Several types of medications can be used to treat depression:
Monoamine oxidase inhibitors (MAOIs)
Most antidepressants must be taken regularly for at least several weeks before they begin to work. Most people with depression need to take antidepressants for 6 to 12 months to prevent relapses. People over 50 may have to take them for up to 2 years.
Side effects vary with each type of antidepressant. Sometimes when treatment with one medication does not relieve depression, a different type (class) or a combination of antidepressant medications is prescribed.
Risk of suicide after starting an antidepressant has been in the news. A few people do become more agitated, depressed, and anxious shortly after an antidepressant is started or after the dose is increased. Some people, especially children and adolescents, become increasingly suicidal if these symptoms are not detected and rapidly treated. This finding was first reported with SSRIs, but the risk probably does not differ among classes of antidepressants. The person's doctor should be notified if symptoms worsen after antidepressants are started or the dose is increased (or for any reason). Because having suicidal thoughts is also a symptom of depression, doctors may have difficulty determining what role antidepressants play in suicidal thoughts and behavior. Some studies cast doubt on the connection.
Selective serotonin reuptake inhibitors (SSRIs)
Selective serotonin reuptake inhibitors (SSRIs) are now the most commonly used class of antidepressants. SSRIs are effective in treating depression as well as other mental health disorders that often coexist with depression.
Although SSRIs can cause nausea, diarrhea, tremor, weight loss, and headache, these side effects are usually mild or go away with continued use. Most people tolerate the side effects of SSRIs better than the side effects of heterocyclic antidepressants. SSRIs are less likely to adversely affect the heart than heterocyclic antidepressants.
However, a few people may seem more agitated, depressed, and anxious the first week after they start SSRIs or the dose is increased. These people, especially children and adolescents, may become increasingly suicidal if these symptoms are not detected and rapidly treated. People taking SSRIs and their loved ones should be warned of this possibility and instructed to call their doctor if symptoms worsen with treatment. However, because people with untreated depression also sometimes complete suicide, people and their doctors must balance this risk against the risks associated with prescribed medications.
Abruptly stopping some of the SSRIs may result in a discontinuation syndrome that includes dizziness, anxiety, irritability, fatigue, nausea, chills, and muscle aches.
Norepinephrine-dopamine reuptake inhibitors, serotonin modulators, and serotonin-norepinephrine reuptake inhibitors
The following classes of antidepressants are as effective and safe as SSRIs and have similar side effects:
Norepinephrine-dopamine
Serotonin-norepinephrine
As may occur with SSRIs, the risk of suicide may be temporarily increased when these medications are first started, and abruptly stopping serotonin-norepinephrine reuptake inhibitors may result in a discontinuation syndrome.
Other side effects vary depending on the medication (see table Medications Used to Treat Depression).
Heterocyclic (including tricyclic) antidepressants
Heterocyclic antidepressants, once the mainstay of treatment, are now used infrequently because they have more side effects than other antidepressants. They often cause drowsiness and lead to weight gain. They can also cause an increase in heart rate and a decrease in blood pressure when a person stands (called orthostatic hypotension). Other side effects, called anticholinergic effects, include blurred vision, dry mouth, confusion, constipation, and difficulty starting to urinate. Anticholinergic effects are often more severe in older adults.
Abruptly stopping heterocyclic antidepressants, as with SSRIs, may result in a discontinuation syndrome.
Monoamine oxidase inhibitors (MAOIs)
Monoamine oxidase inhibitors (MAOIs) are very effective but are rarely prescribed except when other antidepressants have not worked. People who use MAOIs must adhere to a number of dietary restrictions and take special precautions to avoid a serious reaction involving a sudden, severe rise in blood pressure with a severe, throbbing headache (hypertensive crisis). This crisis can cause a stroke. Precautions include
Not eating foods or beverages that contain tyramine, such as beer on tap, red wines (including sherry), liqueurs, overripe foods, salami, aged cheeses, fava or broad beans, yeast extracts (marmite), canned figs, raisins, yogurt, cheese, sour cream, pickled herring, caviar, liver, extensively tenderized meats, and soy sauce
norepinephrine reuptake inhibitors. Taking an MAOI with another antidepressant can cause a dangerously high body temperature, breakdown of muscle, kidney failure, and seizures. These effects, called neuroleptic malignant syndrome, can be fatal.
Abruptly stopping MAOIs, as with SSRIs, may result in a discontinuation syndrome.
