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.

• In 2021, an estimated 61% U.S. adults aged 18 or older with major depressive episode received treatment in the past year.
• In 2021, depression was higher among females (10.3%) compared to males (6.2%), highest in the age groups 18 to 25 years (18.6%), and highest among adults reporting two or more races or ethnic groups (13.9%).
• Of all U.S. adults, 5.7% (14.5 million) had severe depressive impairment in 2021. Among those individuals with major depressive episode with severe impairment, an estimated 74.8% received treatment in the past year.

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:

• biological and genetic traits
• adverse medical conditions
• situational events such as job loss, divorce, stress, trauma, or violence
• severe grief after the death of a loved one
• side effects due to prescription medications
• alcohol use and substance abuse

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.

• Drug therapy used in treatment involves medications that alter the chemical messengers (neurotransmitters) in the brain.
• It generally takes 4 to 8 weeks for most patients to feel the full effects of antidepressant medications, but partial relief may occur sooner. A faster-acting oral medicine for postpartum depression is now approved.
• Many patients will need to continue antidepressant medications for six months to a year, or longer.

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.

• It is given as a once-daily treatment for 14 days. It is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM).
• In studies, treatment with Zurzuvae 50 mg once daily significantly improved symptoms of PPD at Day 15 and as early as Day 3 in some patients, with a sustained effect out to Day 45. 

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:

• anxiety
• bed-wetting
• bulimia nervosa
• neuropathy, nerve-related pain
• fibromyalgia
• hot flashes
• migraine headache prevention
• obsessive-compulsive disorder (OCD)
• panic disorder
• post-traumatic stress disorder (PTSD)
• premenstrual dysphoric disorder
• treatment-resistant depression

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:

• insomnia (trouble sleeping)
• sexual dysfunction (loss of libido, delayed ejaculation, absent or delayed orgasm)
• nervousness, anxiety
• dizziness, lightheadedness
• headache
• nausea, stomach upset
• possible weight gain
• sweating
• diarrhea
• constipation
• dry mouth
• confusion
• QT prolongation

Pros and Cons of SSRIs:

• Fluoxetine, citalopram and sertraline associated with less weight gain than paroxetine. Paroxetine may be associated with higher rates of withdrawal symptoms, sexual side effects, sedation, weight gain. Has relatively higher anticholinergic side effects. Paroxetine is shown similar to duloxetine for pain treatment in patients with depression.
• Sertraline may result in higher rates of diarrhea. Lower rate of possible drug interactions due to weak CYP2D6 inhibition.
• Fluoxetine is associated with lower rates of withdrawal symptoms due to longer half-life (4 to 16 days of parent drug and active metabolite). SSRIs with shorter half-lives may result in withdrawal symptoms such as insomnia, headache, dizziness, irritability.
• Citalopram / escitalopram: less anxiety symptoms associated with treatment; lower rate of possible drug interactions due to weak CYP 2D6 inhibition.
• Fluvoxamine is a potent CYP inhibitor (3A4, 2C19, 1A2) with possibility of many drug interactions; used mainly for OCD and panic disorder. Short half-life of 16 hours may lead to withdrawal symptoms quickly.
• SSRIs except fluoxetine should undergo a slow withdrawal if discontinued due to shorter half-lives and risk for discontinuation syndrome.
• Increased risk for stomach bleeding with SSRI treatment as a class.

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:

Pros and Cons of SNRIs:

• Once-a-day dosing with most formulations.
• SNRIs may be linked with more nausea and vomiting than SSRIs but this typically subsides within one week.
• SNRIs may be more effective than SSRIs in resistant or refractory (difficult-to-treat) depression.
• Duloxetine also approved to treat certain pain syndromes (fibromyalgia, chronic musculoskeletal pain, peripheral neuropathy). Milnacipran is approved to treat chronic pain caused by fibromyalgia (chronic pain throughout the body) but not depression.
• Venlafaxine or other SNRIs may increase blood pressure.

