Antidepressant medications include: Serotonin-specific reuptake inhibitors (SSRI’s) fluoxetine, sertraline, citalopram, escitalopram, paroxetine, fluvoxamine; Serotonin-norepinephrine reuptake inhibitors (SNRI’s) venlafaxine, duloxetine, and desvenlafaxine; and atypical agents, bupropion, nefazodone, mirtazapine, and trazodone. Older agents such as Tricyclic antidepressants (TCA’s) and Monoamine Oxidase inhibitors (MAO’s) have more significant side effects and drug interactions and are now used infrequently, but may have utility in the treatment of more severe or refractory mood disorders. Choice of anti-depressant therapy should consider efficacy and tolerability, co-morbid medical conditions, and potential drug-drug interactions. The relatively low side effect burden of SSRI’s makes then first line treatment for most patients. However, depressed patients with co-morbid physical symptoms such as headache, pain and fatigue may respond less well to SSRI’s than those without such symptoms [35], raising concerns that childhood cancer survivors with physical late effects may be at risk for more refractory symptoms of depression.

It is important to note that the onset of effect for SSRI’s is usually 2–3 weeks, and it may take 4–6 weeks for full effect. The most common adverse effects of SSRI’s include nausea, tremor, headache, excessive sweating, activation or sedation, insomnia, dizziness, rash and dry mouth [36]. Many of these side effects are dose-dependent, and generally subside with time. There is also a rare side effect of toxicity and serotonin syndrome, especially when there are multiple serotonergic agents being taken. Emergence of sexual dysfunction including decreased libido, erectile dysfunction, delayed ejaculation and anorgasmia may occur, and can be a source of non-adherence to treatment [37]. Among the SSRI’s, Citalopram is noted to have the fewest inhibitory effects on cyp450 isoenzymes [38], making it potentially useful when these interactions are of concern to prescribers. Recent US Food and Drug Administration (FDA) warnings about increased risk of prolonged QTc at doses above 40 mg may limit use of Citalopram in higher doses among patients with existing cardiac risk factors [39]

In 2003, the FDA in the United States received unpublished data from placebo-controlled trials which suggested that paroxetine taken by pediatric patients with major depressive disorder might be associated with an elevated risk of “suicide attempts” and “possibly suicide-related” events. In 2007, the FDA made revisions to labeling for SSRI’s and extended caution to young adults, stating that when compared to placebo, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.

Data from large epidemiological studies examining rates of suicidal behavior have found no statistically significant effect of antidepressants on the likelihood of actual suicide attempt [40]. A study of four older antidepressant medications (fluoxetine, paroxetine, amitriptyline, and dothiepin) also concluded there were no significant associations between the use of a particular study antidepressant and the risk of suicide, although the risk of suicidal behavior was observed to be increased in the first month after starting antidepressants [41].

Although survivors of childhood cancer have increased rates of suicidal ideation that is associated with depression [4, 5], there is no data that SSRI treatment is specifically associated with suicidality in these patients.

Survivors who present with symptoms of depression require a careful history, consideration of non-pharamacologic approaches and potential medical causes, and close follow-up. General medical clinicians who use pharmacotherapy should prescribe recommended dosing for antidepressants, with specific caution and dose adjustments in patients with hepatic or renal insufficiency, or cardiac risk factors. Patients should be monitored regularly for treatment efficacy, side effects, and suicidal ideation, especially during initial dose titration. Patients with refractory symptoms need re-assessment and likely referral to specialized mental health clinicians.