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William Coryell

, MD, Carver College of Medicine at University of Iowa

Last full review/revision Mar 2020| Content last modified Mar 2020

The disorder depression is a feeling of sadness intense enough to interfere with functioning and/or a decreased interest or pleasure in activities. It may follow a recent loss or other sad event but is out of proportion to that event and lasts beyond an appropriate length of time.

  • Heredity, side effects of drugs, emotionally distressing events, changes in levels of hormones or other substances in the body, and other factors can contribute to depression.
  • Depression can make people sad and sluggish and/or lose all interest and pleasure in activities they used to enjoy.
  • Doctors base the diagnosis on symptoms.
  • Antidepressants, psychotherapy, and sometimes electroconvulsive therapy can help.

People often use the term depression to describe the sad or discouraged mood that results from emotionally distressing events, such as a natural disaster, a serious illness, or death of a loved one. People may also say they feel depressed at certain times, such as during the holidays (holiday blues) or on the anniversary of a loved one's death. However, such feelings do not usually represent a disorder. Usually, these feelings are temporary, lasting days rather than weeks or months, and occur in waves that tend to be tied to thoughts or reminders of the distressing event. Also, these feelings do not substantially interfere with functioning for any length of time.

After anxiety, depression is the most common mental health disorder. About 30% of people who visit a primary care practitioner have symptoms of depression, but fewer than 10% of these people have major depression.

Depression typically develops during a person's mid teens, 20s, or 30s, although depression can begin at almost any age, including during childhood.

An episode of depression, if untreated, typically lasts about 6 months but sometimes lasts for 2 years or more. Episodes tend to recur several times over a lifetime.

Spotlight on Aging: Depression

Depression affects about 1 of every 6 older people. Some older people have had depression earlier in their life. Others develop it for the first time during old age.

Causes of Depression in Older People

Some causes of depression may be more common among older people. For example, older people may be more likely to experience emotionally distressing events that involve a loss, such as the death of a loved one or a loss of familiar surroundings, as when moving away from a familiar neighborhood. Other sources of stress, such as reduced income, a worsening chronic illness, a gradual loss of independence, or social isolation, may also contribute.

Disorders that can lead to depression are common among older people. Such disorders include cancer, heart attack, heart failure, thyroid disorders, stroke, dementia, and Parkinson disease.

Depression Versus Dementia

In older people, depression can cause symptoms that resemble those of dementia: slower thinking, decreased concentration, confusion, and difficulty remembering. However, doctors can distinguish depression from dementia because when depression is treated, people with depression regain their mental function. People with dementia do not. Also, people with depression may complain bitterly about their memory loss and rarely forget important current events or personal matters. In contrast, people with dementia often deny memory loss.

Diagnosis of Depression in Older People

Depression is often difficult to diagnose among older people for several reasons:

  • The symptoms may be less noticeable because older people may not work or may have less social interaction.
  • Some people believe that depression is a weakness and are reluctant to tell anyone that they are experiencing sadness or other symptoms.
  • The absence of emotion may be interpreted as indifference rather than depression.
  • Family members and friends may regard a depressed person's symptoms simply as evidence that the person is getting older.
  • The symptoms may be attributed to another disorder, such as dementia.

Because depression may be difficult to identify, many doctors routinely ask older people questions about their mood. Family members should be alert for subtle changes in personality, especially lack of enthusiasm and spontaneity, loss of sense of humor, and new forgetfulness.

Treatment of Depression in Older People

Selective serotonin reuptake inhibitors (SSRIs) are the antidepressants used most often for older people who are depressed because SSRIs are less likely to have side effects. Citalopram and escitalopram are particularly useful.

Causes of Depression

The exact cause of depression is unclear, but a number of factors may make depression more likely. Risk factors include

  • A family tendency (heredity)
  • Emotionally distressing events, particularly those involving a loss
  • Female sex, possibly involving changes in hormone levels
  • Certain physical disorders
  • Side effects of certain drugs

Depression does not reflect a weakness of character and may not reflect a personality disorder, childhood trauma, or poor parenting. Social class, race, and culture do not appear to affect the chance that people will experience depression during their lifetime.

