A systematic review and meta-analysis of randomised controlled trials of medication in treating anxiety disorders in children and adolescents

Ipser JC, Stein DJ, Hawkridge S, Hoppe L

Published Online:

June 16, 2010

Anxiety disorders are a potentially disabling group of disorders which frequently occur in childhood and adolescence. Increasing recognition of the early onset of anxiety disorders and of the effectiveness of medication in treating adult anxiety disorders has contributed to a growing interest in the use of medication in treating paediatric patients. 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.

Abstract (click to read)

Background:

Anxiety disorders are a potentially disabling group of disorders which are prevalent in childhood and adolescence. The recognition of the early onset of anxiety disorders, and their successful treatment with medication in adults, has led to the growing interest in using medication for paediatric anxiety disorders.

Objectives:

To assess the efficacy and tolerability of medication for treating paediatric anxiety disorders.

Search strategy:

We searched the Cochrane Depression, Anxiety & Neurosis Group specialised register (CCDANCTR-Studies), MEDLINE (via PubMed 1966 to August 2008), EMBASE (1966 to August 2008), and PsycINFO (1972 to August 2008). Various electronic registers were searched for unpublished studies. Reference lists of retrieved articles were searched for additional studies.

Selection criteria:

All randomised controlled trials (RCTs) of pharmacotherapy in childhood/adolescent anxiety disorders.

Data collection and analysis:

Two raters independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. Investigators were contacted to obtain missing data. Summary statistics were stratified by medication class, and by medication agent for the selective serotonin reuptake inhibitors (SSRIs). Dichotomous and continuous measures were calculated using a random effects model, heterogeneity was assessed, and subgroup/sensitivity analyses were undertaken.

Main results:

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%).

Authors' conclusions:

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.

This record should be cited as:

Ipser JC, Stein DJ, Hawkridge S, Hoppe L. Pharmacotherapy for anxiety disorders in children and adolescents. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD005170. DOI: 10.1002/14651858.CD005170.pub2

Assessed as up to date:

August 8, 2008

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Primary Review Group:

Depression, Anxiety and Neurosis Group

Health topics:

Mental health > Anxiety disorders > Non-specific

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Independent high-quality evidence for health care decision making

A systematic review and meta-analysis of randomised controlled trials of medication in treating anxiety disorders in children and adolescents

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