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Antidepressants: Options, Advantages, and Precautions

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on April 10, 2024.

How Common is Depression?

Feeling sad or blue is not unusual; it happens to most of us. But ongoing feelings of despair, frequent tearfulness, trouble with eating and sleeping, and withdrawal from family and friends may mean there is a more serious concern of depression.

According to the National Institute of Mental Health (NIMH), major depressive disorder (MDD) is one of the most common mental illnesses in the United States. Depression does not play favorites: it can impact anyone regardless of age, race or socioeconomic status.

According to the 2021 National Survey on Drug Use and Health as reported by the National Institute of Mental Health (NIMH) - their most recent data - roughly 21 million adults in the US had at least one major depressive episode in the previous year. This number represented 8.3% of all US adults.

What Causes Depression?

The exacts causes of depression are not fully known. In general, depression does not have a single cause and the reason why a patient is depressed is often hard to pinpoint. Depression may be due to a mixture of:

The good news is that medical treatment can be very effective and potentially life-saving for major depressive disorder (MDD). Options for treatment for MDD include antidepressant drug therapy, psychotherapy such as cognitive behavioral therapy (CBT), or a combination of the two.

Who Should Be Screened for Depression?

The United States Preventive Services Task Force (USPSTF) recommends screening for depression in the general adult population, including pregnant and postpartum women and older adults (65 years of age and older). The Veterans Health Administration (VA) suggests that all patients not currently receiving treatment for depression be screened.

Learn More: Depression: Symptoms, Subtypes and Diagnosis

Treatment Options for Depression

The cornerstone treatments for depression are prescription antidepressants and talk therapy with a trained specialist (psychotherapy) -- and they are often used together most effectively.

Psychotherapy (talk therapy) and / or single drug treatment may be recommended as an initial treatment choice for most patients with uncomplicated major depressive disorder, based on patient preference.

No single antidepressant medication has been found to be the best treatment for every patient. In general 40% to 60% of patients (4 to 6 out of 10 patients) will have a positive response to the first antidepressant medication they try.

Second generation antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are used preferentially over first generation antidepressants like tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs) because of a better tolerated side effect profile.

Typically, it takes from 4 to 8 weeks to have a full clinical response to an antidepressant. If the first treatment does not work, your doctor might suggest increasing the dose or taking a different antidepressant from the same - or different - class.

In August 2023, a faster-acting antidepressant known as Zurzuvae (zuranolone) from Sage Therapeutics / Biogen was approved by the FDA to treat postpartum depression (PPD) in adults.

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients older than 24 years of age.

Generic medications may be significantly more affordable. If cost is an issue, patients should tell their physician they prefer generics when possible, and they should check with their pharmacist for available options. There are many affordable generic options for the more commonly used antidepressants.

In addition to depression, certain antidepressants may also be used to treat a range of other conditions, for example:

Selective serotonin reuptake inhibitors (SSRIs)

SSRIs increase levels of serotonin in the brain by preventing the reuptake of serotonin by nerve cells. They are often selected as a first-line drug treatment for depression due to effectiveness and a lower risk of side effects compared to older antidepressants. Most SSRIs are now available in generic form, making them very affordable.


Table 1: SSRIs Used for Depression

Generic name Brand name examples
citalopram Celexa
escitalopram Lexapro
fluoxetine Prozac
fluvoxamine Luvox (brand discontinued in U.S.)
paroxetine Brisdelle, Paxil, Paxil CR
sertraline Zoloft

Common side effects of SSRIs may include:

Pros and Cons of SSRIs:

All serotonin reuptake inhibitors may increase the risk of bleeding, especially in those taking other medicines that increase the risk of bleeding such as NSAIDs, aspirin, warfarin or other drugs that affect coagulation or bleeding.

See also: Selective serotonin reuptake inhibitors (SSRIs)

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs block or delay the reuptake of two neurotransmitters in the brain, serotonin and norepinephrine. By blocking reuptake, the neurotransmitter concentrations are increased in the nerve synapse to help elevate mood or treat other conditions.

These agents may also be selected as a first-line treatment option, especially in patients with more severe depression. Several generic SNRIs are now available.

Table 2: SNRIs Used for Depression

Generic name Brand name examples
desvenlafaxine Pristiq
duloxetine Cymbalta, Drizalma Sprinkle, Irenka
levomilnacipran Fetzima
venlafaxine Effexor, Effexor XR

Common side effects of SNRIs may include:

  • nausea
  • dry mouth
  • insomnia (difficulty sleeping)
  • drowsiness
  • dizziness
  • anxiety
  • sexual problems
  • headache
  • sweating
  • loss of appetite

Pros and Cons of SNRIs:

See also: Serotonin norepinephrine reuptake inhibitors (SNRIs)

Atypical Antidepressants

Atypical antidepressants work by altering one or more neurotransmitters, but do not fit into one specific class. Drugs in this class may be selected as a first-line drug to help avoid a specific side effect, such as sexual dysfunction or weight gain, or for patients who have an inadequate response with first-line agents such as SSRIs or SNRIs. Generics are available.

