depression center

Most Common Antidepressants for Depression: Types and Side Effects

What Is Depression?

Picture of a teenger looking at a box and pills.
Picture of a teenger looking at a box and pills

Clinical depression is not just grief or sadness. It is an illness that can challenge the person's ability to perform even routine daily activities. At its worst, depression may lead the person to contemplate or commit suicide. Depression represents a burden for the person and his or her family. Sometimes that burden can seem overwhelming.

Several different types of mood disorders exist.

  • Major depression is a change in mood that lasts for weeks or months. It is one of the most severe types of depression. Major depression usually involves a low or irritable mood and/or a loss of interest or pleasure in usual activities. It interferes with the person's normal functioning. The person may experience only one episode of depression, but repeated episodes often occur over the person's lifetime.
  • Dysthymia is less severe than major depression but usually goes on for a longer period, often several years. Usually periods of feeling fairly normal occur between episodes of low mood. The symptoms usually do not completely disrupt the person's normal activities.
  • Bipolar disorder involves episodes of depression, usually severe, alternating with episodes of extreme elation or irritablility called mania. This condition is sometimes called by its former name, manic depression. Antidepressant medications may be used for depressive episodes of bipolar disorder, but they are usually combined with other medications indicated for mood stabilization. Caution is warranted because antidepressants may induce mania in individuals with bipolar disorder.
  • Seasonal depression, which medical professionals call seasonal affective disorder, or SAD, is depression that occurs only at a certain time of the year, usually in winter. It is sometimes called the winter blues. Although SAD is predictable, it can be very severe.

Clinical depression affects about 19 million Americans annually, and it is estimated to contribute to half of all suicides. Up to 10 percent of people experience at least one major depressive episode during their adult life. Depression affects people of all races, incomes, and ages, but it is more common in elderly people than in young people.

The good news is that depression can be diagnosed and treated effectively in most people. The biggest barrier to overcome is recognizing that someone is depressed and seeking appropriate treatment. Clinical depression always requires attention from a medical or mental health professional.

What causes depression?

The cause of depression is largely unknown, although several theories exist. One theory is that depression is due to the reduced function of one or more neurotransmitter chemicals in the brain such as norepinephrine, dopamine, or serotonin. Another theory that has been researched is that chemical receptor sites may not optimally bind the chemicals serotonin or norepinephrine.

Other factors that may affect why some people are more likely to experience depression include the following:

  • heredity and family history of depression,
  • personality,
  • lower socioeconomic status,
  • medical conditions,
  • medications,
  • substance abuse,
  • advanced age,
  • sex (females have a higher incidence),
  • lack of social support, and
  • inadequate diet.

Risks of depression

Depression interferes with the ability to perform routine daily tasks and take care of oneself or others. Appetite changes, weight loss or gain, energy loss, inability to sleep, or excessive sleep may accompany depression. Suicidal thoughts or actions may eventually occur. People with depression who are not adequately treated may also more frequently have other medical problems.

Antidepressants Treatment for Depression Warning

Special warning for all antidepressants

The US Food and Drug Administration (FDA) has issued a public health advisory regarding suicidality (suicidal thinking and behavior) in children, adolescents, and adults with major depression whether or not they are being treated with antidepressant medications. Close observation by health care providers, family, and others is necessary to watch for worsening depression and suicidality, especially when beginning or discontinuing antidepressants or when increasing or decreasing the dose. Although a concern exists that in some people antidepressants may worsen depression or induce suicidality, this risk has not been established with antidepressants. The FDA is continuing to evaluate this issue. For more information, visit the following Web site: FDA, Antidepressant Use in Children, Adolescents, and Adults

Selective Serotonin Reuptake Inhibitors (SSRI)

Selective serotonin reuptake inhibitor (SSRI) medications affect the levels of serotonin in the brain. For many people, these medications are the first choice to treat depression. Examples of these medications are:

How do SSRIs work?

The antidepressant action of SSRIs is not thoroughly understood but is possibly due to the ability of SSRIs to block the uptake of serotonin, thereby providing higher levels of serotonin at the brain receptor site.

Who should not use these medications?