Genetic factors contribute to depression in about half the people who have it. For example, depression is more common among first-degree relatives (particularly in an identical twin) of people with depression. Genetic factors can affect the function of substances that help nerve cells communicate (neurotransmitters). Serotonin, dopamine, and norepinephrine are neurotransmitters that may be involved in depression.

Women are more likely than men to experience depression, although the reasons are not entirely clear. Of physical factors, hormones are the ones most involved. Changes in hormone levels can cause mood changes shortly before menstruation (as part of premenstrual syndrome), during pregnancy, and after childbirth. Some women become depressed during pregnancy or during the first 4 weeks after giving birth (called baby blues or, if the depression is more serious, postpartum depression). Abnormal thyroid function, which is fairly common among women, may also be a factor.

Depression may occur with or be caused by a number of physical disorders and factors. Physical disorders may cause depression directly (as when a thyroid disorder affects hormone levels) or indirectly (as when rheumatoid arthritis causes pain and disability). Often, a physical disorder both directly and indirectly causes depression. For example, AIDS may cause depression directly if the human immunodeficiency virus (HIV), which causes AIDS, damages the brain. AIDS may cause depression indirectly by having an overall negative effect on the person’s life.

Many people report feeling sadder in late autumn and winter and blame this tendency on the shortening of daylight hours and colder temperatures. However, in some people, such sadness is severe enough to be considered a type of depression (called seasonal affective disorder).

The use of some prescription drugs, such as some beta-blockers (used to treat high blood pressure), can cause depression. For unknown reasons, corticosteroids often cause depression when the body produces them in large amounts as part of a disorder (as in Cushing syndrome), but when they are given as a drug, they tend to cause hypomania (a less severe form of mania) or, rarely, mania. Sometimes stopping a drug can cause temporary depression.

A number of mental health disorders can predispose a person to depression. They include certain anxiety disorders, alcohol use disorder, other substance use disorders, and schizophrenia. People who have had depression are more likely to have it again.

Emotionally distressing events, such as loss of a loved one, can sometimes trigger depression, but usually only in people who are predisposed to depression, such as those who have family members with depression. However, depression may arise or worsen without any apparent or significant life stresses.

Some Causes of Depression



Brain and nervous system disorders

Brain tumors

Dementia (in early stages)

Head injury

Multiple sclerosis

Parkinson disease

Sleep apnea


Seizures that affect the temporal lobe (complex partial seizures)


Cancer spreading throughout the body (metastatic)

Cancer of the pancreas

Connective tissue disorders

Systemic lupus erythematosus (lupus)

Hormonal disorders

Addison disease

Cushing syndrome

Diabetes mellitus

High levels of parathyroid hormone (hyperparathyroidism)

Low or high levels of thyroid hormone (hypothyroidism or hyperthyroidism)

Low levels of pituitary hormones (hypopituitarism)

Low levels of testosterone (hypogonadism)





Syphilis (late stage)


Viral hepatitis

Viral pneumonia

Mental disorders other than mood disorders

Substance use disorders

Antisocial personality disorder

Anxiety disorders

Borderline personality disorder

Dementia in the early stages


Nutritional disorders

Pellagra (vitamin B6 deficiency)

Pernicious anemia (a form of vitamin B12 deficiency)

Other disorders

Coronary artery disease


Kidney failure

Liver failure



Amphetamine withdrawal

Amphotericin B

Antipsychotic drugs

Beta-blockers (some)


Contraceptives (oral)



Hormone ( estrogen or progesterone) therapy









Symptoms of Depression

Symptoms of depression typically develop gradually over days or weeks and can vary greatly. For example, a person who is becoming depressed may appear sluggish and sad or irritable and anxious.

Many people with depression cannot experience emotions—including grief, joy, and pleasure—in a normal way. The world may appear to have become colorless and lifeless. They lose interest or pleasure in activities that they used to enjoy.

Depressed people may be preoccupied with intense feelings of guilt and self-denigration and may not be able to concentrate. They may experience feelings of despair, loneliness, and worthlessness. They are often indecisive and withdrawn, feel helpless and hopeless, and think about death and suicide.

Most depressed people have difficulty falling asleep and awaken repeatedly, particularly early in the morning. Some people with depression sleep more than usual.

Poor appetite and weight loss may lead to emaciation, and in women, menstrual periods may stop. However, overeating and weight gain are common in people with mild depression.

