Depression Symptoms Treatment

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On average, all antidepressants are equally effective. Without a personal or family history of response to a particular agent, side effects are the most influential factors when selecting treatment.

Both longitudinal and cross-sectional factors should be considered when selecting an antidepressant for major depression:

• What were the course, duration, and severity of any previous episodes of depression?

• Is there a history of antidepressant response?

• How well was the antidepressant tolerated?

• Is there a family member with a history of antidepressant response; if so, to which medication?

• If there is a history of antidepressant failure, were the trials of an adequate dose and duration?

• Are melancholic, atypical, or psychotic features present?

• Does the patient have a history of sensitivity to anticholinergic, histaminic, α-adrenergic, serotonergic, or noradrenergic side effects?

• Does the patient have suicidal features or a history of impulsivity that may increase the risk for potential overdose?

• Does the patient have a history of a cardiac conduction delay or recent myocardial infarction (which would contraindicate the use of TCAs)?

• Does the patient have a history of symptoms suggestive of mania (or more minor variants of manic episodes)? If so, avoid tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs)

• Does the patient presently take or need sympathomimetics (which would contraindicate the use of MAOIs)?

• If an antidepressant trial has failed, was the patient a partial responder or a nonresponder?

• Were any augmentation strategies employed?

Special Considerations in the Selection of an Antidepressant

The following factors should be considered when selecting an antidepressant agent.

Gender Women may have slower gastrointestinal absorption than men due to less gastric acid and slower gastric emptying. A woman’s volume of distribution differs as well, given her increased ratio of adipose tissue to lean body mass. Water retention associated with the menstrual cycle may also affect the volume of distribution. Oral contraceptives can alter the hepatic metabolism of tricyclic antidepressants (TCAs).

Ethnic and Racial Factors African-Americans may be more likely than those of European descent to be slow metabolizers of antidepressant due to possible genetic differences in metabolic enzyme expression; a growing number of studies suggest that African-Americans will have higher plasma levels per dose of antidepressant. This has been primarily demonstrated with TCAs; data with selective serotonin reuptake inhibitors (SSRIs) are lacking. Some data suggest that Asians are slower to metabolize nortriptyline than other groups.

The greatest concern regarding race and ethnicity is suggested in a study of prescribing practices in Westchester County (New York) mental health clinics, which found that minorities were less likely than nonminorities to be offered antidepressant treatment, independent of diagnosis.

Age Is the patient elderly? If so, selective serotonin reuptake inhibitors (SSRIs) are indicated as half-lives and steady-state concentrations of these agents are only minimally affected by age (although paroxetine may be an exception to this).

Comorbidities Patients with renal impairment may require dose adjustment for many antidepressants; fluoxetine and sertraline appear to be the exception. Liver disease can increase levels of tricyclic antidepressants (TCAs) — blood levels should be monitored. SSRIs are extensively metabolized in the liver and lower doses should be given in hepatic-impaired patients. Nefazodone is not indicated due to association with hepatic injury.

Pregnant women and nursing mothers Clinicians must consider whether the potential benefits of treatment justify the potential risk to the fetus. The risks of untreated depression are well-described, and the risks of medication treatment during pregnancy and lactation are less well-known. In general, studies have not shown increases in fetal malformations from antidepressant exposure. Reports of withdrawal syndromes among neonates have led some experts to recommend tapering and discontinuing antidepressants 10 to 14 days before the mother’s due date. Antidepressants are excreted in varying degrees in breast milk, so breastfeeding in antidepressant-treated women should be done with caution.

Predictors of poor response In assessing the likelihood of success, the following predictors of poor response have been identified: neurovegetative symptoms such as hypersomnia, hyperphagia, psychomotor agitation, anxiety and irritability, personality features (such as neurotic, hypochondriacal, and hysterical traits), multiple prior episodes, delusions, and psychomotor agitation.

Continuation: Drug Selection and Initiation of Treatment for Major Depression. Treatment