Today, physicians can choose from a wide range of antidepressant medications. These include selective serotonin reuptake inhibitors (SSRIs), tricyclics, tetracyclics, dopamine reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and monoamine oxidase (MAO) inhibitors.
There are several advantages to treating depression with antidepressant medications:
The disadvantages are:
Because of these factors, many people do not have an adequate trial of a therapeutic dose for a sufficient period of time. Older individuals and those with chronic illnesses are more susceptible to the adverse effects of antidepressants.
How Antidepressants Work
Researchers believe that antidepressants work by affecting levels of neurotransmitters—chemical messengers in the brain that facilitate communication between nerve cells. However, physicians cannot predetermine which medication will be the most effective in any particular individual. Drug selection relies largely on a process of educated guesses, although most people do have some positive response to the first antidepressant they try.
Choosing a Depression Medication
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% 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.
Suicide and Antidepressants
All antidepressants must be used with caution if a person is suicidal. When this is the case, the person will need to see his or her doctor for frequent follow-up visits and will receive a prescription for a relatively small number of pills at a time. Suicide attempts or suicidal thoughts are common symptoms of depression, and the risk of suicide may increase as depression begins to respond to treatment because the person might regain just enough energy and motivation to follow through on a suicidal urge.
In 2004, a federal panel of drug experts said that antidepressants could increase the risk of suicide in children and teenagers. Later that year, the U.S. Food and Drug Administration (FDA) required the makers of antidepressants to add a black box warning to that effect to the drug labels of these medications. In 2005, the agency issued a public health advisory stating that suicidal thoughts and behaviors may also increase among adults on antidepressants. The risk of suicide is higher at the start of drug therapy and when the dosage is changed, according to the FDA.
Antidepressants are the fourth leading cause of drug overdose and the third leading cause of drug-related death when taken improperly. (Tricyclics such as amitriptyline are the most common cause of death from an antidepressant overdose.) In addition, when a person with latent bipolar disorder starts taking antidepressants, manic symptoms may develop and require treatment.
Although up to 70% of people with depression respond positively to antidepressants —and some studies suggest that use of antidepressants, particularly newer SSRIs, decreases the risk of suicide —it is true that some people might have responded just as well to a placebo. But whether a person responds to an antidepressant because of the action of the medication or the placebo effect, or possibly a combination of the two, the fact remains that antidepressants provide real relief to many people. Moreover, because studies of the placebo effect have only followed people for a limited period of time, there are no data showing whether the placebo effect can be sustained in the long term; by contrast, there are data showing that the positive effects of medication are sustained long term.
When it comes to the length of treatment for depression, there is no "one size fits all." However, recent evidence shows that many people require a year or more of antidepressant therapy to treat a major depressive episode adequately. (This includes roughly three months of acute treatment to significantly improve depressive symptoms and an additional six months to a year of continuation/maintenance treatment.) People with severe or recurring depression and older adults may require much longer maintenance therapy.
