Endoxifen: A new, protein kinase C inhibitor to treat acute and mixed mania associated with bipolar I disorder.
YMRS Score
bipolar I disorder
endoxifen
valproate
Journal
Bipolar disorders
ISSN: 1399-5618
Titre abrégé: Bipolar Disord
Pays: Denmark
ID NLM: 100883596
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
19
10
2020
received:
23
08
2020
accepted:
20
12
2020
pubmed:
29
12
2020
medline:
3
11
2021
entrez:
28
12
2020
Statut:
ppublish
Résumé
Endoxifen is a protein kinase C inhibitor. The objective of the present phase III study was to demonstrate the safety and efficacy of endoxifen in treating bipolar I disorder (BPD I) patients. A multicenter, double-blind, active-controlled study was conducted using a daily dose of 8 mg endoxifen compared to 1000 mg divalproex, the current standard treatment, in patients with BPD I acute manic episodes with/without mixed features. The primary endpoint of our study was the mean change in total Young Mania Rating Scale (YMRS) score at day 21. Endoxifen (n = 116) significantly (p < 0.0001) reduced total YMRS score (from 33.1 to 17.8. A significant (p < 0.001) improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) score was observed for endoxifen (4.8 to 2.5). Early time to remission of the disease was observed with endoxifen compared to divalproex. None of the patients required rescue medication and there was no drug-associated withdrawals. Changes in Clinical Global Impressions-Bipolar Disorder and Clinical Global Impression-Severity of Illness scores showed that treatment with endoxifen was well-tolerated. Endoxifen at a low daily dose of 8 mg was as efficacious and safe in patients with BPD I acute manic episodes with/without mixed features.
Substances chimiques
Antipsychotic Agents
0
Tamoxifen
094ZI81Y45
4-hydroxy-N-desmethyltamoxifen
46AF8680RC
Protein Kinase C
EC 2.7.11.13
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
595-603Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Abrial E, Betourne A, Etievant A, et al. Protein kinase C inhibition rescues manic-like behaviors and hippocampal cell proliferation deficits in the sleep deprivation model of mania. Int J Neuropsychopharmacol. 2015;18(2).
Saxena A, Scaini G, Bavaresco DV, et al. Role of protein kinase C in bipolar disorder: a review of the current literature. Mol Neuropsychiatry. 2017;3:108-124.
Manji HK, Lenox RH. Long-term action of lithium: a role for transcriptional and posttranscriptional factors regulated by protein kinase C. Synapse. 1994;16:11-28.
Talaei A, Pourgholami M, Khatibi-Moghadam H, et al. Tamoxifen: a protein kinase C inhibitor to treat mania: a systematic review and meta-analysis of randomized, placebo-controlled trials. J Clin Psychopharmacol. 2016;3:272-275.
Zarate CA, Manji HK. Protein kinase C inhibitors: rationale for use and potential in the treatment of bipolar disorder. CNS Drugs. 2009;7:569-582.
Kulkarni J, Berk M, Wang W, et al. A four week randomised control trial of adjunctive medroxyprogesterone and tamoxifen in women with mania. Psychoneuroendocrinology. 2014;43:52-61.
Carpenter C, Mikelman S, Gnegy M. Novel CNS-Permeant PKC inhibitor and tamoxifen analog reduces amphetamine neurochemical and behavioral effects. FASEB J. 2015;1(768):16.
Zarate CA Jr, Singh JB, Carlson PJ, et al. Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot study. Bipolar Disord. 2007;9:561-570.
Yildiz A, Guleryuz S, Ankerst DP, Ongur D, Renshaw PF. Protein kinase C inhibition in the treatment of mania: a double-blind, placebo-controlled trial of tamoxifen. Arch Gen Psychiatry. 2008;65:255-263.
Amrollahi Z, Rezaei F, Salehi B, et al. Double-blind, randomized, placebo-controlled 6-week study on the efficacy and safety of the tamoxifen adjunctive to lithium in acute bipolar mania. J Affect Disord. 2011;129:327-331.
