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Medications for Treatment of Depression


William Coryell

, MD, University of Iowa Carver College of Medicine

Reviewed/Revised Oct 2023
Topic Resources

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.

Risk of suicide Antidepressants and the risk of suicide Suicide is death caused by an act of self-harm that is intended to be lethal. Suicidal behavior includes completed suicide, attempted suicide, and suicidal ideation (thoughts and ideas). Suicide... 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 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 Several types of medications can be used to treat depression: Selective serotonin reuptake inhibitors (SSRIs) Norepinephrine-dopamine reuptake inhibitors, serotonin modulators, and serotonin-norepinephrine... 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 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.

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.

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.

Norepinephrine-dopamine reuptake inhibitors, serotonin modulators, and serotonin-norepinephrine reuptake inhibitors

The following classes of antidepressants are as effective and safe as SSRIs and have similar side effects:

  • 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 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 ).

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? 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 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 remedies

  • 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 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 and esketamine

Ketamine is an anesthetic. However, researchers have learned that brain mechanisms affected by ketamine play a role in depression and that, when given at sub-anesthetic (lower) doses, can produce rapid though usually transient improvements in depressive symptoms. Esketamine, a form of ketamine, 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 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 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.

Other treatments

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 medications, 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 flowers of St. John’s wort contains numerous biologically active compounds, including hypericin and hyperforin. (See also Overview of Dietary Supplements.) People... 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 medications, people interested in taking this herbal supplement need to discuss possible drug interactions with their doctor.

Drugs Mentioned In This Article

Generic Name Select Brand Names
Prozac, Prozac Weekly, Sarafem, Selfemra
Brisdelle, Paxil, Paxil CR, Pexeva
Aplenzin, Budeprion SR , Budeprion XL , Buproban, Forfivo XL, Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban
Remeron, Remeron SolTab
Desyrel, Oleptro
Effexor, Effexor XR, Venlafaxine
Cymbalta, Drizalma, Irenka
Contac Cold 12 Hour, Dimetapp Decongestant, Drixoral, ElixSure Cold, ElixSure Congestion, Entex, Genaphed , KidKare , Myfedrine, NASAL Decongestant, Nasofed, Nexafed, PediaCare Infants' Decongestant, Pseudo-Time, Silfedrine, Sudafed, Sudafed 12 Hour, Sudafed 24 Hour, Sudafed Children's Nasal Decongestant, Sudafed Congestion, Sudafed Sinus Congestion, Sudogest, Sudogest 12 Hour, Sudogest Children's , Tylenol Children's Simply Stuffy, Zephrex-D
AeroTuss, Buckley's Cough Suppressant , Buckley's DM, Buckley's Mixture, Cough DM, Cough Suppressant , Delsym, Delsym Children's, Delsym Children's Cough Relief, Delsym Cough, Dexalone, ElixSure Cough, ElixSure Cough DM, Giltuss DM, PediaCare Children's Long Acting Cough, PediaCare Infants' Long-Acting Cough, PediaCare Long-Acting Cough , Robafen Cough, Robitussin, Robitussin Children's Cough, Robitussin Cough, Robitussin CoughGels, Robitussin Lingering Cold Long-Acting Cough, Robitussin Pediatric Cough, Scot-Tussin CF, Silphen DM, Theraflu Long Acting Cough Strip, Triaminic Long Acting Cough , Triaminic Long Acting Cough Strip, Tylenol Children's Simply Cough, Vicks DayQuil Cough, Vicks DayQuil Nature Fusion, Vicks Formula 44, Vicks Nature Fusion Cough, Zicam Concentrated Cough, Zicam Cough Max, Zicam Cough Nite
No brand name available
Demerol, Meperitab
Dexedrine, Dexedrine Spansule, DextroStat, Liquadd , ProCentra , XELSTRYM, Zenzedi
Adhansia XR, Aptensio XR, Concerta, Cotempla XR, Daytrana, Jornay, Metadate CD, Metadate ER, Methylin, QuilliChew ER, Quillivant XR, RELEXXII, Ritalin, Ritalin LA, Ritalin SR
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