Depression and Antidepressants: Options, Advantages, and Precautions

What is Major Depressive Disorder (MDD)?

Major depression is more than just feeling sad, guilty or blue from time-to-time. Depression, also called major depressive disorder (MDD), affects daily feelings, actions, thoughts and wellness. Depression can make it difficult to engage in activities such as family life, work, and social events, and may be associated with abnormal biochemical changes in the brain that lead to depressed feelings and sadness. Medical treatment of some type is required as depression will not go away on its own; however, most forms of depression respond well to treatment such as prescription antidepressants and psychotherapy (talk therapy).

Depression is not a trivial illness. Depression not only negatively impacts family, work and social life, depression can adversely affect common physical ailments, such as arthritis, heart disease, cancer, and diabetes. Depression is a serious disorder that can result in a lowered quality of life, isolation, and even suicide.

Depression is not a sign of weakness or the fault of the person who has the diagnosis. However, it is important that anyone who suspects they have depression seek immediate help from trusted family members and healthcare providers. Depression is a treatable disease with a high rate of success.

What Are the Symptoms of Depression?

The most common sign of depression is a chronic, deep, severely low mood, profound sadness, tearfulness, or a sense of hopelessness. For some people, depression symptoms may include chronic irritability, anxiety or moodiness. Enjoying activities that are normally pleasurable becomes difficult. Other signs and symptoms of depression include:1,2

  • Sad, anxious, or empty mood that lasts more than 2 weeks
  • Appetite changes - weight loss or weight gain
  • Changes in sleep habits; trouble sleeping and feeling tired all of the time
  • Agitation, sleeplessness, or mood swings
  • Tearfulness for no apparent reason
  • Rage or anger
  • Chronic self-criticism
  • Engaging in risky activities without thinking
  • Increasing alcohol or drug abuse
  • Withdrawing from family and friends

Suicide Warning Signs

Depression may also involve thoughts of suicide. Learn to recognize these warning signs and get immediate help:

  • Thoughts of hurting or killing oneself
  • Feeling like there is no reason to live
  • Hopelessness
  • Looking for ways to kill yourself
  • Talking about death, dying, or suicide
  • Self-destructive behavior such as use of drugs and alcohol, weapons

A person with symptoms of depression or thoughts of suicide should get immediate help from their healthcare provider, or a trusted friend or family member. A confidential suicide hotline can be accessed in the U.S. by calling 1-800-273-TALK (1-800-273-8255) 24 hours a day, 7 days a week, or online at www.suicidepreventionlifeline.org. Trained, skilled professionals are available to to confidentially discuss any matter.

Who Gets Depression and What Causes It?

According to the U.S. Centers for Disease Control and Prevention (CDC), depression is a common illness that impacts roughly 1 out of every 10 Americans.3 Depression can impact anyone regardless of age, race or economic status, but studies have shown the following groups to be more likely to be affected by depression:

  • Persons 45 to 64 years of age
  • Women
  • Blacks, Hispanics, non-Hispanic persons of other races or multiple races
  • Those with less than a high school education
  • Previously married individuals
  • Those unemployed or unable to work
  • Persons without health insurance coverage

In addition to the above groups, the elderly are at an especially high risk for depression, often compounded by chronic health conditions, loneliness, lack of social support, and limited mobility.

The exacts causes of depression are not known. For many patients, depression does not have a single cause and the reason why they are depressed is hard to pinpoint. Depression may be due to a mixture of:

  • Biological and genetic traits
  • Adverse health conditions
  • Current situations such as job loss, stress, trauma, or violence
  • Severe grief after the death of a loved one
  • Some prescription medications can cause depressive symptoms as a side effect
  • Alcohol use and substance abuse

Depression probably involves changes in the areas of the brain that control mood. Research suggests that changes in levels of certain chemicals in the brain called neurotransmitters, such as serotonin or norepinephrine, may be partly responsible for the occurrence of depression. Chemical reactions or communication  between nerve cells may make it difficult for a person to regulate their mood. Hormonal changes, especially in women, may have a role. Depression may also be genetically linked - an individuals risk for depression may be higher if they have a family history of depression.

What are the Types of Depression?

Depression is not a one-size-fits all illness. There are different types of depression, some are more serious than others, but all of them may lead to a reduced quality-of-life.