Kulkarni J, Garland KA, Scaffidi A, et al. A pilot study of hormone modulation as a new treatment for mania in women with bipolar affective disorder. Psychoneuroendocrinology. 2006;31:543-547.
Sachs GS, Greenberg WM, Starace A, et al. Cariprazine in the treatment of acute mania in bipolar I disorder: a double-blind, placebo-controlled, phase III trial. J Affect Disord. 2015;174:296-302.
Cousins DA, Young AH. The armamentarium of treatments for bipolar disorder: a review of the literature. Int J Neuropsychopharmacol. 2007;10:411-431.
Ahmad A, Sheikh S, Shah T, et al. Endoxifen, a new reatment option for mania: a double-blind, active-controlled trial demonstrates the antimanic efficacy of endoxifen. Clin Transl Sci. 2016;9:252-259.
Ali SM, Ahmad A, Shahabuddin S, Ahmad MU, Sheikh S, Ahmad I. Endoxifen is a new potent inhibitor of PKC: a potential therapeutic agent for bipolar disorder. Bioorg Med Chem Lett. 2010;20:2665-2667.
Ahmad A, Shahabuddin S, Sheikh S, et al. Endoxifen, a new cornerstone of breast cancer therapy: demonstration of safety, tolerability, and systemic bioavailability in healthy human subjects. Clin Pharmacol Ther. 2010;88:814-817.
Lien EA, Wester K, Lønning PE, Solheim E, Ueland PM. Distribution of tamoxifen and metabolites into brain tissue and brain metastases in breast cancer patients. Br J Cancer. 1991;63:641-645.
Saladores P, Mürdter T, Eccles D, et al. Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer. Pharmacogenomics J. 2015;15:84-94.
Hirschfeld RMA, Bowden CL, Gitlin MJ, et al. Practice guideline for the treatment of patients with bipolar disorder, second edition. American Psychiatric Association practice guidelines for the treatment of psychiatric disorders: Compendium 2002. Arlington, VA, US: American Psychiatric Association. 2002;547-634.
Shah N, Grover S, Rao GP. Clinical practice guidelines for management of bipolar disorder. Indian J psychiatry. 2017;59(Suppl 1):S51-S66.
Yatham LN, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20:97-170.
Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978;133:429-435.
Spearing MK, Post RM, Leverich GS, Brandt D, Nolen W. Modification of the clinical global impressions (CGI) scale for use in bipolar illness (BP): the CGI-BP. Psychiatry Res. 1997;73:159-171.
Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382-389.
Guy W. ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: US Department of Heath, Education, and Welfare Public Health Service Alcohol, Drug Abuse, and Mental Health Administration. 1976.
Posner K, Brent D, Lucas C, et al. Columbia-suicide severity rating scale (C-SSRS). New York, NY: Columbia University Medical Center; 2008.
Earley W, Durgam S, Lu K, et al. Clinically relevant response and remission outcomes in cariprazine-treated patients with bipolar I disorder. J Affect Disord. 2018;226:239-244.
Youngstrom E, Zhao J, Mankoski R, et al. Clinical significance of treatment effects with aripiprazole versus placebo in a study of manic or mixed episodes associated with pediatric bipolar I disorder. J Child Adolesc Psychopharmacol. 2013;23:72-79.
Ketter TA, Jones M, Paulsson B. Rates of remission/euthymia with quetiapine monotherapy compared with placebo in patients with acute mania. J Affect Disord. 2007;100:S45-S53.
Yatham LN, Grossman F, Augustyns I, Vieta E, Ravindran A. Mood stabilisers plus risperidone or placebo in the treatment of acute mania: international, double-blind, randomised controlled trial. Br J Psychiatry. 2003;182:141-147.
Sachs G, Chengappa KN, Suppes T, et al. Quetiapine with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind placebo-controlled study. Bipolar Disord. 2004;6:213-223.
