What are the symptoms and treatment options for depression?

Depression Symptoms and Treatment

Core Symptoms of Major Depressive Disorder

Major depressive disorder requires depressed mood or loss of pleasure/interest plus at least 5 total symptoms lasting at least 2 weeks that affect normal functioning. 1

The diagnostic symptoms include:

• Mood symptoms: Depressed mood most of the day, nearly every day; markedly diminished interest or pleasure in most activities 1
• Appetite/weight changes: Significant weight loss or gain, or appetite disturbance 1
• Sleep disturbances: Insomnia or hypersomnia 1
• Psychomotor symptoms: Psychomotor agitation or retardation nearly every day 1
• Energy: Fatigue or loss of energy 1
• Cognitive symptoms: Feelings of worthlessness or excessive/inappropriate guilt; diminished ability to think, concentrate, or make decisions 1
• Suicidal ideation: Recurrent thoughts of death or suicide 1

Physical symptoms are common presenting features, primarily fatigue, pain, or sleep disturbance, and depressed mood may not always be prominent. 2

Screening and Assessment

Use the Patient Health Questionnaire-9 (PHQ-9) as the primary screening tool, with scores ≥8 indicating clinically significant depression requiring intervention. 3 Alternatively, ask two simple screening questions about mood and anhedonia. 3

Critical assessments that must be performed:

• Immediate suicide risk: Any patient identified as at risk of harm to self or others requires emergency evaluation and referral 1
• Bipolar disorder screening: Rule out before starting antidepressants 4
• Psychotic symptoms: Presence requires specialized psychiatric care 4
• Substance use: Active substance use affects treatment selection 4
• Comorbid anxiety: Present in 50-60% of patients with depression 1

First-Line Treatment Selection

Clinicians should select between cognitive behavioral therapy (CBT) or second-generation antidepressants after discussing treatment effects, adverse effects, cost, accessibility, and patient preferences. 1

Psychotherapy Options (All Equally Effective)

The following psychotherapies demonstrate medium-sized effects over usual care (standardized mean difference 0.50-0.73): 4

• Cognitive behavioral therapy (CBT): Identifies and challenges negative thought patterns; includes behavioral activation to increase engagement in pleasurable activities 3, 4
• Behavioral activation: Focuses on increasing engagement in rewarding activities 4
• Interpersonal therapy: Addresses relationship issues and life transitions 4
• Problem-solving therapy: Teaches structured problem-solving skills 4
• Brief psychodynamic therapy: Explores unconscious patterns 4
• Mindfulness-based psychotherapy: Incorporates meditation and present-moment awareness 4

Pharmacotherapy: Second-Generation Antidepressants

All 21 second-generation antidepressants show small to medium-sized effects over placebo (standardized mean difference 0.23-0.48), with no significant differences in efficacy between agents. 1, 4

Medication selection should be based on:

• Adverse effect profiles: SSRIs generally better tolerated than older agents 1
• Drug interactions: Consider current medications 1
• Prior treatment response: Use previously effective agents 1
• Patient preference: Discuss tolerability concerns 1

Common second-generation antidepressants include SSRIs (citalopram, escitalopram, fluoxetine, paroxetine, sertraline), SNRIs (venlafaxine, duloxetine), and others (bupropion, mirtazapine). 1

Combined Treatment for Moderate to Severe Depression

For moderate to severe depression, combined psychotherapy plus antidepressant medication is superior to either treatment alone (standardized mean difference 0.30-0.33 greater improvement than monotherapy). 4 This approach is particularly important for more severe or chronic depression. 4

Treatment Phases and Monitoring

Depression treatment follows three phases: 1

• Acute phase (6-12 weeks): Initial symptom reduction 1
• Continuation phase (4-9 months): Prevent relapse of same episode 1
• Maintenance phase (≥1 year): Prevent recurrence of new episodes 1

Monitoring schedule:

• Assess symptoms biweekly or monthly until remission 3
• Continue treatment for at least 4-9 months after initial response 3
• If no improvement after 8 weeks despite good compliance, alter treatment approach 3

Second-Line Strategies for Treatment-Resistant Depression

When initial antidepressant fails, three strategies have approximately equal likelihood of success: 4

• Switch antidepressants: Change to different medication class 4
• Add second antidepressant: Combine two antidepressants 4
• Augmentation: Add non-antidepressant medication (e.g., atypical antipsychotic) 4

Collaborative Care Model

Implement systematic follow-up and outcome assessment through collaborative care programs, which significantly improve treatment effectiveness (standardized mean difference 0.42 greater improvement than usual care). 4

Special Considerations

Medical causes must be treated first: Address unrelieved symptoms such as pain and fatigue, and rule out delirium from infection or electrolyte imbalance before attributing symptoms to primary depression. 1

Comorbid anxiety: When present (50-60% of cases), usual practice is to treat depression first. 1

Recurrence risk: Depression is a chronic disease with increasing recurrence likelihood after each episode, often requiring prolonged maintenance medication. 2