Drug Treatment for 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 Heterocyclic (including tricyclic) antidepressants Agomelatine, a new type of antidepressant, is a possible treatment for major depressive episodes. Several types of drugs can be used to treat depression: Selective serotonin reuptake inhibitors... read more . 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 younger 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 risk of drug treatment.

Also, with long-term use, SSRIs may have additional side effects, such as weight gain and sexual dysfunction (in one third of people). Some SSRIs, such as fluoxetine, cause loss of appetite. During the first few weeks after SSRIs are started, people may feel drowsy during the day, but this effect is temporary.

Abruptly stopping some of the SSRIs may result in a discontinuation syndrome that includes dizziness, anxiety, irritability, fatigue, nausea, chills, and muscle aches.

Newer antidepressants are as effective and safe as SSRIs and have similar side effects. These drugs include

As may occur with SSRIs, the risk of suicide may be temporarily increased when these drugs are first started, and abruptly stopping serotonin-norepinephrine reuptake inhibitors may result in a discontinuation syndrome.

Other side effects vary depending on the drug (see table below).

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 Dizziness or Light-Headedness When Standing Up In some people, particularly older people, blood pressure drops excessively when they sit or stand up (a condition called orthostatic or postural hypotension). Symptoms of faintness, light-headedness... read more ). Other side effects, called anticholinergic effects Anticholinergic: What Does It Mean? , include blurred vision, dry mouth, confusion, constipation, and difficulty starting to urinate. Anticholinergic effects are often more severe in older people.

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

People who take MAOIs should also avoid taking other types of antidepressants, including heterocyclic antidepressants, SSRIs, bupropion, serotonin modulators, and serotonin-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 Neuroleptic Malignant Syndrome Neuroleptic malignant syndrome is confusion or unresponsiveness, muscle rigidity, high body temperature, and other symptoms that occur when certain antipsychotic (neuroleptic) drugs or anti-vomiting... read more , 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:

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 is an anesthetic drug. However, researchers have learned that brain mechanisms affected by ketamine play a role in depression and that, when given at sub-anesthetic doses, can produce rapid though usually transient improvements in depressive symptoms. Recently, esketamine, a form of ketamine, was given Food and Drug Administration (FDA) approval 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 drugs, which can take several weeks to be effective. In most cases, the effect of ketamine or esketamine begins to decline over one to two 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 Depersonalization/Derealization Disorder Depersonalization/derealization disorder involves a persistent or recurring feeling of being detached from one’s body or mental processes, like an outside observer of one's life (depersonalization)... read more ), feeling a distortion of time and space, and having illusions. These drugs 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 ketamine is a drug that is sometimes used recreationally.