What is the drug of choice for treating mood swings and anxiety in a patient with hypothyroidism?

Treatment of Mood Swings and Anxiety in Hypothyroidism

The first priority is optimizing levothyroxine therapy to achieve euthyroidism, as inadequate thyroid replacement is the primary driver of mood symptoms in hypothyroid patients; if anxiety and mood swings persist despite normalized TSH levels, consider adding selective serotonin reuptake inhibitors (SSRIs) as first-line psychiatric treatment, with beta-blockers reserved for acute somatic anxiety symptoms. 1, 2

Step 1: Optimize Thyroid Hormone Replacement

Ensure adequate levothyroxine dosing first, as this addresses the root cause of mood disturbances in hypothyroidism:

• Target TSH levels between 0.5-2.0 mIU/L (not just within the broad normal range of 0.4-4.0 mIU/L), as patients often require optimization toward the lower end for symptom resolution 3
• Monitor TSH 6-8 weeks after any dose adjustment, then annually once stable 1
• Standard levothyroxine dosing is 1.6 µg/kg/day for most adults, but start lower (25-50 µg/day) in elderly patients or those with cardiac disease 4, 3

Critical pitfall: Up to one-third of levothyroxine-treated hypothyroid patients continue experiencing mood symptoms despite biochemically adequate replacement, indicating that thyroid optimization alone may be insufficient 2, 4

Step 2: Recognize the Bidirectional Thyroid-Anxiety Relationship

The connection between thyroid dysfunction and anxiety is well-established:

• Patients with anxiety disorders have significantly higher rates of comorbid thyroid disorders, and this relationship exists independent of depression 5
• Thyroid hormone receptors are widely expressed throughout the limbic system, directly affecting mood regulation pathways 5, 6
• Hypothyroid patients demonstrate blunted TSH responses to TRH stimulation, suggesting subtle HPT axis dysfunction contributes to anxiety symptoms even when baseline thyroid levels appear normal 5

Step 3: Address Persistent Mood Symptoms After Thyroid Optimization

If anxiety and mood swings persist despite achieving target TSH levels:

First-Line Psychiatric Treatment

• SSRIs remain the standard first-line treatment for anxiety and mood symptoms in hypothyroid patients with normalized thyroid function 2
• Evidence shows that levothyroxine-treated hypothyroid women have 2.08 times higher odds of anxiety and 3.13 times higher odds of depression compared to controls, indicating need for concurrent psychiatric management 2

Adjunctive Thyroid Strategies

• Consider adding T3 (triiodothyronine) to levothyroxine regimen in treatment-resistant cases, as some evidence suggests depression related to hypothyroidism may respond better to combination therapy than T4 monotherapy alone 7
• T3 augmentation has shown efficacy in treatment-resistant depression, though this remains somewhat controversial and should be reserved for cases unresponsive to standard approaches 7

Beta-Blockers for Somatic Anxiety

• Use beta-blockers specifically for peripheral manifestations of anxiety (palpitations, tremor, tachycardia) rather than as primary anxiolytic agents 6
• This is particularly relevant if there's any component of subclinical hyperthyroidism or thyroid hormone over-replacement contributing to symptoms 6

Step 4: Rule Out Over-Replacement

Avoid iatrogenic hyperthyroidism, which paradoxically worsens anxiety:

• Over-replacement with levothyroxine is common in clinical practice and increases risk of atrial fibrillation and osteoporosis 3
• Hyperthyroidism causes anxiety-like symptoms including nervousness, restlessness, palpitations, and increased perspiration that overlap with primary anxiety disorders 6
• Check for signs of over-treatment: suppressed TSH, elevated free T4, or symptoms of hyperthyroidism 6, 3

Key Clinical Considerations

Screen for confounding factors that may impair levothyroxine absorption:

• Poor medication compliance
• Malabsorption syndromes
• Drug interactions (calcium, iron, proton pump inhibitors taken concurrently)
• These factors lead to persistently elevated TSH despite apparently adequate dosing 3

Monitor comprehensively:

• Thyroid function tests every 6-8 weeks during dose adjustments 1
• Assess both psychiatric symptoms and thyroid parameters together, as they are interconnected 5, 2
• Consider that mood symptoms may precede overt thyroid dysfunction, so ongoing monitoring is essential even after achieving euthyroidism 5