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Depression

Highlights

What Is Depression?

Clinical depression is a mood disorder in which overwhelming feelings of sadness, loss of pleasure, guilt, and hopelessness interfere with daily life. People with depression also suffer from sleep problems, difficulty concentrating, fatigue and low energy, changes in appetite, and recurring thoughts of death or suicide.

Types of Depression

There are different subtypes of clinical depression. They include:

American Psychiatric Association Updated Treatment Guidelines

The American Psychiatric Association's updated guidelines for the treatment of patients with major depressive disorder include:

Drug Approval

In 2011, the FDA approved vilazodone (Viibryd) for treatment of major depression in adults. Vilazodone is a new type of dual action selective serotonin reuptake inhibitor (SSRI).

Introduction

Everyone experiences some unhappiness, often as a result of a life change, either in the form of a setback or a loss, or simply, as Freud said, "everyday misery." The painful feelings that accompany these events are usually appropriate and temporary, and can even present an opportunity for personal growth and improvement. However, when sadness persists and impairs daily life, it may indicate a depressive disorder. Severity, duration, and the presence of other symptoms are the factors that distinguish normal sadness from clinical depression.

Clinical depression is classified as a mood disorder. The primary subtypes are major depression, dysthymia (longstanding but milder depression), and atypical depression. Other depressive disorders include premenstrual dysphoric disorder (PDD or PMDD) and seasonal affective disorder (SAD).

Forms of depression
Depression is defined as a mood disorder, and there are several subtypes. Bipolar disorder, also known as manic-depressive illness, is considered in a separate category.

The other major mood disorder is bipolar disorder, formerly called manic-depressive illness, which is characterized by periods of depression alternating with episodes of excessive energy and activity. Bipolar disorder is not discussed in this report. [For more information, see In-Depth Report #66: Bipolar disorder.]

Major Depression

Major depression is also called major depressive disorder. In major depression, at least five of the symptoms listed below must occur for a period of at least 2 weeks, and they must represent a change from previous behavior or mood. Depressed mood or loss of interest must be present. Symptoms include:

1. Depressed mood on most days for most of each day -- irritability may be prominent in children and adolescents

2. Total or very noticeable loss of pleasure most of the time

3. Significant increases or decreases in appetite, weight, or both

4. Sleep disorders, either insomnia or excessive sleepiness, nearly every day

5. Feelings of agitation or a sense of intense slowness

6. Loss of energy and a daily sense of tiredness

7. Sense of guilt or worthlessness nearly all the time

8. Inability to concentrate occurring nearly every day

9. Recurrent thoughts of death or suicide

In addition, other criteria must be met:

Episodes of major depression usually last about 20 weeks.

Depression in Children. Symptoms for major depression in children can differ from those in adults and may include:

Dysthymia (Chronic Depression)

Dysthymia, or chronic depression, afflicts 3 - 6% of the general population and is characterized by many of the same symptoms that occur in major depression. Symptoms of dysthymia are less intense and last much longer, at least 2 years.

The symptoms of dysthymia have been described as a "veil of sadness" that covers most activities. Possibly because of the duration of the symptoms, patients who suffer from chronic minor depression do not exhibit marked changes in mood or in daily functioning, although they have low energy, a general negativity, and a sense of dissatisfaction and hopelessness.

Atypical Depression

About a third of patients with depression have atypical depression. Atypical depression refers to a subtype of depression characterized by mood reactivity, which is the ability to temporarily respond to positive experiences. It is accompanied by two or more associated symptoms such as sensitivity to rejection, hypersomnia (oversleeping), overeating (usually related to carbohydrate craving), and leaden paralysis (feelings of heaviness in the arms and legs).

Seasonal Affective Disorder

Seasonal affective disorder (SAD) is characterized by annual episodes of depression during fall or winter that improve in the spring or summer. Other SAD symptoms include fatigue and a tendency to overeat (particularly carbohydrates) and oversleep in winter. A minority of individuals with SAD have symptoms of under-eating and insomnia. SAD tends to last about 5 months in those who live in the northern part of the U.S.

Seasonal changes affect many people's moods, regardless of gender and whether or not they have SAD. Simply being mildly depressed during the winter does not mean that one has SAD. Living in a northern country with long winter nights does not guarantee a higher risk for depression. Changes in light may not be the only contributor to SAD.

Causes

The causes of depression are not fully known. Most likely a combination of genetic, biologic, and environmental factors plays a role.

Genetic Factors

Because depression often runs in families, it appears that a genetic component is involved. Studies have found that close relatives of patients with depression are two to six times more likely to develop the condition than individuals without a family history.

Biologic Factors

The basic biologic causes of depression are strongly linked to abnormalities in the delivery of certain key neurotransmitters (chemical messengers in the brain). These neurotransmitters include:

Endocrine glands
Endocrine glands release hormones into the bloodstream that are transported to various organs and tissues throughout the body. For instance, the pancreas secretes insulin, which allows the body to regulate levels of sugar in the blood. The thyroid gets instructions from the pituitary gland to secrete hormones that determine the pace of chemical activity in the body. The more thyroid hormone in the bloodstream, the faster the chemical activity; the less hormone, the slower the metabolism.

