Abstract: This long-term extension of an 8-week randomized, naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam (n = 47) and paroxetine (n = 37) over a 3-year total treatment duration. Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine (both taken at bedtime). This study reports data from the long-term period (34 months), following the initial 8-week treatment phase. Thus, total treatment duration was 36 months. Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine, but patients with partial primary treatment success were switched to the combination therapy. At initiation of the long-term study, the mean doses of clonazepam and paroxetine were 1.9 (SD, 0.30) and 38.4 (SD, 3.74) mg/d, respectively. These doses were maintained until month 36 (clonazepam 1.9 [SD, 0.29] mg/d and paroxetine 38.2 [SD, 3.87] mg/d). Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)–Improvement rating than treatment with paroxetine (mean difference: CGI-Severity scale −3.48 vs −3.24, respectively, P = 0.02; CGI-Improvement scale 1.06 vs 1.11, respectively, P = 0.04). Both treatments similarly reduced the number of panic attacks and severity of anxiety. Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine (28.9% vs 70.6%, P < 0.001). The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course. There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events.
From the *Panic and Respiration Laboratory, Institute of Psychiatry, Federal University of Rio de Janeiro, National Institute for Translational Medicine(INCT-TM); †Fluminense Federal University, Niteroi, Rio de Janeiro; ‡Alagoas Federal University, Maceio, Alagoas; §Consultation-Liaison Psychiatry Unit, Pró-Cardíaco Hospital, Rio de Janeiro; and ∥Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, National Institute for Translational Medicine (INCT-TM), São Paulo, Brazil.
Received January 20, 2011; accepted after revision June 29, 2011.
Reprints: Antonio E. Nardi, MD, PhD, Panic and Respiration Laboratory, Institute of Psychiatry, Federal University of Rio de Janeiro, National Institute for Translational Medicine (INCT-TM), Rua Visconde de Piraja 407/702, Rio de Janeiro 22410-003, Brazil (e-mail: email@example.com).
The grant for this trial was provided by the Brazilian Council for Scientific and Technological Development (CNPq) and the National Institute for Translational Medicine (INCT-TM). Drs Nardi, Valença, Nascimento, Hallak, and Crippa are recipients of CNPq Productivity fellowship awards. The authors received editorial/writing support solely in the preparation of this manuscript funded by F. Hoffmann–La Roche Ltd. The funding source had no role in the study design; collection, analysis, and interpretation of data; or in the decision to submit the paper for publication.