Some depressed people neglect personal hygiene or even their children, other loved ones, or pets. Some complain of having a physical illness, with various aches and pains.

The term depression is used to describe several related disorders:

  • Major depressive disorder
  • Persistent depressive disorder
  • Premenstrual dysphoric disorder

Major depressive disorder

People with major depressive disorder are depressed most days for at least 2 weeks. They may appear miserable. Their eyes may be full of tears, their brows may be furrowed, and the corners of the mouth may be turned down. They may slump and avoid eye contact. They may hardly move, show little facial expression, and speak in a monotone.

Did You Know...

  • Depression involves more than feeling sad all the time: People may feel worthless and guilty, lose interest in their normal pleasures, have sleep disorders, or lose or gain weight.

Persistent depressive disorder

People with persistent depressive disorder have been depressed for most of the time for 2 years or more.

Symptoms begin gradually, often during adolescence, and may last for years or decades. How many symptoms are present at one time varies, and sometimes symptoms are less severe than those in major depression.

People with this disorder may be gloomy, pessimistic, skeptical, humorless, and incapable of having fun. Some are passive, lack energy, and keep to themselves. Some constantly complain and are quick to criticize others and reproach themselves. They may be preoccupied with inadequacy, failure, and negative events, sometimes to the point of morbid enjoyment of their own failures.

Premenstrual dysphoric disorder

Severe symptoms occur before most menstrual periods and disappear after they end. Symptoms cause substantial distress and/or greatly interfere with functioning. Symptoms are similar to those of premenstrual syndrome but are more severe, causing great distress and interfering with functioning at work and social interactions.

Premenstrual dysphoric disorder may first appear any time after girls start to menstruate. It may worsen as women approach menopause but ends after menopause. It occurs in about 2 to 6% of women who are menstruating.

Women with premenstrual dysphoric disorder have mood swings, suddenly becoming sad and tearful. They are irritable and anger easily. They feel very depressed, hopeless, anxious, and on edge. They may feel overwhelmed or out of control. They often put themselves down.

As with other types of depression, women with this disorder may lose interest in their usual activities, have difficulty concentrating, and feel tired and without energy. They may eat too much and crave certain foods. They may sleep too little or too much.

Like many women whose period is about to start, these women may have tender, swollen breasts and/or achy muscles and joints. They may feel bloated and gain weight.


Doctors use certain terms to describe specific symptoms that can occur in people with depression. These terms include

  • Anxious distress: People feel tense and unusually restless. They have difficulty concentrating because they worry or fear that something awful may happen or that they may lose control of themselves.
  • Mixed: People also have three or more symptoms of mania. These symptoms include feeling exuberant and/or overly confident, talking more than usual, sleeping little, and racing thoughts. These people do not have all the symptoms required for a diagnosis of bipolar disorder, but they are at risk of developing it.
  • Melancholic: People no longer take pleasure in any activities they used to enjoy. They appear sluggish, sad, and despondent. They speak little, stop eating, and lose weight. They may feel excessively or inappropriately guilty. They often awake early in the morning and cannot go back to sleep.
  • Atypical: People may temporarily cheer up when something good happens, such as a visit from their children. They have an increased appetite, resulting in weight gain. They may sleep for long periods of time. They are excessively sensitive to perceived criticism or rejection. They may feel weighted down, as if they can hardly move their legs.
  • Psychotic: People have false beliefs (delusions), often of having committed unpardonable sins or crimes, of having incurable or shameful disorders, or of being watched or persecuted. People may have hallucinations, usually of voices accusing them of various misdeeds or condemning them to death.
  • Catatonic: People are very withdrawn. Thinking, speech, and general activity may slow down so much that all voluntary activities stop. Some people mimic others’ speech (echolalia) or movements (echopraxia).
  • Seasonal: Episodes of depression occur every year at a particular time of year, usually starting in the fall or winter and ending in the spring. These episodes are more common in extreme northern and southern latitudes, where the winter season is typically longer and harsher. People are sluggish. They lose interest in and withdraw from their usual activities. They may also sleep too much and overeat.


Thoughts of death are among the most serious symptoms of depression. Many depressed people want to die or feel they are so worthless that they should die. As many as 15% of untreated depressed people end their life by suicide.

