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Questioning the ‘neuroprotective’ hypothesis: does drug treatment prevent brain damage in early psychosis or schizophrenia?

  • Joanna Moncrieff (a1)

Summary

The idea that psychotic disorders are characterised by progressive neurodegeneration that can be reversed by drug treatment is used to justify early treatment of increasing numbers of mostly young people. I argue that there is little evidence to support the view that old- or new-generation antipsychotics are ‘neuroprotective’, and some evidence that the drugs themselves may be responsible for the decline in brain matter observed in some studies.

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References

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1 Information Centre for Health and Social Care. Prescription Cost Analysis 2008. NHS Information Centre, 2009.
2 Olfson, M, Blanco, C, Liu, L, Moreno, C, Laje, G. National trends in the outpatient treatment of children and adolescents with antipsychotic drugs. Arch Gen Psychiatry 2006; 63: 679–85.
3 Healy, D. The latest mania: selling bipolar disorder. PLoS Med 2006; 3: e185.
4 Lieberman, JA. Is schizophrenia a neurodegenerative disorder? A clinical and neurobiological perspective. Biol Psychiatry 1999; 46: 729–39.
5 Lieberman, JA, Tollefson, GD, Charles, C, Zipursky, R, Sharma, T, Kahn, RS, et al. Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch Gen Psychiatry 2005; 62: 361–70.
6 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.
7 Moncrieff, J, Leo, J. A systematic review of the effects of antipsychotic drugs on brain volume. Psychol Med 2010; 40: 1409–22.
8 Takahashi, T, Wood, SJ, Yung, AR, Soulsby, B, McGorry, PD, Suzuki, M, et al. Progressive gray matter reduction of the superior temporal gyrus during transition to psychosis. Arch Gen Psychiatry 2009; 66: 366–76.
9 Lawrie, SM, Whalley, HC, Abukmeil, SS, Kestelman, JN, Miller, P, Best, JJK, et al. Temporal lobe volume changes in people at high risk of schizophrenia with psychotic symptoms. Br J Psychiatry 2002; 181: 138–43.
10 Jarskog, LF, Miyamoto, S, Lieberman, JA. Schizophrenia: new pathological insights and therapies. Annu Rev Med 2007; 58: 4961.
11 Chen, DC, Wang, J, Wang, B, Yang, SC, Zhang, CX, Zheng, YL, et al. Decreased levels of serum brain-derived neurotrophic factor in drug-naive first-episode schizophrenia: relationship to clinical phenotypes. Psychopharmacology (Berl) 2009; 207: 375–80.
12 Jarskog, LF, Glantz, LA, Gilmore, JH, Lieberman, JA. Apoptotic mechanisms in the pathophysiology of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 846–58.
13 Morgan, C, Abdul-Al, R, Lappin, JM, Jones, P, Fearon, P, Leese, M, et al. Clinical and social determinants of duration of untreated psychosis in the ÆSOP first-episode psychosis study. Br J Psychiatry 2006; 189: 446–52.
14 Owens, DC, Johnstone, EC, Miller, P, Macmillan, JF, Crow, TJ. Duration of untreated illness and outcome in schizophrenia: test of predictions in relation to relapse risk. Br J Psychiatry 2010; 196: 296301.
15 Bosanac, P, Patton, GC, Castle, DJ. Early intervention in psychotic disorders: faith before facts? Psychol Med 2010; 40: 353–8.
16 McGlashan, TH, Zipursky, RB, Perkins, D, Addington, J, Miller, T, Woods, SW, et al. Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis. Am J Psychiatry 2006; 163: 790–9.
17 Walker, EF, Cornblatt, BA, Addington, J, Cadenhead, KS, Cannon, TD, McGlashan, TH, et al. The relation of antipsychotic and antidepressant medication with baseline symptoms and symptom progression: a naturalistic study of the North American Prodrome Longitudinal Sample. Schizophr Res 2009; 115: 50–7.
18 Hunsberger, J, Austin, DR, Henter, ID, Chen, G. The neurotrophic and neuroprotective effects of psychotropic agents. Dialogues Clin Neurosci 2009; 11: 333–48.
19 Caldero, J, Brunet, N, Tarabal, O, Piedrafita, L, Hereu, M, Ayala, V, et al. Lithium prevents excitotoxic cell death of motoneurons in organotypic slice cultures of spinal cord. Neuroscience 2010; 165: 1353–69.
20 Bai, O, Zhang, H, Li, XM. Antipsychotic drugs clozapine and olanzapine upregulate bcl-2 mRNA and protein in rat frontal cortex and hippocampus. Brain Res 2004; 1010: 81–6.
21 Jarskog, LF, Glantz, LA, Gilmore, JH, Lieberman, JA. Apoptotic mechanisms in the pathophysiology of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 846–58.
22 Keefe, RS, Bilder, RM, Davis, SM, Harvey, PD, Palmer, BW, Gold, JM, et al. Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry 2007; 64: 633–47.
23 Waddington, JL, O'Callaghan, E, Larkin, C, Kinsella, A. Cognitive dysfunction in schizophrenia: organic vulnerability factor or state marker for tardive dyskinesia? Brain Cogn 1993; 23: 5670.

Questioning the ‘neuroprotective’ hypothesis: does drug treatment prevent brain damage in early psychosis or schizophrenia?

  • Joanna Moncrieff (a1)

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