Pharmacological treatments of panic disorder. A systematic review and meta-analysis of antidepressants versus placebo studies

A panic attack is a discrete period of fear or anxiety with a rapid onset, reaching a peak within 10 minutes and in which at least 4 of 13 characteristic symptoms, involv-ing both bodily systems and fearful cognitions, are experienced. The treatment of panic disorder (PD) includes psychological and pharmacological interventions, often used in combination. Given the complexity of the condition and the lack of recent data from systematic reviews in PD we have considered the importance of carrying out a comprehensive review of available drug options, in the framework of network meta-analysis (NMA), to assess which treatments, if any, are the most effective and safe. OBJECTIVES: To determine the efficacy, the acceptability and the adverse effects of anti-depressants in comparison to placebo in the treatment of PD with or without agora-phobia.METHODS: My work is part of a bigger project, a network meta-analysis (NMA), involving other international members of the Cochrane Collaboration Neurosis and Anxiety group (CCDAN).The second reviewer (AC) and I (MC) independently checked the references provid-ed by the CCDAN search and selected 104 out of 1383 abstracts and references, as eligible for our review, of which we retrieved the corresponding full texts, whereas possible. We selected 42 eligible studies, we extracted the data, we performed the “quality assessment” of each study using the “risk of bias tool” provided by the Cochrane Handbook. We performed the data entry using Review Manager 5.3 ver-sion and we got results for the primary outcomes (response rate and drop-outs) and secondary outcomes.RESULTS: The results of this meta-analysis expand current evidence on the efficacy of antidepressants in patients with panic disorder. Interestingly, treatment with TCAs was more acceptable than placebo, while treatment with other antidepressants, when compared to placebo, was not associated with a better acceptability profile. In terms of number of patients experiencing at least one adverse effect, there were too few studies reporting data, and this might be suggestive of a reporting bias.CONCLUSIONS: These results are consistent with the fact that antidepressants, which are widely used in people affected by panic disorder, are better than placebo, in terms of effectiveness and tolerability, and also reducing symptoms of anxiety and depression and improving social functioning. This confirms what is already suggested by the international guidelines (APA 2009, BAP 2005 and NICE 2011), where their use is suggested as first line treatment together with CBT. The unusual data regards TCAs tolerability. We might hypothesize that the benefit of the TCAs over panic symptoms might compensate the low tolerability profile in terms of adherence to treatment. So this could suggest us to reconsider this class of antidepressants (in par-ticular imipramine) as a possibile first choice of treatment, maybe for more severe cases, taking advantage of their sedative profile, in those cases where anxiety raises particularly high levels. There is a need of studies with a higher quality, in particular better reporting of the randomization process and less sponsorship bias that could have influenced the results.