The degree to which these chemical messengers are disturbed may be affected by other factors such as genetic susceptibility.

Reproductive Hormones. In women, the female hormones estrogen and progesterone may play a role in depression.

Environmental Factors

Medications. Many prescription drugs can affect brain chemicals and trigger depression. These medications include certain types of drugs used for acne, high blood pressure, contraception, Parkinson’s disease, inflammation, gastrointestinal relief, and other conditions.

Risk Factors

According to major surveys, major depressive disorder affects nearly 15 million Americans (about 7% of the adult population) in a given year. While depression is an illness that can affect anyone at any time in their life, the average age of onset is 32 (although adults ages 49 - 54 years are the age group with the highest rates of depression.). Other major risk factors for depression include being female, being African-American, and living in poverty.

Depression in Women

Women, regardless of nationality, race, ethnicity, or socioeconomic level, have twice the rate of depression than men. (Women with depression may also have accompanying eating disorders, such as anorexia nervosa and bulimia. [For more information, see In-Depth Report #49: Eating disorders.]) While men are more likely than women to die by suicide, women are twice as likely to attempt suicide.

The causes of such higher rates of depression may be due in part to hormonal factors:

Depression in Men

Depression is not rare in men. In fact, white men over age 85 have the highest rates of suicide of any group. Men may be more likely than women to mask their depression by using alcohol. Some research suggests that depression in men is associated with the following indicators:

Depression and men
Depression is less reported in the male population, but this may be caused by male tendency to mask emotional disorders with behavior such as alcohol abuse.

Depression in Children and Adolescents

Depression can occur in children of all ages, although adolescents have the highest risk. Risk factors for depression in young people include having parents with depression, particularly if the mother is depressed. Early negative experiences and exposure to stress, neglect, or abuse also pose a risk for depression.

Adolescents who have depression are at significantly higher risk for substance abuse, recurring depression, and other emotional and mental health problems in adulthood.

Studies suggest that 3 - 5% of children and adolescents suffer from clinical depression, and 10 - 15% have some depressive symptoms.

Depression in the Elderly

About 1 - 5% of elderly people suffer from depression. The rate increases significantly for those who have other chronic health problems, especially medical conditions that interfere with functional abilities, such as Alzheimer’s, Parkinson’s disease, heart disease, and cancer. Depression also occurs in some elderly people who require home healthcare or hospitalization. In addition, older people often have to contend with significant stressful life changes such as the loss of a spouse. Suicide in the elderly is the third-leading cause of death related to injury. Men account for the majority of these suicides, with divorced or widowed men at highest risk.

Medical Conditions Associated with Increased Risk of Depression

Severe or Chronic Medical Conditions. Any chronic or serious illness, such as diabetes, that is life threatening or out of a person's control can lead to depression. Many medications taken for chronic medical problems can also cause depression.

Thyroid Disease. Hypothyroidism (a condition caused when the thyroid gland does not produce enough hormone) can cause depression. However, hypothyroidism may also be misdiagnosed as depression and go undetected.

Chronic Pain Conditions. Studies have reported a strong association between depression and headaches, including chronic tension-type and migraine. Fibromyalgia, arthritis, and other chronic pain syndromes are also associated with depression.

Stroke and Other Neurological Conditions. Having a stroke increases the risk of developing depression. Also, neurological conditions that impair movement or thinking are associated with depression.

Heart Failure. Patients with heart failure or patients who have suffered a heart attack may also be at increased risk for depression.

Insomnia and Sleep Disorders. Sleep abnormalities are a hallmark of depressive disorders, with many depressed patients experiencing insomnia. Likewise, insomnia or other changes in waking and sleeping patterns can have significant effects on a person's mood, and perhaps worsen or draw out an underlying depression.

Other Risk Factors

Smoking. There is a significant association between cigarette smoking and a susceptibility to depression. People who are prone to depression face a 25% chance of becoming depressed when they quit smoking, and this increased risk persists for at least 6 months. What's more, depressed smokers find it difficult to stop smoking. Smokers with a history of depression are not encouraged to continue smoking, but rather to keep a close watch on recurrence of depressive symptoms if they do stop smoking.

Complications

Depression is often chronic, with episodes of recurrence and improvement. About a third of patients with a single episode of major depression will have another episode within 1 year after discontinuing treatment, and more than half will have a recurrence at some point in their lives. Depression is more likely to recur if the first episode was severe or prolonged, or if there have been prior recurrences. To date, even newer antidepressants have failed to achieve permanent remission in many patients with major depression, although the standard medications are very effective in treating and preventing acute episodes.

Risk for Suicide

Suicidal preoccupation or threats of suicide should always be treated seriously. Depression is the cause of up to two-thirds of all suicides. Suicide attempts are a major risk factor for a later suicide. Suicide is the third most common cause of death among adolescents, and is one of the most devastating events than can happen to a family. Behavioral therapies, combined with antidepressants, may help prevent suicide. However, antidepressants can also raise the risk for suicidality (suicidal thoughts and behavior) in some young people, particularly those ages 18 - 24. [See “Suicidal Risk and Antidepressant Medications” in Drug Treatment Guidelines section in this report.]

