STARD Phase 3- Mirtazapine vs Nortiptyline

PICO question: In adult patients with nonpsychotic depression (P) not alleviated by treatment with two consecutive antidepressants, does switching to a third agent (I) affect remission rates (O). No control (C)
Citation: AJP 2006: 163:7 1161-1172, Fava et al., “A Comparison of Mirtazapine and Nortriptyline Following Two Consecutive Failed Medication Treatments for Depressed Outpatients: A STAR*D Report.”

Design: Phase 3 STAR*D prospective sequentially randomized control trial
Follow up period: 2,4,6,9, and 12 weeks
Setting:. Adult outpatients from multiple sites (18 primary care and 23 psychiatric) with nonpsychotic depression nonremitted on initial citalopram monotherapy and subsequent medication augmentation (buproprion or buspirone) or switch to second agent montherapy (buproprion, sertraline, or venlafaxine).
Participants: Inclusion Criteria: 18-75 y/o, Primary nonpsychotic MDD (HAM-D>14) Exclusion Criteria: Bipolar or psychotic d/o, OCD or eating disorders, medical contraindications, substance dependence requiring inpatient detox, non-response or inability to tolerate treatment during first two steps, pregnant/breastfeeding
Intervention: First Arm-Mirtazapine up to 60 mg daily; Second Arm-Nortriptyline up to 200 mg daily (dosing recommendations were flexible for both arms)
Outcome measures:
Primary: Remission defined as HRSD <7
Secondary: Remission defined as QIDS-SR <5 and Response defined as a >50% reduction from QIDS-SR Level 3 baseline score

Results: No statistically significant difference.
HRSD-17 Remission Rates: Mirtazapine (12.3%) vs Nortriptyline (19.8%)
QIDS-SR-16 Remission Rates: Mirtazapine (8.0%) vs Nortriptyline (12.4%)
QIDS-SR-16 Response Rates: Mirtazapine (13.4%) vs Nortriptyline (16.5%)
Mean Time to Remission: Mirtazapine (5.7wks) vs Nortriptyline (6.3 wks)

Strengths: Real world trial, Good generalizability, Largest sample size yet for this type of study, Clinically significant: remission as the primary outcome
Weaknesses: No control, Nonmasked treatment delivery, Small sample.

Validity Crtieria

Was follow up adequate? Yes
Were the participants randomized? Yes
Was allocation concealed? N/A
Intention to treat? Yes
Were the groups similar at baseline? Yes
Were pts, MDs and analysts blinded? No
Were the groups treated equally? Yes
Was there an a priori hypothesis? Yes
Were the outcome clearly defined? Yes
Did they use validated measurements? Yes
Was the placebo/control appropriate? N/A
Were side effects discussed? Yes
Is the effect clinically important? Yes
Is this congruent with existing studies? No
Is this feasible in your setting? Yes
Were the investigators independent? +/-
Will this change your current practice? No


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