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

• appetite increased
• drowsiness and sedation (54% incidence)
• dizziness
• dry mouth
• headache
• peripheral edema (fluid retention)
• weight gain

Common side effects: bupropion

• constipation
• dizziness
• dry mouth
• headache
• nausea, stomach upset
• sore throat
• trouble sleeping (insomnia)

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.

• Sustained-release bupropion formulations have a lower peak blood level and are associated with a lower incidence of seizures (0.1% to 0.4%) at 300 to 400 mg/day or less, respectively, compared to immediate-release formulations (0.4% with doses of 300 to 450 mg/day).
• Additional data for bupropion immediate-release suggests that the estimated seizure incidence increases almost tenfold between 450 and 600 mg/day.
• The incidence of seizure with bupropion extended-release tablets (XL) has not been formally evaluated in clinical trials. However, the manufacturer states that the risk of seizure can be reduced if the bupropion extended-release tablets (XL) dose does not exceed 450 mg once daily and the titration rate is gradual. Review maximum dosing for bupropion.

Pros and Cons of Atypical Antidepressants:

• Bupropion may be associated with modest weight loss, but mirtazapine can cause weight gain in about 10% or more of patients of 9 lbs. (4 kg) on average.
• The risk of a seizure is higher with bupropion, especially at higher doses and should not be used by anyone with a seizure disorder. Mirtazapine should be used with caution in patients at risk of seizures.
• Bupropion not associated with sexual dysfunction, but mirtazapine has a low risk of sexual problems.
• Mirtazapine has been associated with an increase in cholesterol levels.
• Bupropion may be helpful for depressed patients who feel lethargic or fatigued. Mirtazapine causes a high level of sedation, but may be useful for depressed patients who also have trouble sleeping.
• Bupropion should not be used by anyone with an eating disorder such as bulimia or anorexia.

See also: Atypical Antidepressants

Serotonin Modulators

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

• They primarily act as antagonists and agonists at post-synaptic serotonin receptors and inhibit (block) the reuptake of serotonin.
• Nefazodone (Serzone) may also have a weak effect on norepinephrine reuptake.
• Trazodone is thought to inhibit reuptake of serotonin, and exhibit adrenergic receptor activity, 5HT2a receptor antagonist, 5-HT presynaptic receptor changes, and block histamine (H1) and alpha1-adrenergic receptors.
• Vortioxetine (Trintellix) may exhibit 5-HT3 receptor antagonism and 5-HT1A receptor agonism in addition to inhibition of the reuptake of serotonin (5-HT).
• Viibryd is an SSRI and partial 5-HT1A receptor agonist, but the effect of 5-HT1A agonism on the therapeutic action is not known.

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:

Pros and Cons of Serotonin Modulators:

• Nefazodone labeling contains a Boxed Warning for liver failure; do not use this medicine if you have elevated liver enzymes or liver disease.
• Nefazodone, vortioxetine, and vilazodone have low risk of sexual dysfunction (loss of desire, ejaculation failure), while trazodone has a very low risk. However, trazodone may rarely be associated with priapism, a painful and long-lasting erection considered a medical emergency.
• Trazodone and nefazodone can cause drowsiness, and may be helpful for patients who have trouble sleeping that is associated with their depression. Vortioxetine and vilazodone do not typically cause sedation.
• Vortioxetine can cause nausea (typically highest in the first week of treatment). However, in studies, it had no significant effect on body weight in either short-term or longer-term (6 month) studies. Some reports of weight gain have been received since approval, so discuss this side effect further with your doctor.
• Vilazodone is associated with a high level of stomach distress such as nausea, vomiting and diarrhea.

