Clinical studies of panic disorder

Abstract: Aims: To study efficacy and safety of alprazolam, imipramine, and placebo in treatment of panic disorder, to investigate comorbidity with social phobia, to determine platelet monoamine oxidase (MAO), and to follow the long-term course in a cohort of patients with panic disorder.Subjects and Methods: A double-blind comparison of alprazolam, imipramine, and placebo was performed in 123 Scandinavian outpatients with panic disorder according to DSM-III. Patients were randomly allocated; 41 to each treatment group. Well validated psychiatric instruments were used for weekly ratings of key symptoms. Blood samples for determination of platelet MAO activity were collected and analysed in plasma from 58 patients. In a follow-up after 5 and 15 years, 52 and 55 patients, respectively, were re-assessed with the same instruments as in the initial examination.Results: Alprazolam and imipramine are effective and safe in treating panic disorder. Freedom from panic attacks was obtained for 68% with alprazolam, 61% with imipramine and 34% with placebo. Globally rated by physician and patients, about 60% had complete remission with alprazolam and imipramine and 30% on placebo. Side effects were generally mild with a preponderance of drowsiness for alprazolam and anticholinergic effects for imipramine.Occurrence of social phobia in the 123 panic disorder patients was 26%, and agoraphobia was more frequent in the patients with social phobia (91%) than in those without (69%). Social phobia patients had more psychiatric problems before the age of 18. Panic disorder patients had lower platelet MAO activity than healthy controls. Women with concomitant agoraphobia and social phobia had lower MAO activity than women without. After 5 and 15 years, more than 80% of the patients no longer fulfilled criterias for panic disorder diagnosis. However, after 15 years, the majority (69%) still had anxiety symptoms. After 5 and 15 years, more than 80% reported satisfactory daily functioning, although more than 70% used psychotropic drugs. Conclusion: Alprazolam and imipramine are effective and safe in treatment of panic disorder, and despite recurrent anxiety attacks, panic disorder has a favourable outcome in a substantial proportion of patients in the long-term course. In our patient sample MAO in platelets was lower than in controls. Social phobia is a complicating factor in patients with panic disorder.