Major Depressive Disorder (MDD)

Background

• Major depressive disorder (MDD) is a common and well researched type of depressive disorder which is characterized by a persistent low mood, a lack of positive affect, and a loss of interest in usually pleasurable activities (anhedonia) that is different from the patient's usual self and causes significant distress or impairment for ≥ 2 weeks.
• The prevalence of major depressive disorder in the United States is approximately 7% per year with a lifetime prevalence of 16.6%.
• Some patients may have specific subtypes of depression, which may be clinically useful for predicting outcomes and choosing treatment. They include:
  • melancholic depression (melancholia)
  • depression with atypical features
  • MDD with psychotic features
  • MDD with catatonia
  • MDD with anxious distress
• MDD is classified by severity:
  • mild MDD - the minimum number of symptoms present, symptoms are distressing but manageable, and minor functional impairment
  • moderate MDD - falls between mild and severe
  • severe MDD - substantial excess of required symptoms present, symptoms are unmanageable for patient, and disability in responsibilities is apparent
• Reported risk factors for depression include:
  • a family or personal history of major depression and/or substance abuse
  • chronic medical illness
  • alcohol and substance use
  • stressful life events including loss (including bereavement or divorce)
  • major life changes such as job change or financial difficulty
  • domestic abuse or violence
  • female sex
  • low income and unemployment
  • disability
• The prognosis for MDD is variable. It is unremitting in about 15% of patients and recurrent in about 35% of patients with the risk of recurrence increasing with each additional episode of major depression.
• Screen high-risk patients or patients with suspected depression with a standardized instrument such as the Patient Health Questionnaire-9 (PHQ-9) (Strong recommendation).

Evaluation

• Depression is a clinical diagnosis based on the presence of a depressed mood or anhedonia and associated symptoms, usually defined by either Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) or ICD-10 criteria with the exclusion of other causes.
• Symptoms include:
  • significant change in weight or appetite
  • insomnia or hypersomnia
  • psychomotor agitation or retardation nearly every day (observable by others)
  • fatigue or loss of energy
  • feelings of worthlessness or excessive or inappropriate guilt
  • indecisiveness or decreased ability to concentrate
  • recurrent thoughts of death or suicide
• Important differential diagnoses to consider include other mood disorders, especially bipolar disorder, psychotic disorders, substance abuse, and medical conditions such as hypothyroidism and Cushing disease.
• Careful and ongoing evaluation of suicide risk is necessary for all patients with suspected or diagnosed major depressive disorder (Strong recommendation).

Management

• Hospitalization or immediate specialist consultation is usually needed for patients who pose a serious threat of harm to self or others (Strong recommendation) and should be considered for those that are severely depressed, especially if they lack social supports or have a complicating medical or psychiatric conditions.
• Recommended initial treatment choices:
  • For mild-to-moderate depression in adults:
    • consider cognitive behavioral therapy (CBT) as an initial treatment option (Weak recommendation)
    • consider antidepressants as an alternative initial therapy in some cases (Weak recommendation)
      • a prior history of moderate or severe depression
      • subthreshold symptoms lasting ≥ 2 years
    • consider a combination of psychotherapy plus an antidepressant if there are comorbid psychosocial problems (Weak recommendation)
  • For moderate-to-severe depression:
    • offer monotherapy with either CBT or second-generation antidepressant (Strong recommendation)
    • consider combination therapy with CBT and second-generation antidepressant (Weak recommendation)
  • Consider electroconvulsive therapy (ECT) for severe depression if the patient is unresponsive to psychotherapy plus antidepressants or if there is an urgent need for rapid response (suicidal, food refusal, catatonic) (Weak recommendation).
  • For most patients, optimal medications include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), mirtazapine, or bupropion (Strong recommendation).
  • if patient is pregnant or lactating, individualize medical treatment if psychotherapy has failed as sole treatment.
  • Among important adverse events of antidepressant therapy, there is an increased risk of suicidality, generally in the first 1-2 months of treatment, in young adults aged 18-24 years.
• For patients with treatment-resistant depression
  • in patients who do not respond to initial treatment with adequate dose of second-generation antidepressant as monotherapy, consider 1 of the following options: (Weak recommendation)
    • switching to or augmenting treatment with CBT
    • switching to a different second-generation antidepressant
    • augmenting with a second medication
  • consider esketamine nasal spray in addition to oral antidepressant (FDA approved in adults).
  • consider electroconvulsive therapy (ECT) (Weak recommendation).
• After successful acute treatment, continuation therapy is recommended for 4-9 months or for at least 6 months after a remission is achieved (Strong recommendation).
• When discontinuing antidepressants, supervised tapering of the medication should occur over 6-8 weeks to avoid discontinuation syndrome (flu-like symptoms, insomnia, imbalance, sensory disturbances, and hyperarousal). Cross tapering should be used when switching antidepressants.