Medications Used to Treat Depression
Medication | Some Side Effects | Comments |
|---|---|---|
Selective serotonin reuptake inhibitors (SSRIs) | ||
Sexual dysfunction (primarily, delayed orgasm but also loss of desire and erectile dysfunction in some people), nausea, diarrhea, headache, weight loss (short-term), weight gain (long-term), discontinuation syndrome*, forgetfulness, blunting of emotions, and easy bruising | SSRIs are the most commonly used class of antidepressants. They are also effective for generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, phobic disorder, posttraumatic stress disorder, premenstrual dysphoric disorder, and bulimia. Toxicity due to overdosage is less serious than that with other antidepressants. | |
Norepinephrine-dopamine reuptake inhibitors | ||
Headache, agitation, discontinuation syndrome*, high blood pressure in a few people, and rarely seizures | attention-deficit/hyperactivity disorder or and those trying to stop smoking | |
Serotonin modulators (5-HT2 blockers) | ||
Drowsiness and weight gain | ||
Prolonged drowsiness, painful and persistent erection (priapism), and an excessive decrease in blood pressure when a person stands | ||
Serotonin-norepinephrine reuptake inhibitors | ||
Nausea, dry mouth, discontinuation syndrome*, and, if high doses are taken, an increase in blood pressure | Most of the side effects can be prevented or minimized when low doses are used and when changes in dosages are made slowly. | |
Heterocyclic (including tricyclic) antidepressants | ||
Drowsiness, weight gain, increased heart rate and decreased blood pressure when a person stands (orthostatic hypotension), dry mouth, confusion, blurred vision, constipation, difficulty starting to urinate, delayed orgasm, and discontinuation syndrome* | These medications are usually not prescribed for older adults because side effects are usually more pronounced in them. Overdosage can cause serious, potentially life-threatening toxicity. | |
Monoamine oxidase inhibitors (MAOIs) | ||
Insomnia, nausea, weight gain, sexual dysfunction (loss of desire, delayed orgasm, and erectile dysfunction), pins-and-needles sensation, dizziness, decreased blood pressure (particularly when a person stands), and discontinuation syndrome* | People who take these medications must follow dietary restrictions and avoid using certain medications to avoid a serious reaction involving a sudden, severe increase in blood pressure with a severe, throbbing headache (hypertensive crisis). | |
Psychostimulants | ||
Nervousness, tremor, insomnia, and dry mouth | These medications are usually used with antidepressants. Used alone, they are usually ineffective as antidepressants. | |
Melatonergic antidepressant | ||
Agomelatine | Headache, nausea, and diarrhea | Agomelatine has fewer side effects than most antidepressants. It does not cause daytime drowsiness, insomnia, weight gain, or sexual dysfunction. Agomelatine may increase liver enzyme levels. These levels should be measured before therapy is started and periodically thereafter. |
Dizziness, increased blood pressure, feeling of detachment | ||
Dizziness, increased blood pressure, feeling of detachment | ||
* Discontinuation syndrome consists of dizziness, anxiety, irritability, fatigue, nausea, chills, and muscle aches that occur when a medication is stopped abruptly. | ||
Melatonergic antidepressant
Agomelatine is a melatonergic antidepressant that stimulates melatonin receptors and is used to treat major depressive episodes. It has several benefits:
It causes fewer side effects than most antidepressants.
It does not cause daytime sleepiness, insomnia, or weight gain.
It is not addictive and does not cause withdrawal symptoms.
Agomelatine may cause headache, nausea, and diarrhea. It may also increase liver enzyme levels, so doctors measure these levels before treatment is started and every 6 weeks thereafter. People with liver problems should not take agomelatine.
Ketamine and esketamine
ketamineketamine, is also available for people with major depressive disorder who have not responded to traditional treatments. It is given as a nasal spray. It is used in lower doses than those given for anesthesia.
Most people who are given ketamine or esketamine have a decrease in depression symptoms within 3 to 4 hours. This is a very rapid response compared to that of most antidepressant medications, which can take several weeks to be effective. In most cases, the effect of ketamine or esketamine begins to decline over 1 to 2 weeks. Repeating the dose every week or so often helps but it can stop working after a few months, although a few people can maintain their improvement on one treatment a month.
Side effects may occur within 1 to 2 hours, including increased blood pressure, nausea and vomiting, and mental effects such as people feeling disconnected from themselves (derealization), feeling a distortion of time and space, and having illusions. These medications are usually given in a doctor’s office or a hospital clinic so that doctors can watch the person for side effects for a few hours and because they can be addictive and are sometimes misused.
Other treatments
St. John’s wort, an herbal dietary supplement, is sometimes used to relieve mild depression, although its effectiveness is not proven. Due to potentially harmful interactions between St. John’s wort and many prescription medications, people interested in taking this herbal supplement need to discuss possible drug interactions with their doctor.
