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LETTER TO EDITOR  
Year : 2012  |  Volume : 54  |  Issue : 3  |  Page : 291
Novel use of granulocyte colony stimulating factor as an adjunct for treatment of schizoaffective disorder complicated by sodium valproate induced agranulocytosis


Department of Psychiatry, Caffra Suite, National Centre for Mental Health, Birmingham and Solihull Mental Health NHS Trust, Birmingham, United Kingdom

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Date of Web Publication15-Oct-2012
 

How to cite this article:
Subbarayan S, Thomas S, George M. Novel use of granulocyte colony stimulating factor as an adjunct for treatment of schizoaffective disorder complicated by sodium valproate induced agranulocytosis. Indian J Psychiatry 2012;54:291

How to cite this URL:
Subbarayan S, Thomas S, George M. Novel use of granulocyte colony stimulating factor as an adjunct for treatment of schizoaffective disorder complicated by sodium valproate induced agranulocytosis. Indian J Psychiatry [serial online] 2012 [cited 2019 Sep 21];54:291. Available from: http://www.indianjpsychiatry.org/text.asp?2012/54/3/291/102446


Sir,

Semisodium valproate, licensed for treatment of manic episodes associated with schizoaffective disorder, is a well-tolerated mood stabilizing medication. Although side effects include liver toxicity, thrombocytopenia, and gastrointestinal problems, [1] a less frequent complication is agranulocytosis. [2] Although the etiology for this is unclear, immune-mediated destruction and toxic effects on the bone marrow are considered to play a potential role. The onset of agranulocytosis can be variable ranging from a few days [2] to a month [3] with mortality rates up to 16%. [4] A recombinant form of granulocyte colony-stimulating factor (G-CSF), a glycoprotein which stimulates the bone marrow to produce granulocyte and stem cells, is currently in use for the treatment of agranulocytosis. We report a case of a 23-year-old male patient with refractory schizoaffective disorder, manic type who was treated with G-CSF as an adjunct for sodium valproate-induced agranulocytosis.

This 23-year-old male of Middle Eastern descent was diagnosed with schizoaffective disorder at the age of 14. As Risperidone had poor response, he was switched to Olanzapine. Episodes of his illness were characterized by restlessness and agitation leading to verbal and physical aggression to family and others. Eventually sodium valproate was added to achieve reasonable symptom control. Olanzapine had to be stopped due to weight gain and substituted with amisulpride. By this time, he developed valproate-induced agranulocytosis and therefore it was discontinued. Attempt to manage him on lithium was unsuccessful. He then left UK for Middle East where he was treated with haloperidol and clopixol, but these were discontinued due to extrapyramidal side effects.

Following his return, he had multiple hospital admissions most of them under the Mental Health Act. On three occasions, he needed treatment in the Psychiatric Intensive Care unit (PICU). He was treated with zuclopenthixol depot injections, which have a potential for causing neutropenia. His neutrophil count subsequently dropped to 0.78 (×10 9 /L). He developed tachycardia and sore throat and then presented with periorbital cellulitis which required hospital admission and intravenous antibiotics. He also developed extrapyramidal side effects due to zuclopenthixol and following dosage reduction, he relapsed again. Medications including aripiprazole and quetiapine were tried with no response. It became clear that sodium valproate was the only medication effective in symptom control.

After recommencement of sodium valproate, his neutrophil counts were monitored, which were initially normal (3.84 (×10 9 /L)) but declined within weeks to 0.64 (×10 9 /L). Following hematology consultation, G-CSF was added resulting in reasonable symptom control and increase in neutrophil count. After 3 months of treatment, he refused the G-CSF injection and following this, his neutrophil count dropped to 0.57 (×10 9 /L). This improved with recommencement of G-CSF injections.

We have reported for the first time the successful use of G-CSF in valproate-induced agranulocytosis. Previously, Hsu et al.[5] have reported the use of this strategy in a post-operative neurosurgical patient on valproate. Although this approach should not be the first line of treatment, G-CSF as an adjunct along with sodium valproate should be considered in complex clinical situations where there are facilities for adequate clinical monitoring.

 
   References Top

1.Chateauvieux S, Morceau F, Dicato M, Diederich M. Molecular and therapeutic potential and toxicity of valproic acid. J Biomed Biotechnol 2010;2010:479364.  Back to cited text no. 1
[PUBMED]    
2.Vesta KS, Medina PJ. Valproic acid-induced neutropenia. Ann Pharmacother 2003;37:819-21.  Back to cited text no. 2
[PUBMED]    
3.Storch DD. Severe leukopenia with valproate. J Am Acad Child Adolesc Psychiatry 2000;39:1208-9.  Back to cited text no. 3
[PUBMED]    
4.Juliá A, Olona M, Bueno J, Revilla E, Rosselló J, Petit J, et al. Drug-induced agranulocytosis: Prognostic factors in a series of 168 episodes. Br J Haematol 1991;79:366-71.  Back to cited text no. 4
    
5.Hsu HC, Tseng HK, Wang SC, Wang YY. Valproic Acid-induced Agranulocytosis. Int J Gerontol 2009;3:137-9.0  Back to cited text no. 5
    

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Correspondence Address:
S Subbarayan
Department of Psychiatry, Caffra Suite, National Centre for Mental Health, Birmingham and Solihull Mental Health NHS Trust, Birmingham
United Kingdom
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5545.102446

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1 Sodium valproate
Reactions Weekly. 2013; 1440(1): 30
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