A suicide threat is an emergency. When people threaten to kill themselves, a doctor may hospitalize them so that they can be supervised until treatment reduces the risk of suicide. The risk is especially high in the following situations:

  • When depression is not treated or is inadequately treated
  • When treatment is started (when people are becoming more active mentally and physically but their mood is still dark)
  • When people have a significant anniversary
  • When people alternate between depression and mania (bipolar disorder)
  • When people feel very anxious
  • When people are drinking alcohol or taking recreational drugs
  • In the weeks to months after people have attempted suicide, particularly if they used a violent method

Substance use

People with depression are more likely to use alcohol or other recreational drugs in an attempt to help them sleep or feel less anxious. However, depression leads to alcohol use and other substance use disorders less often than was once thought.

People are also more likely to smoke heavily and to neglect their health. Thus, the risk of developing or worsening other disorders, such as chronic obstructive pulmonary disease, is increased.

Other effects of depression

Depression may reduce the immune system's ability to respond to foreign or dangerous invaders, such as microorganisms or cancer cells. As a result, people with depression may be more likely to get infections.

Depression increases the risk of heart and blood vessel disorders (such as heart attacks) and stroke. The reason may be that depression causes certain physical changes that increase this risk. For example, the body produces more of the substances that help blood clot (clotting factors), and the heart is less able to change how fast it beats in response to different situations.

Diagnosis of Depression

  • A doctor's evaluation
  • Tests to identify disorders that can cause depression

A doctor is usually able to diagnose depression based on symptoms. Doctors use specific lists of symptoms (criteria) to diagnose the different types of depressive disorders. To help distinguish depression from ordinary changes in mood, doctors determine whether the symptoms are causing significant distress or are impairing the person's ability to function. A previous history of depression or a family history of depression helps support the diagnosis.

Excessive worrying, panic attacks, and obsessions are common in depression and may lead the doctor to incorrectly think that the person has an anxiety disorder.

In older people, depression may be difficult to notice, especially if they do not work or have little social interaction. Also, depression may be mistaken for dementia because it can cause similar symptoms, such as confusion and difficulty concentrating and thinking clearly. However, when such symptoms are caused by depression, they resolve when depression is treated. When dementia is the cause, they do not resolve.

Standardized questionnaires are used to help identify depression and determine how severe it is, but they cannot be used alone to diagnose depression. Two such questionnaires are the Hamilton Depression Rating Scale, conducted verbally by an interviewer, and the Beck Depression Inventory, a self-administered questionnaire. For older people, there is a Geriatric Depression Scale questionnaire. Doctors also ask people whether they have any thoughts or plans to harm themselves. Such thoughts indicate that depression is severe.


No test can confirm depression. However, laboratory tests may help a doctor determine whether depression is caused by a hormonal or other physical disorder. For example, blood tests are usually done to detect a thyroid disorder or vitamin deficiency. In younger people, tests may be done to detect drug use.

A thorough neurologic examination is done to check for Parkinson disease, which causes some of the same symptoms.

People who have severely disturbed sleep may need to have testing (polysomnography) to distinguish sleep disorders from depression.

Treatment of Depression

  • Support
  • Psychotherapy
  • Drugs, mainly antidepressants

Most people with depression do not require hospitalization. However, some people should be hospitalized, especially if they are contemplating suicide or have attempted it, are frail because of weight loss, or are at risk of heart problems because of severe agitation.

Treatment depends the severity and type of depression:

  • Mild depression: Support (including frequent doctor visits and education) and psychotherapy
  • Moderate to severe depression: Drugs, psychotherapy, or both and sometimes electroconvulsive therapy
  • Seasonal depression: Phototherapy

Depression can usually be treated successfully. If a cause (such as a drug or another disorder) can be identified, it is corrected first, but drugs to treat depression may also be needed.


Doctors may schedule visits or telephone calls every week or every other week for people with depression. Doctors explain to them and their family members that depression has physical causes and requires specific treatment, which is usually effective. Doctors reassure them that depression does not reflect a character flaw, such as weakness. It is important for family members to understand the disorder, be involved in treatment, and provide support.

