When selecting an antidepressant drug, it is worthwhile to consider that side effects may have a clinical advantage. For example, some TCAs, such as amitriptyline, and atypical antidepressants, such as mirtazapine and trazodone, produce sedation and may be useful for agitated patients and for those who have difficulty getting to sleep. Consequently, treatment is often initiated as a single daily dose administered at bedtime. Although most patients will develop tolerance to antidepressants' sedative effects with continued treatment, the need for soporific agents may diminish with improvement in depressive symptoms.
When selecting antidepressants, either singly or in combination, consider the following:
- Target specific distressing symptoms.
- Evaluate coexistent medical problems that may be exacerbated by particular antidepressants.
- Minimize side effects and avoid worsening of current health status.
- Determine the patient's ability to swallow solid dosage forms; he or she may be able to take an antidepressant in liquid form (e.g., amitriptyline, nortriptyline, doxepin, fluoxetine). Alternatively, some antidepressants are available as parenteral dosage forms (e.g., amitriptyline and imipramine injection).
- Evaluate the patient's medication profile for potential interactions with antidepressant drugs.
Selective serotonin reuptake inhibitors
The postulated mechanism of action of SSRIs involves the blockade of serotonin neuronal reuptake, leading to desensitization of serotonergic feedback receptors. All currently available SSRIs are equally efficacious; they differ primarily in their safety, tolerability, half-lives, and drug-drug interactions. While some side effects are more common with some SSRIs than with others, side effects and tolerability may differ significantly in individual patients. SSRIs have become the first-line treatment for depressive disorders, owing to their better tolerability side effect profile, especially in comparison with the TCAs. As discussed earlier, antidepressant studies conducted in patients with cancer are done mostly with SSRIs or TCAs. None of the clinical trials have included or focused on children and adolescents being treated for cancer.[19,20,21,22][Level of evidence: I] Overall, the evidence on the efficacy of SSRIs for treating cancer-related depression remains limited, and more studies are needed to address the efficacy, safety, tolerability, and drug-drug interaction issues in the context of cancer and cancer treatments. The British Committee on Safety of Medicines considered only one of the SSRIs (fluoxetine) to have a favorable balance of risks and benefits, but it is only considered beneficial in approximately one in ten patients. Consistent with this finding, age-stratified analyses of the child and adolescent studies found that for children younger than 12 years with major depression, only fluoxetine showed benefit over placebo.[Level of evidence: I] As noted, none of the children or adolescents in these studies had cancer, so there are no reports available that address whether there are additional increased risks of adverse events associated with the use of SSRIs following exposure to different chemotherapeutic agents and/or central nervous system (CNS) radiation treatment. Frontline, alternative, effective, behavioral, and pharmacologic treatments for depression should be used for children and adolescents being treated for cancer. However, if the risks of depression are significant and SSRIs are considered, consultation from a child psychiatrist or neurologist is essential, and close monitoring of potential adverse events is crucial. No warning has been issued for adult use of SSRIs.