Use

  • SSRIs may be administered as oral tablets, capsules, or liquid once or twice a day. Prozac Weekly is administered once each week.
  • Do not discontinue these medications abruptly, but gradually taper use to avoid withdrawal-like symptoms such as agitation, anxiety, confusion, dizziness, headache, and insomnia.
  • Elderly individuals typically require lower doses of SSRIs.

Children: Fluoxetine (Prozac) is the only SSRI approved by the FDA for treatment of depression in children aged 8-18 years.

SSRIs Drug or Food Interactions, Side Effects

Tell the doctor what medications are currently being taken because many medicines interact with SSRIs. Do not take any nonprescription or herbal medications without first consulting the doctor or pharmacist. The following are examples of interactions, but they do not represent a complete list.

When an SSRI is administered with 5-HT1 agonists, such as sumatriptan (Imitrex) or zolmitriptan (Zomig), weakness and incoordination, although rare, have been reported.

SSRIs may increase the blood levels and risk of toxicity of certain medications, including the following:

The following substances may increase toxicity of SSRIs:

Side Effects: This is NOT a complete list of side effects reported with SSRIs. A doctor, health care provider, or pharmacist can discuss a more complete list of side effects.
  • Photosensitivity (increased risk of sunburn) (Use protective clothing, such as long sleeves and hats, and sunscreen to decrease the risk of sunburn.)
  • Rash
  • Nausea
  • Dry mouth
  • Constipation
  • Low blood sodium levels (in people who are dehydrated or taking diuretics)
  • Low blood sugar levels
  • Drowsiness (Caution is advised when operating machinery, driving, or performing other tasks that require alertness.)
  • Sexual dysfunction such as delayed ejaculation, erectile difficulties, and impotence (in men) and difficulty reaching climax or orgasm (in women)
  • Withdrawal-like symptoms in newborns (Women who take SSRIs in late pregnancy [third trimester] may have newborns who require prolonged hospitalization due to withdrawal-like symptoms such as shortness of breath, constant crying, feeding difficulty, or low blood sugar levels.)
  • Manic episodes in persons with bipolar disorder (If not combined with a mood-stabilizing medication, SSRIs may induce manic episodes in individuals with bipolar disorder [manic depression].)
  • Kidney or liver impairment precautions (The doctor may draw blood samples to check for kidney or liver impairment before prescribing SSRIs.)

Tricyclic Antidepressants (TCAs)

Tricyclic antidepressants (TCAs) are often prescribed in severe cases of depression or when SSRI medications do not work.

Tricyclic antidepressants include:

How do TCAs work?

TCAs block the uptake of serotonin and norepinephrine, thereby providing higher levels of these neurotransmitters at the brain receptor site. Besides increasing norepinephrine and serotonin, amoxapine also increases the neurotransmitter dopamine.

Who should not use these medications?

  • Individuals who have allergic reactions to TCAs
  • Individuals in the acute recovery phase following a heart attack
  • Individuals with glaucoma
  • Individuals with urine retention
  • Individuals who are currently taking or have taken MAOIs within the past 2 weeks (Phenelzine [Nardil], and tranylcypromine [Parnate], are examples of MAOIs.) (Do not start taking MAOIs for at least two weeks after stopping TCAs. This is a general warning; see drug and food interactions for low-dose use together.)
  • Individuals taking some medications that alter heart rhythm such as thioridazine (Mellaril) or cisapride (Propulsid)

Use

  • Tricyclic antidepressants are taken orally by tablet, capsule, or oral solution.
  • Elderly individuals and adolescents often require lower doses.

Elderly: Elderly individuals require lower doses. Elderly individuals are more susceptible to sedative effects and may feel faint when standing up, therefore increasing the risk of falls and injuries.

Children: The following TCAs are approved in the United States for treating adolescents with depression who are older than 12 years:

  • amitriptyline (Elavil, Endep)
  • desipramine (Norpramin)
  • doxepin (Sinequan, Adapin)
  • nortriptyline (Pamelor, Aventyl)
  • protriptyline
  • trimipramine (Surmontil)
  • amoxapine (approved for persons older than 16 years)

TCAs Drug or Food Interactions, Side Effects

Tell the doctor what medications are currently being taken because many medicines interact with TCAs. Do not take any nonprescription or herbal medications without first consulting the doctor or pharmacist. The following are examples of interactions, but they do not represent a complete list.

