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, 2
• Sleep disturbances: Insomnia or hypersomnia 1
• Psychomotor symptoms: Psychomotor agitation or retardation nearly every day 1, 2
• 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, 2
• 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. 3

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. 4 Alternatively, ask two simple screening questions about mood and anhedonia. 4

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 5
• Bipolar disorder screening: Rule out before starting antidepressants 6
• Psychotic symptoms: Presence requires specialized psychiatric care 6
• Substance use: Active substance use affects treatment selection 6
• Comorbid anxiety: Present in 50-60% of patients with depression 5

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): 6

• Cognitive behavioral therapy (CBT): Identifies and challenges negative thought patterns; includes behavioral activation to increase engagement in pleasurable activities 4, 6
• Behavioral activation: Focuses on increasing engagement in rewarding activities 6
• Interpersonal therapy: Addresses relationship issues and life transitions 6
• Problem-solving therapy: Teaches structured problem-solving skills 6
• Brief psychodynamic therapy: Explores unconscious patterns 6
• Mindfulness-based psychotherapy: Incorporates meditation and present-moment awareness 6

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. 2, 6

Medication selection should be based on:

• Adverse effect profiles: SSRIs generally better tolerated than older agents 2
• Drug interactions: Consider current medications 5
• Prior treatment response: Use previously effective agents 5
• Patient preference: Discuss tolerability concerns 5

Common second-generation antidepressants include SSRIs (citalopram, escitalopram, fluoxetine, paroxetine, sertraline), SNRIs (venlafaxine, duloxetine), and others (bupropion, mirtazapine). 2

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). 6 This approach is particularly important for more severe or chronic depression. 6

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 4
• Continue treatment for at least 4-9 months after initial response 4
• If no improvement after 8 weeks despite good compliance, alter treatment approach 4

Second-Line Strategies for Treatment-Resistant Depression

When initial antidepressant fails, three strategies have approximately equal likelihood of success: 6

• Switch antidepressants: Change to different medication class 6
• Add second antidepressant: Combine two antidepressants 6
• Augmentation: Add non-antidepressant medication (e.g., atypical antipsychotic) 6

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). 6

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. 5

Comorbid anxiety: When present (50-60% of cases), usual practice is to treat depression first. 5

Recurrence risk: Depression is a chronic disease with increasing recurrence likelihood after each episode, often requiring prolonged maintenance medication. 3