Abstract: 22 short-term (<= 16 weeks) RCTs were included in the analysis (2519 participants). The majority of the trials assessed the efficacy of the SSRIs (N = 15). Medication and placebo response occurred in 58.1% and 31.5% of patients, respectively (Number of studies (N) = 14, Number needed to treat (NNT) = 4). Medication was more effective than placebo in reducing overall symptom severity in OCD in a post-hoc comparison (N = 7, Weighted Mean Difference (WMD) = -4.45, 95%CI = -5.94, -2.97, n = 765). Medication was less well tolerated than placebo overall, though the absolute proportion of participants who withdrew due to drug-related adverse events was low (4.9%). Medication treatments can be effective in paediatric anxiety disorders, acting to reduce core symptoms, and should be considered as part of the treatment of these disorders. The greatest number of trials showing efficacy to date have assessed the SSRIs in treating paediatric OCD. There is no clear evidence to show that any particular class of medication is more effective or better tolerated than any other. As quantitative data was only available for the SSRIs and venlafaxine the routine use of benzodiazepines cannot be recommended, especially given concerns of dependency and treatment -related emergent adverse events associated with this class of drugs. Future RCTs could help identify potential clinical moderators of treatment efficacy. Studies of the long-term efficacy of medication treatment, optimal dosage, as well as direct comparisons of pharmacotherapy and psychotherapy are also warranted.

Plain-language summary: This systematic review of randomised controlled trials (RCTs) of pharmacotherapy of anxiety disorders in children and adolescents identified 22 short-term (<= 16 weeks) randomised controlled trials which were eligible for inclusion (2519 participants). Treatment response was significantly greater after treatment with medication (58.1%) than with placebo (31.5%) in 14 trials. Medication was more effective than placebo in reducing overall symptom severity across all of the anxiety disorders (number of studies (N) = 9). The greatest number of trials were for obsessive compulsive disorder (OCD), for which treatment efficacy in reducing symptom severity was also observed . The greatest number of trials showing efficacy to date have used the selective serotonin reuptake inhibitors (SSRIs). No controlled evidence could be found for the effectiveness of benzodiazepines, despite their continued prescription for paediatric anxiety disorders. Medication was less well tolerated than placebo, as indicated by the significant proportion of children and adolescents who dropped out due to adverse effects during the short term trials. Furthermore, while few incidences of suicidal behaviour/ideation in the included trials were attributed to study medication, it is important to be aware of the need for careful monitoring after initiation of SSRIs in treating this population. In conclusion, medication should be considered as part of the treatment of paediatric anxiety disorders over the short-term. Additional research into the optimal dose and duration of medication treatment, as well as the effects of age on the efficacy and tolerability of medication is warranted.