Panic disorder can be treated with pharmacotherapy, psychotherapy or in combination, but the relative merits of combined therapy have not been well established.To review evidence concerning short- and long-term advantages and disadvantages of combined psychotherapy plus antidepressant treatment for panic disorder with or without agoraphobia, in comparison with either therapy alone.The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References) were searched on 11/10/2005, together with a complementary search of the Cochrane Central Register of Controlled Trials and MEDLINE, using the keywords antidepressant and panic. A reference search, SciSearch and personal contact with experts were carried out.Two independent review authors identified randomised controlled trials comparing the combined therapy against either of the monotherapies among adult patients with panic disorder with or without agoraphobia.Two independent review authors extracted data using predefined data formats, including study quality indicators. The primary outcome was relative risk (RR) of "response" i.e. substantial overall improvement from baseline as defined by the original investigators. Secondary outcomes included standardised weighted mean differences in global severity, panic attack frequency, phobic avoidance, general anxiety, depression and social functioning and relative risks of overall dropouts and dropouts due to side effects.We identified 23 randomised comparisons (representing 21 trials, 1709 patients), 21 of which involved behaviour or cognitive-behaviour therapies. In the acute phase treatment, the combined therapy was superior to antidepressant pharmacotherapy (RR 1.24, 95% confidence interval (CI) 1.02 to 1.52) or psychotherapy (RR 1.17, 95% CI 1.05 to 1.31). The combined therapy produced more dropouts due to side effects than psychotherapy (number needed to harm (NNH) around 26). After the acute phase treatment, as long as the drug was continued, the superiority of the combination over either monotherapy appeared to persist. After termination of the acute phase and continuation treatment, the combined therapy was more effective than pharmacotherapy alone (RR 1.61, 95% CI 1.23 to 2.11) and was as effective as psychotherapy (RR 0.96, 95% CI 0.79 to 1.16).Either combined therapy or psychotherapy alone may be chosen as first line treatment for panic disorder with or without agoraphobia, depending on patient preference.