⚡ Advanced Psychiatric Interventions

Treatment-Resistant Depression: Pharmacology and Neuromodulation

General Psychiatry Topic 19

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📊 The TRD Challenge

50% fail to achieve remission with first-line antidepressants

Probability of remission drops with each failed trial
Paradigm shift: Augmentation > Switching
Device-based therapies earlier in trajectory

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🎯 Staging Model

Stage	Failure	Action
I	1 trial	Optimize, assess adherence
II (TRD)	2 trials	Augment; consider TMS
III	Augmentation	Combination; neuromodulation
IV	Neuromodulation	VNS; ECT
V	ECT	MST, DBS, trials

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💊 Augmentation Strategies

Lithium (Gold Standard)

OR 2.34-3.31; NNT ~5
Anti-suicidal: 60-70% ↓ risk
Target: 0.4-0.8 mEq/L

Atypical Antipsychotics

Aripiprazole: Anhedonia
Quetiapine: Anxiety/insomnia
Brexpiprazole: Lower akathisia

California Rocket Fuel: Venlafaxine + Mirtazapine for deep resistance

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🧠 Neuromodulation

Modality	Protocol	Remission
Standard TMS	4-6 weeks	~30%
SAINT/SNT	5 days (50 sessions)	~79%
ECT (Ultrabrief)	RUL preferred	Highest efficacy

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⚠️ Safety: MAOI Washout

CRITICAL: Fluoxetine requires 5-WEEK washout before MAOI (norfluoxetine t½ 7-15 days)

Other SSRIs/SNRIs: 2-week washout
Irreversible MAOIs: 2-week washout before serotonergic agents
Serotonin syndrome: Clonus + agitation/hyperthermia/hypertonia

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