Several types of medications can be used to treat depression:
N-methyl D-aspartate (NMDA) antagonist/sigma-1 agonist (a new class of drug class)
Monoamine oxidase inhibitors (MAOIs)
Choice of medication may be guided by the person's past response to a specific antidepressant, but selective serotonin reuptake inhibitors (SSRIs) are often the medications of choice. These antidepressant medications are often used along with psychotherapy.
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.
Antidepressants and Suicide Risk
Risk of suicide after starting an antidepressant is a potential concern. 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 across 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.
In general, the risk of suicide from untreated depression is thought to be higher than any temporary risk after starting an antidepressant medication. Thus, medication treatment should not be withheld for this reason; instead, people prescribed antidepressants should be monitored closely during the weeks after they start taking the medication.
Classes of Antidepressant Medications
Selective serotonin reuptake inhibitors (SSRIs)
SSRIs, which include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and vilazodone, 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. SSRIs, which include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and vilazodone, 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.
Some people, especially children and adolescents, may become increasingly suicidal the first week after they start SSRIs or the dose is increased. (See Antidepressants and Suicide Risk for more information.)
Insomnia is a common adverse effect of SSRIs that the doctor may manage by reducing the dose, giving the dose in the morning, or adding a low dose of another medication (trazodone) or another sedating antidepressant at bedtime. Insomnia is a common adverse effect of SSRIs that the doctor may manage by reducing the dose, giving the dose in the morning, or adding a low dose of another medication (trazodone) or another sedating antidepressant at bedtime.
Also, with long-term use, SSRIs may have additional side effects, most commonly weight gain and sexual dysfunction. 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.Also, with long-term use, SSRIs may have additional side effects, most commonly weight gain and sexual dysfunction. 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.
Some SSRIs, including fluoxetine, paroxetine, and fluvoxamine, can cause other medications to be more active than usual. People should review their complete medication list closely with their doctor. Abruptly stopping some of the SSRIs may result in a discontinuation syndrome that includes dizziness, anxiety, irritability, fatigue, nausea, chills, and muscle aches.Some SSRIs, including fluoxetine, paroxetine, and fluvoxamine, can cause other medications to be more active than usual. People should review their complete medication list closely with their doctor. Abruptly stopping some of the SSRIs may result in a discontinuation syndrome that includes dizziness, anxiety, irritability, fatigue, nausea, chills, and muscle aches.
If a person is pregnant, a doctor will discuss the risks and benefits of using SSRIs, if they are still needed. However, paroxetine should not be used because it may cause heart defects.If a person is pregnant, a doctor will discuss the risks and benefits of using SSRIs, if they are still needed. However, paroxetine should not be used because it may cause heart defects.
Serotonin modulators, serotonin-norepinephrine reuptake inhibitors, and norepinephrine-dopamine reuptake inhibitors
The following classes of antidepressants are as effective and safe as SSRIs and have similar side effects though bupropion and mirtazapine do not appear to cause sexual dysfunction: The following classes of antidepressants are as effective and safe as SSRIs and have similar side effects though bupropion and mirtazapine do not appear to cause sexual dysfunction:
Serotonin modulators (such as mirtazapine and trazodone)Serotonin modulators (such as mirtazapine and trazodone)
Serotonin-norepinephrine reuptake inhibitors (such as venlafaxine and duloxetine)reuptake inhibitors (such as venlafaxine and duloxetine)
Norepinephrine-dopamine reuptake inhibitors (such as bupropion)reuptake inhibitors (such as bupropion)
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 anxiety, irritability, nausea, and flu-like symptoms.
Other side effects vary depending on the medication (see table ).
N-methyl -aspartate (NMDA) antagonist/sigma-1 agonist
The combination of bupropion/dextromethorphanbupropion/dextromethorphan is in a class by itself and achieves its antidepressant effects through a different mechanism of action.
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
Not taking pseudoephedrine, contained in many over-the-counter cough and cold remediesNot taking pseudoephedrine, contained in many over-the-counter cough and cold remedies
Not taking dextromethorphan (a cough suppressant), reserpine (an antihypertensive medication), or meperidine (an analgesic)Not taking dextromethorphan (a cough suppressant), reserpine (an antihypertensive medication), 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 roomCarrying 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-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 unpleasant symptoms.
