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Cited by 213Bipolar Disorder and TreatmentSchizophrenia research and treatmentTreatment of Major Depression

Protein Kinase C Inhibition in the Treatment of Mania: A Double-blind, Placebo-Controlled Trial of Tamoxifen

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Yildiz, Ayşegül, Guleryuz, Sebnem, Ankerst, Donna Pauler, Öngür, Dost, Renshaw, Perry F.·2008·Archives of General Psychiatry
DOI 10.1001/archgenpsychiatry.2007.43
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Abstract

CONTEXT: Findings that protein kinase C (PKC) activity may be altered in mania, and that both lithium carbonate and valproate sodium inhibit PKC-associated signaling in brain tissue, encourage development of PKC inhibitors as candidate antimanic agents. OBJECTIVE: To perform a controlled test of antimanic efficacy of the centrally active PKC inhibitor tamoxifen citrate. DESIGN: Three-week, randomized, double-blind, placebo-controlled, parallel-arms trial. SETTING: A university medical center inpatient psychiatric unit in Izmir, Turkey. PATIENTS: Sixty-six patients aged 18 to 60 years, diagnosed as having DSM-IV bipolar I disorder on the basis of the Structured Clinical Interview for DSM-IV, currently in a manic or mixed state, with or without psychotic features, with initial scores on the Young Mania Rating Scale (YMRS) greater than 20. INTERVENTION: Treatment with tamoxifen or identical placebo tablets for up to 3 weeks. Adjunctive lorazepam was allowed up to 5 mg/d. MAIN OUTCOME MEASURES: Primary: change in YMRS scores; secondary: change in Clinical Global Impressions-Mania scores, weekly ratings of depression and psychosis, and adjunctive use of lorazepam. RESULTS: The 21-day trial was completed by 29 of 35 subjects randomized to receive tamoxifen (83%) and 21 of 31 given placebo (68%) (P = .25). Intent-to-treat analysis of available measures on all 66 subjects indicated that tamoxifen treatment yielded mean decreases in scores on the YMRS and Clinical Global Impressions-Mania of 5.84 and 0.73 point per week, respectively, compared with mean increases of 1.50 and 0.10 point per week, respectively, with placebo; both drug-placebo contrasts differed significantly (P < .001). CONCLUSIONS: Tamoxifen demonstrated antimanic properties and was remarkably well tolerated. The findings encourage further clarification of the role of PKC in the pathophysiologic mechanism of bipolar I disorder and development of novel anti-PKC agents as potential antimanic or mood-stabilizing agents. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00411203 and isrctn.org Identifier: ISRCTN97160532.

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Authors
Yildiz, A., Guleryuz, S., Ankerst, D. P., Öngür, D., & Renshaw, P. F.
Affiliations
  • Helmholtz Munich (DE)
  • Harvard University (US)
ORCID
Venue
Archives of General Psychiatry
Publisher
American Medical Association (AMA)
Published
2008-03-01
Volume
65
Issue
3
Pages
255
ISSN
0003-990X (ISSN-L)
DOI
10.1001/archgenpsychiatry.2007.43
OpenAlex
W2051262966
Cited by
213
References
54
Citations by year
2026: 4 · 2025: 2 · 2024: 10 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 7 · 2019: 5 · 2018: 9 · 2017: 12 · 2016: 19 · 2015: 7 · 2014: 14 · 2013: 14 · 2012: 18
FWCI
16.59
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Archives of General Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
protein kinase C inhibition, tamoxifen, mania, bipolar I disorder, mood stabilizers, lithium carbonate, valproic acid, Young Mania Rating Scale, psychosis
MeSH terms
Adolescent, Adult, Bipolar Disorder, Double-Blind Method, Female, Humans, Male, Middle Aged, Protein Kinase C, Tamoxifen, Treatment Outcome, Antimanic Agents, Protein Kinase Inhibitors

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