Can lithium worsen anxiety?

Does Lithium Worsen Anxiety?

No, lithium does not worsen anxiety and may actually help reduce anxiety symptoms, particularly in patients with bipolar disorder and comorbid anxiety disorders. 1

Evidence Supporting Lithium's Anxiolytic Effects

The available evidence demonstrates that lithium can be beneficial for anxiety rather than worsening it:

• In bipolar patients with comorbid anxiety disorders, adding a second mood stabilizer (olanzapine or lamotrigine) to lithium maintenance therapy significantly reduced anxiety symptoms as measured by the Hamilton Rating Scale for Anxiety, with both combinations showing statistical significance (p < .001). 1

• Lithium augmentation of tricyclic antidepressants has shown rapid and dramatic improvement in panic disorder resistant to antidepressant monotherapy, with symptom resolution occurring within 48-60 hours of lithium addition at therapeutic levels (0.8 mEq/L). 2

• Low-dose lithium significantly decreased anxiety by 65% (p < .001) in adults with depression and anxiety disorders, particularly in those with CACNA1C gene polymorphisms. 3

Important Caveats and Monitoring Considerations

While lithium itself does not worsen anxiety, certain clinical scenarios require attention:

• Lithium can contribute to serotonin syndrome when combined with serotonergic agents (trazodone, amitriptyline), which may present with anxiety, restlessness, tremor, and hyperreflexia—symptoms that could be mistaken for worsening anxiety. 4

• Lithium-induced akathisia or agitation from toxicity (levels >1.5 mEq/L) could be misinterpreted as worsening anxiety, emphasizing the need for regular serum level monitoring every 3-6 months once stable. 5, 6

• Baseline and ongoing monitoring should include thyroid function, as lithium-induced hypothyroidism could present with anxiety-like symptoms. 5

Clinical Application Algorithm

For patients with bipolar disorder and anxiety:

• Lithium should be the first-line mood stabilizer before adding antidepressants. 7
• If anxiety persists on lithium monotherapy, consider augmentation with lamotrigine or olanzapine. 1

For patients with treatment-resistant panic disorder:

• Consider lithium augmentation (600-900 mg/day, targeting 0.6-1.0 mEq/L) if tricyclic antidepressants alone are ineffective. 2

Monitoring requirements:

• Check lithium levels twice weekly during acute phase until stabilized. 6
• Monitor for signs of toxicity (confusion, tremor, ataxia) that could mimic anxiety. 6
• Avoid NSAIDs and ensure adequate hydration to prevent toxicity. 6