Activation syndrome in children and adolescents treated with selective serotonin reuptake inhibitors

Introduction and objectives

Selective serotonin reuptake inhibitors (SSRIs) are medications used in child and adolescent psychiatry mainly for the treatment of depression, anxiety and obsessive compulsive disorder. In general, these medications are safe and well tolerated. However, they can cause adverse effects such as activation syndrome, which if not identified can negatively affect adherence and response to treatment. Activation syndrome has received little attention and can be difficult to recognise due to the lack of a clear definition and objective diagnostic measures, and also because it can be confused with a worsening of the psychiatric disorder or mania triggered by the antidepressants. For all the above, it is important that professionals who prescribe antidepressants in the paediatric population are able to identify and manage activation syndrome when it occurs. Our aim was to carry out a narrative review of activation syndrome in children and adolescents treated with SSRIs in terms of definition, prevalence, pathophysiology, associated factors, relationship with suicide risk, management strategies and recommendations for reducing the risk of suicidal behaviours when using antidepressants in this population.

Methods

We performed a non-systematic narrative review of activation syndrome in children and adolescents which involved finding information in PubMed, Ovid, EBSCO, ProQuest and Embase. Review articles, prospective and retrospective investigations, systematic reviews, meta-analyses and other articles related to activation syndrome in children and adolescents were selected. The search was limited to studies published in English and Spanish that involved children and adolescents and no limits were applied to the publication date or study design.

Results

A total of 62 articles were included, 61 of them in English. The results were grouped into the following topics: definition; prevalence; pathophysiology; associated factors; relationship with suicide risk; management strategies; and recommendations for reducing the risk of suicidal behaviours when using antidepressants in this population. Activation syndrome refers to a set of symptoms consisting of impulsiveness, restlessness, increased activity, insomnia, irritability, disinhibition and agitation. This syndrome is poorly characterised in terms of its definition, prevalence, risk factors and pathophysiology, a situation that limits its recognition and evaluation. There are many factors that predispose the development of the syndrome such as age, differences in brain development in the paediatric population, the characteristics of the patient or the antidepressant, disorders of neurological development, and the doses and plasma levels of the medications. It has been thought that activation syndrome may be related to suicidal tendencies. However, the evidence in support of this link is inconsistent and further studies are therefore necessary.

Conclusions

Activation syndrome with SSRI is a particularly important adverse effect in children and adolescents and, when it occurs, can cause lack of adherence to or discontinuation of treatment. Strict vigilance is therefore recommended during the use of these medications.