What are the diagnostic criteria and treatment options for major depressive disorder (MDD)?

Major Depressive Disorder: Diagnostic Criteria and Treatment Options

Diagnostic Criteria

Major depressive disorder (MDD) is defined as the presence of five or more characteristic symptoms during a 2-week period, with at least one symptom being depressed mood or loss of interest/pleasure in activities, accompanied by significant distress or functional impairment. 1

The nine DSM-5 diagnostic criteria for MDD include:

1. Depressed mood most of the day, nearly every day
2. Markedly diminished interest or pleasure in almost all activities
3. Significant weight loss/gain or decreased/increased appetite
4. Insomnia or hypersomnia
5. Psychomotor agitation or retardation
6. Fatigue or loss of energy
7. Feelings of worthlessness or excessive/inappropriate guilt
8. Diminished ability to think or concentrate, or indecisiveness
9. Recurrent thoughts of death or suicidal ideation

The severity of MDD can be categorized as:

• Mild: 5-6 symptoms with mild severity and minimal functional impairment
• Moderate: Symptoms/impairment between mild and severe
• Severe: Most or all symptoms present with significant functional impairment, or presence of specific features like psychotic symptoms, suicide plan/intent, or severe functional impairment 2

Screening and Assessment

Screening for MDD is recommended in the general adult population when resources are available for diagnosis, management, and follow-up 1. Validated screening tools include:

• Patient Health Questionnaire-9 (PHQ-9)
• Beck Depression Inventory for Primary Care (BDI-PC)
• Hamilton Depression Rating Scale (HAM-D)

Laboratory tests may be considered to rule out medical conditions that can mimic depression, such as thyroid disorders, vitamin deficiencies, or anemia.

Treatment Approach

Initial Treatment for Uncomplicated MDD

For moderate to severe MDD, initial treatment should be either cognitive behavioral therapy (CBT) monotherapy or a second-generation antidepressant (SGA) monotherapy, with the choice based on patient preferences, symptom profile, and side effect considerations. 3

Treatment options:

1. Pharmacotherapy Options:

   • First-line: Second-generation antidepressants (SGAs)

     • SSRIs (citalopram, escitalopram, sertraline) are preferred due to favorable side effect profiles 4
     • SNRIs (venlafaxine, duloxetine)
     • Others: bupropion, mirtazapine

   • Medication Selection Considerations:

     • For sexual dysfunction concerns: bupropion (100-400 mg/day) 4
     • For comorbid pain: SNRIs 4
     • For insomnia: mirtazapine 4
     • For weight concerns: bupropion (promotes weight loss) 4

2. Psychotherapy Options:

   • Cognitive Behavioral Therapy (CBT)
   • Short-term Psychodynamic Psychotherapy (STPP) 2
   • Interpersonal Therapy
   • Acceptance and Commitment Therapy

3. Combination Therapy:

   • CBT plus SGA may be more effective than either treatment alone for moderate to severe depression 4, 3

Treatment for Mild MDD

For mild MDD, cognitive behavioral therapy monotherapy is suggested as initial treatment. 3

Treatment Duration and Monitoring

• Begin assessment of response within 1-2 weeks of starting treatment 4
• Monitor for therapeutic response, side effects, and emergence of suicidal thoughts
• Treatment should continue for at least 4-9 months after achieving remission for first-episode depression 4
• For recurrent depression, treatment should continue for at least 1 year 4

Treatment-Resistant Depression

For patients who do not respond to initial treatment with an adequate dose of an SGA, consider:

1. Switching to or augmenting with CBT 3

2. Switching to a different SGA 3

3. Augmenting with a second medication:

   • Second-generation antipsychotics 2
   • Other antidepressants
   • Mood stabilizers

4. For severe treatment-resistant cases:

   • Repetitive Transcranial Magnetic Stimulation (rTMS) 2
   • Electroconvulsive Therapy (ECT)
   • Ketamine or esketamine 2

Common Side Effects of SGAs

Approximately 63% of patients experience at least one adverse effect from SGAs 4:

• Sexual dysfunction
• Gastrointestinal symptoms (nausea, diarrhea)
• Headache
• Insomnia or somnolence
• Weight changes
• Dry mouth
• Dizziness
• Sweating
• Tremor

Special Considerations

• Bipolar Disorder: Avoid SSRIs in patients with bipolar depression due to risk of triggering mania 4
• Young Adults (18-24): Higher risk of suicidality; require closer monitoring 4
• Elderly with Dementia: SSRIs are effective and well-tolerated; avoid tricyclics due to anticholinergic effects 4
• Telehealth: Virtual care delivery is effective for behavioral health interventions for MDD 2

Treatment Phases

MDD treatment follows three phases 2:

1. Acute Phase (6-12 weeks): Goal is symptom reduction
2. Continuation Phase (4-9 months): Prevents relapse
3. Maintenance Phase (≥1 year): Prevents recurrence, especially important for recurrent depression