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

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.