Depression in adults

INTRODUCTION — Depression is a medical condition characterized by a wide variety of psychological and physical symptoms. Extreme sadness is often the most pronounced symptom. Depression is differentiated from occasional blues and from grief (a normal reaction to loss) by its persistence and its interference with daily activities and relationships.

In the past, depression was poorly understood and carried an unfortunate social stigma. Depression is common; the risk of suffering from a major depressive episode at some time during life is up to 12 percent for men and 25 percent for women. The condition can affect people of all ages, including children and older adults.

Depression is a treatable condition. Psychotherapy (counseling), drug therapy, and other treatments can alleviate symptoms and help people with depression return to rich and productive lives. Treatment is most successful in persons who are receptive to and participate in their treatment. Persons with depression should work closely with a clinician to ensure that treatment is effective.

CAUSE OF DEPRESSION — Research has helped clarify the complex biologic basis of depression, although the exact cause of depression is still uncertain. Studies suggest that depression results from an imbalance of neurochemicals in the brain, including serotonin, norepinephrine, and dopamine. These neurochemicals allow cells to communicate with each other and play an essential role in all brain functions, including movement, sensation, memory, and emotions. That depression represents an actual biologic disorder is supported by the results of genetic studies and the response of depression to drug therapy and other therapies that alter levels of brain neurochemicals.

RISK FACTORS — Although anyone can develop depression, certain factors increase a person's risk for this condition, including: Female gender A history of depression in a first degree relative (parent, sibling, or child) A prior episode of major depression

Other factors have been identified as secondary (weaker) risk factors for depression: A history of depression in a family member who is not a first degree relative Lack of social supports Significant stressful life events Current alcohol or substance abuse

SYMPTOMS/DEFINITIONS — Extreme sadness may be a symptom of depression, although depression can cause other psychological and physical symptoms. The hallmark of depression is that these symptoms are persistent and interfere with daily activities and relationships.

Unfortunately, there is no single sign or symptom that serves as a marker for depression, and the condition can be tricky to identify. In fact, many people do not recognize that they are depressed or that their physical symptoms (aches and pain, appetite and sleep changes) are related to depression. One study revealed that 29 percent of people visiting their doctors for a physical symptom had a depressive disorder or an anxiety disorder [1].

The symptoms of depression for the three distinct types of depression (major depression, dysthymia, and atypical depression) will be discussed here.

Major depression — The diagnosis of major depression is based upon the presence of at least five of nine symptoms: Sadness most of the day, particularly in the morning Markedly diminished pleasure or interest in almost all activities nearly every day Significant weight loss or weight gain Insomnia or excessive sleep Agitated movements or very slow movement Fatigue or loss of energy Feelings of worthlessness or guilt Impaired concentration and indecisiveness Recurring thoughts of death or suicide

The symptoms must be present during the same time period and must persist for at least two weeks. One of the symptoms must be either depressed mood or loss of interest.

Dysthymia — Dysthymia is a low-grade depression that persists for a long period of time. Dysthymia is usually diagnosed when a person has had depressive symptoms for at least two consecutive years. The prominent symptoms of dysthymia include an absence of pleasure or interest in activities, low self-esteem, and low energy.

Atypical depression — Atypical depression is the most common type of depression seen in a primary care setting. People with atypical depression have some of the same features of major depression listed above, but do not have five of the nine symptoms required for a diagnosis of major depression. Instead, they often have prominent physical symptoms, including weight gain and sleep disturbances, especially excessive sleep.

Seasonal affective disorder — Seasonal affective disorder (SAD) is a form of major depression that varies with the seasons. Most patients with SAD have episodes of depression that begin in the fall and continue through the winter.

SAD is characterized by several features: Symptoms of depression that regularly appear during a particular time of year (unrelated to stressful events associated with specific seasons) Full remission of depression (or a change from depression to mania) during other times of year Two major episodes of depression during the associated season in the last two years and an absence of depression during other times of the year

Grief — Grief is a normal reaction to many situations, following the death of a loved one, loss of a close relationship or job, or the loss of health or independence. This section discusses one of the most common types of grief that occurs after the death of a family member or friend.

Grief following death — Immediately following death, whether or not the death has been anticipated, survivors usually experience feelings of numbness, shock, and disbelief. Intense feelings of sadness, yearning for the deceased, anxiety about the future, disorganization, and emptiness commonly arise in the weeks after the death.

