What is the effect of antipsychotics on thyroid function tests?

Effect of Antipsychotics on Thyroid Function Tests

Yes, antipsychotics do affect thyroid function tests, with the most clinically significant effect being dose-related decreases in thyroid hormone levels (particularly T4), though TSH elevations requiring treatment occur less commonly. 1, 2

Mechanism and Pattern of Thyroid Effects

Antipsychotics interfere with thyroid function through multiple mechanisms depending on drug class:

• Phenothiazines (typical antipsychotics) alter iodine capture, complex and deactivate iodine, and decrease TSH response to TRH 2
• Non-phenothiazine typical antipsychotics can induce thyroid autoantibody formation and elevate TSH levels 2
• Atypical antipsychotics may decrease TRH-stimulated TSH response 2

Specific Antipsychotic Effects

Quetiapine

Quetiapine causes the most well-documented thyroid effects among atypical antipsychotics:

• Produces dose-related decreases in total and free T4 of approximately 20% at higher therapeutic doses, maximal within the first 6 weeks of treatment 1
• In clinical trials, 3.4% of quetiapine patients had shifts to low total T4 versus 0.6% on placebo 1
• TSH elevations occur in approximately 3.2% of quetiapine patients versus 2.7% on placebo 1
• The mechanism appears related to competitive metabolism of thyroid hormones and quetiapine by UDP-glucuronosyltransferase 3
• Effects reverse upon cessation of treatment regardless of treatment duration 1

Olanzapine

• Associated with lower fT4 levels in naturalistic studies (p=0.018) 4
• Particularly problematic when used in polypharmacy with other psychotropic drugs 4

Risperidone and Aripiprazole

• Less pronounced effects on thyroid function compared to quetiapine and olanzapine 3, 4

Clinical Significance and Monitoring

Baseline and Follow-up Testing

Both TSH and free T4 should be measured together, as TSH alone may not accurately reflect thyroid status when antipsychotics affect the hypothalamic-pituitary axis: 1

• Measure TSH and free T4 at baseline before initiating antipsychotic treatment 5, 1
• Recheck at 6 weeks (when quetiapine effects are maximal) 1
• Monitor every 3-6 months during ongoing treatment 5
• Check more frequently if symptoms develop or in patients with pre-existing thyroid antibodies 5

Pediatric Considerations

In children and adolescents treated with antipsychotics:

• 2.9% developed elevated TSH versus 0.7% on placebo 1
• 2.8% had decreased total thyroxine versus 0% on placebo 1
• One patient had simultaneous low free T4 with elevated TSH at end of treatment 1

High-Risk Populations Requiring Closer Monitoring

Patients requiring intensified thyroid monitoring include: 2, 6

• Those with history of thyroid disease or prior thyroid treatment
• Patients receiving phenothiazines, quetiapine, or olanzapine 2, 4
• Those on antipsychotic polypharmacy, especially combined with antidepressants (p<0.001 for lower fT4) 4
• Patients with pre-existing thyroid autoantibodies 5

Treatment Implications

When to Initiate Thyroid Replacement

• TSH >5 mIU/L with low free T4 warrants consideration of levothyroxine 1
• About 0.7% of quetiapine patients require thyroid hormone replacement 1
• In mania adjunct studies, 3 of 24 quetiapine patients with elevated TSH had simultaneous low free T4 requiring treatment 1

Important Caveats

Avoid testing during acute psychiatric decompensation or metabolic instability, as results may be misleading due to euthyroid sick syndrome: 5, 7, 8

• If tests are performed during acute illness and show abnormalities, repeat after metabolic stabilization 7, 8
• Most patients with T4 decreases on quetiapine remain clinically euthyroid and asymptomatic 3
• Routine monitoring in patients without thyroid disease history taking quetiapine alone is not recommended, but monitoring is warranted for those with risk factors 3

Prevalence of Baseline Thyroid Abnormalities

Patients with schizophrenia have high baseline rates of thyroid dysfunction independent of medication:

• 18% had abnormal T3 resin uptake, 13% had abnormal TSH, and 9% had abnormal total T4 at baseline before treatment 3
• 12.9% of patients with severe mental disorders had previously undiagnosed deviant thyroid states 4