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Drug Treatment for Depression


William Coryell

, MD, Carver College of Medicine at University of Iowa

Last full review/revision Aug 2021| Content last modified Aug 2021
Click here for the Professional Version
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Psychostimulants Drug therapy Attention-deficit/hyperactivity disorder (ADHD) is poor or short attention span and/or excessive activity and impulsiveness inappropriate for the child’s age that interferes with functioning... read more , such as dextroamphetamine and methylphenidate, as well as other drugs, are sometimes used, often with antidepressants. Psychostimulants are used to increase mental alertness and awareness.

St. John’s wort St. John’s Wort The reddish substance in the plant’s flowers contains numerous biologically active compounds, including hypericin and hyperforin. (See also Overview of Dietary Supplements.) People take St.... read more , 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 drugs, people interested in taking this herbal supplement need to discuss possible drug interactions with their doctor.

Most antidepressants must be taken regularly for at least several weeks before they begin to work. Most people 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 drug does not relieve depression, a different type (class) or a combination of antidepressant drugs is prescribed.

Risk of suicide Antidepressants and the risk of suicide Suicide is death caused by an intentional act of self-harm that is designed to be lethal. Suicidal behavior includes completed suicide, attempted suicide, and suicidal ideation. Suicide usually... read more 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 younger 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 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

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

  • Norepinephrine-dopamine reuptake inhibitors (such as bupropion)

  • Serotonin modulators (such as mirtazapine and trazodone)

  • Serotonin-norepinephrine reuptake inhibitors (such as venlafaxine and duloxetine)

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 (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 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? Drugs, the most common medical intervention, are an important part of medical care for older people. Without drugs, many older people would function less well or die at an earlier age. Older... read more 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)

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

  • Not taking pseudoephedrine, contained in many over-the-counter cough and cold remedies

  • Not taking dextromethorphan (a cough suppressant), reserpine (an antihypertensive drug), or meperidine (an analgesic)

  • Carrying an antidote, such as chlorpromazine tablets, at all times and, if a severe, throbbing headache occurs, taking the antidote at once and going to the nearest emergency room

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.


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-like drugs

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.

Drugs Mentioned In This Article

Generic Name Select Brand Names
No US brand name
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