effect of tamoxifen and lithium on treatment of acute mania symptoms in children and adolescents

how to cite this article: fallah e, arman a, najafi m, shayegh b. effect of tamoxifen and lithium on treatment of acute mania symptoms in children and adolescents. iran j child neurol. spring 2016; 10(2):16-25. abstract objective many studies have supported the role of protein kinase c (pkc) inhibitors in the physiopathology and treatment of bipolar disorder in adults. tamoxifen is one of the drugs with the effect of pkc inhibition. this study aimed to determine the effect of tamoxifen on the rate of improvement mania symptoms in the sample of children and adolescents with acute mania. materials & methods in this randomized, placebo-controlled clinical trial study, registered in www.irct.ir with the code of irct201410126418n3, overall 44 patients with bipolar disorder with acute manic episode were randomly assigned into treatment and control groups. the serum levels of lithium and tamoxifen among the participants in the treatment groups were 0.8 -1.1 mg and 20-40 mg per day respectively. serum level of lithium among participants in the control group was similar. the main comparisons were made based on the young mania rating scale (ymrs) and children depression inventory (cdi) scores of the participants at baseline and at the end of each study week. the pharmacological side effects of serum level of lithium were examined weekly. analysis of covariance(ancova) test was used for the statistical analysis. results there was no difference in the baseline score of ymrs and cdi in the treatment and control groups while a statistical significant difference (p < 0.05) in these scores was found between and within the groups. conclusion the addition of tamoxifen to lithium causes a significant difference in reducing the symptoms of mania and depression in the treatment group compared to the control group.   references manji hk, lenox rh. ziskind- somerfeld research award. protein kinase c signaling in the brain: molecular transduction of mood stabilization in the treatment  of manic-depressive illness. biol psychiatry 1999; 46(10):1328-51. calabrese b, halpain s. essential role for the pkc target marcks in maintaining dendritic spine morphology. neuron 2005; 48(1)77-90. craske ml, fiveaz m, batad nn, meyer t. spines and neurite branches function as geometric attractors that enhance protein kinase c action. j cell biol 2005; 170(7): 1147-58. friedman e, hoan yan w, lewinson d, connell ta, singh h, altered platelet protein kinase c activity in bipolar affective disorder, manic episode. biol psychiatry 1993; 33(7):520-5. wang hy, freidman e. enhanced protein kinase c activity and translation in bipolar affective disorder brain. biol psychiatry 1996;40(7)568-75. einat h, yuan p, szaho st, dogra s, manji hk. protein kinase c inhibition by tamoxifen antagonizes manic like behavior in rats: implications for the development of novel therapeutics for bipolar disorders. neuropsychology 2007: 55(34): 123-31. harisson-read pe. models of mania and antimanic drug actions: progressing the endophenotype approach. j psychophar macol 2008;23(3):334-7. gimbalvo ct. protein kinase c and dopamine transport-2. effects of amphetamine in ultro. neuropharmacology 1992; 31(12): 1211-22. gimbalor ct. protein kinase c and dopamine transport-2. effects of amphetamine in ultro. neuropharmacology 1992; 31(12): 1201-10. genegy me, hong p, ferell st. phosphorylation of neuromodulin in rat striatum after acute and repeated, intermittent amphetamine. brain res mol brain res 1993; 20(4): 289-98. calabrese b, halpain s. essential role for the pkc target marcks in maintaining dendritic spine morphology. neuron 2005; 48(1)77-90. jordan vc. molecular mechanisms of anti-estrogen action in breast cancer. breast cancer res treat 1994; 31(1): 41-52. r. love r. effects of tamoxifen on bone mineral density in post-menopausal women with breast cancer. n engl j med 1992; 326: 1023-28. national cancer institute unioh, tamoxifen: questions and answers, 2010; 11. desmaria j. interaction between tamoxifen and antidepressants via cytochrome p4502d6. j clin psychiatr 2009; 20(12):1688-1697. s. goel s. effect of anti-estrogen on mes and their interaction with anti-epileptics in wista- pats. pharmacology online 2009; 1(3):24-30. geller b, craneg jl, bolhofner k, nickelsburg mj, williams m. phenomenology and longitudinal course of children with a prepubertal and early adolescent bipolar disorder phenotype. bipolar disorder in childhood and early adolescence. guilford 2003:25-50. suppes t, leverich gs, keck pe, nolen