What is the best approach to manage a middle-aged adult patient with a history of major depressive disorder (MDD) and potential co-occurring medical or psychiatric conditions?

Psychopathology and Clinical Interview in Major Depressive Disorder

Diagnostic Criteria and Assessment

MDD diagnosis requires at least 5 symptoms present during a 2-week period, with at least one being either depressed mood or anhedonia (loss of interest/pleasure). 1

Core Diagnostic Symptoms

• Depressed mood or anhedonia must be present as one of the five required symptoms 1, 2
• Additional symptoms include: insomnia or hypersomnia, psychomotor agitation or retardation, fatigue or loss of energy, feelings of worthlessness or excessive guilt, poor concentration or indecisiveness, significant weight changes or appetite disturbance, and recurrent thoughts of death or suicidal ideation 1, 2
• Symptoms must cause clinically significant distress or functional impairment in social, occupational, or other important areas 1

Structured Diagnostic Interviews

• Use the Mini International Neuropsychiatric Interview or Structured Clinical Interview based on DSM-5 criteria for formal diagnosis 1
• These structured tools provide systematic assessment and reduce diagnostic variability compared to unstructured clinical interviews 1

Severity Assessment Tools

Begin monitoring with validated instruments at baseline and continue at regular intervals throughout treatment. 1, 3

Primary Assessment Instruments

• Patient Health Questionnaire-9 (PHQ-9) is recommended for both screening and monitoring treatment response 1, 2
• Hamilton Depression Rating Scale (HAM-D) provides clinician-rated assessment of depression severity 1
• Montgomery-Åsberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) are alternative validated tools for assessing severity 1
• Treatment response is defined as ≥50% reduction in severity scores on these validated instruments 1

Critical Psychopathological Features to Assess

Suicidality Assessment

• All patients must be monitored for suicidal ideation, plans, and intent at every visit, especially during the first 1-2 weeks of treatment initiation or dose changes 3, 4
• Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (ages 18-24) with MDD 4
• Screen for recurrent thoughts of death, suicidal ideation, specific plans, previous attempts, and access to lethal means 4

Bipolar Disorder Screening

• Prior to initiating antidepressant treatment, conduct detailed psychiatric history to screen for bipolar disorder risk 4
• Obtain family history of suicide, bipolar disorder, and depression 4
• A major depressive episode may be the initial presentation of bipolar disorder, and treating with antidepressants alone may precipitate manic/mixed episodes 4

Warning Signs of Clinical Worsening

• Monitor for anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania 4
• These symptoms may represent precursors to emerging suicidality or worsening depression 4
• Families and caregivers should be educated to monitor for these symptoms and report them immediately 4

Comorbidity Assessment

Co-occurring Psychiatric Conditions

• Screen for comorbid anxiety disorders, as patients with both conditions experience more chronic illness course, increased suicidal thoughts, and greater functional impairment 5
• Assess for accompanying symptoms including insomnia, low energy, and somatization 6
• Evaluate for substance use disorders, which are common in untreated depression 7

Medical Comorbidities

• Consider laboratory tests to assess for significant medical comorbidities, differential diagnoses, or contraindications to treatment 2
• Rule out secondary depression attributable to other medical illnesses or medications 8

Severity Classification for Treatment Planning

Severity classification guides initial treatment selection and is based on symptom count, intensity, and degree of functional impairment. 1

Mild Depression

• Consider starting with cognitive behavioral therapy (CBT) alone, as it has equivalent effectiveness to antidepressants 1
• Complementary and alternative medicine options (acupuncture, meditation, omega-3 fatty acids, SAMe, St. John's wort) may be considered 5

Moderate to Severe Depression

• Initiate second-generation antidepressants (SSRIs or SNRIs) selected based on adverse effect profiles, cost, and patient preferences 1
• CBT or second-generation antidepressants are both strongly recommended as first-line treatments with similar effectiveness 6, 1

Severe Depression with High-Risk Features

• Classify as severe regardless of symptom count and initiate antidepressants immediately with close monitoring 1
• Consider combination therapy (medication plus psychotherapy) for improved response rates 5

Monitoring Timeline and Treatment Response

Initial Monitoring Phase

• Begin monitoring within 1-2 weeks of treatment initiation, focusing on suicidality, agitation, irritability, and unusual behavioral changes 3
• Assess for therapeutic effects, adverse effects, and treatment adherence 3

Response Assessment

• Evaluate treatment response at 6-8 weeks; if inadequate, modify treatment through dose adjustment, switching agents, or adding augmentation strategies 1, 3
• An adequate trial requires sufficient dose and duration (minimum 4 weeks) 1

Treatment Duration

• Continue treatment for 4-9 months after satisfactory response for first episodes 1, 3
• For patients with 2 or more depressive episodes, consider years to lifelong maintenance therapy 3
• Longer duration (≥1 year) is beneficial for recurrent episodes 1

Common Pitfalls to Avoid

• Inadequate dosing or premature discontinuation before therapeutic effects are achieved (typically 4-6 weeks) 1
• Failure to continue treatment long enough to prevent relapse (minimum 4-9 months after response) 1
• Not screening for bipolar disorder before initiating antidepressants 4
• Insufficient monitoring for suicidality, especially during the initial treatment period and after dose changes 3, 4
• Failing to educate families and caregivers about warning signs of clinical worsening 4
• Abrupt discontinuation of antidepressants without proper tapering 4