  • Major Depression (also called major depressive disorder) - A mood disorder in which feelings of sadness, loss, anger, or frustration interfere with everyday life for weeks or longer.
  • Dysthymia (also called dysthymic disorder) - Dysthymia is a chronic type of depression in which a person's moods are regularly low. However, symptoms are not as severe as with major depression.
  • Seasonal Affective Disorder (SAD) -  A depressive mood disorder that occurs and disappears at roughly the same time each year. The most common type is winter depression and it is characterized by excess morning fatigue, low energy, increased appetite and weight gain, and a craving for carbohydrates, all of which remit in the spring.
  • Depressive Psychosis - Depressive psychosis is a combination of a depressed mood along with psychosis, or a loss of touch with reality. The person may have delusions (false beliefs) or hallucinations (seeing or hearing things that are not there).
  • Postpartum Depression - It is common to have the blues short-term after the birth of a baby, as the mother and baby adjust to a new lifestyle and schedule. But new mothers who have depressed feelings two or more weeks after the birth of a new baby may have postpartum depression. Women with postpartum depression may be restless, anxious, fatigued, irritable, tearful and feel inadequate. The mother may have a lack of interest or negative feelings towards the baby. Hormonal changes after the birth of a child may contribute to postpartum depression.
  • Premenstrual Dysphoric Disorder (PMDD) - In PMDD, extreme mood shifts may start to occur in women beginning seven to 10 days before their period starts and may continue into the first few days of the period. Other typical symptoms that occur during a period, like breast tenderness, bloating, fatigue, and appetite changes may also occur, but the mood disorder is severe and may include symptoms such as sadness, anxiety, irritability, or aggravation. Hormonal changes may be the cause of some of the symptoms.

These types of depression do not usually go away on their own. People who are affected by any of these types of depression should seek advice and treatment from a qualified healthcare provider. Talk therapy and medication may be needed, and treatments may differ depending upon the diagnosis.

What are the Medical Treatments for Depression?

The cornerstone treatments for depression are prescription medications and talk therapy with a trained specialist (psychotherapy) - and they are often used together. 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 percent of patients (4-6 out of every 10 patients) will have a positive response to the first antidepressant medication they try. Second generation antidepressants (i.e., 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.

Pros and Cons of Common Antidepressant Treatments2,4,5

Selective Serotonin Reuptake Inhibitors (SSRIs)

Common Brand Names:

Lower-cost Generics:

Common Side Effects of SSRIs:

  • Insomnia
  • Sexual problems
  • Nervousness, anxiety
  • Dizziness
  • Headache
  • Stomach upset
  • Possible weight gain
  • Sweating
  • Diarrhea
  • Constipation

Pros of Select SSRIs:

  • Fluoxetine, citalopram and sertraline associated with less weight gain than paroxetine
  • Response rates between fluoxetine daily and fluoxetine weekly are similar
  • Fluoxetine may be associated with lower rates of withdrawal symptoms
  • Paroxetine shown similar to duloxetine for pain treatment in patients with depression

Cons of Select SSRIs

  • Paroxetine may cause more weight gain, sexual problems than other SSRIs
  • Paroxetine may be associated with higher rates of withdrawal symptoms
  • Sertraline may cause  higher rates of diarrhea
  • Increased risk for stomach bleeding with SSRI treatment as a class
  • Increased risk for  bone fractures in patients on high-dose citalopram, fluoxetine, paroxetine, and sertraline
  • Increased risk for diabetes on recent, long-term (>24 mo) use of paroxetine or venlafaxine

See also: Selective serotonin reuptake inhibitors (SSRIs)

Serotonin-Norepinephrine Reuptake Inhibitors

Common Brand Names:

Lower-cost Generics:

Common Side Effects of SNRIs:

  • Nausea
  • Dry mouth
  • Insomnia, drowsiness
  • Dizziness
  • Anxiety
  • Sexual problems
  • Headache
  • Sweating

Pros of Select SNRIs:

  • Once-a-day dosing with most formulations
  • Venlafaxine may be slightly more effective in refractory or resistant depression
  • Venlafaxine had lower discontinuation rates due to lack of effectiveness
  • Duloxetine shown similar to paroxetine for pain treatment in patients with depression
  • Venlafaxine may be associated with higher rates of withdrawal symptoms

Cons of Select SNRIs:

  • Nausea and vomiting 52 percent more common with venlafaxine than with SSRIs
  • Duloxetine may increase blood pressure and sweating
  • Higher rates of discontinuation due to side effects associated with duloxetine and venlafaxine

See also: Serotonin norepinephrine reuptake inhibitors (SNRIs)

Other Antidepressants

Other Antidepressants fall outside of the main classes, but are often effectively used for treatment.

Lower-cost Generics

Common Side Effects

  • Dry mouth
  • Headache
  • Nausea
  • Weight gain or loss
  • Constipation or diarrhea
  • Sweating
  • Agitation or confusion
  • Drowsiness or insomnia
  • Dizziness
  • Abnormal dreams

Pros

  • Bupropion may be associated with modest weight loss
  • Bupropion, trazodone or nefazodone less likely to cause sexual dysfunction
  • Bupropion may be helpful for depressed patients who feel lethargic or fatigued
  • Trazodone, nefazodone, and mirtazapine may be helpful for patients who have trouble sleeping associated with their depression
  • Mirtazapine may have a faster onset of action than some other antidepressants

Cons

  • Seizure risk with higher bupropion doses
  • Do not use bupropion in patients with seizure disorder or risk
  • Mirtazapine associated with weight gain
  • Trazodone and mirtazapine may be more sedating

