Updated: Apr 29, 2016
  • Author: Jerry L Halverson, MD; Chief Editor: David Bienenfeld, MD  more...

Practice Essentials

Major depressive disorder has significant potential morbidity and mortality, contributing to suicide (see the image below), incidence and adverse outcomes of medical illness, disruption in interpersonal relationships, substance abuse, and lost work time. With appropriate treatment, 70-80% of individuals with major depressive disorder can achieve a significant reduction in symptoms.

From 1991-2006, the suicide rate was consistently From 1991-2006, the suicide rate was consistently higher among males. Suicide rates declined among both sexes from 1991-2000; the rate among males decreased from 24.64 to 20.67 suicides per 100,000 and 5.48 to 4.62 suicides per 100,000 among females. From 2000-2006, however, the suicide rates gradually increased among females. Note: All rates are age-adjusted to the standard 2000 population. Rates based on less than 20 deaths are statistically unreliable. Source: Centers for Disease Control and Prevention. National suicide statistics at a glance: Trends in suicide rates among persons ages 10 years and older, by sex, United States, 1991-2006. Available at: Accessed: May 5, 2010.

Signs and symptoms

Most patients with major depressive disorder present with a normal appearance. In patients with more severe symptoms, a decline in grooming and hygiene may be observed, as well as a change in weight. Patients may also show the following:

  • Psychomotor retardation
  • Flattening or loss of reactivity in the patient's affect (ie, emotional expression)
  • Psychomotor agitation or restlessness

Major depressive disorder

Among the criteria for a major depressive disorder, at least 5 of the following symptoms have to have been present during the same 2-week period (and at least 1 of the symptoms must be diminished interest/pleasure or depressed mood) [1] :

  • Depressed mood: For children and adolescents, this can also be an irritable mood
  • Diminished interest or loss of pleasure in almost all activities (anhedonia)
  • Significant weight change or appetite disturbance: For children, this can be failure to achieve expected weight gain
  • Sleep disturbance (insomnia or hypersomnia)
  • Psychomotor agitation or retardation
  • Fatigue or loss of energy
  • Feelings of worthlessness
  • Diminished ability to think or concentrate; indecisiveness
  • Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or specific plan for committing suicide


Screening instruments

Self-report screening instruments for depression include the following:

  • Patient Health Questionnaire-9 (PHQ-9): A 9-item depression scale; each item is scored from 0-3, providing a 0-27 severity score.
  • Beck Depression Inventory (BDI) or the Beck Depression Inventory-II (BDI-II): 21-question symptom-rating scales providing a 0-63 severity score.
  • BDI for primary care: A 7-question scale adapted from the BDI.
  • Zung Self-Rating Depression Scale: A 20-item survey.
  • Center for Epidemiologic Studies-Depression Scale (CES-D): A 20-item instrument that allows patients to evaluate their feelings, behavior, and outlook from the previous week.

In contrast to the above self-report scales, the Hamilton Depression Rating Scale (HDRS) is performed by a trained professional, not the patient. The HDRS has 17 or 21 items, scored from 0-2 or 0-4; a total score of 0-7 is considered normal, while scores of 20 or higher indicate moderately severe depression.

The Geriatric Depression Scale (GDS), although developed for older adults, has also been validated in younger adults. The GDS contains 30 items; a short-form GDS has 15 items.

Laboratory studies

No diagnostic laboratory tests are available to diagnose major depressive disorder, but focused laboratory studies may be useful to exclude potential medical illnesses that may present as major depressive disorder.


In all patient populations, the combination of medication and psychotherapy generally provides the quickest and most sustained response. [2, 3]


Drugs used for treatment of depression include the following:

  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin/norepinephrine reuptake inhibitors (SNRIs)
  • Atypical antidepressants
  • Tricyclic antidepressants (TCAs)
  • Monoamine oxidase inhibitors (MAOIs)
  • St. John's wort ( Hypericum perforatum)


Evidence-based psychotherapeutic treatments for adults with major depressive disorder include the following: [4]

  • Interpersonal psychotherapy (IPT)
  • Cognitive-behavioral therapy (CBT)
  • Problem-solving therapy (PST)
  • Behavioral activation (BA)/contingency management

Evidence-based psychotherapeutic treatments for children and adolescents with major depressive disorder include the following: [5]

  • Interpersonal psychotherapy (IPT)
  • Cognitive-behavioral therapy (CBT)
  • Behavior therapy (BT)

Many of these treatments incorporate a parent/family component when working with children or adolescents.

In mild cases, psychosocial interventions are often recommended as first-line treatments. The American Psychiatric Association (APA) guideline supports this approach but notes that combining psychotherapy with antidepressant medication may be more appropriate for patients with moderate to severe major depressive disorder. [6]

Electroconvulsive therapy

Electroconvulsive therapy (ECT) is a highly effective treatment for depression. The indications for ECT include the following:

  • Need for a rapid antidepressant response
  • Failure of drug therapies
  • History of good response to ECT
  • Patient preference
  • High risk of suicide
  • High risk of medical morbidity and mortality

Stimulation techniques

Transcranial magnetic stimulation (TMS) is approved by the FDA for treatment-resistant major depression.

Vagus nerve stimulation (VNS) has been approved by the FDA for use in adult patients who have failed to respond to at least 4 adequate medication and/or ECT treatment regimens. The stimulation device requires surgical implantation.