Clomipramine and initial worsening in panic disorder: beyond the 'jitteriness syndrome'.

The time course and the phenomenology of the initial response to clomipramine (10-20 mg/day) was investigated in 70 patients with panic disorder with or without agoraphobia. Nineteen (27.1%) patients reported worsening of their clinical state which, on average, began 28 h after the first dose and lasted for 5 days. Increase in the frequency and severity of panic attacks was the most frequent finding (14 patients), followed by psycho- stimulant (jitteriness; n=9), depressive (n=8) and tonic anxiety symptoms (n=7). This pattern of initial worsening is different from the 'jitteriness syndrome' described for other antidepressants. Its implications for the understanding of the pathophysiology of panic disorder are discussed.