This article originally appeared in the June 2004 Harvard Women's Health Watch and is provided courtesy of Harvard Health Publications.

Treating depression: Update on antidepressants

Antidepressants are a mainstay of depression treatment. We’ve learned more about what they do and how best to use them.

Depression. The ancient Greeks were on the right track when they called it “melancholia” and described it as a disabling illness rather than a passing bout of sadness, dejection, or feeling down in the dumps. As anyone who has experienced it knows, depression settles in and takes over. It can rob us of sleep, the desire to eat, the ability to concentrate, and, perhaps worst of all, the capacity to take pleasure in anything, including family and friends. All over the world, this debilitating experience is more common in women than in men. In the United States, where more than 19 million adults suffer from some type of depression every year, the ratio is two to one.

Most depression can be treated effectively. For example, talk therapy can help a woman understand and address sources of depression, such as loss, trauma, and internal conflicts. Medications can treat some of the faulty neurochemistry thought, in many cases, to underlie some aspects of the disorder. Either approach is effective for mild to moderate depression; optimally, they should be used together.

According to a National Mental Health Association survey, many women believe depression is “normal” during certain stages of their lives and may not seek help. But depression is not normal at any age. Given its enormous impact on the quality of life, no woman should hesitate to ask for help from her primary care doctor or a psychologist, psychiatrist, pastoral counselor, or other qualified mental health professional. The range of therapies now available makes it possible to receive individually tailored treatment that can be adjusted as circumstances change.

This article is an update on antidepressant options and their use. Look for a discussion of psychotherapeutic approaches in the August 2004 issue of the Harvard Women’s Health Watch.

Choosing an antidepressant
Most antidepressants increase circulating levels of neurotransmitters (chemicals that permit communication among nerve cells) in the brain. The targeted neurotransmitters are serotonin, norepinephrine, and dopamine. Antidepressants are not “uppers.” They improve mood only in people who are depressed, and the improvement is slow (it may take 4–6 weeks) and can be quite subtle.

Depression is different in every woman. We don’t all respond to the same antidepressants, nor to the same doses of them. Any given antidepressant won’t work in 10%–30% of people who take it, so it may take several months to find the right medication and dose. If one medication doesn’t work, you may need a supplemental one, or a different drug altogether. The goal is complete relief of symptoms, which can include sleep problems, significant weight change, unrelieved sadness or tearfulness, trouble concentrating, and an overwhelming sense of worthlessness or guilt. Your clinician should follow you closely to make sure that treatment is working and to monitor for side effects or any other problems.

All have side effects
Tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and several newer drugs all have different mechanisms and side effects (see “Medications for treating depression”). Reducing the dose, adding a counteracting drug, or switching to a different class of drug can overcome some side effects. For example, SSRIs very often reduce libido and interfere with the ability to reach orgasm. Wellbutrin and Remeron are less likely to cause these problems. Weight gain, a common complaint with TCAs and MAOIs, is less likely to occur with Effexor and Wellbutrin.

There are many ways to resolve side effects, so don’t hesitate to let your clinician know if you’re experiencing any.

About SSRIs
SSRIs were introduced in the 1980s, unseating tricyclic antidepressants (TCAs) as the first-line medications for treating depression, because they have slightly fewer side effects, are easier to use (no blood level monitoring is required), and are safer in case of an overdose. TCAs may work better, however, in certain situations, such as when pain or insomnia is involved. Prozac, the first SSRI developed for treating depression, has become particularly well known because of popular books, such as Peter D. Kramer’s Listening to Prozac (1997) and Lauren Slater’s Prozac Diary (1999). Prozac is now widely used for other psychiatric conditions, including anxiety, bulimia, and phobias, and is marketed to women as Sarafem to relieve premenstrual dysphoric disorder.

Prozac has also gained notoriety because of scattered reports associating it with an increased risk for suicide. The FDA has urged the manufacturers of Prozac and several other antidepressants to include stronger warnings that patients taking these drugs should be monitored for suicidal thoughts, especially early in treatment or when the dose is adjusted. As yet, there’s no clear evidence of a direct link between Prozac and suicide.

Not addicting, but avoid quick stops
If you’ve been prescribed an antidepressant, expect to stay on it for at least six months. Research suggests that longer may be better. But many people quit sooner, partly because of side effects.

Although antidepressants aren’t considered addictive, they can cause some uncomfortable withdrawal symptoms —known as a discontinuation syndrome — if they’re stopped too abruptly. Each of the major antidepressant classes has its own typical discontinuation syndrome. People who suddenly quit taking SSRIs or skip several doses may experience dizziness, trouble with balance or coordination, tingling, electric-shock-like sensations, and flulike symptoms. Drugs that take longer to clear the body, such as Prozac, produce fewer and milder symptoms. The riskiest symptoms follow abrupt withdrawal from MAOIs, which can cause agitation, sleeplessness, and sometimes psychosis with hallucinations or paranoia. (This class of medications is rarely used.)

The solution to discontinuation syndrome is to taper very gradually, and if symptoms appear, to resume taking the usual dose and taper more slowly from there.