Antidepressants Side Effects: Pediatric Mental Health Minute Series

Antidepressants are medications commonly used to treat depressive and anxiety disorders in children and adolescents. These medications are generally divided into selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

Scope in Pediatrics

• SSRIs are the first line of psychopharmacologic treatment for anxiety and depressive disorders.
• Antidepressant selection should be evidence-based and currently the strongest evidence exists for SSRIs including escitalopram, fluoxetine, and sertraline. SNRIs may be less effective in children and adolescents.
• Dosing and titration should be guided by data from clinical trials which suggests starting low, but actively titrating medication to ensure the highest likelihood of success.
• Side effects of SSRIs may occur in 1 of 10 children or adolescents. Some side effects relate to blood levels (eg, exposure) while others are related to pharmacodynamic factors. Frequently, the management strategy is to reduce the dose or discontinue the medication.
• SSRIs include a black-box warning with regard to the risk of suicidal ideation in children and adolescents. Although the risk is low, it is very important to monitor for any clue that the patient may be experiencing this side effect. 
• One challenge in treating anxiety disorders is managing the dose to minimize the side effects without reducing the dose to a point where the benefit of the SSRI is lost. At times, side effects outweigh the medication’s benefit and a change in medication is needed.
• Although FDA approved for depression, once a drug is licensed, it can be used “off-label” based on available evidence for safety and efficacy at the discretion of the prescribing clinician. 

Teaching Points

• SSRIs block serotonin reuptake at the pre-synaptic neuron, although they vary in the degree to which they block other receptors. Blocking the serotonin transporter, increases the concentrations of serotonin at the synapse. Blocking the norepinephrine transporter—as is the case with SNRIs—increases the concentrations of norepinephrine (as well as causing a slight increase in dopamine).
• Side effects are generally mild and dissipate relatively quickly, although some may require dose adjustment or—in some cases—a change in medication.
• The most common and most problematic side effects are abdominal symptoms, activation, and tiredness/insomnia.
• Clinicians selecting antidepressant medications to treat pediatric patients need to understand the cause of side effects as well as management strategies, particularly as antidepressant side effects increase the likelihood of discontinuation, slow the trajectory of improvement and potentially limit titration to effective doses.