Children, adolescents, and young adults who are prescribed antidepressant medication should be carefully monitored by both their parents and doctors, especially during the first few months of treatment, for any worsening of depression symptoms or changes in behavior.

The following are danger signs in young people:

Risk factors for suicide include a history of neglect or abuse, history of deliberate self-harm, a family member who committed suicide, access to firearms, and living in communities where there have been recent outbreaks of suicide among young people. A romantic break-up is often the trigger for a suicidal attempt in teenagers. Feeling connected with parents and family can help protect young people with depression from suicide.

Effect on Physical Health

Major depression in the elderly or in people with serious illness may reduce survival rates, even independently of any accompanying illness. Decreased physical activity and social involvement certainly play a role in the association between depression and illness severity.

Heart Disease and Heart Attacks. Data suggest that depression itself may be a risk factor for heart disease as well as its increased severity. Patients with heart disease who are depressed tend to have more severe cardiac symptoms than those who are not depressed, and a poorer quality of life. Depression can worsen the prognosis of heart disease and increase the risk of death.

While the evidence is less conclusive, studies also indicate that depression in healthy people may increase the risk for developing heart disease. The more severe the depression, the greater the risk.

Depression and heart disease
Studies are now showing that depression may contribute to poor outcomes for patients with heart disease.

Obesity. People, especially adolescents, who are depressed have a high risk for obesity. Conversely, obese people are about 25% more likely than non-obese people to develop depression or other mood disorders.

Mental Decline. Depression in the elderly is associated with a decline in mental functioning, regardless of the presence of dementia.

Cancer. Depression does not increase the risk for cancer, but cancer can physically trigger depression by affecting chemicals in the brain. Sometimes depressive symptoms can manifest even before the cancer is diagnosed.

Impact on Daily Activities and Relationships

Effects of Parental Depression on Children. Depression in parents may increase the risk for childhood depression.

Effects on Marriage. People who suffer from psychiatric disorders tend to have higher divorce rates than healthy people. Spouses of partners with depression are themselves at higher risk for depression.

Effect on Work. Depression can adversely affect a person's work life. It significantly increases the risk for unemployment and lower income.

Substance Abuse

Alcohol and Drug Abuse. Many people with major depression also have an alcohol use disorder or drug abuse problems. Studies on the connections between alcohol dependence and depression have still not resolved whether one causes the other or if they both share some common biologic factor.

Smoking. Depression is a well-known risk factor for smoking, and many people with major depression are nicotine dependent. Nicotine may stimulate receptors in the brain that improve mood in some people with depression.

Diagnosis

A diagnosis of depression is based on symptoms meeting specific criteria. [See Introduction section of this report.] Many people who are depressed first seek help from their family doctors. Guidelines recommend that family doctors screen for depression in adults and adolescents (ages 12 - 18), as long as these doctors have appropriate systems in place to ensure accurate diagnosis, treatment, and follow-up of their patients.

To check if you have depression, your doctor may ask questions such as:

Individuals who have certain factors might ask their doctor if they should be screened for depression. These factors include:

Screening Tests

Mental health professionals may administer a screening test such as the Beck Depression Inventory or the Hamilton Rating Scale, both of which consist of about 20 questions that assess the individual for depression. However, most mental health professionals generally diagnose depression based on symptoms and other criteria.

Symptoms of depression can vary depending on a person’s cultural and ethnic background. For example, people from non-Western countries are more apt to report physical symptoms (such as headache, constipation, weakness, or back pain) related to the depression, rather than mood-related symptoms.

Ruling Out Other Conditions

Depression can sometimes be confused with other medical illnesses. Weight loss and fatigue, for example, accompany many conditions, some serious, but they can also occur with depression.

Treatment

Depression is a treatable illness, with many therapeutic options available including psychotherapy, antidepressants, or both. In general, the treatment choice depends on the degree and type of depression and other accompanying conditions. It also may depend on age, pregnancy status, or other individual factors.

In choosing treatment options, it is important for the patient to be fully involved in the decision-making process.

Patients with Major Depression. Numerous studies support a combination of cognitive behavioral therapy (CBT) plus antidepressants, typically a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI). Although some people may feel better after taking antidepressants for a few weeks, most people need to take medication for at least 4 - 9 months to ensure a full response and to prevent depression from recurring. Research indicates that patients respond better to medications when drug therapy is combined with CBT. Exercise may also help relieve depressive symptoms.

Patients with Treatment-Resistant Depression. For patients with severe depression who are not helped by SSRIs or SNRIs, other types of antidepressants are available. Sometimes an atypical antipsychotic drug may be given in combination with an antidepressant for patients with severe major depressive disorder.

Brain stimulation techniques, such as electroconvulsive therapy (ECT), are options for treatment-resistant depression. Experimental procedures, such as repetitive transcranial magnetic stimulation and vagus nerve stimulation, may be helpful. Researchers are also investigating new types of drugs (such as ketamine), which may provide rapid, if temporary, improvement. In general, the more treatment strategies that patients need, the less likely they are to recover completely from depression.