Table 3: Atypical Antidepressants Used for Depression

Generic name Brand name examples
bupropion Aplenzin, Budeprion SR, Forfivo XL, Wellbutrin SR, Wellbutrin XL
mirtazapine Remeron, Remeron SolTab

Common side effects: mirtazapine

Common side effects: bupropion

Seizures can occur with higher doses of bupropion and appears to be a dose-related effect. Your doctor will evaluate your risk factors for seizures and determine the appropriate dose if you are eligible for bupropion treatment.

Pros and Cons of Atypical Antidepressants:

See also: Atypical Antidepressants

Serotonin Modulators

Serotonin modulators have multiple mechanisms that exert their antidepressant effect, and they may fall into other groups.

Table 4: Serotonin Modulators Used for Depression

Generic Name Brand Name Examples
nefazodone none available in US
trazodone none available in US
vortioxetine Trintellix
vilazodone Viibryd

Common side effects with Serotonin Modulators may include:

  • blurred vision
  • constipation
  • diarrhea
  • difficulty sleeping (insomnia)
  • drowsiness, sedation
  • dry mouth
  • dizziness
  • headache
  • nausea, vomiting
  • orthostatic hypotension
  • sexual dysfunction
  • weakness

Pros and Cons of Serotonin Modulators:

See also: Miscellaneous Antidepressants

Monoamine Oxidase Inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) were the first antidepressant class to be developed, but have been replaced by safer antidepressants today, such as SSRIs and SNRIs.

Monoamine oxidase inhibitors (MAOIs) work by irreversibly blocking the enzyme monoamine oxidase (both MAO-A and MAO-B when used for depression), and preventing the breaking down of neurotransmitters such as serotonin, norepinephrine, and dopamine.

MAOIs are typically used as a third or fourth line of treatment due to severe side effects, diet restrictions, and the possibility of serotonin syndrome.

Use caution when starting or stopping MAOI treatment to avoid serious side effects like a hypertensive crisis or serotonin syndrome.

Serious drug-drug and drug-food interactions can occur. Consult with your health care provider before starting treatment and using any prescription, over-the-counter (OTC), vitamin, or herbal medicine. Discuss food and drug interactions with your doctor before starting treatment. You may need to avoid some common foods and beverages, like cheese, wine and smoked or processed meats.

Table 5: MAOIs Used for Depression

Generic Name Brand Name Examples
isocarboxazid Marplan
phenelzine Nardil
selegiline transdermal Emsam
tranylcypromine Parnate

Common side effects with MAOIs may include:

  • dizziness
  • drowsiness
  • orthostatic hypotension
  • headache
  • insomnia (difficulty sleeping)
  • muscle jerks
  • nausea, vomiting
  • skin reaction (with patch)
  • constipation
  • dry mouth
  • agitation or anxiety
  • sexual dysfunction
  • urinary hesitancy
  • weight gain

Pros and Cons:

See also: Monoamine oxidase inhibitors (MAOIs)

Tricyclic Antidepressants

Tricyclic antidepressants (TCAs) are an early class of antidepressant from the 1960's and were the first-line drug of choice for depression until the late 1980's.

TCAs block the reuptake of both the serotonin and norepinephrine neurotransmitters to exert their antidepressant effect. Alpha-adrenergic receptors and histamine receptors may also be blocked, causing side effects like hypotension and sedation.

Most TCAs are available in a lower-cost generic form but are infrequently used as a first-line agent due to availability of the SSRIs / SNRIs with a more tolerable side effect profile.

Table 6: TCAs Used for Depression

Generic Name Brand Name Examples
amitriptyline none available in US
amoxapine none available in US
clomipramine Anafranil
desipramine Norpramin
doxepin none available in US for depression (Silenor used for insomnia)
imipramine Tofranil
nortriptyline Pamelor
protriptyline none available in US
trimipramine none available in US

Related: Anticholinergic Drugs to Avoid in the Elderly

Common side effects in this class may include:

Pros and Cons of TCAs:

See also: Tricyclic antidepressants (TCAs) and tetracyclic antidepressants

Other Depression Treatments

Atypical Antipsychotics

Atypical antipsychotics are most often used to treat schizophrenia and bipolar disorder. However, some atypical (second generation) antipsychotics are approved as an add-on therapy for patients who do not have an optimal response to first-line depression treatment with a single agent. Although not classified as antidepressants, some are approved used for this purpose and are often combined with SSRI antidepressants. They may also be used with an antidepressant for psychotic depression.

Although not all atypical antipsychotics are FDA-approved for use in major depressive disorder, some may be prescribed "off-label". Off-label use of a drug is when your doctor prescribes a medicine for a generally accepted use not specifically approved by the FDA and listed in package labeling.

Table 7: Atypical Antipsychotics Used for Depression

Generic Name Brand Name Examples
aripiprazole Abilify, Abilify MyCite
brexpiprazole Rexulti
cariprazine* Vraylar
fluoxetine and olanzapine Symbyax
olanzapine (when combined with fluoxetine) Zyprexa, Zyprexa Zydis
risperidone* Risperdal
quetiapine* Seroquel, Seroquel XR
ziprasidone* Geodon

*Off-label use for major depressive disorder (MDD).

