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Clozapine for mitochondrial psychosis
J. Finsterer, S. Zarrouk-Mahjoub
To cite this version:
J. Finsterer, S. Zarrouk-Mahjoub. Clozapine for mitochondrial psychosis. Molecular Genetics and
Metabolism Reports, Elsevier, 2017, 10, pp.50. �10.1016/j.ymgmr.2016.12.010�. �hal-01565818�
Correspondence
Clozapine for mitochondrial psychosis
Letter to the Editor
With interest we read the article by Demily et al. about a 30 year old male with neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome due to the mutation m.8993T
NC, clinically manifesting as cerebellar ataxia, pyramidal syndrome, and psychosis
[1]. Upon antipsy-chotic medication the patient developed dystonia, akathisia, and extra- pyramidal symptoms with falls
[1]. Switching to clozapine resolvedpsychosis but triggered fatigue, myoclonus, and falls. We have the fol- lowing comments and concerns.
Psychosis is an increasingly recognised phenotypic central nervous system (CNS) manifestation in various mitochondrial disorders (MIDs). Since MIDs are frequently multisystem disorders either already at onset or become multisystemic during the disease course, antipsy- chotic treatment becomes challenging due to its multiple CNS and extra-CNS side effects. Particularly dif
ficult is the treatment of MID pa- tients who additionally present with movement disorders, cardiac dis- ease, or hematological involvement.
Cardiac side effects of clozapine include dilated cardiomyopathy, myocarditis, long-QT syndrome, atrial
fibrillation, and sudden cardiac death
[2]. Did the patient develop any cardiac manifestations upon ad-ministration of antipsychotic drugs, in particular clozapine?
MIDs may manifest also with hematological abnormalities, in particular anemia, thrombocytopenia, or eosinophilia
[3]. Did the de-scribed patient develop hematological manifestations either as a manifestation of the genotype or as a side of clozapine, which may induce leucopenia and even agranulocytosis, anemia, and throbocytopenia
[4]?How do the authors explain the extrapyramidal side effects of cloza- pine in the light of recent
findings showing that clozapine metabolites
exhibit a neuroprotective effect on dopaminergic neurons through inhi- bition of microglial NADPH oxidase
[5]?It also should be discussed if the mutation occurred spontaneously or was inherited. Were
first-degree relatives investigated for clinical manifestations of MIDs?
Overall, this interesting case could pro
fit from further studies on the interaction of clozapine with wild-type and mutated mitochondria and from cardiac, hematological and CNS monitoring during the further course.
References
[1]C. Demily, C. Duwime, A. Poisson, N. Boddaert, A. Munnich, Low dose clozapine con- trols adult-onset psychosis associated with the neurogenic ataxia-retinitis pigmentosa (NARP) mutation, Mol. Genet. Metab. Rep. 10 (2016) 20–22.
[2]M. Alawami, C. Wasywich, A. Cicovic, C. Kenedi, A systematic review of clozapine in- duced cardiomyopathy, Int. J. Cardiol. 176 (2014) 315–320.
[3] J. Finsterer, Hematological manifestations of primary mitochondrial disorders, Acta Haematol. 118 (2007) 88–98.
[4]J. Lee, H. Takeuchi, G. Fervaha, V. Powell, A. Bhaloo, R. Bies, G. Remington, The effect of clozapine on hematological indices: a 1-year follow-up study, J. Clin. Psychopharmacol.
35 (2015) 510–516.
[5]L. Jiang, X. Wu, S. Wang, S.H. Chen, H. Zhou, B. Wilson, C.Y. Jin, R.B. Lu, K. Xie, Q. Wang, J.S. Hong, Clozapine metabolites protect dopaminergic neurons through inhibition of microglial NADPH oxidase, J. Neuroinflammation 13 (2016) 110.
Josef Finsterer Krankenanstalt Rudolfstiftung, Vienna, Austria Corresponding author at: Postfach 20, 1180 Vienna, Austria.
E-mail address:
fi[email protected].Sinda Zarrouk-Mahjoub University of Tunis El Manar, Genomics Platform, Pasteur Institute of Tunis, Tunisia 31 December 2016
Molecular Genetics and Metabolism Reports 10 (2017) 50http://dx.doi.org/10.1016/j.ymgmr.2016.12.010
2214-4269/© 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