Patients with Minor Depression. Patients with minor depression (fewer than five symptoms that persist for fewer than 2 years) may respond well to watchful waiting to see if antidepressants are necessary. Counseling or cognitive behavioral therapy may be helpful, as is regular exercise.

Patients with Depression and Other Psychiatric Problems. Other psychiatric problems often coexist with depression. If patients also suffer from anxiety, treating the depression first often relieves both problems. More severe psychiatric problems, such as bipolar disorder or schizophrenia, require specialized treatments.

Patients with Depression and Medical Conditions. Depression can worsen many medical conditions and may even increase mortality rates from some disorders, such as heart attack and stroke. Depression should be aggressively treated in anyone with a serious medical problem.

Patients with Depression and Substance Abuse Problems. Treating depression in patients who abuse alcohol or drugs is important and can sometimes help patients quit. However, absence from substance abuse is considered essential for adequate treatment of depression.

Choosing a Therapist

Most people with depression can be treated in an office setting by a psychiatrist, psychologist, or other therapist. Infrequently, the level of dysfunction may be serious enough to warrant hospitalization to provide protection from further deterioration or self-harm.

Health professionals who can prescribe antidepressants include:

Although other mental health professionals cannot prescribe drugs, most therapists have arrangements with a psychiatrist for providing medications to their patients. In general, mental health professionals are categorized by their training:

Tips for selecting a therapist:

Treating Depression During and After Pregnancy

Up to a quarter of women experience depressive symptoms during pregnancy, and some women develop full-blown postpartum depression following delivery. Although a mother's depression during and after pregnancy can have serious effects on her child, researchers are still trying to determine the best methods for preventing and treating pregnancy-related depression.

The American College of Obstetricians and Gynecologists (ACOG) recommends that pregnant women with depression receive care from a multidisciplinary team that includes the patient’s obstetrician, primary care physician, and mental health clinician. Any woman who has suicidal or psychotic symptoms during depression should immediately seek treatment from a psychiatrist.

The use of antidepressants during pregnancy is controversial, especially for women with major depression who regularly take antidepressant medication. Most doctors advise women to avoid, if possible, any medications during pregnancy and nursing. But women with depression who stop taking antidepressants during pregnancy may be likely to have a relapse of depression, which can have negative consequences for prenatal care and subsequent mother-child bonding. The risks for negative outcomes are highest when depression occurs during the late second or early third trimester. Depression during pregnancy may also increase the risk of developing postpartum depression.

ACOG and the American Psychiatric Association (APA) recommend that women who are pregnant or thinking about becoming pregnant should not stop taking antidepressants without first talking to their doctors. Women who have mild or no depressive symptoms for at least 6 months before becoming pregnant may be able to taper off or discontinue antidepressant medication, under supervision of their doctor. Stopping medication may be more difficult for women with a history of severe recurrent depression. Psychotherapy (preferably cognitive behavioral therapy or interpersonal therapy) may be helpful in addition to, or in replacement of, antidepressant medication. Electroconvulsive therapy (ECT) may be an option for pregnant women with severe depression.

Studies have been inconsistent as to whether serotonin reuptake inhibitors (SSRIs) drugs increase the risk for birth defects. In general, the risks appear to be low, but doctors are still not sure. There is evidence that paroxetine (Paxil, generic) may cause major birth defects -- including heart abnormalities -- if taken during the first trimester of pregnancy. ACOG recommends that doctors not prescribe paroxetine to women who are pregnant or planning on becoming pregnant. Some studies have indicated that sertraline (Zoloft, generic) and citalopram (Celexa, generic) may also increase the risk of heart defects. SSRIs, and most tricyclic antidepressants, are considered safe to use during breastfeeding but more research is needed to clarify the effects of SSRI on infant and child development. [For more information, see "Selective Serotonin-Reuptake Inhibitors (SSRIs)" in Medications section.]

In terms of non-drug treatment of postpartum depression, doctors recommend that women with signs of postpartum depression receive intensive and individualized psychotherapy within a month after giving birth.

Treating Depression in the Elderly

Some doctors recommend only psychotherapy for elderly patients with mild depression. In many older patients, a regular exercise program may be sufficient to improve mood. The use of antidepressants in the elderly is problematic:

Treating Depression in Children and Adolescents

Studies suggest that when children or adolescents are treated for depression, most recover. Still, up to a half of these young people have a recurrence of depression within 2 years of their first episode of depression.

It is important to recognize that childhood depression differs from adult depression and that children may respond differently than adults to antidepressant medication. These variances are due to childhood brain development processes as well as age-related differences in drug metabolism. Children may experience medication side effects not seen in adults, and some antidepressants that are effective for adults may not work for children.

Mild-to-Moderate Depression. The pediatrician may want to monitor a child with mild depression for 6 - 8 weeks before deciding whether to prescribe psychotherapy, antidepressant medication, or a referral to a mental health professional. Once medication has been started, the doctor will decide if the dosage needs to be increased after another 6 - 8 weeks. Medication may need to be continued for 1 year after the symptoms have resolved, and the doctor should continue to monitor the child on a monthly basis for 6 months after full remission of depression. For psychotherapy, cognitive therapy may be the best approach for children and adolescents with depression. Other types of psychotherapy, such as family therapy and supportive therapy, may also be effective.