  • TCAs may increase the blood levels and/or risk of toxicity of the following medications:
    • MAOIs (These may cause serious and sometimes fatal reactions; some TCAs have been used safely with MAOIs, but the dose of TCAs must be increased very slowly and the person must strictly adhere to MAOI dietary restrictions.)
    • Sympathomimetics such as pseudoephedrine (Sudafed)
  • The following substances may increase the toxicity of TCAs:
  • Other interactions include the following:
    • TCAs may decrease the ability for clonidine (Catapres) to lower blood pressure levels.
    • carbamazepine (Tegretol, Tegretol XR, Equetro, Carbatrol) may decrease TCA effectiveness.
    • St. John's wort may decrease TCA effectiveness and increase the risk of serotonin syndrome.

Side Effects: This is NOT a complete list of possible side effects reported with TCAs. A doctor, health care provider, or pharmacist can discuss a more complete list of side effects.

  • Confusion, agitation, or hallucinations (Contact a doctor immediately if these occur.)
  • Severe diarrhea, fever, sweating, muscle stiffness, or tremors (These may be symptoms of neuroleptic malignant syndrome. Contact a doctor immediately.)
  • Rapid or abnormal heartbeat or fainting (Contact a doctor immediately if these occur.)
  • Changes in sexual interest or ability
  • Manic episodes in persons with bipolar disorder (If not combined with a mood-stabilizing medication, SSRIs may induce manic episodes in individuals with bipolar disorder [manic depression].)
  • Drowsiness (Caution is advised when operating machinery, driving, or performing other tasks that require alertness.)
  • Photosensitivity (increased risk of sunburn) (Use protective clothing, such as long sleeves and hats, and sunscreen to decrease the risk of sunburn.)
  • Rash
  • Nausea
  • Dry mouth
  • Urine retention
  • Blurred vision
  • Constipation
  • Lightheadedness when standing up from a sitting or lying position (Stand up gradually from lying down or sitting positions.)
  • Seizures (TCAs lower the threshold for seizures, that is, seizures may occur more easily in the person taking TCAs. Caution is advised for individuals prone to seizures or those who have a history of seizures.)

Monoamine Oxidase Inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) include isocarboxazid (Marplan), phenelzine (Nardil), and tranylcypromine (Parnate). These medications are rarely used because of strict dietary requirements and life-threatening drug and food interactions. Because of these drug and food interactions, MAOIs may not be taken with many other types of medicines, and some foods that are high in tyramine, dopamine, or tryptophan must be avoided as well.

How do MAOIs work?

These drugs inhibit monoamine oxidase. Monoamine oxidase is an enzyme in the body that is responsible for metabolizing (breaking down) neurotransmitters such as norepinephrine, epinephrine, dopamine, and serotonin. The result of MAOIs is an increase in the concentration of neurotransmitters. Some of these neurotransmitters increase blood pressure.

Who should not use these medications?

In many circumstances, the use of MAOIs is dangerous.

  • Individuals who are allergic to MAOIs
  • Individuals with diseases, such as pheochromocytoma or hypertension, that cause increased blood pressure
  • Individuals with diseases, such as heart failure or other heart disease, severe impaired renal function, and stroke or other cerebrovascular disease, in which increased blood pressure is likely to aggravate the condition
  • Individuals with a history of headache
  • Individuals with liver disease
  • Individuals using other drugs that may elevate blood pressure or cause additive effects (see drug interactions)
  • Individuals consuming foods with high tyramine content—MAOIs may lead to dangerously elevated blood pressure (see food interactions)
Use
  • MAOIs are administered orally.
  • MAOIs are rarely the first antidepressant drug prescribed, but they are an option when initial treatments do not work or are not tolerated.
  • MAOIs are not a good choice for elderly or debilitated individuals.

Children: Phenelzine is not approved for children younger than 16 years. Tranylcypromine is not approved for children or adolescents.

MAOIs Drug or Food Interactions, Side Effects

Tell the doctor what medications are currently being taken because many drugs interact with MAOIs. Do not take any nonprescription or herbal medications without first consulting the doctor or pharmacist. The following are examples of interactions, but they do not represent a complete list.

