Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Arch Gen Psychiatry. 2008 Mar;65(3):255-63. doi: 10.1001/archgenpsychiatry.2007.43.

Protein kinase C inhibition in the treatment of mania: a double-blind, placebo-controlled trial of tamoxifen.

Author information

  • 1Department of Psychiatry, Dokuz Eylül University, Huzur Mah, Saffet Baba Sok, No. 27/12 PK: 35320 Narlidere, Izmir, Turkey. agul_yildiz@hotmail.com

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.

Comment in

PMID:
18316672
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems
    Loading ...
    Write to the Help Desk