Severe Depression. The American Academy of Child and Adolescent Psychiatry recommends an SSRI antidepressant for children and adolescents with very severe depression that does not respond to psychotherapy. Tricyclic antidepressants do not tend to help adolescents and children and these drugs have many side effects. MAOIs are also not commonly prescribed.

Many SSRIs appear to be safe and effective, but at this time fluoxetine (Prozac, generic) and escitalopram (Lexapro) are the only ones approved for adolescents (ages 12 - 17), and fluoxetine is the only antidepressant approved for children age 8 and older. The FDA strongly advises against the use of some specific SSRIs, such as paroxetine (Paxil, generic), due to concerns about an increased risk for suicidal behavior as well as the lack of any evidence supporting the drug's efficacy in pediatric patients. Some recent research indicates that the overall benefits of antidepressants for children and adolescents may outweigh the risks for suicidal behavior. For optimal results, SSRIs should be combined with either cognitive-behavioral or interpersonal psychotherapies.

Due to potential suicide risks, children and adolescents should be monitored regularly during the initial months of antidepressant treatment. [For more detailed information, see "Suicide Risk and Antidepressant Medications" in Drug Treatment Guidelines section of this report.]

Drug Treatment Guidelines

Major Classes of Antidepressants and General Treatment Guidelines

Major classes of antidepressants include:

All of these drugs appear to work equally well, although they may vary in terms of side effects. Your doctor will select an antidepressant based on side effects, cost, and your personal preference.

Approach and Duration of Initial Treatment. The guidelines for the duration of an initial antidepressant regimen are generally:

Treating Recurrence. Recurrence of depression is very common. About a third of patients will relapse after a first episode within a year of ending treatment, and more than half will experience a recurring bout of depression at some point during their lives. Among those at highest risk for early relapse and who may require ongoing antidepressants are:

There is no risk for addiction with current antidepressants, and many of the common antidepressants, including most standard SSRIs, have been proven safe when taken for a number of years.

Common Side Effects of Most Antidepressants. No matter how well a drug treats depression, the ability of patients to tolerate its side effects strongly influences their compliance with therapy. Side effects can be avoided or moderated if any regimen is started at low doses and built up over time. Although specific side effects are discussed under individual drugs, there are a few that are common to many of them:

Suicide Risk and Antidepressant Medications

In recent years, there has been concern that SSRI antidepressants can increase the risk for suicidal behavior. Of particular concern is a greater risk for suicide in young people taking these medications. While depression is itself the major risk factor for suicide, and antidepressant medication may revitalize suicidal attempts in patients who were too despondent before treatment to make the effort, evidence suggests that in some cases the medication itself can cause suicidal thoughts and behavior (suicidality). Paroxetine (Paxil, generic) appears to have the strongest association with increased suicidal risk, particularly in younger adults.

In the U.S., all antidepressant medications now carry “black box” warnings on their prescribing label explaining the association between antidepressant use and increased risk for suicidality in children, adolescents, and young adults ages 18 - 24, especially during the first few months of treatment. The FDA’s data do not show an increased risk for suicidality in adults older than age 24. Adults age 65 years and older taking antidepressants have a decreased risk for suicidality.

The FDA recommends that caregivers monitor children, adolescents, and young adults being treated with antidepressants for sudden behavioral changes, and immediately notify their doctor if such changes occur. These behavioral signs include:

The FDA’s guidelines for medication usage also recommend that all patients see their doctors regularly after initiating drug treatment. The recommended schedule is:

Patients should immediately contact their doctor if depression symptoms worsen or if suicidal thoughts or behavior increase.

Medications

Selective Serotonin-Reuptake Inhibitors (SSRIs)

Selective serotonin-reuptake inhibitors (SSRIs) are the first-line treatment for major depression. They work by increasing levels of serotonin in the brain. Because they act specifically on serotonin, SSRIs have fewer side effects than older antidepressants, which have more widespread effects in the body.

SSRIs include fluoxetine (Prozac, generic), sertraline (Zoloft, generic), paroxetine (Paxil, generic), fluvoxamine (Luvox, generic), citalopram (Celexa, generic), and escitalopram (Lexapro). There do not appear to be significant differences among SSRI brands in effectiveness, although individual drugs may have different side effects or benefits for specific patients.

At this time, fluoxetine and escitalopram are the only antidepressants approved for treatment of major depressive disorder in adolescents (ages 12 - 17). Fluoxetine is also approved for children age 8 and older.

Candidates for SSRIs. SSRIs appear to best help people with the following conditions:

Duration of Effectiveness and Use. SSRIs take, on average, 2 - 4 weeks to be effective in most adults. They may take even longer, up to 12 weeks, in the elderly and in those with dysthymia. By 14 weeks, depression should be in remission in those who respond to the drugs. Unfortunately, recurrence is common once the drugs are stopped. Studies indicate that the standard SSRIs are generally safe to be taken long term, although it is still unclear which patients most benefit from on-going medication. Some doctors recommend withdrawing from medication after a year. If depression recurs, then the patient should go back on the antidepressant.

