Hyperprolactinemia vs. Thyroid Autoimmunity: Which is a Greater Concern with Atypical Antipsychotics?
Authors: Mandal Sweta , Chowdhury Subhankar , Saha Pradip Kumar , Chowdhury Jyothi 
Published: October 2024

Introduction: Atypical antipsychotics (AAPs) are often prescribed to patients with psychosis, but they have become stigmatized due to their association with hyperprolactinemia. It is known that the prolactin (PRL) response to olanzapine is weaker than that to risperidone. However, there are confounding results regarding PRL response to treatment duration and drug dose. Additionally, there is limited information about the impact of AAPs on thyroid function. Aim: Our objectives are threefold: first, to observe how two different AAPs (olanzapine and risperidone) affect prolactin levels and thyroid function; second, to determine the impact of AAP-induced thyroid autoimmunity on thyroid function; and third, to investigate any correlation between thyroid autoimmunity and hyperprolactinemia.
Methodology: A longitudinal cohort study was conducted between 2 groups of drug-naive patients (18 - 45 years); one group (55 patients) received olanzapine monotherapy, and the other group (54 patients) received risperidone monotherapy. Hormone levels (PRL, thyroid stimulating hormone (TSH), free T4 (FT4), total T3 (TT3)) and anti-thyroid peroxidase (anti-TPO) antibody level were assessed at baseline, and then again after one month and three months of treatment. Patients were selected from the psychiatry outpatient department with their consent. Patients with chronic illnesses, pregnant or lactating women, those on Lithium therapy, and individuals taking oral contraceptives, high doses of SSRI (selective serotonin reuptake inhibitor), TCA (tricyclic antidepressant), or any medication known to cause hyperprolactinemia were excluded from the study.
Results: The PRL levels in the risperidone group significantly changed over time (p < 0.001); there is an overall increase from baseline to the 3-month time point. A detailed analysis showed a statistically significant increase (p < 0.001) from baseline to the 1-month time point, whereas a statistically significant decrease (p = 0.007) from the 1-month time point to the 3-month time point of risperidone treatment. Furthermore, 24.1% of patients had hyperprolactinemia at baseline, 63% at one month, and 44.4% at three months in the risperidone group. In contrast, there was no statistically significant change in PRL levels in the olanzapine group (although the number of patients with hyperprolactinemia increased over time; 23.6% of patients at baseline, 23.6% at one month, and 40% at three months). The relationships between hyperprolactinemia with drug dose and BMI could not be determined in either group. In both groups, the number of patients with positive anti-TPO antibodies increased over time. However, no association was found with hyperprolactinemia. A numerical increase in hypothyroidism was observed in both groups, though it did not reach a significant level during the 3-month study period (p = 0.108 in the olanzapine group and p = 0.717 in the risperidone group).
Conclusion: The risperidone group showed a relatively low rise in PRL levels, and some of them displayed reversibility. This reversibility of hyperprolactinemia may be explained by the upregulation of D2 receptors in the TIDA (tubero-infundibular dopamine neuron) system. On the other hand, olanzapine did not (significantly) increase PRL levels over three months. Furthermore, the PRL response to AAPs is not related to drug dose or BMI changes.
AAPs may trigger thyroid autoimmunity. The drug itself, regardless of hyperprolactinemia, could be the potential cause of this thyroid autoimmunity by altering the function of different immune cells. Furthermore, research also suggests that AAPs may alter the peripheral levels of pro-inflammatory, anti-inflammatory, and growth factor molecules, or may induce class II major histocompatibility complex antigens, like the typical antipsychotic phenothiazines.