Aspirin and celecoxib may help to rectify a neurotransmission imbalance in bipolar disorder

Mood stabilizers with disparate chemical structures are approved for treating bipolar disorder, but their mechanisms of action are not agreed on. However, when administered to unanesthetized rats at clinically relevant doses, they modulate neurotransmission involving arachidonic acid and brain activ...

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Bibliographic Details
Published in:Medical hypotheses 2021-04, Vol.149, p.110536-110536, Article 110536
Main Author: Rapoport, Stanley I.
Format: Article
Language:English
Subjects:
Acetylsalicylic acid
Animals
Antimanic Agents - therapeutic use
Arachidonic acid
Aspirin
Aspirin - therapeutic use
Bipolar disorder
Bipolar Disorder - drug therapy
Brain
Celecoxib
Celecoxib - therapeutic use
COX-2
Cyclooxygenase
Humans
Imbalance
Mood stabilizer
Neurotransmission
Rat
Rats
Synaptic Transmission
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Summary:Mood stabilizers with disparate chemical structures are approved for treating bipolar disorder, but their mechanisms of action are not agreed on. However, when administered to unanesthetized rats at clinically relevant doses, they modulate neurotransmission involving arachidonic acid and brain activity of COX-2, which oxidizes arachidonic acid within the arachidonic acid metabolic cascade. Inhibiting COX-2 directly might enhance mood stabilizer effects in bipolar disorder patients. This paper reviews randomized controlled trials that showed that celecoxib, a selective COX-2 inhibitor, or low-dose aspirin, which inhibits COX-1 and inhibits/acetylates COX-2, reduced bipolar symptoms in patients on mood stabilizers. More convincing are two population based pharmacoepidemiological studies that each demonstrated that chronic low dose aspirin reduced bipolar severity markers in patients on mood stabilizers. This clinical evidence is consistent with the hypothesis that low-dose chronic aspirin and celecoxib, which can inhibit COX-2 and enter brain, can be repurposed in bipolar disorder to enhance mood stabilizer effects on arachidonic acid metabolism and neurotransmission.
ISSN:0306-9877
1532-2777
DOI:10.1016/j.mehy.2021.110536