wa, denicoff kd, zarate ca, singh jb, carlsan pj, quiroz j, jolkovsky l, luckcu baugh da, et al. the stanley foundation bipolar treatment outcome network. demographics and illness characteristics at the first 261 patients. j affct disord 2001; 67: 45-59. smarty s, find ling rl, yildiz a, guleryuz s, ankerst dp, ongur d, renshaw pf. psychopharmacology of pediatric bipolar disorder: a review. psychopharmacology 2007; 191: 39-54. del bello mp, findling rl. a pilot controlled trial of topiramate for mania in children and adolescents with bipolar disorder. j am acad child adolesc psychiatry 2005; 44: 539-47. gabrielle a, carlson stephanie e, meyer c. early onset bipolar disorder. test book of psychiatry, kaplan and sadock, 2009: 3663-3670. sachs gs, gardner- schuster ee. adjunctive treatment of acute mania: a clinical overview. acta psychiatry scand suppl 2007; (434): 27-34. fagiolini a, chengappa kn. weight gain and metabolic issues of medicines used for bipolar disorder. curr psychiatry rep 2007; 9(6): 521-8. manji hk, zarate ca. molecular and cellular mechanisms underlying mood stabilizations for the development of improved therapeutics. mol psychiatry 2002; 7: 51-7. manji hk, bebchuk jm, moore gj, glitz d, hasanatka, chen g. modulation of cns signal transduction pathways and gene expression by mood-stabilizing agents: clin psychiatry 1999; 60: 27-39. lawrence se, faught ka, vethamat y, lawson ml. beneficial effects of raloxifen and tamoxifen in the treatment of pubertal gynecomastia. j pediatr 2004; 145: 71-76. bebchuk jm, artkan cl, dolan-manji s, murphy j, hasanat k, manji hk. a preliminary investigation of a protein kinase c inhibitor in the treatment of acute mania. arch gen psychiatry 2000; 57(1): 95-7. gould td, einat h. animal models of bipolar disorder and mood stabilize efficacy: a critical head for improvement. neurosci bio behave rev 2007; 31(6): 825-31. ghanizadeh a, mohammadi mr. psychometric properties of the farsi translation of the kids, schedule for affective disorders and schizophrenia. bmc psychiatry 2006; 6:10. young storm ea. toward and integration of parent and clinical report on the ymrs. j affect disord 2003; 77:179-90. karimi s (2009). normalization, reliability, validity and analysis of coax depression inventory questionnaire in students in secondary school, ma thesis in psychology, department of postgraduate education, islamic azad university, khorasgan branch. charles f, armstrong l, goldman m, lance l. drug information handbook- tamoxifen. 2013; 1478-1480. carlson ga. meyer se. bipolar disorder. textbook of child and adolescent psychiatry mina k. dulcan 2010; 280-295. eugster ea, rabin sd, raiter eo. tamoxifen treatment for precocious puberty in mccune-albright syndrom: a multi-center trial. j pediatr 2003; 143: 60-66. neriss c, kreher, erica a. eugster and r. ravi shankar a, pediatrics, 2005; 116; 1513. lawrence se, faught ka, vethamat y, lawson ml. beneficial effects of raloxifen and tamoxifen in the treatment of pubertal gynecomastia. j pediatr 2004; 145: 71-76. walter aw, gajjar a, reavdon da. tamoxifen and cauhoplutin for children with low grade gliomas: a pilot study at st. jude children’s research hospital. j pediatr hematol oncol 2000; 22: 247-251. bebchuk jm, artkan cl, dolan-manji s, murphy j, hasanat k, manji hk. a preliminary investigation of a protein kinase c inhibitor in the treatment of acute mania. arch gen psychiatry 2000; 57(1): 95-7. kullcarni j, garaland ka, scaffidi a, headey b, anderson r, castella de a, et al. a pilot study of hormone modulation as a new treatment for manic in women with bipolar affective disorder. psych-neuroendocrinology 2006; 31(4): 543-7. suppes t, leverich gs, keck pe, nolen wa, denicoff kd, zarate ca, singh jb, carlsan pj, quiroz j, jolkovsky l, luckcu baugh da, et al. efficacy of a protein kinase c inhibitor (tamoxifen) in the treatment of acute mania. a pilot study. bipolar disorder 2007; (9) (6): 561-70. smarty s, find ling rl, yildiz a, guleryuz s, ankerst dp, ongur d, renshaw pf. protein kinase c inhibition in the treatment of manic: a double blind, placebo controlled of tamoxifen. arch gen psychiatry 2008; 65(3): 255-63. amrollahi z, rezaei f, salehi b, modabbernia ah maroufi a, esfandiari g, et al. efficacy and safety of the tamoxifen adjunctive to lithium in acute bipolar mania. j affec disord 2011; 327-331. bebchuk jm. a preliminary investigation of a protein kinase c inhibitor in the treatment of acute mania. arch gen psychiat 2005; 31(4): 543-547. kelly c, lee a. tamoxifen treatment and new-onset depression in breast cancer patients. psychosomatics 2007; 48(3): 205-210.