What medication should be added for a 62-year-old woman on venlafaxine (Effexor) 75 mg who has insomnia, a decreased need for sleep, preserved energy, and restlessness?

Immediate Discontinuation of Venlafaxine and Initiation of Mood Stabilization

This patient is exhibiting classic symptoms of venlafaxine-induced hypomania/mania (decreased need for sleep with preserved energy and restlessness), and the appropriate medication to add is a mood stabilizer—not a sleep aid—while simultaneously tapering the venlafaxine.

Recognition of Antidepressant-Induced Mood Elevation

• The clinical presentation of decreased need for sleep (not insomnia) with preserved energy and restlessness in a patient recently started on venlafaxine 75 mg is pathognomonic for antidepressant-induced hypomania or emerging mania, not primary insomnia 1.
• True insomnia presents with difficulty sleeping accompanied by daytime fatigue and impaired functioning—this patient has preserved energy despite reduced sleep, which is a cardinal feature of mood elevation 1.
• Venlafaxine, as a serotonin-norepinephrine reuptake inhibitor (SNRI), carries significant risk for inducing manic switches, particularly at doses ≥75 mg 2, 3.

Immediate Management Algorithm

Step 1: Do NOT Add a Hypnotic Agent

• Adding a sleep medication (benzodiazepine, Z-drug, trazodone, or any sedating agent) to ongoing venlafaxine in this context is contraindicated because it fails to address the underlying mood destabilization and may worsen the manic syndrome 4, 2.
• The American Academy of Sleep Medicine explicitly recommends that insomnia persisting beyond 7–10 days of treatment requires evaluation for underlying causes, and antidepressant-induced mania is a critical differential that must be ruled out before prescribing hypnotics 1.

Step 2: Initiate Mood Stabilizer and Taper Venlafaxine

• Begin a mood stabilizer immediately (e.g., lithium, valproate, or lamotrigine depending on patient factors and psychiatric consultation) while simultaneously initiating a gradual taper of venlafaxine over 2–4 weeks to prevent withdrawal symptoms 4.
• Low-dose sedating antidepressants such as trazodone or mirtazapine carry a low risk of inducing mania when used at hypnotic doses (trazodone 25–50 mg, mirtazapine 7.5–15 mg) in patients already on mood stabilizers, but should NOT be used as monotherapy in this acute presentation 4.

Step 3: Short-Term Symptomatic Management (Only After Mood Stabilizer Initiation)

• If the patient requires immediate symptomatic relief of agitation or sleep disturbance after a mood stabilizer has been started, consider:
  • Low-dose quetiapine 25–50 mg at bedtime (not for insomnia per se, but for acute mood stabilization in the context of emerging mania) 5.
  • Lorazepam 0.5–1 mg PRN for severe agitation, recognizing this is a temporizing measure only 6.
• Do NOT use trazodone, mirtazapine, or any other sedating antidepressant as monotherapy without concurrent mood stabilization, as this may worsen the manic episode 4, 2.

Critical Pitfalls to Avoid

• Misinterpreting decreased need for sleep with preserved energy as primary insomnia and prescribing hypnotics (zolpidem, eszopiclone, doxepin, ramelteon) without recognizing the underlying mood elevation 1.
• Continuing venlafaxine while adding a sleep aid, which allows the manic process to progress unchecked and may lead to full-blown mania requiring hospitalization 4, 2.
• Using trazodone or mirtazapine without a mood stabilizer in a patient with emerging mania, as even low doses can exacerbate mood instability when used as monotherapy 4.

Evidence Supporting This Approach

• A prospective study of venlafaxine-treated depressed inpatients found that trazodone addition improved insomnia but did not address underlying inner tension/anxiety, suggesting that when sleep disturbance occurs with venlafaxine, the underlying cause (mood destabilization) must be treated first 2.
• Research on sleep-promoting antidepressants demonstrates that low doses of trazodone (25–50 mg) and mirtazapine (7.5–15 mg) are safe in bipolar disorder only when combined with a mood stabilizer, not as monotherapy 4.
• The American Academy of Sleep Medicine guidelines emphasize that persistent insomnia despite appropriate treatment warrants evaluation for underlying psychiatric conditions, including antidepressant-induced mood elevation 1.

Recommended Immediate Action Plan

1. Urgent psychiatric consultation to confirm diagnosis of venlafaxine-induced hypomania and initiate mood stabilizer 4.
2. Begin venlafaxine taper (reduce by 37.5 mg every 3–7 days) while starting mood stabilizer 2.
3. Avoid all hypnotic agents until mood stabilization is achieved 1, 4.
4. Consider low-dose quetiapine 25–50 mg at bedtime for acute symptom management only after mood stabilizer is on board 5.
5. Reassess in 3–5 days for response to mood stabilizer and resolution of sleep/energy symptoms 4.