  • The risk for serotonin syndrome may be increased by SSRIs, TCAs, atomoxetine (Strattera), duloxetine (Cymbalta), dextromethorphan (in many cough syrups), dexfenfluramine, 5-HT1 agonists [such as sumatriptan (Imitrex) or zolmitriptan (Zomig)], venlafaxine (Effexor), St. John's wort, or ginkgo. Serotonin syndrome is a serious side effect and may be fatal. Symptoms include fever, muscle stiffness, and changes in mental status such as confusion or hallucinations.
  • The risk of neuroleptic malignant syndrome (restlessness, sweating, fever, confusion, and muscle stiffness) may increase with lithium (Eskalith, Lithobid) and tramadol (Ultram).
  • Morphine, meperidine (Demerol), and other narcotic pain relievers may cause hypotension and depress the central nervous system and respirations.
  • The following drugs may increase the risk of hypertensive crisis when taken with MAOIs or within two weeks of stopping MAOIs:
  • MAOIs may increase side effects of the following drugs:
  • Do not eat foods high in tyramine, dopamine, or tryptophan while taking MAOIs or for two weeks after discontinuing MAOIs. Tyramine, dopamine, and tryptophan are chemicals that can interact with MAOIs and cause hypertensive crisis, which is an extremely dangerous side effect. Foods high in these chemicals should be avoided. They include the following:
    • Dairy products
      • Cheese, particularly Blue, Camembert, Cheddar, Emmenthaler, Stilton, and Swiss, which contain very high amounts of tyramine
      • Yogurt
    • Meat and fish products
      • Anchovies
      • Beef or chicken liver
      • Other meats or fish that have not been refrigerated, are fermented, or are spoiled
      • Caviar
      • Fermented sausages such as bologna, pepperoni, salami, and summer sausage
      • Game meat
      • Meats prepared with tenderizer
      • Herring
      • Shrimp paste
    • Alcoholic beverages
      • Beer
      • Red wine, especially Chianti
      • Sherry
      • Distilled spirits and liqueurs
    • Fruits and vegetables
      • Fruits such as bananas, raspberries, dried fruits, and overripe fruits (especially avocados and figs)
      • Bean cure, miso soup, sauerkraut, soy sauce, and yeast extracts (such as Marmite)
    • Foods containing other chemicals that increase blood pressure

Side Effects: This is NOT a complete list of side effects reported with MAOIs. A doctor, health care provider, or pharmacist can discuss a more complete list of side effects.

  • Hypertensive crisis (Hypertensive crisis is the most serious reaction and involves dramatic increases in blood pressure and requires immediate care from the doctor. The hypertensive crisis usually occurs within several hours after ingestion of a drug or food that interacts with MAOIs. Hypertensive crisis can be fatal. Symptoms include severe headache, rapid heart rate, chest pain, neck stiffness, nausea, vomiting, sweating [may include a fever or cold, clammy skin], dilated pupils, and eye sensitivity to light.)
  • Manic episodes in persons with bipolar disorder [If not combined with a mood-stabilizing drug, MAOIs may induce manic episodes in individuals with bipolar disorder (manic depression).]
  • Increased heart rate or blood pressure in people with hyperthyroid conditions
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Atypical Antidepressants Types and Usages

Atypical antidepressants may be prescribed when SSRIs or TCAs have not worked. Atypical antidepressants include:

  • bupropion (Wellbutrin, Wellbutrin SR, Wellbutrin XL),
  • duloxetine (Cymbalta),
  • maprotiline (Ludiomil),
  • mirtazapine (Remeron),
  • nefazodone (Serzone),
  • trazodone (Desyrel), and
  • venlafaxine (Effexor).

How do atypical antidepressants work?

Each of these drugs inhibit uptake of the various neurotransmitters in the brain.

Who should not use these medications?