"Searching behaviors," including visual and auditory hallucinations of the deceased person, are common and may lead the bereaved person to fear that he or she is "going crazy." Despair and sadness are common as it becomes clear that the deceased will not return. Sleeplessness, appetite disturbances, agitation, chest tightness, sighing, and exhaustion are common.

These reactions are usually transient and resolves in over 90 percent of people by 13 months after the loss. However, losses can trigger depression in some people; as an example, 15 to 35 percent of people who lose their spouse develop depression in the following year [2].

Some patients who grieve may develop complicated grief (or traumatic grief), which is defined as persistence of at least four of the following feelings for six months or more: Numbness/detachment Bitterness Feelings that life is empty without the deceased Trouble accepting the death A sense that the future holds no meaning without the deceased Being on edge or agitated Difficulty trusting others since the loss

Grief versus depression — It is often difficult to know if a person who is grieving also suffers from depression. Patients who have feelings of hopelessness, helplessness, worthlessness, and guilt, as well as severe symptoms of early grief may be depressed. Patients whose grief is complicated by depression often benefit from an antidepressant medication in addition to individual or group psychotherapy. Group therapy in a bereavement group can be particularly useful for patients with grief and depression. In contrast, persons suffering only with grief are more likely to benefit from psychotherapy alone.

Bipolar depression — People with bipolar disorder (manic depression) have depression as part of the syndrome. Bipolar II disorder is relatively common and involves periods of depression interspersed with periods of "hypomania," which are prolonged periods (weeks to months) of high energy, decreased sleep, and some agitation. People with bipolar II disorder may have a poor or agitated response to antidepressant medications; a psychiatrist is recommended to assist in the treatment of people with this disorder. (See "Patient information: Bipolar disorder").

DIAGNOSIS — The diagnosis of depression is based upon a patient's symptoms, the duration of symptoms, and the overall effects of these symptoms on a patient's life. There is currently no medical test that identifies depression, although blood tests are often done to rule out other medical conditions that could be causing depression (such as hypothyroidism).

A diagnosis of major depression requires that symptoms are severe enough to interfere with a person's daily activities, and the ability to take care of oneself, maintain relationships, engage in work activities, and to support oneself. A diagnosis also requires that the symptoms have occurred on a daily basis for at least two weeks.

TREATMENT — The goals of the treatment of depression include: Treating the symptoms Addressing family, environment, and social issues that may play a role in depression Enabling the depressed person to understand what brought about depression and what changes are necessary to resolve symptoms and prevent a relapse

Many people are reluctant to accept a diagnosis of depression and to pursue treatment. Patients may worry about the social stigma of depression, and may be embarrassed to discuss the need for treatment with family or friends. In addition, some patients may not believe that physical problems such as aches and pains, fatigue, and difficulty sleeping are caused by depression. It is important to understand that early and successful treatment of depression shortens the duration of illness, reduces the likelihood of persistent symptoms, and reduces the likelihood of a relapse.

For severe depression, treatment is usually initiated when depression is diagnosed. For mild or moderate depression, a clinician may first ask a person to keep a diary of their symptoms for several weeks.

The treatment of depression usually entails psychotherapy (counseling), drug therapy, or some combination of these therapies. In many cases, depression can be treated by a primary care provider; however, in cases of severe depression or depression that doesn't respond well to treatment, depression is usually treated by a psychiatric specialist (a social worker, psychologist, or psychiatrist).

Psychotherapy (counseling) — Psychotherapy helps alleviate symptoms in about 50 percent of people with major depression [3]. In some people, this therapy may be as effective or more effective than drug therapy. There are several different types of psychotherapy, including cognitive therapy, behavioral therapy, and interpersonal therapy.

Psychotherapy can be provided by any healthcare professional who has appropriate training in psychotherapy, including licensed psychologists, psychiatrists, clinical social workers, and clinical nurse specialists. The initial therapy sessions often focus on a better understanding of depression and may entail simple "homework activities" to begin to address the factors that may be contributing to depression. Although psychotherapy can lessen depression within several weeks, the maximal effectiveness of this therapy may not be apparent for 8 to 10 weeks.

Drug therapy — Therapy with antidepressant drugs helps reestablish the normal balance of neurochemicals in the brain. Several different classes of antidepressants effectively relieve the symptoms of depression. About half of all people with major depression have at least a 50 percent improvement in their symptoms when treated with antidepressants [4].

Time required for a response — Some people respond to drug therapy after about two weeks, but for most, the effects of antidepressants do not become noticeable for four to six weeks. Your clinician may recommend switching to another drug or may recommend treatment by a psychiatric specialist if a drug is still ineffective after 8 to 12 weeks at the maximum dose.