Medications Used to Treat Depression
Medication | Some Side Effects | Comments |
|---|---|---|
Selective serotonin reuptake inhibitors (SSRIs) | ||
CitalopramCitalopram EscitalopramEscitalopram FluoxetineFluoxetine FluvoxamineFluvoxamine ParoxetineParoxetine SertralineSertraline VilazodoneVilazodone | 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 with other antidepressants. |
Serotonin modulators (5-HT2 blockers) | ||
MirtazapineMirtazapine | Drowsiness and weight gain | Mirtazapine does not cause nausea or sexual dysfunction.Mirtazapine does not cause nausea or sexual dysfunction. |
TrazodoneTrazodone | 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 Trazodone is most often given at bedtime to people who have both depression andinsomnia. |
Serotonin-norepinephrine reuptake inhibitors | ||
DesvenlafaxineDesvenlafaxine DuloxetineDuloxetine LevomilnacipranLevomilnacipran Milnaciprin VenlafaxineVenlafaxine VortioxetineVortioxetine | 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. |
Norepinephrine-dopamine reuptake inhibitors | ||
BupropionBupropion | Headache, agitation, discontinuation syndrome*, high blood pressure in a few people, and rarely seizures | Bupropion is useful for people with depression who also have Bupropion is useful for people with depression who also haveattention-deficit/hyperactivity disorder or cocaine use disorder and those trying to stop smoking. Bupropion does not cause sexual dysfunction. . Bupropion does not cause sexual dysfunction. |
N-methyl D-aspartate (NMDA) antagonist/sigma-1 agonist | ||
Bupropion/dextromethorphanBupropion/dextromethorphan | Common side effects include dizziness, headache, diarrhea, sleepiness, dry mouth, sexual dysfunction, excessive sweating Serious side effects include seizures, mania, acute angle-closure glaucoma, elevated blood pressure, and serotonin syndrome | — |
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* With clomipramine and maprotiline, seizures With clomipramine and maprotiline, seizures | 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). 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.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. |
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. Agomelatine is not available in the United States. |
Ketamine and esketamineKetamine and esketamine | ||
KetamineKetamine | Nausea, dizziness, headache, increased blood pressure, increased heart rate, anxiety, feeling of detachment, addiction | Ketamine is an anesthetic.Ketamine is an anesthetic. Ketamine (used in lower doses than used for anesthesia) is used in combination with oral antidepressants for treatment-resistant depression.Ketamine (used in lower doses than used for anesthesia) is used in combination with oral antidepressants for treatment-resistant depression. Ketamine can be given intravenously, orally, or as a nasal spray.Ketamine can be given intravenously, orally, or as a nasal spray. Ketamine is sometimes used as a drug of abuse.Ketamine is sometimes used as a drug of abuse. |
EsketamineEsketamine | Nausea, dizziness, headache, feeling of detachment | Esketamine is used in combination with other oral antidepressants for treatment-resistant depression.Esketamine is used in combination with other oral antidepressants for treatment-resistant depression. Esketamine is available as a nasal sprayEsketamine is available as a nasal spray |
* Discontinuation syndrome consists of dizziness, anxiety, irritability, fatigue, nausea, chills, and muscle aches that occur when a medication is stopped abruptly. | ||
Melatonergic antidepressant
Agomelatine (not available in the United States) is a melatonergic antidepressant that stimulates melatonin receptors and is used to treat major depressive episodes. It is as effective as other antidepressants and has several benefits:
It causes fewer side effects than most antidepressants.
It does not cause daytime sleepiness, insomnia, sexual side effects, or weight gain.
It 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
Ketamine and esketamine are used as medications to treat some patients with depression if symptoms have not improved with other antidepressant medications (this is called "treatment-resistant depression").
Ketamine can also be given by doctors as an anesthetic. Outside of medical use, it is sometimes used as a drug of abuse.
Brain mechanisms affected by ketamineand esketamine seem to play a role in depression. When used as recommended by an appropriate mental health care professional, these medications can produce rapid improvements in depressive symptoms. Maintaining a successful treatment effect usually requires repeated doses several times a week or less frequently.
As a treatment for depression, ketamine is given intravenously.
Esketamine given as a nasal spray. Esketamine given as a nasal spray.
