What are the guidelines for managing a patient with major depressive disorder, considering their medical history and potential suicidal ideation?

Management of Major Depressive Disorder

First-Line Treatment Selection

The American College of Physicians strongly recommends initiating either cognitive behavioral therapy (CBT) or second-generation antidepressants (SGAs) as first-line treatment for MDD, as both demonstrate equivalent effectiveness based on moderate-quality evidence. 1, 2

Treatment Selection Algorithm:

• For mild depression: Start with CBT alone, as it has equivalent effectiveness to antidepressants with fewer adverse effects 2
• For moderate to severe depression: Initiate second-generation antidepressants (SSRIs or SNRIs preferred) selected based on adverse effect profiles, cost, and patient preferences 2
• For severe depression with high-risk features: Begin antidepressants immediately with close monitoring, regardless of symptom count 2

Pharmacotherapy Specifics

Medication Selection:

• Preferred agents: SSRIs (fluoxetine, sertraline, paroxetine, escitalopram) or SNRIs as first-line SGAs 1
• Alternative SGAs: Bupropion, mirtazapine, nefazodone, or trazodone 1
• Avoid first-generation antidepressants (tricyclics, MAOIs) due to higher toxicity in overdose despite similar efficacy 1

Critical Monitoring Requirements:

Monitor closely for suicidal ideation, agitation, irritability, or unusual behavioral changes during the initial 1-2 months of treatment, as suicide risk is highest during this period. 3, 4, 5

• Assessment timeline: Evaluate within 1-2 weeks of initiation for therapeutic effects, adverse effects, and suicidality 2, 6
• Specific warning signs to monitor: Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, or mania 4, 5
• Action required: If these symptoms emerge, consider changing the therapeutic regimen or discontinuing medication, especially if symptoms are severe, abrupt in onset, or not part of presenting symptoms 4, 5

Treatment Response and Adjustment

Response Criteria:

• Definition of response: ≥50% reduction in measured severity using PHQ-9 or HAM-D scales 1, 2, 6
• Definition of remission: HAM-D score ≤7 1

Treatment Modification Timeline:

• If inadequate response by 6-8 weeks: Modify treatment through dose adjustment, switching agents, or adding augmentation strategies 2, 6
• For treatment-resistant depression: Defined as failure to respond to two or more adequate antidepressant trials (sufficient dose and minimum 4 weeks duration) 2

Treatment Duration

Continuation Phase:

• First episode: Continue treatment for minimum 4-9 months after satisfactory response 1, 2, 6, 3
• Recurrent episodes: Continue for ≥1 year (maintenance phase) 1, 2, 6, 3

Treatment Phases:

• Acute phase: 6-12 weeks to achieve response 1, 2
• Continuation phase: 4-9 months to prevent relapse 1, 2
• Maintenance phase: ≥1 year to prevent recurrence in patients with multiple episodes 1, 2

Psychotherapy Options

CBT demonstrates moderate-quality evidence for effectiveness equivalent to SGAs as monotherapy. 1, 2

• Combination therapy: No significant difference in response or remission when comparing SGA monotherapy versus SGA plus CBT, though combination may benefit specific patients 1
• Other validated psychotherapies: Interpersonal therapy, acceptance and commitment therapy, cognitive therapy, and psychodynamic therapies 1

Assessment Tools

Use standardized tools to quantify severity and track treatment response: 1, 2

• Patient Health Questionnaire-9 (PHQ-9) 1, 2, 7
• Hamilton Depression Rating Scale (HAM-D) 1, 2
• Montgomery-Åsberg Depression Rating Scale (MADRS) 2
• Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) 2

Comorbidity Screening

Evaluate for substance use disorders and comorbid anxiety disorders, as these conditions increase chronicity, suicidal thoughts, and functional impairment. 2

Critical Pitfalls to Avoid

• Inadequate dosing or premature discontinuation: Therapeutic effects typically require 4-6 weeks 2
• Insufficient monitoring for suicidality: Especially critical during initial treatment period when risk is highest 2, 6, 4, 5
• Premature treatment discontinuation: Stopping before minimum 4-9 months increases relapse risk 2, 3
• Failure to screen for bipolar disorder: Treating bipolar depression with antidepressants alone may precipitate manic episodes; obtain detailed psychiatric and family history before initiating antidepressants 5
• Ignoring emergent warning signs: Severe rash, systemic symptoms, or neuropsychiatric changes require immediate evaluation and possible discontinuation 4, 5