FLORENCE, Italy — Patients with severe mental disorders are more likely to have altered thyroid function, which may in part be linked to the use of commonly prescribed antipsychotic agents, new research suggests.

A study of 2300 participants showed that those with severe mental disorders were three times more likely to have hypothyroidism and twice as likely to have hyperthyroidism compared to healthy control persons.

Moreover, the findings indicated that the use of antipsychotics, in particular, olanzapine (Zyprexa, Lilly) and quetiapine (Seroquel, AstraZeneca), was associated with significantly lower plasma levels of free thyroxin (fT4).

According to investigators led by Trude Seselie Jahr Iversen, PhD, University of Oslo and Oslo University Hospital, Norway, the findings indicate a notable prevalence of undetected deviant thyroid function in the patient population and that "the use of commonly prescribed antipsychotics may contribute to the lower fT4 observed in these patients."

The findings, said Dr Iversen, warrant "renewed attention to the role of thyroid function in severe mental disorders and the association with antipsychotic drugs."

The findings were presented here at the Schizophrenia International Research Society (SIRS) 2018 Biennial Meeting.

Thyroid Testing Warranted?

Although altered hypothalamic-pituitary-thyroid axis function is linked to severe mental disorders and, in turn, may be affected by their medical treatments, the association between antipsychotic drug use and thyroid function has not been systematically investigated.

The researchers studied 1345 patients with schizophrenia or bipolar spectrum disorders and 989 healthy control persons from an ongoing study of individuals aged 18 to 65 years living in and around Oslo.

All patients underwent diagnostic evaluation, somatic screening, and assessment of medication data. Plasma levels of fT4 and thyroid-stimulating hormone (TSH) were measured in both patients and control participants. This led to the exclusion of 28 individuals with known thyroid function disorders.

Although the proportion of women in the patient and control groups was similar, at 47%, the patients were significantly younger than the healthy control persons, at median of 29.0 years vs 33.0 years.

Adjusting for patient/control status, age, sex, and use of other psychopharmacologic agents, the team found that patients had significantly higher TSH levels than control persons, at a median of 1.92 mIU/L vs 1.57 mIU/L (P < .001).

In contrast, patients had significantly lower median fT4 levels than control persons, at 13.70 pmol/L vs 14.00 pmol/L (P < .001).

Compared to control participants, patients were also more likely to be in a hypothyroid state (10.7% vs 3.3%) or in a hyperthyroid state (2.2% vs 1.2%; P < .001 for trend).

Further analysis revealed that the use of antipsychotics was significantly associated with reduced fT4 levels (P = .001), but not with TSH levels (P = .157).

In addition, female sex and increasing age were associated with lower levels of both fT4 and TSH (P < .001 for all). Being a patient was associated with significantly higher TSH levels (P < .001), and there was a trend for higher fT4 levels (P = .066).

The team also examined associations between thyroid function and use of olanzapine, quetiapine, aripiprazole (Abilify, Otsuka), and risperidone (Risperdal, Janssen) monotherapy in a subset of 480 patients.

Adjusting for age, sex, and diagnosis, they found that current olanzapine monotherapy was significantly associated with lower fT4 levels (P = .018), as was current quetiapine use (P = .005). Moreover, the dose of quetiapine was negatively correlated with fT4 levels (P = .004).

Speaking to Medscape Medical News, Iversen said that on the basis of these findings, it is "not unreasonable" to include thyroid function testing "as part of the package for examining" patients with severe mental disorders.

However, she pointed out that the differences between patients and control persons were "rather small," and so the study has potentially greater relevance in terms of its implications for the prodromal mechanisms, in addition to the association with current symptoms.

Nevertheless, she noted that patients with severe mental disorders are "not the best to seek medical attention, so perhaps adding thyroid hormones to the general examination is not a bad idea."

"Profound" Long-term Implications

Approached for comment, William T. Carpenter, MD, professor of psychiatry and pharmacology, University of Maryland School of Medicine, Baltimore, said, "There are numerous adverse metabolic effects which vary among antipsychotic drugs," and thyroid function may be one of them.

He told Medscape Medical News that such metabolic effects "begin early in treatment but are not experienced by the patient in the way that head pain, sedation or nausea, etc, are experienced and may lead to nonadherence, but the long-term implications are profound."

Because drug selection at the time of initiation is potentially "dominated by present symptoms and concern with future relapse, future metabolic effects need to be considered at the time of selecting and initiating treatment," he added.

However, he pointed out that the "high utilization of drugs with adverse metabolic profiles in the context of the availability of more benign choices suggests that the long-term consequences are not sufficiently taken into account by prescribing doctors."

Given that patients with severe mental disorders die about 25 years before the average life expectancy, "doctors need to have high concern for the metabolic effects of drugs," Carpenter said.

The research was supported by the Research Council of Norway, the South-East Regional Health Authority, and the KG Jensen Foundation. Dr Iversen has disclosed no relevant financial relationshiips. Other authors have received speaker's honoraria from Lundbeck and Lilly and institutional grants from AstraZeneca, Novo Nordisk, Sanofi, Lilly, Boehringer Ingelheim and Merck Sharp & Dohme.

Schizophrenia International Research Society (SIRS) 2018 Biennial Meeting. Poster T229, presented April 5, 2018.

For more Medscape Psychiatry news, join us on Facebook and Twitter.