Duration — In most cases, antidepressant drugs should be taken for at least six to nine months. In people who experience relapses when exposed to certain events (such as stress or loss), drug therapy should be continued until these events are addressed. Some people require long-term therapy (see "Maintenance drug therapy" below).

Antidepressants and pregnancy — Women who are taking antidepressants and considering pregnancy should talk with their healthcare provider about the risks and benefits of drug therapy during pregnancy. Most antidepressants are safe for the mother and baby when taken during pregnancy.

However, paroxetine (Paxil®) has been associated with an increased risk of birth defects in babies whose mothers took the drug during the first trimester. In addition, newborns whose mothers took paroxetine or fluoxetine (Prozac®) during the third trimester have an increased risk of temporary behavior changes. These behavior changes can include tremors or slightly increased breathing rate, but rarely include more serious problems. Behavior changes usually disappear one to two weeks after birth.

There have been no reports of long-term developmental or behavioral problems in children who were exposed to antidepressants during their mother's pregnancy.

Choice of antidepressants — Many different classes of antidepressants are effective for relieving depression [5]. Thus, the choice among antidepressants depends upon other factors, including the presence of other medical conditions, the possibility of drug interactions, and the potential side effects.

It is important to discuss the expected benefits and possible side effects of antidepressants before starting treatment. It is also important to follow the guidelines for taking these drugs and to avoid combining antidepressant drugs unless you are instructed to do so. Selective serotonin reuptake inhibitors — The selective serotonin reuptake inhibitors (SSRIs) increase brain levels of the neurochemical serotonin. Low levels of serotonin have been implicated as one cause of depression. Drugs in this class include fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), and escitalopram (Lexapro®).

Compared with most other antidepressants, the SSRIs have fewer side effects. These side effects may include jitteriness, restlessness, agitation, headache, diarrhea and nausea, and insomnia. Sexual side effects (loss of sexual desire, diminished arousal, and difficulty having an orgasm) may also occur with prolonged use of the SSRIs; however, the addition of other drugs (such as bupropion [Wellbutrin®] or buspirone [BuSpar®]) to therapy can often relieve these sexual side effects. Bupropion — Bupropion (Wellbutrin®) alters levels of several neurochemicals in the brain but does not appear to have any direct effect on levels of serotonin. Bupropion has a mild stimulant action and may be especially effective in people with depression who have symptoms of fatigue and poor concentration.

Bupropion has few side effects, but it has been associated with seizures in people with eating disorders; it is not recommended for people who have bulimia or anorexia. The drug carries a small risk of seizures in other people. Other side effects of bupropion may include mild anxiety or insomnia and appetite suppression with weight loss. Unlike other antidepressants, bupropion does not have sexual side effects. It is sometimes used at low doses to help counter the sexual side effects of other antidepressants. Serotonin norepinephrine reuptake inhibitors — The serotonin norepinephrine reuptake inhibitors venlafaxine (Effexor®) and duloxetine (Cymbalta®) alter levels of several different neurochemicals in the brain. For unknown reasons, these drugs may be especially effective in people who have a poor response to other antidepressants. Duloxetine may be of benefit in persons with depression as well as significant physical pain from medical (eg, arthritis) or orthopaedic (eg, spinal disc disease) sources, although there have not been studies comparing duloxetine to other antidepressants for this purpose.

Common side effects include nausea, dizziness, insomnia, sedation, and constipation. Rarely, these drugs also cause increased sweating. People taking venlafaxine should have regular blood pressure checks since it may cause blood pressure to rise. Tricyclic antidepressants — The tricyclic antidepressants alter levels of several different neurochemicals in the brain. Drugs in this class include imipramine (Tofranil®), amitriptyline (Elavil®), desipramine (Norpramin®), nortriptyline (Pamelor®), and clomipramine (Anafranil®).

Because of the numerous side effects associated with these drugs and the development of the SSRIs and other newer antidepressants, the tricyclic antidepressants are less commonly used as first-line antidepressant therapy. The side effects of tricyclic antidepressants may include dry mouth, blurred vision, constipation, nausea, difficulty urinating, drowsiness, weight gain, sexual problems, and rapid heart beat. In older adults, the side effects may include memory impairment, confusion, and hallucinations. Some people with heart diseases may not be able to take tricyclic antidepressants. Nevertheless, many patients use these drugs safely, and their antidepressant activity equals that of antidepressants from other classes. Monoamine oxidase (MAO) inhibitors — The monoamine oxidase (MAO) inhibitors were the first drugs used to treat depression. These drugs block an enzyme that breaks down neurochemicals. Drugs in this class include tranylcypromine (Parnate®) and phenelzine (Nardil®).

