Valproate Adjuvant Cognitive Behavioral Therapy in Panic Disorder Patients With Comorbid Bipolar Disorder: Case Series and Review of the Literature

Abstract

Anxiety disorders are the most common comorbid psychiatric disorders in patients with bipolar disorder. Managing anxiety symptoms in comorbid conditions is challenging and has received little research interest. The findings from preclinical research on fear conditioning, an animal model of anxiety disorder, have suggested that memory reconsolidation updating (exposure-based therapy) combined with valproate might facilitate the amelioration of fear memories. Here, three cases of successful amelioration of agoraphobia and panic symptoms through valproate adjuvant therapy for cognitive behavioral therapy in patients who failed to respond to two to three consecutive standard pharmacotherapy trials over several years are described. To the best of the author’s knowledge, this is the first attempt to combine CBT with valproate in patients with panic disorder, agoraphobia, and comorbid bipolar disorder. Additionally, the background preclinical research on this combination therapy based on the reconsolidation-updating mechanism, the inhibition of histone deacetylase 2, and critical period reopening, off-label use of valproate in panic disorder, plasticity-augmented psychotherapy, and how to combine valproate with CBT is discussed.

Methylome-wide association studies of traumatic injury identifies differential DNA methylation of synaptic plasticity and GABAergic-signalling

“…[83] Evidence, although limited, suggests that use of VPA in conjunction with cognitive behaviour therapy may reduce symptoms of panic disorders and improve fear extinction. [84][85][86] Roseberry et al, suggest that Valproate could provide a possible therapeutic route for anxiety disorders. [87] This is consistent with VPA, prescribed for the treatment of bipolar disorder, as a possible therapeutic approach to trauma, particularly for irritability associated with trauma.…”

Trichostatin A relieves anxiety-and depression-like symptoms in APP/PS1 mice

“…Similar phenomena are also found in the autopsy of anxiety patients and animals ( Sah et al, 2019 ; Peng et al, 2021 ). Moreover, several studies show that histone deacetylase inhibitor (HDACi) can ameliorate anxiety- and depression-like behavior in patients and rodents ( Sah et al, 2019 ; Peng et al, 2021 ; Choi, 2022 ; Baek et al, 2023 ). Taken together, these findings suggest that is closely involved in the pathophysiology of anxiety and depression is closely related to histone acetylation.…”