Psychopharmacological Intervention for Depression

When we think about psychiatric strategies for treating young patients with depression—undercontrolled (UC) and overcontrolled (OC) styles of coping alike—it is important to consider several nuances of pediatric pharmacotherapy:

• 80% of medications are not approved by the FDA for use in children.
• There are far fewer evidence-based studies in adolescent psychiatry than adult psychiatry.
• Placebo effect is greater in kids than adults, which blunts the effects observed in short-term studies.
• There can be stigma against using medications in treating mental illness, particularly for pediatric patients.

These realities mean that psychiatrists working with children and adolescents often must use their best judgment based on the adult literature, clinical experience and recommended practice parameters/guidelines. If medication is indicated, SSRIs are a good place to start—some medications have been approved for children as young as eight years old, and several options may be viable based on the clinical presentation and circumstances of the adolescent.

Although the SSRIs are well tolerated as a class, their distinct secondary effects on the body—including interactions with various neurotransmitter receptors— may produce slightly different side effect profiles (i.e. stimulating vs. sedating). These secondary effects can be advantageous or disadvantageous depending on the circumstances, including whether the young patient has overcontrolled or undercontrolled depression. For example, activating effects can be helpful for patients with extreme psychomotor retardation but can lead to added distress and polypharmacy among patients with anxiety or panic disorder (which often coexists with depression) when combined with benzodiazepines. Although it is impossible to anticipate exactly how a given person will respond to a particular SSRI, thoughtful consideration of possible differences in secondary effects may help the clinician to make the most favorable match between patient and medication.

Another prescribing consideration is SSRI-induced activation syndrome in children and adolescents. While SSRIs are the most commonly used psychotropics in the pediatric population, developmental differences (related to pharmacodynamics and pharmacokinetics) cause a difference in response in children compared to adults. Signs and symptoms of activation syndrome generally emerge within 2-3 weeks of SSRI administration and include: irritability, agitation, somatic manifestations of anxiety, panic attacks, restlessness, hostility, aggression and insomnia. Given the severity of these symptoms, activation syndrome is a major reason a young patient may withdraw from pediatric clinical trials. Because activation frequently emerges early in treatment and following an increase in dose, it can be managed and frequently resolves when the antidepressant dose is decreased or discontinued. Furthermore, activation related disinhibition may exacerbate impulse control problems. In youth at increased risk for developing activation (UC depression, ADHD and family history of borderline personality disorder), starting at low doses with slow, planned titrations may decrease the likelihood of treatment-related activation. For young patients and families seeking alternatives to medication for treating depression, there is evidence that certain nutraceuticals, including omega-3 fatty acid and inositol (vitamin B8), may lead to positive outcomes when combined with psychotherapy. Also, daily exercise has been shown to improve depressive symptoms in adolescents, and repetitive transcranial magnetic stimulation (rTMS) shows promise as an alternative intervention in pediatric patients.

Regardless of the medication, dose or psychiatric approach, one thing is clear: All children and adolescents with depression should engage in a combination of pharmacotherapy plus psychotherapy. Studies show these interventions used in tandem reduce suicidal thoughts and behaviors and that patients tend to have improved outcomes relative to those that engage in pharmacotherapy alone to treat depression.