Learning about depression can help people understand and deal with the disorder. For example, people learn that the path to recovery is often bumpy and that episodes of sadness and dark thoughts may recur but they will stop. Thus, people can put any setbacks in perspective and are more likely to continue their treatment and not give up.

Becoming more active—taking walks and exercising regularly—can help, as can interacting more with others.

Support groups (such as the Depression and Bipolar Support Alliance—DBSA) can help by providing a forum to share common experiences and feelings.


Psychotherapy alone may be just as effective as drug therapy for mild depression. When used with drugs, it can be useful for severe depression.

Individual or group psychotherapy can help people with depression gradually resume former responsibilities and adapt to the normal pressures of life. Interpersonal therapy focuses on the person's past and present social roles, identifies problems with how the person interacts with other people, and provides guidance as the person adjusts to changes in life roles. Cognitive-behavioral therapy can help change hopelessness and negative thinking.

Drug therapy for depression

Several types of antidepressants are available (see table Drugs Used to Treat Depression). They include the following:

  • Selective serotonin reuptake inhibitors (SSRIs)
  • Newer antidepressants
  • Heterocyclic antidepressants
  • Monoamine oxidase inhibitors (MAOIs)
  • Ketamine-like drugs

Psychostimulants, 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, 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.

Electroconvulsive therapy

Electroconvulsive therapy (in the past sometimes called shock therapy) is sometimes used to treat people with severe depression, including people who are psychotic, threatening to commit suicide, or refusing to eat. It is also used to treat depression during pregnancy when drugs are ineffective.

This type of therapy is usually very effective and can relieve depression quickly, unlike most antidepressants, which can take up to several weeks. The speed with which it takes effect can save lives. After electroconvulsive therapy is stopped, episodes of depression can recur. To help prevent them, doctors often prescribe antidepressants.

For electroconvulsive therapy, electrodes are placed on the head, and an electrical current is applied to induce a seizure in the brain. For reasons that are not understood, the seizures relieve depression. Usually, at least five to seven treatments, one treatment every other day, are given.

Because the electrical current can cause muscle contractions and pain, general anesthesia is required during treatments. Electroconvulsive therapy may cause some temporary memory loss and, rarely, permanent memory loss.


Phototherapy using a light therapy box is the most effective treatment for seasonal depression but may be helpful for other types of depressive disorders.

Phototherapy involves sitting a specific distance from a light box that provides light with the necessary intensity. People are instructed not to look directly at the light and to remain in front of the light for 30 to 60 minutes a day. Phototherapy can be done at home.

If people go to sleep and get up late, phototherapy is most effective in the morning. If people go to sleep and get up early, phototherapy is most effective between the late afternoon and early evening.

Other therapies

Other therapies that stimulate the brain may be tried when other treatments are ineffective. They include

  • Repetitive transcranial magnetic stimulation
  • Stimulation of the vagus nerve

The stimulated cells are thought to release chemical messengers (neurotransmitters), which help regulate mood and may thus relieve symptoms of depression. These therapies may help people with severe depression that does not respond to drugs or psychotherapy.

For repetitive transcranial magnetic stimulation, an electromagnetic coil is placed against the forehead near an area of the brain thought to be involved in regulating mood. The electromagnet produces painless magnetic pulses that doctors think stimulate nerve cells in the targeted area of the brain. The most common side effects are headaches and discomfort near where the coil was placed.

For vagus nerve stimulation, a device that looks like a heart pacemaker (vagus nerve stimulator) is implanted under the left collarbone and is connected to the vagus nerve in the neck with a wire that runs under the skin. (The pair of vagus nerves run from the brain stem, located near the base of the skull, through the neck and down each side of the chest and abdomen to organs, such as the heart and lungs.) The device is programmed to periodically stimulate the vagus nerve with a painless electrical signal. It may be useful for depression when other treatments are ineffective, but it usually takes 3 to 6 months to take effect. Side effects of vagus nerve stimulation include hoarseness, cough, and deepening of the voice when the nerve is stimulated.


Types of antidepressants include

  • Selective serotonin reuptake inhibitors (SSRIs)
  • Newer antidepressants
  • Heterocyclic antidepressants
  • Monoamine oxidase inhibitors (MAOIs)

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 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. 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 commit 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). 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 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, can be fatal.