Smulevich AB, Khanna S, Eerdekens M, Karcher K, Kramer M, Grossman F. Acute and continuation risperidone monotherapy in bipolar mania: a 3-week placebo-controlled trial followed by a 9-week double-blind trial of risperidone and haloperidol. Eur Neuropsychopharmacol. 2005;15:75-84.
Sekhar S, Kalra B, Mendhekar DN, Tekur U. Efficacy of sodium valproate and haloperidol in the management of acute mania: a randomized open-label comparative study. J Clin Pharmacol. 2010;50:688-692.
Berwaerts J, Lane R, Nuamah IF, Lim P, Remmerie B, Hough DW. Paliperidone extended-release as adjunctive therapy to lithium or valproate in the treatment of acute mania: a randomized, placebo-controlled study. J Affect Disord. 2011;129:252-260.
Yildiz A, Nikodem M, Vieta E, Correll CU, Baldessarini RJ. A network meta-analysis on comparative efficacy and all-cause discontinuation of antimanic treatments in acute bipolar mania. Psychol Med. 2015;45:299-317.
Kroemer HK, Eichelbaum M. "It's the genes, stupid". Molecular bases and clinical consequences of genetic cytochrome P450 2D6 polymorphism. Life Sci. 1995;56:2285-2298.
Salloum NC, McCarthy MJ, Leckband SG, Kelsoe JR. Towards the clinical implementation of pharmacogenetics in bipolar disorder. BMC Med. 2014;12:90. https://doi.org/10.1186/1741-7015-12-90.
Tohen M, Chengappa K, Suppes T, et al. Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy. Arch Gen Psychiatry. 2002;59:62-69.
Fagiolini A, Chengappa KN. Weight gain and metabolic issues of medicines used for bipolar disorder. Curr Psychiatry Rep. 2007;9:521-528.
Saquib N, Flatt SW, Natarajan L, et al. Weight gain and recovery of pre-cancer weight after breast cancer treatments: evidence from the women's healthy eating and living (WHEL) study. Breast Cancer Res Treat. 2007;105:177-186.
Zhang Y-X, Shen C-H, Lai Q-L, et al. Effects of antiepileptic drug on thyroid hormones in patients with epilepsy: a meta-analysis. Seizure. 2016;35:72-79.
Dziewulska-Bokiniec A, Wojtacki J, Skokowski J, Kortas B. The effect of tamoxifen treatment on serum cholesterol fractions in breast cancer women. Neoplasma. 1994;41:13-16.
Zuberi NA, Baig M, Bano S, Batool Z, Haider S, Perveen T. Assessment of atherosclerotic risk among patients with epilepsy on valproic acid, lamotrigine, and carbamazepine treatment. Neurosciences (Riyadh). 2017;22:114-118.
Buoli M, Serati M, Botturi A, Altamura AC. The risk of thrombocytopenia during valproic acid therapy: a critical summary of available clinical data. Drugs R D. 2018;18:1-5.
Yao JC, Thomakos N, McLaughlin P, Buchholz TA, Kudelka AP. Tamoxifen-induced thrombocytopenia. Am J Clin Oncol. 1999;22:529-532.
Keck PE Jr, Versiani M, Potkin S, West SA, Giller E, Ice K. Ziprasidone in the treatment of acute bipolar mania: a three-week, placebo-controlled, double-blind, randomized trial. Am J Psychiatry. 2003;160:741-748.
Chakrabarti S. Treatment-adherence in bipolar disorder: a patient-centred approach. World J Psychiatry. 2016;6:399-409.
Cuzick J, Sestak I, Cawthorn S, et al. IBIS-I Investigators Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol. 2015;16:67-75.
Jochim J, Rifkin-Zybutz RP, Geddes J, Cipriani A. Valproate for acute mania. Cochrane Systematic Rev - Intervention. 2019; https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004052.pub2/full.
Yildiz A, Vieta E, Leucht S, Baldessarini RJ. Efficacy of antimanic treatments: meta-analysis of randomized, controlled trials. Neuropsychopharmacology. 2011;36:375-389.