The MAO inhibitors are usually not a first choice for the treatment of depression, but they may be especially effective for the treatment of atypical depression and depression that does not respond to other drugs. Side effects of MAO inhibitors may include dizziness, dry mouth, gastrointestinal upset, difficulty urinating, headache, unpredictable muscle contractions, and afternoon fatigue.

People who take MAO inhibitors must avoid foods and beverages that contain tyramine. These include fermented cheeses; imported beer; Chianti and some other wines; champagne; soy sauces; avocados; bananas; overripe or spoiled food; and any fermented, smoked, or aged fish or meat. People who accidentally consume tyramine while taking MAO inhibitors may experience severe hypertension (high blood pressure). Trazodone — The specific actions of trazodone (Desyrel®) in the brain are uncertain, but this drug appears to alter levels of serotonin. Because trazodone may not be as effective as other antidepressant drugs and because of its potential side effects, this drug is usually not a first choice for the treatment of depression.

The most common side effect of trazodone is sedation; other side effects may include lightheadedness upon standing and nausea. The rare but potentially serious side effects of trazodone may include irregular heart beat and priapism (a persistent erection that requires medical treatment). Mirtazapine — Mirtazapine (Remeron®) is one of the newest antidepressants. This drug alters levels of several neurochemicals in the brain, including levels of serotonin. Mirtazapine has antianxiety and sedative effects and may be especially effective in people with depression who have symptoms of anxiety and insomnia.

The side effects of mirtazapine include sedation, which is actually more common at lower drug doses. Other side effects include increased appetite, weight gain, and dry mouth. Mirtazapine is less likely than other antidepressants to have sexual side effects. Rarely, the use of mirtazapine may cause a fall in the number of white blood cells and changes in liver function.

Minimizing side effects — It is important to tell your doctor if you experience side effects while taking antidepressant drugs. Your clinician may recommend one of several different measures that can minimize or eliminate these side effects: Starting at low doses and very gradually increasing the dose Taking other drugs to counter the side effects Using lower doses of the drugs Taking the drugs at a different time of the day Switching to a different drug in the same class or to a different class of drugs

It is particularly important to consult with your clinician if you decide to stop taking antidepressants. It commonly takes several weeks for a person to adjust after discontinuing antidepressants, and doctors often recommend a gradual tapering of these drugs to prevent any serious withdrawal effects.

Maintenance drug therapy — Maintenance drug therapy (long-term drug therapy) may be appropriate for people who are at risk for a relapse of depression. One study found that 37 percent of people who were treated for depression experienced a relapse within 12 months of stopping antidepressant therapy [6].

It is impossible to predict for certain whether a person will have a relapse, but two factors have been associated with a greater likelihood of relapse: A persistence of low-level depressive symptoms seven months after starting antidepressant therapy A history of two or more episodes of major depression or chronic depressive symptoms for two years

Clinicians may recommend maintenance therapy for people who have had one or more relapses of depression.

Therapy with other drugs — In some people, depression may be accompanied by other psychiatric conditions, such as panic attacks or mania. Clinicians may therefore recommend combined therapy with antidepressants and drugs such as antipsychotics, antianxiety drugs, mood-stabilizing drugs, or anticonvulsants.

Drug therapy versus psychotherapy — It is generally accepted that patients with severe depression require drug therapy, with or without additional psychotherapy. Mild or moderate depression can probably be treated with either drug therapy or psychotherapy. There are no clear predictors of which therapy may be a better choice for any given individual. Some people, especially people who have severe depression or a history of recurrent depression, may experience the greatest relief of depression when treated with both drug therapy and psychotherapy.

Treatment of other medical conditions — Depression often occurs in people who have other medical conditions, including stroke, diabetes, dementia, cancer, hypothyroidism, chronic fatigue syndrome, fibromyalgia, lupus, heart disease, Sjögren's syndrome, seizure disorders, and anxiety and panic disorders. Depression can also be associated with the use of certain drugs, such as corticosteroids.

In many cases, a cause-and-effect relationship between the medical condition or the drug and depression has not been proven. However, treatment of a medical condition or discontinuation of certain drugs often resolves depression.

Other treatment options — Several other treatment options may alleviate depression in some people.