Common side effects in this class may include:

More serious side effects with this class include: metabolic syndrome, neuroleptic malignant syndrome (NMS) and tardive dyskinesia.

Pros and Cons:

Boxed Warnings

All antipsychotics are associated with an increased risk of death when used in elderly people, especially those with dementia-related psychosis, and they are not approved for this use.

The Latest Approvals for Depression

Zurzuvae (zuranolone) Oral Capsule

In August 2023 the FDA approved Zurzuvae (zuranolone) from Sage Therapeutics. It is the first oral medicine FDA-approved to treat postpartum depression (PPD) in adults. It is given as a once-daily oral capsule for a 14 day treatment course.

Zurzuvae is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). GABA is the major inhibitor signaling pathway in the central nervous system and helps regulate brain function.

Zurzuvae is classified as a Schedule IV controlled substance by the DEA.

Spravato (esketamine) Nasal Spray

In March 2019, the FDA approved Janssen’s Spravato (esketamine), a rapid acting, nasal spray formulation and non-competitive N-methyl D-aspartate (NMDA) receptor antagonist used in combination with an oral antidepressant for adults with treatment-resistant major depressive disorder (MDD). In August 2020, it was further cleared to treat adults with major depressive disorder (MDD) with acute suicidal ideation or behavior.

Esketamine is a Schedule III controlled substance and will only be available through a restricted distribution system (REMS) due to side effects and the potential for abuse.

Patients will self-administer the drug under supervision at a certified doctor's office and cannot take the medicine home. Patients must be monitored for at least two hours after receiving a dose.

Zulresso (brexanolone)

Zulresso (brexanolone) injection from Sage Therapeutics was approved in March 2019 for the treatment of Postpartum Depression (PPD) in adult women. PPD is a major depressive episode that occurs following childbirth or during pregnancy with symptoms of sadness, loss of interest, inability to feel pleasure, and lack of self-worth. Postpartum depression can also interfere with the maternal-infant bond or lead to suicidality.

Less common depression treatments may include:

Important Precautions with Antidepressants

Risk of suicide

Antidepressants are usually safe and may be a life-saving therapy for many patients. However, the U.S. Food and Drug Administration has required labeling on all antidepressants to include a Black Box Warning, the strictest warning for a prescription medication, about increased risks of suicidal thinking and behavior in children, adolescents and young adults under 25 years of age. The risk may be greater in the first few weeks after starting treatment or when the dose is changed. However, it is important to remember that depression and other psychiatric problems are linked to suicide, as well. When depression is not treated, the risk of suicide can go up.

Patients who are using antidepressant therapy should be closely monitored by family and healthcare providers for suicidal signs and symptoms. Contact a healthcare provider immediately if changes in depression symptoms or behavior occur, or if signs of a possible suicide emerge. Observe the patient closely within the first few months of treatment and when there is any change in dose.

Clinical trial evidence is not sufficient to determine if any one antidepressant is more or less likely to result in suicidal thoughts or action.

Learn More: Depression, Risk of Suicide, and Treatment Options

Abrupt discontinuation

It is important to speak with a physician prior to stopping an antidepressant medication. Abruptly stopping an antidepressant can lead to antidepressant withdrawal symptoms. Paroxetine (Paxil, Paxil CR) and venlafaxine (Effexor, Effexor XR) are especially prone to cause these symptoms if they are abruptly stopped; fluoxetine (Prozac, Prozac Weekly) is less likely to cause this problem.

A health care provider may recommend that the antidepressant be slowly tapered (slowly stopped using decreasing doses) to help prevent withdrawal side effects (often called discontinuation syndrome). These side effects may include:

If an antidepressant is causing an unpleasant side effect that does not subside, the physician may lower the antidepressant dose or prescribe a different class of antidepressant if treatment should not be discontinued.

Serotonin syndrome

Many antidepressants, such as SSRIs and SNRIs, raise the levels of serotonin in the brain. Serotonin is a neurotransmitter that helps to facilitate chemical messages in the brain and it is thought this helps with the symptoms of depression. However, too much serotonin can lead to symptoms such as:

Serotonin syndrome is a rare reaction but may occur when two drugs that elevate serotonin in the brain are taken at the same time. It is important that a drug interaction review is performed by a physician or pharmacist any time a new medication (prescription or over-the-counter drug, vitamin, or herbal product) is taken while also taking antidepressant therapy. Examples of drugs that may cause serotonin syndrome include:

Use in Pregnancy and Breastfeeding

Many antidepressants can be continued during pregnancy or breastfeeding, but this decision is made with your doctor case-by-case looking at the risks and benefits of treatment. If you are pregnant or planning a pregnancy, speak to your doctor first before use of any medication.

Other Information: Antidepressants

Specific antidepressant drug interactions may be viewed by using the Drug Interaction Checker. To fully review the product label and common and serious side effects, including warnings, search for your specific drug at Always talk with your healthcare provider about safety and warnings for any medication and follow their dosing directions exactly.

Learn More: Antidepressants and Alcohol Interactions

More resources

U.S. Suicide Hotline


Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.