How can I differentiate between Major Depressive Disorder (MDD) and bipolar disorder in a patient?

Differentiating Major Depressive Disorder from Bipolar Disorder

Screen all patients presenting with depression for bipolar disorder before initiating antidepressant treatment by obtaining a detailed psychiatric history including family history of bipolar disorder, suicide, age of depression onset, and prior manic/hypomanic symptoms, as treating undiagnosed bipolar disorder with antidepressants alone may precipitate manic episodes. 1, 2

Critical Screening Questions

History of Manic or Hypomanic Episodes:

• Ask specifically about distinct periods (≥7 days for mania, ≥4 days for hypomania) of abnormally elevated, expansive, or irritable mood that represented a marked departure from baseline functioning 3
• The mood disturbance must be observable by others and cause marked functional impairment or require hospitalization 3
• Symptoms must be evident across different realms of life (work, home, social settings), not just context-dependent 3

Key Distinguishing Symptoms During Mood Episodes:

• Mood elevation: Periods of feeling "up," euphoric, or unusually energized 4
• Decreased need for sleep: Feeling rested after only 2-3 hours of sleep (not just insomnia) 4
• Increased goal-directed activity or psychomotor agitation 3
• Grandiosity: Inflated self-esteem or unrealistic beliefs about abilities 3
• Increased talkativeness or pressured speech 5
• Racing thoughts or flight of ideas 3
• Increased risk-taking or impulsive behaviors 3

Demographic and Clinical Features Favoring Bipolar Disorder

Age and Course of Illness:

• Earlier age of depression onset (typically before age 25) suggests bipolar disorder over MDD 6, 7
• Multiple prior depressive episodes (≥3) increase likelihood of bipolar disorder 7
• Family history of bipolar disorder is a critical risk factor 1, 2

Associated Features:

• History of antidepressant-induced manic or hypomanic episodes counts toward bipolar diagnosis and is a specific risk factor 3, 1, 2
• Comorbid substance use disorders are more common and strongly linked to bipolar disorder, whereas comorbid anxiety disorders are more prevalent in MDD 6
• Psychotic features during mood episodes 6

Suicidality Risk Profile:

• Bipolar disorder carries substantially higher suicide risk than MDD, with lifetime suicide attempt prevalence of 29.2% in bipolar disorder versus 5.6% in MDD 6
• Patients with bipolar disorder have 8.66 times higher risk of suicidal behavior compared to general population 6

Validated Screening Tools

Rapid Mood Screener (RMS):

• A pragmatic 6-item tool specifically designed to differentiate bipolar I disorder from MDD in patients presenting with depression 4
• When 4 or more items are endorsed, sensitivity is 0.88 and specificity is 0.80 4
• Superior to the Mood Disorder Questionnaire while using 60% fewer items 4

Mood Disorder Questionnaire (MDQ):

• Widely used screening tool, though less efficient than the RMS 4

Common Diagnostic Pitfalls to Avoid

Non-Specific Symptoms:

• Irritability, reckless behaviors, and increased energy occur in multiple conditions and lack specificity for bipolar disorder 3
• Manic-like symptoms of irritability and emotional reactivity may be found in disruptive behavior disorders, PTSD, and pervasive developmental disorders 3
• Do not rely on simple checklists without considering longitudinal patterns and functional impairment 3

Inadequate Assessment:

• Failing to obtain collateral information from family members or other observers about longitudinal course of symptoms leads to misdiagnosis 3
• Not using a life chart to characterize the course of illness and identify patterns of mood episodes 3
• Overlooking that depressive episodes in bipolar disorder do not differ substantially in presentation from MDD episodes 8, 7

Clinical Algorithm for Assessment

1. Initial Screening: Ask about any history of periods with elevated mood, decreased need for sleep, increased energy, or impulsive behavior 4

2. If Positive Screen: Conduct detailed assessment of symptom duration (≥7 days for mania), functional impairment, and whether symptoms represented departure from baseline 3

3. Obtain Collateral History: Interview family members about observed mood changes and behavioral patterns over time 3

4. Document Course: Use a life chart to map mood episodes, treatment responses, and psychosocial stressors chronologically 3

5. Assess Risk Factors: Document age of depression onset, number of prior episodes, family psychiatric history, substance use, and prior antidepressant responses 1, 2, 5

Treatment Implications

Critical Distinction:

• Bipolar depression should be excluded from MDD treatment studies and protocols, as it is part of bipolar disorder requiring different treatment approaches 6
• Antidepressants have demonstrated little or no efficacy for depressive episodes in bipolar disorder and should only be used as adjunct to mood stabilizers 8
• Treating bipolar disorder with antidepressants alone may precipitate mixed or manic episodes 1, 2

Monitoring After Diagnosis:

• Both conditions require close monitoring for suicidality, especially during initial treatment and dose changes 1, 2
• Bipolar disorder requires longer periods of monitoring following hospital discharge due to higher suicide risk 6