 495-500.

Schooler NR, Relapse prevention and recovery in the treatment of schizophrenia. J Clin Psychiatry

2006 ; 67 suppl 5: 19-23.

Leucht S, Barnes TRE, Kissling W, Engel RR, Correll C, Kane JM. Relapse prevention in schizophrenia with new-generation antipsychotics: A systematic review and exploratory meta-analysis of randomized, controlled trials. Am J Psychiatry 2003; 160: 1209- 1222.

Wyatt RJ, Neuroleptics and the natural course of schizophrenia. Schizophrenia Bulletin 1991; 17(2): 325-351.

Cetin M, Clozaphobia: Fear of prescribers of clozapine for treatment of schizophrenia. Bulletin of Clinical Psychopharmacology 2014; 24: 295-301.

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Conflict of interest: None Declared

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Murray and colleagues could be offering a therapeutic dead-end.

Stanley V. Catts, Professor (honorary) in Psychiatry, School of Medicine, University of Queensland
Brian I. O'Toole, Senior Clinical Lecturer, Brain & Mind Centre University of Sydney
18 January 2017

Murray and colleagues’ confident advice (1) conveyed to psychiatrists, encouraging them to leave fewer patients with schizophrenia on long-term medication, is based on one of several possible interpretations of a selected literature, and little clinical evidence. We consider that at times Murray and colleagues misrepresented the literature in their descriptions of what some papers report: sometimes these descriptions are misleading (e.g., their references 17, 30, and 31) or incorrect (their reference 8). If the evidence so strongly supports the authors’ recommendations, why have they relied so heavily on single case reports and personal communication and on qualifying words such as “doubts”; “possibilities”; “suggest”; “appear”; “raise the possibilities”; “several Japanese groups have suggested” and given prominence to a study (their reference 38) that they admit has a “major confounder” and another study (their reference 42) that Murray and colleagues describe as “a study less open to bias”, which others consider grossly flawed (reviewed in [2]). And why do they consistently use the phrase “low or no dose”, without ever describing the conditions that discriminate these indications? Murray and colleagues assert that continuous antipsychotic medication loses its effectiveness over time but do not present any clinical evidence for this, and that this putative treatment resistance is due to antipsychotic-induced dopamine receptor supersensitivity that has been found in animal studies. Indeed, the authors rely heavily on animal studies generally to make their case for a range of issues without highlighting the fact that the relevant animal studies were all carried out on HEALTHY animals. The authors seem overly confident that the results of these animal studies can be applied directly to the clinical situation where no psychiatrist uses antipsychotic medication in healthy humans. The authors fail to see the complete disconnect between healthy animal research and clinical research on patients with schizophrenia. It seems to us that the reliance on animal studies by Murray and colleagues has resulted in their treatment recommendations being almost the opposite to ones based on clinical literature (2). We suggest that Murray and colleagues are proposing a therapeutic dead-end. With current practice, most patients stop their medication anyway, mainly due to non-adherence to oral medication, within 60 days after hospital discharge in 60% of first-episode patients (3): so how will taking more patients off their antipsychotic medication improve the current overall recovery rates in schizophrenia of 13.5% (4), and the death rates that all agree are unacceptably high? Murray and colleagues’ answer is more psychosocial intervention but they present no evidence for its effectiveness in un-medicated patients. The clinical evidence for antipsychotic medication reducing the mortality rate at all stages of the illness is of high quality and very consistent (summarised in [5]): the simple truth is that taking more patients off maintenance medication will result in more patients dying unnecessarily – the ultimate therapeutic dead-end.

References:

1.Murray RM, Quattrone D, Natesan S, van Os J, Nordentoft M, Howes O, Di Forti M, Taylor D. Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics? Br J Psychiatry 2016, 209, 361-365.

2.Catts SV & O’Toole BI. The treatment of schizophrenia: Can we raise the standard of care? Aust & NZ J Psychiatry 2016 50, 12, 1128-1138.

3.Tiihonen J, Haukka J, Taylor M, Haddad PM, Patel Mx, Korhonen P. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry 2011, 168, 6, 603-609.

4.Jaaskelainen E, Juola P, Hirvonen N, McGrath JJ, Saha S, Isohanni M, Veijola J, Miettunen J. A systematic review and meta-analysis of recovery in schizophrenia. Schiz Bull 2013, 39, 6, 1296-1306.

5.Tiihonen J Editorial: real-world effectiveness of antipsychotics. Acta Psychiatrica Scandinavica 2016, 134,371-373.

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Conflict of interest: SVC has received funding for acting in the role of an advisory board member, as a sponsored educational speaker, and for research projects from the following pharmaceutical companies: Janssen-Cilag Pty Ltd, Eli Lilly Australia Pty Ltd, Lundbeck Australia Pty Ltd, Novartis Pharmaceuticals Australia Pty Ltd, Pfizer Australia Pty Ltd, Bristol-Myers Squibb Pty Ltd, Sanofi-Aventis Australia Pty Ltd, Hospira Australia Pty Ltd, and AstraZeneca Pty Ltd. The author is a Trustee for the Psychosis Australia Trust and the Queensland Schizophrenia Research Foundation. He is a board member of Clearthinking Queensland Ltd. BIO has no conflicts of interest to declare.

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