Side Effects of SSRIs. Side effects may include:

Drug Interactions. SSRIs can interact with other antidepressants such as tricyclics and, in particular, monoamine oxidase inhibitors (MAOIs). Due to a potentially fatal condition called serotonin syndrome, SSRIs should never be taken in combination with an MAOI or within 2 weeks after discontinuing MAOI treatment. (For more on serotonin syndrome, see MAOI section below.) Other serious interactions can occur with meperidine (Demerol, generic) and illegal substances (such as LSD, cocaine, or ecstasy). SSRIs also interact with the antibiotic linezolid (Zyvox), the painkiller tramadol (Ultram, generic), and the osteoporosis medication raloxifene (Evista). People who take SSRIs may drink alcohol in moderation, although the combination may compound any drowsiness experienced with SSRIs, and some SSRIs increase the effects of alcohol.

Withdrawal Symptoms. Cognitive problems, sleep disturbances, increase in depressive symptoms, and electric shock-like symptoms can occur with sudden discontinuation of SSRIs. The symptoms are more likely to occur with antidepressants with shorter half-lives as compared with fluoxetine, which has a long half-life. The dose of the antidepressant should be slowly reduced before stopping.

Other Neurotransmitter Inhibitors

These antidepressants target other neurotransmitters, such as norepinephrine or dopamine, alone or in addition to serotonin.

Dual Action Inhibitors. Dual action inhibitors act directly on serotonin and another neurotransmitter.

Venlafaxine (Effexor, generic), desvenlafaxine (Pristiq), duloxetine (Cymbalta), and mirtazapine (Remeron) are serotonin norepinephrine reuptake inhibitors (SNRIs). They target serotonin and the neurotransmitter norepinephrine and are approved for treatment of major depression in adults.

Vilazodone (Viibryd) is a new type of dual action inhibitor that acts both as an SSRI and as a 5-HT1-A receptor partial agonist. It was approved in 2011 for treatment of depression in adults.

These drugs share many of the side effects as SSRIs, including dry mouth, nausea, and drowsiness. Additional side effects include:

Multiple Neurotransmitter Inhibitors (Bupropion). Bupropion (Wellbutrin, generic) affects the reuptake of serotonin, norepinephrine, and dopamine -- a third important neurotransmitter. In addition to depression, bupropion is also approved for treating seasonal affectiveness disorder (SAD) and, under the tradename Zyban, for smoking cessation. Bupropion causes less sexual dysfunction than SSRIs. About 25% of patients experience initial weight loss. Side effects include restlessness, agitation, sleeplessness, headache, and stomach problems. Bupropion has a risk for seizures, which increases with higher doses. High doses may also cause dangerous heart arrhythmias.

In 2009, the FDA warned that bupropion products may cause symptoms such as changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide. Most of these symptoms were reported in patients who took bupropion to help stop smoking. However, the FDA also warns that patients who have major depressive disorder or other psychiatric illnesses (schizophrenia, bipolar disorder), may experience worsening of their symptoms while taking bupropion

Tricyclic Antidepressants

Before the introduction of SSRIs, tricyclics were the standard treatment for depression.

Tricyclics are sometimes grouped into two categories:

Less commonly used tricyclics include doxepin (Sinequan), amoxapine (Asendin), maprotiline (Ludiomill), protriptyline (Vivactil), and trimipramine (Surmontil). These are all available as generics.

Tricyclics are as effective for treating depression but they have many side effects. They may offer benefits for many people with dysthymia, who generally do not respond to SSRIs. They may also be prescribed in lower dosages to be taken at night to help with insomnia.

Side Effects of Tricyclics. Side effects are common with these medications. In an analysis of studies, more tricyclic users discontinued their drugs due to side effects than did SSRI or MAOI users. Side effects most often reported include:

Tricyclics can have serious, although rare, side effects:

Monoamine Oxidase Inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) block monoamine oxidase, an enzyme which has negative effects on many of the neurotransmitters that are important for well-being. MAOIs include phenelzine (Nardil, generic), isocarboxazid (Marplan, generic), and tranylcypromine (Parnate, generic).

Newer MAOIs, such as selegiline (Eldepryl, Movergan, generic), target only one form of the MAOI enzyme. They may cause fewer side effects than older MAOIs. A skin patch form of selegiline (Emsam) is also available for treatment of major depressive disorder in adults.

Candidates for MAOIs. Because these drugs can have very severe side effects, they are usually prescribed only for severe depression or when other types of antidepressants do not help (treatment-resistant depression). MAOIs may also be effective for the following conditions:

Side Effects. MAOIs commonly cause the following side effects:

Serotonin Syndrome. Serotonin syndrome is a potentially fatal condition that can occur from interactions with other antidepressants, including SSRIs. Symptoms include confusion, agitation, sweating and shivering, and muscle spasms. There should be at least a 2-week break between taking MAOIs and other antidepressants. MAOIs can have serious interactions with other drugs as well, including some common over-the-counter cough medications. In such cases, severe high blood pressure or dangerous reactions can occur. It is important that patients discuss with their doctors any other medications they are taking.

