Double-blind, randomized, placebo-controlled 6-week study on the efficacy and safety of the tamoxifen adjunctive to lithium in acute bipolar mania

Amrollahi, Zohreh; Rezaei, Farzin; Salehi, Bahman; Modabbernia, Amirhossein; Maroufi, Azad; Esfandiari, Gholam-Reza; Naderi, Mehrangiz; Ghebleh, Fariba; Ahmadi-Abhari, Seyed-Ali; Sadeghi, M R; Tabrizi, Mina; Akhondzadeh, Shahin

doi:10.1016/j.jad.2010.08.015

Cited by 77 publications

(60 citation statements)

References 10 publications

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“…TMX is also effective as an adjunct to lithium or valproic acid [78]. In a longer double-blind, randomized, placebo-controlled 6-week study, it was demonstrated that the combination of TMX with Li was superior to Li alone for the rapid reduction of manic symptoms [79]. Furthermore, TMX has also been reported to be an effective antimanic treatment in pediatric population [80].…”

Section: Pkc Translocation and Activitymentioning

confidence: 99%

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

et al. 2017

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Bipolar disorder (BD) is a major health problem. It causes significant morbidity and imposes a burden on the society. Available treatments help a substantial proportion of patients but are not beneficial for an estimated 40-50%. Thus, there is a great need to further our understanding the pathophysiology of BD to identify new therapeutic avenues. The preponderance of evidence pointed towards a role of protein kinase C (PKC) in BD. We reviewed the literature pertinent to the role of PKC in BD. We present recent advances from preclinical and clinical studies that further support the role of PKC. Moreover, we discuss the role of PKC on synaptogenesis and neuroplasticity in the context of BD. The recent development of animal models of BD, such as stimulant-treated and paradoxical sleep deprivation, and the ability to intervene pharmacologically provide further insights into the involvement of PKC in BD. In addition, the effect of PKC inhibitors, such as tamoxifen, in the resolution of manic symptoms in patients with BD further points in that direction. Furthermore, a wide variety of growth factors influence neurotransmission through several molecular pathways that involve downstream effects of PKC. Our current understanding identifies the PKC pathway as a potential therapeutic avenue for BD.

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Section: Pkc Translocation and Activitymentioning

confidence: 99%

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

et al. 2017

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“…A study therefore examined the relationship between platelet [95], as an adjunctive treatment to lithium [96,97], or in lorazepam-treated patients [98,99], tamoxifen resulted in a significant antimanic effect, stronger than that of lithium [96,100]. Rates of response, determined as the percentage of patients with 50% reduction in Young Mania Rating Scale (YMRS) score from baseline to trial completion, varied from 48% to 95%.…”

Section: Abnormalities Of the Pkc System In Patients With Mood Disordersmentioning

confidence: 99%

“…Nevertheless, a question that future clinical studies should focus on is whether a PKC inhibitor, efficient in treating mania, may trigger a mood switch from mania to depression. Four out of the five clinical studies on tamoxifen and bipolar mania have already started to answer that issue and showed that tamoxifen was without any significant effect on depression scores, at least for the period investigated [95,96,98,99].…”

Section: Abnormalities Of the Pkc System In Patients With Mood Disordersmentioning

confidence: 99%

A Role for the PKC Signaling System in the Pathophysiology and Treatment of Mood Disorders: Involvement of a Functional Imbalance?

et al. 2011

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Mood disorders, such as bipolar and major depressive disorders, are frequent, severe, and often disabling neuropsychiatric diseases affecting millions of individuals worldwide. Available mood stabilizers and antidepressants remain unsatisfactory because of their delayed and partial therapeutic efficacy. Therefore, the development of targeted therapies, working more rapidly and being fully effective, is urgently needed. In this context, the protein kinase C (PKC) signaling system, which regulates multiple neuronal processes implicated in mood regulation, can constitute a novel therapeutic target. This paper reviews the currently available knowledge regarding the role of the PKC signaling pathway in the pathophysiology of mood disorders and the therapeutic potential of PKC modulators. Current antidepressants and mood stabilizers have been shown to modulate the PKC pathway, and the inhibition of this intracellular signaling cascade results in antimanic-like properties in animal models. Disrupted PKC activity has been found both in postmortem brains and platelet from patients with mood disorders. Finally, the PKC inhibitor tamoxifen has recently demonstrated potent antimanic properties in several clinical trials. Overall, emerging data from preclinical and clinical research suggest an imbalance of the PKC signaling system in mood disorders. Thus, PKC may be a critical molecular target for the development of innovative therapeutics.

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“…139 In addition, several clinical studies have shown that tamoxifen (TMX) -a PKC inhibitor -is effective in treating acute mania. [140][141][142] Based on these observations, PKC inhibition was proposed as a promising therapeutic mechanism in the treatment of BD. 143 Recently, our laboratory showed that TMX protected against d-AMPH-induced hyperactivity, mitochondrial complex damage, and oxidative stress in the brains of rats.…”

Section: Animal Models Of Bipolar Disordermentioning

confidence: 99%

Contributions of animal models to the study of mood disorders

Valvassori

Budni

Varela

et al. 2013

Rev. Bras. Psiquiatr.

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Mood disorders are a leading cause of morbidity and mortality, yet their underlying pathophysiology remains unclear. Animal models serve as a powerful tool for investigating the neurobiological mechanisms underlying psychiatric disorders; however, no animal model developed to date can fully mimic the ''corresponding'' human psychiatric disorder. In this scenario, the development of different animal models contributes to our understanding of the neurobiology of these disorders and provides the possibility of preclinical pharmacologic screening. The present review seeks to provide a comprehensive overview of traditional and recent animal models, recapitulating different features and the possible pathologic mechanisms of mood disorders emulated by these models.

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Double-blind, randomized, placebo-controlled 6-week study on the efficacy and safety of the tamoxifen adjunctive to lithium in acute bipolar mania

Cited by 77 publications

References 10 publications

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

A Role for the PKC Signaling System in the Pathophysiology and Treatment of Mood Disorders: Involvement of a Functional Imbalance?

Contributions of animal models to the study of mood disorders

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