  • Individuals with a prior allergic reaction to any atypical antidepressant
  • Individuals with seizure disorders (Do not use bupropion and maprotiline.)
  • Individuals taking MAOIs (Do not use duloxetine, maprotiline, and venlafaxine.)
  • Other contraindications include the following:
    • Bupropion (Wellbutrin, Wellbutrin SR, Wellbutrin XL): Individuals with bulimia or anorexia nervosa, or those in the process of withdrawal from alcohol or sedatives should not take bupropion.
    • Duloxetine (Cymbalta): Individuals with uncontrolled narrow-angle glaucoma should not take duloxetine.
    • Maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), and trazodone (Desyrel): Individuals who have experienced a recent heart attack should not take these medications.
    • Nefazodone (Serzone): Individuals should not take nefazodone if they have liver impairment or are currently using cisapride (Propulsid), pimozide (Orap), carbamazepine (Tegretol), or triazolam (Halcion).
Use
  • Atypical antidepressants are administered orally.
  • Mirtazapine (Remeron SolTab) is a tablet that dissolves when placed in the mouth instead of swallowing with water.
  • Some atypical antidepressants are available as sustained-release tablets or capsules and should only be swallowed whole (do not crush, divide, or chew).
  • Abrupt discontinuation of some atypical antidepressants, such as duloxetine, may cause withdrawal-like symptoms such as agitation, anxiety, confusion, dizziness, headache, and insomnia. Ask a doctor or pharmacist if the medication dose should be gradually tapered down to avoid these symptoms.
Children: Safety and efficacy of duloxetine, bupropion, maprotiline, mirtazapine, nefazodone, and trazodone have not been established in children younger than 18 years.

Drug or food interactions: Tell the doctor what medications are currently being taken because many drugs interact with atypical antidepressants. Do not take any nonprescription or herbal medications without first consulting the doctor or pharmacist. The following are examples of interactions, but they do not represent a complete list.

Atypical Antidepressants Side Effects and Interactions

This is NOT a complete list of side effects reported with atypical antidepressants. The doctor, health care provider, or pharmacist can discuss a more complete list of side effects.

  • Manic episodes in persons with bipolar disorder (If not combined with a mood-stabilizing drug, atypical antidepressants may induce manic episodes in individuals with bipolar disorder.)
  • Seizures (Atypical antidepressants may lower the threshold for seizures; that is, seizures may occur more easily. Caution is advised for individuals prone to seizures or those who have a history of seizures.)
  • Drowsiness (Caution is advised when operating machinery, driving, or performing other tasks that require alertness.)
  • bupropion (Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban)
    • Contains the same active ingredient found in Zyban, which is used as an aid in smoking cessation treatment (Do not use bupropion with Zyban or other medications containing bupropion.)
    • More likely to cause seizures than other antidepressants, especially with doses above 450 mg/day (Seizures are also more likely in patients who have bulimia or anorexia nervosa and are treated with bupropion.)
    • Caution in narrow-angle glaucoma
    • Caution in slow gastric emptying (often present in diabetes)
  • maprotiline (Ludiomil), mirtazapine (Remeron)
  • nefazodone (Serzone)
    • May cause liver impairment (Contact the doctor immediately if dark urine, anorexia, stomach or abdominal pain, or yellowing of the skin or eyes occurs.)
    • Caution in heart disease and abnormal heart rhythms
    • Lightheadedness or fainting when standing up from a sitting or lying position (Stand up gradually from lying down or sitting positions.)
  • trazodone (Desyrel)
    • Caution in heart disease and abnormal heart rhythms
  • venlafaxine (Effexor)
    • May cause sustained increases in blood pressure
    • May cause weight loss
    • May cause anxiety and insomnia
    • Decreased dose required for individuals with kidney or severe liver impairment

Bupropion (Wellbutrin, Wellbutrin SR, Wellbutrin XL) Side Effects and Interactions

  • Bupropion (Wellbutrin, Wellbutrin SR, Wellbutrin XL) may increase the blood levels and/or risk of toxicity of the following drugs:
    • Alcohol or other drugs that depress the central nervous system such as drugs taken for insomnia
    • SSRIs
    • TCAs
    • Beta blockers such as propranolol (Inderal)
    • Antiarrhythmic drugs such as flecainide (Tambocor) or propafenone (Rythmol)
    • warfarin (Coumadin)
  • The following drugs may increase bupropion blood levels or toxicity:

Duloxetine (Cymbalta) Side Effects and Interactions

  • Duloxetine (Cymbalta) may increase the blood levels and/or risk of toxicity of the following drugs:
    • Alcohol or other drugs that depress the central nervous system such as drugs taken for insomnia
    • Antiarrhythmic drugs such as flecainide (Tambocor) or propafenone (Rythmol)
    • Phenothiazines such as thioridazine (Mellaril)
    • TCAs
    • MAOIs
    • warfarin (Coumadin)
  • The following drugs may increase duloxetine blood levels or toxicity:

Maprotiline (Ludiomil), mirtazapine (Remeron) Side Effects and Interactions

  • Maprotiline (Ludiomil) may increase the blood levels and/or risk of toxicity of the following drugs:
    • Alcohol or other drugs that depress the central nervous system such as drugs taken for insomnia
    • Drugs with similar side effects such as TCAs or antihistamines (Benadryl)
  • The following drugs may increase maprotiline blood levels or toxicity:
    • Thyroid medication may add to the risk of increased heart rate and abnormal rhythm.
    • Phenothiazines and benzodiazepines [such as diazepam (Valium)] increase risk for seizures.

Nefazodone (Serzone) Drug Interactions

  • Nefazodone (Serzone) may increase the blood levels and/or risk of toxicity of the following drugs:
    • Alcohol or other drugs that depress the central nervous system such as drugs taken for insomnia
    • buspirone (Buspar)
    • carbamazepine (Tegretol)
    • cisapride (Propulsid)
    • cyclosporine (Neoral, Sandimmune)
    • digoxin (Lanoxin)
    • pimozide (Orap)
    • thioridazine (Mellaril)
    • triazolam (Halcion)
    • St. John's wort
    • SSRIs
    • TCAs
    • Drugs that may cause abnormal heart rhythms (check with the doctor or pharmacist)
    • Drugs indicated to treat high cholesterol such as simvastatin (Zocor) or atorvastatin (Lipitor)
  • The following drugs may increase nefazodone blood levels or toxicity:
    • buspirone (Buspar)
    • sibutramine (Meridia)
    • sumatriptan (Imitrex) or other similar drugs for migraine headache

Trazodone (Desyrel) Drug Interactions

  • Trazodone (Desyrel) may alter the blood levels and/or risk of toxicity of the following drugs:
    • Alcohol or other drugs that depress the central nervous system such as drugs taken for insomnia
    • clonidine (Catapres) (enhances blood pressure lowering effect)
    • digoxin (Lanoxin)
    • MAOIs
    • phenytoin or fosphenytoin (Dilantin, Cerebyx)
    • warfarin (Coumadin)
  • The following drugs may increase trazodone blood levels or toxicity:
    • Antifungal agents such as itraconazole (Sporanox) or ketoconazole (Nizoral)
    • carbamazepine (Tegretol)
    • Phenothiazines such as thioridazine (Mellaril)
    • ritonavir (Norvir)
    • SSRIs, sibutramine (Meridia), sumatriptan (Imitrex), trazodone (Desyrel), venlafaxine (Effexor), and St. John's wort (These medications may increase the risk for serotonin syndrome - symptoms include hypertension, fever, muscle tremor, or confusion.)
    • Drugs that may cause abnormal heart rhythms (check with the doctor or pharmacist)

Venlafaxine (Effexor) Drug Interactions

  • Venlafaxine (Effexor) may alter the blood levels and/or risk of toxicity of the following drugs:
    • clozapine (Clozaril)
    • desipramine (Norpramin)
    • haloperidol (Haldol)
    • indinavir (Crixivan)
    • SSRIs, sibutramine (Meridia), sumatriptan (Imitrex), trazodone (Desyrel), and St. John's wort (These medications may increase the risk for serotonin syndrome - symptoms include hypertension, fever, muscle tremor, or confusion.)
    • warfarin (Coumadin)
  • The following drugs may increase venlafaxine blood levels or toxicity:
    • cimetidine (Tagamet)
    • MAOIs
    • SSRIs, nefazodone (Serzone), St. John's wort, and venlafaxine (These medications may increase the risk for serotonin syndrome - symptoms include hypertension, fever, muscle tremor, or confusion.)

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Medically reviewed by Ashraf Ali, MD; American Board of Psychiatry & Neurology

REFERENCE:

Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects
UpToDate.com

Atypical antidepressants: Pharmacology, administration, and side effects
UpToDate.com