Atypical Antipsychotics

If patients fail to respond to antidepressants, doctors may try adding on a different type of drug. (This combination strategy is called “augmentation” or “adjunctive treatment”.) Atypical antipsychotics are drugs that are usually prescribed for schizophrenia or bipolar disorder, but they can also play a role in the treatment of severe depression. Two atypical antipsychotics, aripiprazole (Abilify) and quetiapine (Seroquel), are currently approved in combination with antidepressant therapy for treatment of adults with major depressive disorder.

Investigational Drugs

Ketamine. Ketamine, an anesthetic drug, may be helpful for patients with severe treatment-resistant or bipolar depression. In preliminary studies a single intravenous dose of ketamine helped patients quickly recover from depression within 2 hours, and some patients sustained benefits for up to a week. (Standard antidepressant drugs usually take about 8 weeks to have an effect.) Ketamine blocks the NMDA brain protein receptor, which is involved in glutamate regulation. Glutamate is a brain chemical that is thought to be involved in depression.

Psychotherapy

Among the various psychotherapeutic "talk therapies," cognitive-behavioral therapy appears to be the most effective approach. If psychotherapy is used alone without medications, benefits should be evident within 8 weeks and symptoms should be fully resolved by 12 weeks. If these conditions are not met, then the patient should strongly consider antidepressant drugs.

Cognitive Behavioral Therapy

For many patients, cognitive behavioral therapy (CBT) works as well as antidepressants in treating severe depression. Like all psychotherapies, much of the success depends on the skill of the therapist. Many studies suggest that combining cognitive therapy with antidepressants offer the greatest benefits. Studies also indicate that the benefits of cognitive therapy persist after treatment has ended.

Best Candidates. Although helpful for all patients with depression, CBT may be particularly helpful for the following patients:

Approach. CBT focuses on identification of distorted perceptions that patients may have of the world and themselves, on changing these perceptions, and on discovering new patterns of actions and behavior. These perceptions, known as schemas, are negative assumptions developed in childhood that can precipitate and prolong depression. CBT works on the principle that these schemas can be recognized and altered, thereby changing the response and eliminating the depression.

Over time, such exercises help build confidence and eventually alter behavior. Patients may take group or individual cognitive therapy. CBT is a time-limited treatment, typically lasting 12 - 14 weeks.

Interpersonal Therapy (IPT)

Interpersonal therapy, which is related to psychodynamic therapy, acknowledges the childhood roots of depression, but focuses on symptoms and current issues that may be causing problems. IPT is not as specific as cognitive or behavioral therapy, and all work is done during the sessions. The therapist seeks to redirect the patient's attention, which has been distorted by depression, toward the daily details of social and family interaction. The goals of this treatment method are improved communication skills and increased self-esteem within a short period of time (3 - 4 months of weekly appointments). Among the forms of depression best served by IPT are those caused by distorted or delayed mourning, unexpressed conflicts with people in close relationships, major life changes, and isolation.

Supportive Psychotherapy or Attention Intervention

The intent of supportive psychotherapy or attention intervention is to provide the patient with a nonjudgmental environment by offering advice, attention, and sympathy. Supportive therapy may be particularly helpful for improving compliance with medications by giving reassurance, especially when setbacks and frustration occur.

Other Treatments

Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is commonly called shock treatment. It has received bad press, in part for its potential memory-depleting effect. Since its introduction in the 1930s, ECT has been significantly refined, and is now considered an effective and safe treatment for severe depression in the appropriate situation. It is especially effective for patients who have not been helped by medication and those with severe depression who experience delusions and hallucinations. Maintenance ECT may also help prevent relapse.

Candidates for ECT. ECT may be helpful for the following patients with severe depression:

The Procedure. In general, hospitalization is not necessary. ECT involves the following steps:

Side Effects. Side effects of ECT may include temporary confusion, memory lapses, headache, nausea, muscle soreness, and heart disturbances. Concerns about permanent memory loss appear to be unfounded.

The ECT procedure affects heart rate and blood pressure. Doctors should perform a medical evaluation of patients before they receive ECT. Patients, (especially those who are elderly), who have high blood pressure, atrial fibrillation, asthma, or other heart or lung problems may be at increased risk for heart-related side effects.

Transcranial Magnetic Stimulation and Deep Brain Stimulation

Repetitive transcranial magnetic stimulation (rTMS) uses high frequency magnetic pulses that target affected areas of the brain. It is generally regarded as a second line treatment after ECT. Researchers are continuing to refine rTMS techniques to attempt to improve treatment outcomes.

An implantable deep brain stimulation device (Reclaim), similar to a pacemaker and devices used for treating movement disorders like Parkinson’s disease, has been approved for treatment of severe obsessive-compulsive disorder. It is currently in clinical trials for treatment-resistant depression. The device uses four electrodes that are surgically implanted into the brain and connected to a small generator that is implanted near the abdomen or collar bone. The generator delivers precisely controlled electrical pulses to target specific areas of the brain.

Vagus Nerve Stimulation

Vagus nerve stimulation (VNS) is a procedure that is effective for certain patients with epilepsy, and is now showing some success in patients with treatment-resistant depression

VNS involves implanting a battery-powered device under the skin in the upper left of the chest. The neurologist programs the device to deliver mild electrical stimulation to the vagus nerve. The two vagus nerves are the longest nerves in the body. They run along each side of the neck, then down the esophagus to the gastrointestinal tract. The vagus nerve travels to areas of the brain that control functions such as sleep and mood.

