Numerous studies have shown increased rates of depression in physically ill children and adolescents, including patients with inflammatory bowel disease, cancer, and asthma (Apter et al. 2003; Mrazek 2003; Szigethy et al. 2004). First-line treatment for depression should include nonpharmacological interventions. However, for children who present with moderate or severe depressive symptoms or with impaired functioning, treatment should incorporate medications, generally in combination with psychotherapy such as cognitive-behavioral therapy (Boylan et al. 2007) or interpersonal psychotherapy (Mufson et al. 2004). To date, there have been no studies on the use of antidepressants for the treatment of mild depression in children or adolescents.


The majority of controlled treatment study data for antidepressant efficacy in youth are for SSRIs, which have become the drug treatment of choice for depression due to their effectiveness, safety, and side-effect profiles (Brent et al. 2008; Flanagan 2008; Kersun and Elia 2007). There have been several randomized, controlled trials demonstrating the efficacy of the SSRIs in treating children and adolescents with major depression (Boylan et al. 2007; Bridge et al. 2005).

By contrast, studies of the TCAs have shown no greater efficacy compared with placebo, and they are not currently recommended due to their unfavorable side-effect profile and risk of lethality following overdose (Boylan et al. 2007). However, clinical indications for their use at lower dosages exist for specified situations, for example, enuresis and migraine prophylaxis. There are data to support the use of venlafaxine in the treatment of adolescents with major depression (Bridge et al. 2005) and bupropion for children with comorbid major depression and ADHD (Daviss et al. 2001).

Medication algorithms for childhood major depression have been developed to guide treatment, including the Texas Children's Medication Algorithm Project (Hughes et al. 2007). In the case of the physically ill child, there may be specific circumstances that influence the choice of a therapeutic agent. The choice of a specific antidepressant is usually directed by consideration of its side effects, half-life, and potential drug interactions. For example, in children with chronic pain syndromes, venlafaxine may have dual benefits in terms of its demonstrated antide-pressant and analgesic actions (Kiayias et al. 2000). For patients with low energy or attentional issues, bupropion may have additional benefits. For patients on multiple medications for their physical illness, where drug interactions are a concern, escitalo-pram may have benefits over other SSRIs commonly recognized as first-line agents, including fluoxetine.


Psychostimulants have long been recognized to have euphoric and alerting properties that suggest their usefulness in treating depressive disorders (Orr and Taylor 2007). The available literature, primarily from studies with adults, suggests that psychostimulants have useful antidepressant properties and may be used as adjuncts to standard antidepressants in refractory depression, particularly in physically ill patients or those with terminal illness.

In a Cochrane database review, Candy et al. (2008) identified 24 randomized, controlled trials on the use of psychostimulants, including dexam-phetamine, methylphenidate, methamphetamine, pemoline, and modafinil, to treat depression. Three studies suggested that psychostimulants used as monotherapy significantly reduced short-term depressive symptoms as well as symptoms of fatigue. The authors concluded that there may be specific clinical situations, including the physically ill child, in which psychostimulants may play a particular role.

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