What is the recommended treatment for a patient with stabilized mood on Lithium (lithium carbonate) 600 mg daily who is experiencing increased anxiety?

Management of Increased Anxiety in a Patient Stabilized on Lithium

For a patient with stabilized mood on lithium 600 mg daily who develops increased anxiety, first rule out lithium-induced hypothyroidism and ensure therapeutic lithium levels are appropriate (0.2-0.6 mEq/L for maintenance), then add either buspirone for mild-to-moderate anxiety or consider augmentation with an SSRI (particularly sertraline) or a benzodiazepine for more severe symptoms. 1, 2

Initial Assessment and Monitoring

Before adding any anxiolytic medication, critical evaluation steps include:

• Check thyroid function immediately, as lithium-induced hypothyroidism commonly presents with anxiety-like symptoms and could be the underlying cause of new-onset anxiety 2, 3
• Verify current lithium levels to ensure they remain in the therapeutic range of 0.2-0.6 mEq/L, as levels outside this range could contribute to anxiety symptoms 1, 3
• Assess for signs of lithium toxicity (confusion, tremor, ataxia) that could mimic anxiety 2
• Review medication adherence and hydration status, as well as any new NSAID use that could alter lithium levels 2

Pharmacological Treatment Options

First-Line: Buspirone for Mild-to-Moderate Anxiety

• Start buspirone 5 mg twice daily, which can be increased to a maximum of 20 mg three times daily 1
• Buspirone is particularly useful for mild-to-moderate agitation and anxiety in patients already on mood stabilizers 1
• Important caveat: Buspirone requires 2-4 weeks to become effective, so patients need counseling about delayed onset 1
• This option avoids benzodiazepine dependence risk and has no significant drug interactions with lithium 1

Alternative: SSRI Augmentation

If anxiety is more severe or accompanied by depressive features:

• Sertraline is preferred among SSRIs due to fewer effects on metabolism of other medications, starting at 25-50 mg daily up to 200 mg daily 1
• Citalopram (10-40 mg daily) is also well-tolerated with some patients experiencing initial nausea and sleep disturbances 1
• Monitor closely for serotonin syndrome within the first 24-48 hours after initiation, watching for mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity 4
• Lithium at current dose (600 mg) can effectively augment antidepressant therapy at blood levels of 0.2-0.6 mEq/L 4

Benzodiazepines for Acute or Severe Anxiety

When immediate relief is needed:

• Lorazepam, oxazepam, or temazepam are preferred as they have short half-lives and are least problematic in terms of accumulation 1
• Alprazolam 0.25-0.5 mg orally three times daily can be used, though elderly patients should start at 0.25 mg two or three times daily 1
• Benzodiazepines should be gradually reduced when decreasing or discontinuing therapy 1
• Critical warning: Elderly patients are especially sensitive to benzodiazepine effects 1

Evidence-Based Augmentation Strategies

Research supports specific augmentation approaches:

• Adding olanzapine (5-10 mg/day) or lamotrigine (50-200 mg/day) to lithium has demonstrated efficacy in reducing anxiety symptoms in bipolar patients with comorbid anxiety disorders, with both showing significant HAM-A score reductions 5
• Low-dose lithium augmentation (300-450 mg/day) achieving plasma levels around 0.33 mEq/L has shown effectiveness with minimal side effects, though your patient is already at 600 mg 6

Monitoring Requirements

Ongoing surveillance should include:

• Lithium levels every 3-6 months once stable, with thyroid function, renal function (BUN, creatinine), and urinalysis at the same intervals 3
• More frequent monitoring initially when adding new medications, particularly serotonergic agents 4
• Assessment for medication interactions, especially if NSAIDs or other drugs affecting lithium clearance are introduced 2

Common Pitfalls to Avoid

• Do not assume anxiety is purely psychiatric without ruling out lithium-induced thyroid dysfunction first 2
• Avoid abrupt lithium discontinuation, as withdrawal increases relapse risk dramatically (>90% in noncompliant patients versus 37.5% in compliant patients) 3
• Do not combine multiple serotonergic agents without careful monitoring for serotonin syndrome 4
• Ensure adequate hydration and avoid NSAIDs to prevent lithium toxicity that could worsen anxiety symptoms 2