Monoamine Oxidase Inhibitors (MAOIs)

Common Brand Names

Lower-cost Generics

Common Side Effects

  • Dizziness or drowsiness
  • Edema or weight gain
  • Orthostatic hypotension
  • Headache
  • Insomnia
  • Nausea and vomiting
  • Constipation
  • Dry mouth
  • Agitation or Anxiety
  • Sexual dysfunction

Pros of Select MAOIs

  • May be used as second or third-line agent for patients who do not respond to other treatments

Cons of Select MAOIs

  • Rarely 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, death.
  • Other serious drug-drug interactions, consult with health care provider

See also: Monoamine oxidase inhibitors (MAOIs)

Tricyclic Antidepressants

Common Names

Lower-cost Generics Available?

  • Yes - Most TCAs are available in generic form

Common Side Effects

  • Dry mouth
  • Dizziness
  • Constipation
  • Orthostatic hypotension
  • Blurred vision
  • Fatigue or drowsiness
  • Urine retention
  • Increased heart rate
  • Increased appetite and weight gain

Pros

  • Lower cost agents that can be used second line if newer second generation antidepressants are not effective.

Cons

  • TCAs are first generation (older) antidepressants and are rarely used as initial treatment
  • TCAs have multiple side effects; can cause drowsiness and anticholinergic side effects (dry mouth, blurred vision, constipation, confusion, trouble urinating)
  • Most TCAs not recommended for use in the elderly. or severely depressed patients at risk for suicide
  • Serious toxicity can result from excessive doses or overdose

See also: Tricyclic antidepressants (TCAs)

Other Depression Treatments

Other less common depression treatments include:

Important Precautions

Risk of Suicide

The U.S. Food and Drug Administration has required labeling on all antidepressants to include boxed warnings about increased risks of suicidal thinking and behavior, known as suicidality,  in children, adolescents and young adults during initial treatment (generally the first one to two months). However, it is important to remember that depression and other psychiatric problems are linked to suicide, as well.

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.6

Clinical trial evidence is not sufficient to determine if any one antidepressant is more or less likely to result in suicidal thoughts or action.5

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 the medication should not be discontinued.5

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
  • Nausea or 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 is taken while also taking antidepressant therapy. Examples of drugs that may cause serotonin syndrome include:

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.

More Reading

See Also:

References:

  1. U.S. Department of Veterans Affairs. Veterans Crisis Line.  Website. Accessed Dec 12, 2012. http://veteranscrisisline.net/SignsOfCrisis/Default.aspx
  2. Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression: An Update of the 2007 Comparative Effectiveness Review: Comparative Effectiveness Review Executive Summary No. 46 (AHRQ Pub. No. 12-EHC012-1 From: Gartlehner G, Hansen RA, Thieda P, et al. Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression [Internet]. Rockville, MD: Agency for Healthcare Research and Quality (US); 2007 Jan. Comparative Effectiveness Reviews, No. 7. Available at: http://effectivehealthcare.ahrq.gov/ehc/products/210/863/CER46_Antidepressants-update_20111206.pdf
  3. Centers for Disease Control and Prevention (CDC). An estimated 1 in 10 U.S. Adults Report Depression [Internet]. Atlanta, GA. Updated March 31, 2011. Accessed Dec 12, 2012. Available at: http://www.cdc.gov/features/dsdepression/
  4. Second-Generation Antidepressants for Treating Adult Depression: An Update. Clinician Research Summary. AHRQ Publication No. 12-EHC-012-3. Updated July 2012. Accessed January 7, 2012. Available at: http://effectivehealthcare.ahrq.gov/ehc/products/210/1143/sec_gen_anti_dep_clin_fin_to_post.pdf
  5. Medicines for Treating Depression: A Review of the Research for Adults. AHRQ Publication No. 12-EHC-012-A. Updated July 2012. Accessed January 7, 2012. Available at:
    http://effectivehealthcare.ahrq.gov/ehc/products/210/1142/sec_gen_anti_dep_cons_fin_to_post.pdf
  6. U.S. Food and Drug Administration (FDA). Antidepressant Use in Children, Adolescents and Adults. Last updated 8/10/2010. Accessed 1/7/2013. Available at: http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/UCM096273
  7. American Psychiatric Association (APA). Practice guideline for the treatment of patients with major depressive disorder. 3rd ed. Arlington (VA): American Psychiatric Association (APA); 2010 Oct. Available at: http://www.guidelines.gov/content.aspx?id=24158
  8. Trangle M, Dieperink B, Gabert T, Haight B, Lindvall B, Mitchell J, Novak H, Rich D, Rossmiller D, Setterlund L, Somers K. Institute for Clinical Systems Improvement. Major Depression in Adults in Primary Care.

Last updated: 2013-11-03 by Leigh Anderson, PharmD.

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