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:

Pros and Cons:

• May be used for patients with severe depression that does not respond to several other antidepressant treatments first.
• Not used as initial treatment due to side effects, and serious drug and food interactions (i.e., foods with high amounts of tyramine such as dried fruits, red wine, cheese, pickles, smoked or processed meats, ripe figs, fava beans) and nutritional supplements. The combination may lead to an increase in blood pressure, headache, nausea and vomiting, confusion, seizures, or death. Avoid tyramine for 2 weeks after discontinuation of a MAOI.
• Selegiline not associated with sexual dysfunction, but tranylcypromine, phenelzine and isocarboxazid are all linked with high levels of sexual dysfunction.
• All MAOI products associated with very low levels of anticholinergic side effects like dry mouth, blurred vision, trouble urinating, constipation, and dizziness. They all tend to have very low levels of stomach upset (nausea, vomiting, diarrhea) as well.
• Most agents have a low incidence of insomnia (trouble sleeping) or drowsiness.
• Tranylcypromine, selegiline and isocarboxazid cause less weight gain and sedation than phenelzine, although overall the risk is low in this class.
• The 6 mg per 24 hours patch form of selegiline (brand name: Emsam) does not result in MAOI-B inhibition in the gastrointestinal tract and tyramine dietary restrictions are not required. Higher selegiline patch doses (9 mg per 24 hours and 12 mg per 24 hours) require tyramine dietary restrictions.
• Other antidepressants should be stopped before starting treatment with a MAOI (usually for 2 weeks, but for 5 weeks with fluoxetine due to its extended half-life). When stopping MAOI treatment, do not start another antidepressant until at least 2 weeks have elapsed.

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

• The tertiary amine TCAs have a greater effect at blocking serotonin (over norepinephrine) and include: amitriptyline, clomipramine, doxepin, imipramine, and trimipramine.
• Tertiary amines tend to have more bothersome side effects than secondary amines due to anticholinergic effects (such as constipation, dry mouth, blurred vision) and more a more sedating effect.
• The secondary amine TCAs preferentially block norepinephrine and include: amoxapine, desipramine, nortriptyline, and protriptyline.
• Amoxapine inhibits norepinephrine reuptake and also blocks dopamine receptors. These differences in neurotransmitter inhibition can lead to differences in side effects.

Related: Anticholinergic Drugs to Avoid in the Elderly

Common side effects in this class may include:

• blurred vision
• heart toxicity in those at risk
• constipation
• dizziness
• dry mouth
• fatigue or drowsiness
• increased heart rate
• increased appetite and weight gain
• orthostatic hypotension
• sexual problems
• urinary retention

Pros and Cons of TCAs:

• TCAs are first generation (older) antidepressants and are rarely used as initial treatment for depression. However, these low cost agents may be used as a second or third line treatment if more common antidepressants such as SSRIs or SNRIs are not effective or tolerated.
• Secondary amines like amoxapine, nortriptyline and desipramine tend to be better tolerated than tertiary amines; however, desipramine can be linked with extreme drowsiness.
• TCAs have multiple side effects that often lead to discontinuation in patients, such as drowsiness and anticholinergic side effects (dry mouth, blurred vision, constipation, confusion, trouble urinating).
• Most TCAs are not recommended for use in the elderly (see the Beers Criteria) or severely depressed patients at risk for suicide due to the risk for overdose with TCAs.
• Excessive doses of TCAs can lead to heart toxicity such as arrhythmias (fast or irregular heart rate), seizures, and orthostatic hypotension (low blood pressure upon rising), leading to falls and possible injury.

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:

• difficulty concentrating or speaking
• changes in blood pressure
• constipation
• difficulty sleeping
• drooling
• drowsiness or sedation
• mask-like face
• restlessness or need to keep moving (akathisia)
• sexual dysfunction
• shuffling walk
• tremor
• vision problems (blurred or double vision)
• weight gain.

