A 52-year-old man with a 6-month history of Major Depressive Disorder was started on sertraline 50 mg daily 8 weeks ago. He reports modest improvement in mood and sleep but persistent anhedonia, fatigue, and concentration difficulties. He denies suicidal ideation. His current sertraline level is therapeutic. What is the most appropriate next step in management?

## Management of Partial Response to Antidepressant Therapy **Key Point:** This patient shows partial response (some mood improvement, persistent neurovegetative and cognitive symptoms) at 8 weeks on a subtherapeutic dose. Dose optimization is the first step before switching or augmentation. ### Treatment-Response Algorithm ```mermaid flowchart TD A[SSRI at standard dose for 4-6 weeks]:::action --> B{Response?}:::decision B -->|Full remission| C[Continue, monitor]:::outcome B -->|Partial response| D[Increase dose or optimize]:::action B -->|No response| E[Switch or augment]:::action D --> F[Reassess at 2-4 weeks]:::action F --> G{Remission?}:::decision G -->|Yes| C G -->|No| H[Switch SSRI/SNRI or augment]:::action E --> I[Switch to SNRI/TCA or add augmentation agent]:::action ``` ### Dose Optimization in This Case **High-Yield:** Sertraline 50 mg is a **starting dose**, not a therapeutic dose. Standard therapeutic dosing is 50–200 mg daily; most patients require 100 mg or higher for full response. | Antidepressant | Starting Dose | Therapeutic Range | Max Dose | |---|---|---|---| | Sertraline | 50 mg | 100–200 mg | 200 mg | | Fluoxetine | 20 mg | 20–40 mg | 80 mg | | Escitalopram | 10 mg | 20 mg | 20 mg | | Venlafaxine | 75 mg | 150–300 mg | 375 mg | | Paroxetine | 20 mg | 40–60 mg | 60 mg | ### Why Increase Sertraline to 100 mg? 1. **Dose-response relationship:** Sertraline shows dose-dependent efficacy; 50 mg is insufficient for many patients. Increasing to 100 mg (within therapeutic range) is standard practice. 2. **Timing:** 8 weeks is adequate time to assess response at the current dose; dose escalation is now appropriate. 3. **Partial response pattern:** Mood improvement suggests serotonergic activity; persistent anhedonia and fatigue may respond to higher dose or addition of noradrenergic activity. 4. **Guidelines:** APA, NICE, and RANZCP recommend dose optimization before switching or augmentation in partial responders. **Clinical Pearl:** The "dose titration window" is typically 4–6 weeks at each dose level. If no improvement after 8–12 weeks at therapeutic dose, then consider switching or augmentation. ### Why Not the Other Options? **Option 1 (Switch to venlafaxine):** Premature. Venlafaxine is a SNRI (serotonin + norepinephrine reuptake inhibitor) and is appropriate for SSRI non-responders or those with specific symptom profiles (e.g., fatigue, pain). However, this patient is a partial responder at a subtherapeutic SSRI dose; optimization should precede switching. **Option 2 (Add aripiprazole):** Augmentation is appropriate for treatment-resistant depression (TRD, defined as failure of ≥2 adequate antidepressant trials). This patient has had only one inadequate trial (subtherapeutic dose). Aripiprazole is FDA-approved for MDD augmentation but is premature here. **Option 3 (Refer for ECT):** Electroconvulsive therapy is reserved for severe, psychotic, or treatment-resistant depression with imminent suicide risk, catatonia, or failure of multiple medication trials. This patient is not acutely suicidal and has not exhausted pharmacotherapy options. **Mnemonic:** **DOSE FIRST, SWITCH SECOND, AUGMENT THIRD** — Optimize dose → wait 4–6 weeks → if still partial, switch class → if still no response, augment with atypical antipsychotic or lithium.