A 28-year-old woman with bipolar disorder II presents with a depressive episode (PHQ-9 score 18) lasting 3 weeks. She has had two hypomanic episodes in the past year. She was previously on lithium but developed polyuria and hypothyroidism. What is the drug of choice for this bipolar II depressive episode?

Question

Accepted Answer

C. Lamotrigine. ## First-Line Treatment of Bipolar II Depressive Episode

**Key Point:** Lamotrigine is the first-line mood stabilizer for bipolar II depression and is the only anticonvulsant with evidence-based efficacy specifically for the depressive phase of bipolar disorder.

### Why Lamotrigine Is First-Line for Bipolar II Depression

1. **Mechanism**: Inhibits glutamate release; does NOT work for acute mania (unlike lithium or valproate)
2. **Efficacy**: 50–60% response rate in bipolar depression; superior to placebo in RCTs
3. **Safety in bipolar II**: No risk of mood destabilization or switch to hypomania (unlike SSRIs)
4. **Dosing**: Start 25 mg daily, titrate slowly to 100–200 mg daily (slow titration reduces rash risk)
5. **Maintenance**: Effective for preventing depressive relapse in bipolar II

### Bipolar II vs. Bipolar I: Treatment Differences

| Feature | Bipolar I | Bipolar II |
|---------|-----------|----------|
| **Mania severity** | Full mania (severe) | Hypomania only (mild–moderate) |
| **Depressive burden** | ~40% of episodes | ~70% of episodes |
| **First-line for depression** | Lithium, quetiapine | **Lamotrigine** |
| **SSRI risk** | High switch risk | Lower but still present |
| **Mood stabilizer choice** | Lithium, valproate | Lamotrigine, quetiapine |

**Clinical Pearl:** Bipolar II patients spend more time depressed than hypomanic, so antidepressant selection is critical. Lamotrigine's lack of manic switch risk makes it ideal for this population.

**High-Yield:** Lamotrigine is **ineffective for acute mania** but **excellent for bipolar depression and maintenance**. This is a frequent NEET PG trap — students confuse it with valproate or lithium.

**Mnemonic:** **LAM** = **L**amotrigine for **A**ffective (depressive) **M**ood in bipolar II.

### Why SSRIs Alone Are Contraindicated

- Risk of mood switch to hypomania/mania (10–30% in bipolar II)
- Must always be paired with a mood stabilizer if used
- Lamotrigine avoids this risk entirely

**Warning:** Sertraline monotherapy (option A) violates the cardinal rule: never use antidepressants alone in bipolar disorder without a mood stabilizer. The patient has already had hypomanic episodes, so SSRI monotherapy risks destabilization.

Answer

A. Fluoxetine with lithium

Answer

B. Bupropion

Answer

D. Sertraline monotherapy

Explanation

First-Line Treatment of Bipolar II Depressive Episode

Why Lamotrigine Is First-Line for Bipolar II Depression

Bipolar II vs. Bipolar I: Treatment Differences

Why SSRIs Alone Are Contraindicated

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Feature	Bipolar I	Bipolar II
Mania severity	Full mania (severe)	Hypomania only (mild–moderate)
Depressive burden	~40% of episodes	~70% of episodes
First-line for depression	Lithium, quetiapine	Lamotrigine
SSRI risk	High switch risk	Lower but still present
Mood stabilizer choice	Lithium, valproate	Lamotrigine, quetiapine