Studies report response rates of 35 - 46% in appropriate candidates with treatment-resistant depression. VNS is approved by the FDA for long-term treatment of chronic depression in adults who have not responded to typical treatments for their major depressive episode. Patients who use VNS may continue to show improvement in both their depression symptoms and quality of life.

Vagal stimulation can cause shortness of breath, hoarseness, sore throat, coughing, ear and throat pain, or nausea and vomiting. These side effects can be reduced or eliminated by reducing the intensity of stimulation. Long-term studies on patients with epilepsy have reported no serious adverse side effects, although the treatment may cause lung function deterioration in some people with existing lung disease.

Treatment of epilepsy
The vagus nerves branch off the brain on either side of the head and travel down the neck, along the esophagus to the intestinal tract. They are the longest nerves in the body, and affect swallowing and speech. The vagus nerves also connect to parts of the brain involved in seizures. In many seizures disorders, electrical stimulation of the vagus nerves may help relieve symptoms.

Phototherapy (Light Therapy)

Phototherapy, also called light therapy, may be recommended as treatment for seasonal affective disorder (SAD), particularly for patients who do not wish to use antidepressants.

The procedure is noninvasive and simple. It is best performed immediately after waking in the morning. The patient sits a few feet away from a box-like device that emits very bright fluorescent light (10,000 lux) for about 30 minutes every day.

Some people report mood improvement as early as 2 days after treatment. In others, depression may not lift for 3 - 4 weeks. If no improvement is experienced after that, depressive symptoms will be unlikely to respond to phototherapy. Phototherapy may work best when combined with cognitive behavioral therapy.

Side Effects. Side effects include headache, eye strain, and irritability, although these symptoms tend to disappear within a week. Patients taking light-sensitive drugs (such as those used for psoriasis), certain antibiotics, or antipsychotic drugs should not use light therapy. Patients should be examined by an ophthalmologist before undergoing this treatment.

Lifestyle Changes

Exercise and Other Healthy Behaviors

Exercise. Both aerobic exercise and resistance training can help provide some improvement in mood symptoms for patients with depression. Aerobic workouts can raise chemicals in the brain, such as endorphins, adrenaline, serotonin, and dopamine that produce the so-called runner's high. Yoga practice, which involves rhythmic stretching movements and breathing, may help improve and stabilize mood. Meditation may also be helpful.


 Click the icon to see an image of yoga. 

Sleep Hygiene. Patients with depression who suffer from insomnia (either as a result of the condition or medications) may be helped by learning sleep hygiene techniques. [For more information, see In-Depth Report #27: Insomnia.]

Nutrition and Diet. A healthy diet low in saturated foods and rich in whole grains, fresh fruits, and vegetables is important for anyone. Patients should be sure to maintain a regular healthy diet, particularly if they have experienced weight gain from medications. They should also try to decrease their use of alcohol and tobacco.

Social Support. A strong network of social support is important for both prevention and recovery from depression. Support from family and friends must, however, be healthy and positive. It is helpful for family members to become educated about depression and antidepressant medications.

Herbal Remedies and Dietary Supplements

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

St. John's wort. St. John's wort (Hypericum perforatum) is probably the most studied herbal remedy. Although its efficacy has not been proven, there is evidence it may help some patients with mild-to-moderate depression. It does not appear to help patients with severe depression.

St. John's Wort
The herb St. John's wort is believed to be helpful in relieving mild-to-moderate depression, but should only be taken under a doctor's supervision. Manufacturers of herbal supplements do not need FDA approval to sell the products.

The following guidelines are recommended:

Side effects are uncommon but may include nausea, dry mouth, allergic reactions, and fatigue. This herb may increase sensitivity to light (photosensitivity).

SAM-e. S-adenosyl methionine, better known as SAM-e, is a molecule found in the human body and is involved in the processing of the neurotransmitters dopamine and serotonin. Studies have shown that levels of SAMe are lower in patients with severe major depressive disorder. Some studies have indicated that SAM-e dietary supplements may be helpful for patients with depression, but more data are needed.

Fish Oil. Some studies have suggested omega-3 fatty acids may be helpful for depression Omega-3 fatty acids are found in fish oil, canola oil, soybeans, flaxseed, and certain nuts and seeds. Their main chemical compounds -- eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) – are also available in combination dietary supplement form. Some research has suggested that the Mediterranean Diet, which is high in omega-3 rich foods as well as vegetables and fruit and low in saturated fats from meat, may help reduce the risk of developing depression.

Omega-3 fatty acids
Omega-3 fatty acids, found in oily fish and flaxseed and canola oils, may be beneficial to people with depression.

Vitamins. Certain B vitamins may be associated with some protection against depression.

Acupuncture

Some small studies have suggested that acupuncture may help in relieving depression. Larger studies are needed to confirm its benefits. Based on the current evidence, it does not appear that acupuncture is helpful for major depression.

Resources

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Review Date: 2/8/2012
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
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