Medications for Treatment of Depression

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.

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 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) 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.

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.

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.

Psychostimulants

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.