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Antidepressants: Options, Advantages, and Precautions

Medically reviewed on Sep 27, 2018 by L. Anderson, PharmD

Depression is common, but not always treated

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. According to the National Institute of Mental Health (NIMH), major depressive disorder 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 2016 National Survey on Drug Use and Health as reported by the NIMH, roughly 16.2 million adults (6.7%) in the U.S. had at least one major depressive episode in 2016. It's higher among females (8.5%) than males (4.8%), highest in the age groups 18 to 25 years (10.9%), and highest among adults reporting two or more races or ethnic groups (10.5%). Of adults with major depressive episode diagnosed in 2016, 64% had severe impairment. What's also very concerning is that of adults with major depressive episode, 37% of adults with did not receive any treatment -- either psychotherapy or medication. 

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

What is known is that for most patients, medical treatment can be very effective and possibly life-saving. There are many options for medical drug treatment for depression, including psychotherapy such as cognitive behavioral therapy, medications, or a combination of the two. The American Psychiatric Association states antidepressant medication is recommended as an initial treatment choice for most patients with major depressive disorder, from mild to severe.

Medical treatments 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. Drug therapy used in treatment involves medications that alter the chemical messengers (neurotransmitters) in the brain. It generally takes four to eight weeks for most patients to feel the full effects of antidepressant medications. Many patients will need to continue antidepressant medications for six months to a year, but some people will need a longer period for treatment.

No single antidepressant medication has been found to be the best treatment for every patient, but in general 40% to 60% of patients (4 to 6 out of every 10 patients) will have a positive response to the first antidepressant medication they try. Second generation antidepressants (i.e., selective serotonin reuptake inhibitors [SSRIs], SNRIs) are used preferentially over first generation antidepressants (i.e., TCAs, MAOIs) because of a less toxic side effect profile and a better patient tolerability.

Typically, it takes from 4 to 6 weeks to have a full clinical response to an antidepressant. If the first treatment does not work, a healthcare provider might suggest increasing the dose or taking an antidepressant from a different class.

Generically available 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.

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
  • panic disorder
  • post-traumatic stress disorder (PTSD)
  • premenstrual dysphoric disorder.

Common antidepressant medications

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.

Generic name Brand name examples
citalopram Celexa
escitalopram Lexapro
fluoxetine Prozac, Prozac Weekly, Rapiflux, Sarafem, Selfemra
fluvoxamine Luvox (brand discontinued), Luvox CR
paroxetine Brisdelle, Paxil, Paxil CR, Pexeva
sertraline Zoloft

Common side effects in this class may include:

  • insomnia (difficulty sleeping)
  • sexual problems
  • nervousness, anxiety
  • dizziness
  • headache
  • stomach upset
  • possible weight gain
  • sweating
  • diarrhea
  • constipation

Pros and cons:

  • Fluoxetine, citalopram and sertraline associated with less weight gain than paroxetine.
  • Paroxetine may be associated with higher rates of withdrawal symptoms, sexual problems.
  • Sertraline may cause higher rates of diarrhea.
  • Fluoxetine may be associated with lower rates of withdrawal symptoms.
  • Paroxetine shown similar to duloxetine for pain treatment in patients with depression.
  • Increased risk for stomach bleeding with SSRI treatment as a class.

See also: Selective serotonin reuptake inhibitors (SSRIs)

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs block the reuptake of two neurotransmitters, serotonin and norepinephrine, elevating the concentration 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.

Generic name Brand name examples
desvenlafaxine Khedezla, Pristiq
duloxetine Cymbalta, Irenka
levomilnacipran Fetzima
milnacipran (used for fibromyalgia, not depression) Savella
venlafaxine Effexor, Effexor XR

Common side effects in this class may include:

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

Pros and cons:

  • 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).
  • 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. 

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

Most common side effects: mirtazapine

  • appetite increased 
  • drowsiness and sedation (>25% incidence)
  • dry mouth
  • peripheral edema
  • headache
  • weight gain

Most common side effects: bupropion

  • anxiety
  • dizziness
  • dry mouth
  • excessive sweating
  • fast or irregular heart rate
  • headache
  • nausea, stomach upset
  • sinusitis
  • tremor
  • trouble sleeping (insomnia)

Seizures can occur with higher doses of bupropion and appears to be a dose-related effect. Extended-release and sustained-release bupropion formulations have a lower peak blood level and are associated with a lower incidence of seizures (0.1% to 0.4%) compared to immediate-release formulations (0.4% with doses less than 450 mg/day). See maximum dosing for bupropion.

Pros and Cons:

  • Bupropion may be associated with modest weight loss, but mirtazapine can cause weight gain.
  • Seizure risk with higher bupropion doses; bupropion is contraindicated in patients with a seizure disorder.
  • Bupropion not associated with sexual dysfunction; mirtazapine has a low risk of sexual problems.
  • Bupropion may be helpful for depressed patients who feel lethargic or fatigued.
  • Bupropion may have a greater effect on potent CYP450 enzyme inhibition (CYP2D6) and resultant drug interactions than mirtazapine.
  • Mirtazapine can be useful for patients with depression who have trouble sleeping.
  • Mirtazapine may have a faster onset of action than some other antidepressants

See also: Atypical Antidepressants

Serotonin Modulators

Serotonin modulators have multiple mechanisms that exert their antidepressant effect. They primarily act as antagonists and agonists at postsynaptic serotonin receptors and inhibit reuptake of serotonin. Nefazodone may also have a weak effect on norepinephrine reuptake.

