Unfinished business

Readers of this News Blog will know that the NIHR CLAHRC WM has a strong mental health theme. Professor Swaran Singh (University of Warwick) drew the Director’s attention to a recent provocative paper by Wunderink et al.[1] This is a seven year follow-up of a randomised controlled trial (RCT) comparing standard maintenance antipsychotic chemotherapy with an early dose reduction/ discontinuation strategy in patients with first-episode psychosis. While the reduction/ discontinuation strategy resulted in a higher relapse rate within two years, this difference had disappeared at seven years and patients in the reduction/ discontinuation arm had better functional status. Since exposure to antipsychotic drugs has been shown to be associated with reduced brain volume in humans (even after trying to control for illness severity),[2] and in normal primates,[3] [4] this study has potentially massive implications for the future research agenda in schizophrenia. For instance, it would be informative to understand the effect of these medicines, which cross the placental and blood-brain-barriers with ease,[5] on the foetal brain.[6]

–Richard Lilford, Director of CLAHRC WM

References

[1] 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 Psych. 2013; 70(9): 913-20.

[2] Ho B, Andreasen NC, Ziebell S, Pierson R, Magnotta V. Long-term Antipsychotic Treatment and Brain Volumes: A Longitudinal Study of First-Episode Schizophrenia. Arch Gen Psychiatry. 2011;68(2):128-137.

[3] 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(9):1649-61.

[4] Konopaske GT, Dorph-Petersen KA, Sweet RA, et al. Effect of chronic antipsychotic exposure on astrocyte and oligodendrocyte numbers in macaque monkeys. Biol Psychiatry. 2008; 63(8): 759-65.

[5] Masud Iqbal M, Aneja A, Rahman A, et al. The Potential Risks of Commonly Prescribed Antipsychotics. Psych. 2005; 2(8): 36-44.

[6] Bodén R, Lundgren M, Brandt L, Reutfors J, Kieler H. Antipsychotics During Pregnancy: Relation to Fetal and Maternal Metabolic EffectsArch Gen Psychiatry. 2012;69(7):715-721

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