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

Pros and Cons:

• The effectiveness appears to be comparable among agents. The selection of an agent will depend upon side effects, possible drug interactions, and affordability for the patient.
• Atypical antipsychotics may lead to akathisia (restlessness), weight gain, sedation, elevated blood sugar, diabetes, metabolic syndrome and lipid changes (high cholesterol, LDL). Your doctor will monitor you for these effects.
• Lower doses are are often used for major depressive disorder compared to doses for schizophrenia or bipolar depression.
• Risperidone may have higher rates of extrapyramidal symptoms (EPS), which are uncontrollable abnormal body movements, than olanzapine.
• Risperidone and ziprasidone may have higher rates of sexual dysfunction compared with quetiapine.
• The benefit of using an adjunctive atypical antipsychotic in major depressive disorder typically occurs within the first two weeks of treatment.

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.

• Approval for PPD was based on results from two Phase 3 clinical trials. In the SKYLARK study, treatment with Zurzuvae 50 mg once daily significantly improved symptoms of PPD at Day 15 (HAMD-17 total score). Improvement began as early as Day 3 with a sustained effect to Day 45. HAMD-17 is a common measure of depression severity.
• The label carries a Boxed Warning for driving impairment or engaging in hazardous activities due to drowsiness (somnolence). Patients should not drive or engage in hazardous activities until at least 12 hours after Zurzuvae administration for the entire 14-day treatment course.
• The most common (>5%) side effects were somnolence, dizziness, diarrhea, fatigue and urinary tract infection (UTI). 

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.

• In Phase 3 studies of MDD in over 1,700 adults, all patients received an oral antidepressant, and either intranasal placebo or esketamine. In the group that received esketamine, superior improvement in depression symptoms was seen at four weeks, compared to the placebo plus oral antidepressant group. However, most of Spravato’s treatment difference compared to placebo was observed at 24 hours.
• Patients receiving Spravato plus an oral antidepressant were also 51% less likely to relapse as compared to patients on placebo nasal spray plus an oral antidepressant.
• The most common side effects were disassociation (feeling detached from one’s surroundings), dizziness, nausea, sedation, dizziness, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting and feeling drunk.

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.

• Zulresso is a gamma-aminobutyric acid A (GABA-A) receptor positive allosteric modulator and is the first approval for PPD.
• It is given as an intravenous (IV) infusion over 60 hours (2.5 days) in a healthcare facility and is prescribed via a restricted REMS program due to possible loss of consciousness in the patient. A healthcare provider must be available to continuously monitor the patient.
• In clinical studies, Zulresso demonstrated superiority to placebo in improvement of moderate and severe PPD symptoms at the end of the first infusion and at the end of a 30-day follow-up period.
• Commonly reported side effects are sedation or somnolence, dry mouth, loss of consciousness, and flushing.

Less common depression treatments may include:

• electroconvulsive therapy (ECT)
• acupuncture
• vagus nerve stimulation
• light therapy
• herbal or dietary supplements such as St. John's Wort and Sam-E

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:

• anxiety
• feelings of depression or sadness
• moodiness and irritability
• fatigue
• headaches
• dizziness
• nausea
• vomiting
• diarrhea

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:

• confusion
• hallucinations
• loss of coordination
• fever
• fast heart rate (tachycardia)
• nausea and vomiting

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:

• Migraine medications such as triptans - examples include eletriptan (Relpax), rizatriptan (Maxalt), sumatriptan (Imitrex), zolmitriptan (Zomig).
• Monoamine oxidase inhibitors (non-selective) - examples include isocarboxazid, selegiline transdermal, and phenelzine
• L-tryptophan
• St. John's Wort herbal supplement
• Dextromethorphan cough suppressant
• Meperidine (Demerol)
• Some illicit drugs of abuse, such as Ecstasy and LSD

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 Drugs.com Drug Interaction Checker. To fully review the product label and common and serious side effects, including warnings, search for your specific drug at Drugs.com. 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

• Call 988 for the Suicide and Crisis Lifeline, a free and confidential nationwide network of crisis centers, available 24 hours a day, 7 days a week. It is available to anyone struggling with emotional distress or in need of suicide prevention services. It is available for you or your loved ones.
• You may also still call 1-800-273-TALK (8255), as well. Both phone numbers will remain active.

Further information

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

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