Encyclopedia / D / Depression (Major Depressive Disorder)

Depression (Major Depressive Disorder)

What Is Depression?

Depression is a mood disorder characterized by a persistent sad or empty feeling, irritability, and a loss of interest in everyday activities. The condition is twice as common in women as in men and is usually episodic. But unlike normal sadness or grieving, most bouts of depression last for weeks, months, or even years. Some people with depression have a chronic, low-grade form of the condition called dysthymia. A smaller number suffer from bipolar disorder—bouts of depression interspersed with periods of elevated (manic) mood.

Although depression is usually not considered life-threatening, it can lead to thoughts of and attempts at suicide. As many as 70% of suicides in the United States are related to depression, and up to 15% of severely depressed people commit suicide. Fortunately, the overwhelming majority of people with depression can be helped by counseling (psychotherapy), antidepressant drugs, or other therapies, thus lowering the suicide risk.

Who Gets Depression?

The incidence of depression has risen every year since the early 20th century. There are probably many reasons for this, though most studies point to significant socioeconomic changes experienced by the post-World War II “baby boomer” generation.

In the United States, one in six people experience a depressive episode during their lifetime. Only 50% of the people who meet the criteria for diagnosis seek treatment for depression, which affects the ability to determine how many people actually suffer from this disorder.

The reported prevalence of depressive disorders varies throughout the world. The lowest rates are reported in Asian and Southeast Asian countries. Western countries typically report higher rates. Also, countries plagued by protracted civil strife, such as Bosnia and Northern Ireland, report higher rates of depression.


  • Persistent feelings of sadness, apathy, or hopelessness lasting more than two weeks.
  • Diminished interest in most daily activities, particularly pleasurable ones.
  • Loss of energy, the effects of which compound the effects of depression, when work, school, and family obligations are compromised.
  • Feelings of worthlessness or excessive or inappropriate guilt.
  • Decreased appetite and subsequent weight loss; increased appetite and weight gain.
  • Lack of sleep (insomnia), frequent awakening throughout the night, or conversely, an increased need for sleep.
  • Anxiety; diminished ability to think or concentrate.
  • Older people may initially focus on physical or cognitive complaints brought on by their depression. Insomnia and agitation are also more common in older patients.

Causes/Risk Factors

  • Although the cause of most cases of depression is unknown, it is thought to be associated with a combination of medical, genetic, and environmental factors.

  • Imbalances of chemicals that transmit nerve signals (neurotransmitters) in the brain may play a role.

  • The condition appears to run in families, although no specific genes have been identified.

  • Episodes may be connected to major life events, such as the death of a loved one or loss of a job.

  • People with season-related depression (seasonal affective disorder [SAD]) are usually depressed during the fall and winter, and become healthier in spring and summer. The cause for this may be a result of reduced melatonin (a hormone that helps regulate the sleep-wake cycle) secretion in the brain.

  • In about 15% of cases, depression develops in response to a medical illness (especially heart disease, cancer, or a neurologic disorder such as Parkinson’s disease or stroke) or from long-term use of some medications, including beta-blockers for high blood pressure and corticosteroids for arthritis. Other causes of this “secondary depression” include alcoholism, an underactive thyroid gland, vitamin deficiencies, and schizophrenia.


  • Because there are no reliable laboratory tests to diagnose depression, physical examination and psychological evaluation are essential.

  • Expression of either of the first two symptoms of depression, in conjunction with other symptoms, for a period of two or more consecutive weeks.

  • A positive family history of depression or a prior depressive episode helps establish the diagnosis.


  • Psychotherapy is as effective as drug treatment in mild cases. Its goal is to change self-perception and behavior. Psychotherapy may also be used in conjunction with drug therapy.

  • Antidepressant medications—which include selective serotonin reuptake inhibitors (SSRIs), non-SSRIs, tricyclic antidepressants (TCAs), and monoamine oxidase (MAO) inhibitors—are mainstays of treatment. Because of their superior safety profile, SSRIs and non-SSRIs have largely replaced the older TCAs and MAOIs, which are generally considered as an option only when other treatments have failed.

Examples of these include:

  • SSRIs: citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft). Common side effects include sexual side effects, sun sensitivity, and modest weight gain over time (sometimes preceded by initial weight loss).
  • Non-SSRIs: bupropion (Wellbutrin), mirtazapine (Remeron), venlafaxine (Effexor), duloxetine (Cymbalta). Side effects include dizziness, dry mouth, nausea, and sleepiness.
  • TCAs: amitriptyline (Elavil), amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), and others. In high doses, TCAs may cause severe side effects such as seizures, stroke, and heart attack.
  • MAOIs: phenelzine (Nardil), isocarboxazid (Marplan). Side effects are similar to those caused by TCAs and a potentially fatal condition called tyramine-induced hypertensive crisis•
  • Electroconvulsive therapy (using an electric current to cause a brief convulsion) is sometimes used in severe cases. ECT increases neurotransmitter (i.e., serotonin, dopamine, norepinephrine) levels in the brain, which improves neurotransmission and elevates mood.
  • Exposure to bright light, known as light therapy, may be effective, particularly when depression is related to seasonal changes (seasonal affective disorder).
  • In secondary depression, the underlying cause is addressed, although antidepressant therapy may also be prescribed.


  • Although the initial onset of depression cannot be prevented, recurrent episodes may be controlled or avoided altogether with ongoing psychotherapy and/or drug therapy. The longer a person stays in treatment, the less likely a relapse will occur.

When To Call Your Doctor

  • Anyone with symptoms of depression should see a doctor for an evaluation and possible referral to a mental health professional.

  • EMERGENCY Anyone who has persistent thoughts of suicide should get immediate psychological or medical treatment.

Reviewed by Christos Ballas, M.D., Attending Psychiatrist, Hospital of the University of Pennsylvania, Philadelphia, PA.  Review provided by VeriMed Healthcare Network.