Generic Name Brand Name Examples
nefazodone Serzone (brand discontinued)
trazodone Desyrel (brand discontinued), Oleptro
vilazodone Viibryd
vortioxetine Trintellix

Common side effects in this class may include:

  • blurred vision
  • constipation
  • diarrhea
  • difficulty sleeping (insomnia)
  • drowsiness, sedation
  • dry mouth
  • dizziness
  • headache
  • nausea, vomiting
  • orthostatic hypotension (low blood pressure upon standing which may increase risk for fainting or falling)
  • sexual dysfunction
  • weakness

Pros and Cons:

  • Trazodone or nefazodone less likely to cause sexual dysfunction.
  • Nefazodone is a potent inhibitor of CYP3A4 with risk for serious drug interactions, although other serotonin modulators are substrates for various CYP enzymes and may have interactions, as well.
  • Nefazodone labeling contains a boxed warning for liver failure; contraindicated with elevated liver enzymes or liver disease.
  • Trazodone, nefazodone cause drowsiness; may be helpful for patients who have trouble sleeping that is associated with their depression.
  • Trazodone may rarely be associated with priapism, a painful and long-lasting erection considered a medical emergency.
  • Vortioxetine linked with high rates of nausea (typically highest in the first week of treatment).

See also: Miscellaneous Antidepressants

Monoamine Oxidase Inhibitors (MAOIs)

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. Typically used as a third or fourth line treatment due to severe side effects, diet restrictions, and the possibility of serotonin syndrome. Monoamine oxidase inhibitors (MAOIs) were the first class of antidepressants to be developed.

Generic Name Brand Name Examples
isocarboxazid Marplan (brand discontinued)
phenelzine Nardil
selegiline transdermal Emsam
tranylcypromine Parnate

Common side effects in this class may include:

  • dizziness
  • drowsiness
  • orthostatic hypotension (low blood pressure upon standing which may increase risk for fainting or falling)
  • headache
  • insomnia (difficulty sleeping)
  • muscle jerks
  • nausea and vomiting
  • constipation
  • dry mouth
  • agitation or anxiety
  • sexual dysfunction
  • urinary hesitancy
  • weight gain

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). 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.
  • Phenelzine may cause less insomnia than tranylcypromine.
  • Tranylcypromine causes less weight gain, sedation, and sexual dysfunction than phenelzine.
  • Serious drug-drug and drug-food interactions can occur, consult with your health care provider before using any prescription or over-the-counter medication, vitamin, or herbal product.
  • The 6 mg/24 hours patch form of selegiline does not result in MAOI-B inhibition in the gastrointestinal tract and tyramine dietary restrictions are not required. Higher selegiline patch doses (9 mg/24 hours and 12 mg/24 hours) require tyramine dietary restrictions.
  • Use caution when starting or stopping MAOI treatment to avoid a hypertensive crisis or serotonin syndrome. Continue a low tyramine diet for 2 weeks after stopping a MAOI.
  • 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 now, but are infrequently used as a first-line agent due to availability of the SSRIs with a more tolerable side effect profile.

Generic Name Brand Name Examples
amitriptyline Elavil (brand discontinued), Endep (brand discontinued)
amoxapine Asendin (brand discontinued)
clomipramine Anafranil
desipramine Norpramin
doxepin Adapin (brand discontinued), Sinequan (brand discontinued)
imipramine Tofranil
nortriptyline Aventyl (brand discontinued), Pamelor
protriptyline Vivactil
trimipramine Surmontil

The tertiary amine TCAs have a greater effect at blocking serotonin (compared to norepinephrine) and include: amitriptyline, clomipramine, doxepin, imipramine, and trimipramine. The secondary amine TCAs preferentially block norepinephrine and include: desipramine, nortriptyline, and protriptyline.

Tertiary amines tend to have more bothersome side effects than secondary amines due to anticholinergic effects (e.g., constipation, dry mouth, blurred vision) and more a more sedating effect. Maprotiline (Ludiomil, brand discontinued) is classified as a tetracyclic antidepressant, but preferentially inhibits norepinephrine. Amoxapine inhibits norepinephrine reuptake and also blocks dopamine receptors. These differences in neurotransmitter inhibition can lead to differences in side effects.

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 (low blood pressure upon standing which may increase risk for fainting or falling)
  • urinary retention

Pros and Cons:

  • Lower cost agents that can be used second or third line if newer antidepressants such as SSRIs or SNRIs are not effective.
  • TCAs are first generation (older) antidepressants and are rarely used as initial treatment.
  • Tertiary amines like nortriptyline and desipramine tend to be tolerated best by most patients.
  • TCAs have multiple side effects that often lead to discontinuation, 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 (i.e., 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 cardiac toxicity such as arrhythmias (fast or irregular heart rate), seizures, and orthostatic hypotension, leading to falls and possible injury.

See also: Tricyclic antidepressants (TCAs)

Other depression treatments

Other less common depression treatments include:

Important precautions

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 boxed 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, too.

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 a dose change.

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

Abrupt discontinuation

It is important to speak with a physician prior to stopping an antidepressant medication. Abruptly stopping an antidepressant can lead to a host of 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 to help prevent withdrawal side effects, which may include:

  • anxiety
  • feelings of depression or sadness
  • moodiness and irritability
  • fatigue
  • headaches and dizziness
  • nausea and 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 screen 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:

Other information: Antidepressants

Specific interactions of antidepressants with other medications may be viewed by using the Drugs.com Drug Interactions Checker. To fully review the product label and common and serious side effects, including warnings, search for your specific drug at Drugs.com Drug Index.

More resources

  • U.S. Suicide Hotline: Call 1-800-273-TALK (1-800-273-8255) 24/7, free and confidential, nationwide network of crisis centers.

Sources

Further information

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

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