For a person with a first-time episode of moderate to severe depression and no other psychological symptoms or medical conditions, the choice of medication is generally based on avoidance of side effects. For example, the tricyclic antidepressant amitriptyline can lower blood pressure and cause drowsiness and confusion —side effects that are especially troublesome for older people. The drug nortriptyline (Aventyl, Pamelor) is less likely to cause these side effects.

Family history can also help predict which drugs are most likely to be effective, as well as which ones are most likely to cause side effects. In addition, older people are typically started on lower doses than younger people to reduce the risk of side effects.

By themselves, antidepressant medications usually produce a significant improvement by four to six weeks, although it may take up to 12 weeks on a therapeutic dose to see the full benefit. If a person’s depression responds fully to medication after this period, treatment moves on to the continuation phase, which lasts for six months to one year at the same dosage level, and then to the maintenance phase. Those who have improved somewhat but still have a few symptoms after six weeks should be reassessed six weeks later (many are likely to improve further during this time). At the reassessment, the physician may adjust the dosage to improve response.

When a drug does not work, a doctor may prescribe an antidepressant from a different class of medications, because drugs in the same class tend to work similarly. When a drug from one class is producing good results but causes unacceptable side effects, switching to a different drug within the same class can often help.

In 20 to 50 percent of people, adding the drug lithium can help boost the action of an antidepressant. However, the addition of lithium increases the risk of side effects and adverse drug interactions, requiring close monitoring by a physician.

If maintenance treatment is no longer needed, drugs are discontinued slowly over a period of one to three weeks to avoid withdrawal symptoms. Relapses are most common during the first two months after a person stops taking an antidepressant. It is therefore important for individuals to remain in contact with their physicians during this period. Should a relapse occur, the same drug that was used successfully the first time often proves effective again.

Publication Review By: Karen L. Swartz, M.D.

Published: 04 Mar 2011

Last Modified: 11 Sep 2013