Clomipramine augmentation in treatment-resistant depression

Amsterdam, Jay D.; García‐España, Felipe; Rosenzweig, Martin

doi:10.1002/(sici)1520-6394(1997)5:2<84::aid-da4>3.0.co;2-5

Cited by 30 publications

(2 citation statements)

References 23 publications

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“…Clomipramine is a tricyclic antidepressant used in the treatment of MDD with both serotonergic and noradrenergic effects (Amsterdam et al, 1997), and thus our results suggest that we may have identified a functionally valid set of mRNA changes, which can be used to identify compounds which elicit similar functional effects.…”

Section: Discussionmentioning

confidence: 79%

Transcriptomic profiling of human hippocampal progenitor cells treated with antidepressants and its application in drug repositioning

et al. 2017

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Current pharmacological treatments for major depressive disorder (MDD) are ineffective in a significant proportion of patients, and the identification of new antidepressant compounds has been difficult. ‘Connectivity mapping’ is a method that can be used to identify drugs that elicit similar downstream effects on mRNA levels when compared to current treatments, and thus may point towards possible repositioning opportunities. We investigated genome-wide transcriptomic changes to human hippocampal progenitor cells treated with therapeutically relevant concentrations of a tricyclic antidepressant (nortriptyline) and a selective serotonin reuptake inhibitor (escitalopram). We identified mRNA changes common to both drugs to create an ‘antidepressant mRNA signature’. We used this signature to probe the Library of Integrated Network-based Cellular Signatures (LINCS) and to identify other compounds that elicit similar changes to mRNA in neural progenitor cells. Results from LINCS revealed that the tricyclic antidepressant clomipramine elicited mRNA changes most similar to our mRNA signature, and we identified W-7 and vorinostat as functionally relevant drug candidates, which may have repositioning potential. Our results are encouraging and represent the first attempt to use connectivity mapping for drug repositioning in MDD.

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Section: Discussionmentioning

confidence: 79%

Transcriptomic profiling of human hippocampal progenitor cells treated with antidepressants and its application in drug repositioning

et al. 2017

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“…There is uncertainty as to which TCAs cause clinically significant rises in serotonin levels. Clomipramine exerts a notable serotonergic effect whereas amitriptyline does not 55 56. 5HT 3 antagonists such as ondansetron may have a role in the development of serotonin syndrome, but this is still uncertain 57…”

Section: Serotonin Syndromementioning

confidence: 99%

Neuropsychiatric complications of commonly used palliative care drugs

Jackson

Doherty²,

Coulter³

2008

Postgraduate Medical Journal

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Monoaminergic‐based Pharmacotherapy for Depression

Papakostas¹,

Fava²

2005

Biology of Depression

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Although recent advances in neuropharmacology, neuroendocrinology, molecular biology, and pharmacogenetics have been instrumental in bringing about potential treatments for depression which are fundamentally unrelated to their predecessors, including substance P antagonists, glutaminergic agents, and corticotropinreleasing factor (CRF) antagonists, nevertheless it was agents that influenced the function of monoamine receptors and transporters that were discovered initially by serendipity and then developed as treatments for depression. The development of such compounds also served as a framework for the understanding of depression as a medical illness affecting brain functioning. As a result of these efforts, our field has gained further understanding of the role of monoamines in depression. In previous chapters, the relevance of monoamines in the underlying pathophysiology of depression was reviewed. In the following chapter we will focus on describing the contemporary role of monoaminergic agents in the treatment of depression. 6.

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Clomipramine augmentation in treatment-resistant depression

Cited by 30 publications

References 23 publications

Transcriptomic profiling of human hippocampal progenitor cells treated with antidepressants and its application in drug repositioning

Transcriptomic profiling of human hippocampal progenitor cells treated with antidepressants and its application in drug repositioning

Neuropsychiatric complications of commonly used palliative care drugs

Monoaminergic‐based Pharmacotherapy for Depression

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