St. John's wort — St. John's wort (Hypericum perforatum) appears to alter levels of several neurochemicals in the brain. Studies suggest that for the treatment of mild to moderate depression, St. John's wort is more effective than a placebo and as effective as tricyclic antidepressants, with fewer side effects [7]. However, the long-term effectiveness of St. John's wort is unknown.

St. John's wort is not approved by the United States Food and Drug Administration for the treatment of depression. Because the composition of St. John's wort products varies widely, some products may be less effective than others for relieving depression. The products that are most likely to be effective are those that are standardized at 0.3 percent hypericin. The dose in most studies is 300 mg three times per day, although doses as low as 250 mg twice per day may be effective.

The side effects of St. John's wort may include gastrointestinal symptoms, dizziness or confusion, sedation or tiredness, and dry mouth. Rarely, some people who take St. John's wort may notice that their skin becomes extremely sensitive to sunlight. The long-term safety of St. John's wort is unknown.

It is important to tell your clinician if you use St. John's wort. This herb can reduce the effectiveness of drugs used to treat a variety of other medical conditions, including oral contraceptives. Of particular concern are interactions with medications used to treat HIV and cancer. In general, patients on chemotherapy or antiviral therapy for HIV should not take St. John's wort. Furthermore, St. John's wort should not be used in combination with other antidepressants, particularly the selective serotonin reuptake inhibitors (SSRIs).

Studies suggest that pregnant or breast-feeding women should not take St. John's wort, and some evidence has raised concerns that the herb may lower fertility. St. John's wort is inappropriate for people with severe depression who are at risk for suicide.

A good source for updated information about St. John's wort can be found at the National Center for Complementary and Alternative Medicine, a branch of the National Institutes of Health (www.nccam.nih.gov/health/stjohnswort/).

Electroconvulsive therapy (ECT) — During electroconvulsive therapy (ECT), an electrical current is passed through the brain, triggering a seizure. For unknown reasons, the seizure helps to restore the normal balance of neurochemicals in the brain. ECT is especially effective for people with depression who also have delusions (powerful, irrational beliefs) and for people who have severe depression despite maximal drug therapy. ECT can be used in pregnant women or in persons who cannot tolerate antidepressant medications, and is especially useful in persons who need a rapid-onset antidepressant treatment. (See "Medical consultation for electroconvulsive therapy").

Patients who undergo ECT are given general anesthesia and require careful monitoring. Side effects of this therapy include brief confusion and memory loss. Although ECT has been negatively portrayed in the media, this therapy often provides rapid and dramatic relief of depression and has very few side effects. Most people who undergo ECT find it a helpful treatment for their depression.

Repetitive transcranial magnetic stimulation (rTMS) — During repetitive transcranial magnetic stimulation (rTMS), a powerful magnetic field is used to stimulate the brain. This therapy does not require anesthesia or cause any confusion or memory loss. The effectiveness of rTMS for the treatment of depression is still being studied.

Exercise — Exercise can improve depressive symptoms, although the effects occur more slowly than seen with antidepressant drugs. One study found that the depression-relieving benefit of exercise was equal to that of a selective serotonin reuptake inhibitor (SSRI) after 16 weeks [8].

Light therapy — Light therapy can very effectively relieve the depression of seasonal affective disorder (SAD). The usual dose is 10,000 lux, beginning with one 10 to 15 minute session per day, gradually increasing to 30 to 45 minutes per day depending upon response. It may take four to six weeks to see a response, although some patients improve within days. Therapy is continued until sufficient daily light exposure is available through other sources, typically from springtime sun.

Preventing suicide — Suicide is a tragic and preventable consequence of severe depression. If a clinician suspects that a person is depressed, he or she will often ask about suicidal thoughts. It is absolutely imperative to tell your clinician if you have thoughts about harming yourself or ending your life. A person who is likely to attempt suicide is given emergency treatment, including hospitalization and intensive therapy to relieve the depression that prompts suicidal thoughts.

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Institute of Mental Health

(www.nimh.nih.gov)
American Psychiatric Association

(www.psych.org)
American Psychological Association

(www.apa.org)
American Academy of Child and Adolescent Psychiatry

(www.aacap.org)
Depression and Related Affective Disorders Association

(www.drada.org)
Depression and Bipolar Support Alliance (DBSA)

(www.DBSAlliance.org)
National Foundation For Depressive Illness

(www.depression.org)
National Mental Health Association

(www.nmha.org)
National Alliance for the Mentally Ill

(www.nami.org)



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