Slow vs standard up-titration of paroxetine in the treatment of panic disorder: A prospective randomized trial


Massimiliano Buoli, MD, Department of Psychiatry, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy. Email:


Aim:  Patients with panic disorder (PD) might be sensitive to the stimulating effects of selective serotonin reuptake inhibitors (SSRI), thus requiring low dosages at treatment initiation. The aim of the present study was to assess eventual differences in terms of effectiveness and tolerability between a slow up-titration with paroxetine and a standard one.

Methods:  In an open randomized, multicenter, primary-care study, 60 patients (44 women and 16 men) with PD with or without agoraphobia were enrolled and randomized to receive a slow up-titration with paroxetine (increments of 2.5 mg/day every 2 days) or a standard one (increments of 10 mg/day every week) up to a maximum daily dose of 20 mg. Repeated-measures anova on sub-items scores of the Panic Attack Anticipatory Anxiety Scale (PAAS) and Dosage Record and Treatment Emergent Symptom Scale (DOTES), respectively, used as outcome measures of effectiveness and tolerability, were performed. Significance level was set at 0.05 and it was not corrected.

Results: anova showed no differences between the two treatments in terms of effectiveness and tolerability. Post hoc analysis found only one significant difference in the intensity of spontaneous panic attacks (Panic and Anticipatory Anxiety Scale) in the first 9 days of treatment between the two treatment groups, which was that this item was less intense in the slow-titration group (treatment effect: F = 4.89, P = 0.03, effect size = 0.1).

Conclusion:  Present findings suggest only a small superiority for a slow up-titration regimen of paroxetine compared to a standard one in the first 9 days of treatment but no differences at end-point.