01 / 08

Polypharmacy in Treatment-Resistant Depression

Evidence-Based Strategies

02 / 08

TRD Scope

30%

of MDD patients have TRD

STAR*D: Remission drops from 37% → 16% after second trial

03 / 08

Augmentation Efficacy

StrategyResponse
Combination Antidepressants45%
Aripiprazole44%
Quetiapine42%
Lithium40%
Switching19%
04 / 08

CYP450 Interactions

DrugCYP2D6Risk
ParoxetineStrongHigh
FluoxetineStrongHigh
EscitalopramMinimalLow

⚠️ Paroxetine + Aripiprazole = 3-4x antipsychotic levels

05 / 08

Lithium Monitoring

Target Levels: 0.6-0.8 mmol/L (maintenance)

Renal: Baseline + ongoing creatinine, BUN, eGFR

Thyroid: TSH/T4 at baseline, 3mo, then q6mo

06 / 08

Serotonin Syndrome

Hunter Criteria (84% sensitive, 97% specific)

• Spontaneous clonus

• Inducible clonus + agitation/diaphoresis

• Tremor + hyperreflexia

• Hypertonia + temp >38°C + clonus

07 / 08

Maudsley De-prescribing 2024

MedicationTaper
SSRI/SNRI10% every 2-4 weeks
Benzodiazepines25% every 1-2 weeks
Antipsychotics10-25% every 2-4 weeks
08 / 08

Key Takeaways

1. Augmentation beats switching (45% vs 19%)

2. Screen CYP450 interactions

3. Know Hunter Criteria for serotonin syndrome

4. Use hyperbolic tapering (Maudsley)

01 / 08