Abruptly stopping MAOIs, as with SSRIs, may result in a discontinuation syndrome.

Drugs Used to Treat Depression


Some Side Effects


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

Bupropion is useful for depressed people who also have attention-deficit/hyperactivity disorder or cocaine use disorder and those trying to stop smoking. Bupropion does not cause sexual dysfunction.

Serotonin modulators (5-HT2 blockers)


Drowsiness and weight gain

Mirtazapine does not cause nausea or sexual dysfunction.


Prolonged drowsiness, painful and persistent erection (priapism), and an excessive decrease in blood pressure when a person stands

Trazodone is most often given at bedtime to people who have both depression and insomnia.

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

  • Amitriptyline
  • Amoxapine
  • Clomipramine
  • Desipramine
  • Doxepin
  • Imipramine
  • Maprotiline
  • Nortriptyline
  • Protriptyline
  • Trimipramine

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*

With clomipramine and maprotiline, seizures

These drugs are usually not prescribed for older people because side effects are usually more pronounced in them.

Overdosage can cause serious, potentially life-threatening toxicity.

Monoamine oxidase inhibitors (MAOIs)

  • Isocarboxazid
  • Phenelzine
  • Selegiline
  • Tranylcypromine

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 drugs must follow dietary restrictions and avoid using certain drugs to avoid a serious reaction involving a sudden, severe increase in blood pressure with a severe, throbbing headache (hypertensive crisis).

Selegiline is available as a patch. With the patch, people do not have to follow the dietary restrictions unless the patch contains a high dose.


  • Dextroamphetamine
  • Methylphenidate

Nervousness, tremor, insomnia, and dry mouth

These drugs are usually used with antidepressants. Used alone, they are usually ineffective as antidepressants.

Melatonergic antidepressant


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 every 6 weeks thereafter.

Ketamine-like drug


Dizziness, increased blood pressure, feeling of detachment

Esketamine is related to the anesthetic ketamine.

Esketamine is used in combination with other oral antidepressants for treatment-resistant depression.

Esketamine is available as a nasal spray

* Discontinuation syndrome consists of dizziness, anxiety, irritability, fatigue, nausea, chills, and muscle aches that occur when a drug is stopped abruptly.

Ketamine-like drug

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 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 esketamine begins to decline over one to two weeks. Repeating the dose every week or so usually 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. The drug is 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.

More Information about Depression

  • Depression and Bipolar Support Alliance (DBSA), Depression: General information on depression, including access to crisis lines and support groups
  • Mental Health America (MHA), Depression: General information on depression, including its various types, access to crisis lines and support groups, and links to other resources
  • National Alliance on Mental Illness (NAMI), Depression: General information on depression, including its causes, symptoms, diagnosis, and treatment
  • National Institutes of Mental Health (NIMH), Depression: General information on many aspects of depression, including treatment and therapies, educational materials, and information on research and clinical trials

Drugs Mentioned In This Article

Generic Name Select Brand Names
dextroamphetamine DEXEDRINE
dextromethorphan DELSYM
methylphenidate CONCERTA, RITALIN
Tranylcypromine PARNATE
pseudoephedrine AFRINOL, SUDAFED
Levomilnacipran FETZIMA
chlorpromazine No US brand name
Metoclopramide REGLAN
Desvenlafaxine PRISTIQ
Isocarboxazid MARPLAN
Protriptyline VIVACTIL
Nortriptyline AVENTYL
testosterone DELATESTRYL
Trimipramine Trimipramine
progesterone CRINONE
escitalopram LEXAPRO
Clomipramine ANAFRANIL
mirtazapine REMERON
Cycloserine SEROMYCIN
Vincristine MARQIBO KIT
Desipramine NORPRAMIN
Fluvoxamine LUVOX
venlafaxine EFFEXOR XR
Sertraline ZOLOFT
Methyldopa No brand name
duloxetine CYMBALTA
Selegiline ELDEPRYL
Cimetidine TAGAMET
Esketamine Esketamine
Imipramine TOFRANIL
Citalopram CELEXA
Vilazodone Vilazodone
Phenelzine NARDIL
meperidine DEMEROL
Paroxetine PAXIL
fluoxetine PROZAC, SARAFEM
trazodone OLEPTRO
Ketamine KETALAR

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