TSH and PRL, side-effect markers in aripiprazole treatment: adjunctive aripiprazole-induced thyrotropin oversuppression in a young man with schizophrenia

Abstract

A 26-year-old Japanese man was admitted to our unit with exacerbated paranoid schizophrenia. Prior to his admission, daily administration of olanzapine had been sufficient to maintain a partial remission of his schizophrenia, but due to an exacerbation of his delusions, he had then also been prescribed aripiprazole, which had been followed by no improvement in symptoms and a gradual further exacerbation of auditory delusions. Physical examinations, brain MRI and neurophysiological assessment were unremarkable. Blood analysis, however, revealed extremely low thyroid-stimulating hormone (TSH) and prolactin-releasing hormone (PRL) concentration. Interestingly, after aripiprazole discontinuation, he returned to partial remission with an increase in plasma TSH and PRL concentration.

Abnormally low prolactin levels in schizophrenia patients after switching to aripiprazole in a randomized trial: a biomarker for rebound in psychotic symptoms?

“…As an exploratory analysis, this study chose the criterion of abnormally low PRL based on the lower boundary of the prolactin range in an Asian population cited in a case report [ 19 ]. Despite the slight differences in the definition, the estimated prevalence of having an abnormally low PRL in this study (40% at the 56th Day) were similar to the existing studies, e.g., 45% in patients who had received combination therapy with aripiprazole (≤ 3 ng/mL) [ 16 ] and 44% in patients during a long retrospective follow-up period after aripiprazole use (≤ 3.57 ng/mL for males and ≤ 6.12 ng/mL for females) [ 18 ].…”

“…Another possibility is that aripiprazole may disrupt the hypothalamus’ secretion of thyroid-releasing hormone, resulting in a decrease in plasma levels of prolactin-releasing hormone and thyroid-stimulating hormone [ 19 ]. Hence, a mere lowering in prolactin may not be indicative of the partial agonist effect of aripiprazole, which may explain why some patients with abnormally low PRL did not experience a rebound in psychotic symptoms.…”

“…Based on the normal range of PRL (3.7–16.3 ng/ml) reported in an Asian population [ 19 ], we used a PRL of < 3.7 ng/ml to define abnormally low PRL at either the 14th Day or 56th Day. Hence, patients needed to have at least one follow-up measurement of prolactin level to be included in this study.…”

“…A review of 11 trials of aripiprazole in children and adolescents found, using 2 ng/mL as the threshold, that approximately 60% of participants exhibited subnormal PRL [ 15 ]. Case reports and retrospective studies among adult schizophrenia patients receiving aripiprazole also showed abnormally low PRL, with varying thresholds [ 16 – 19 ].…”

Redefining the Cut-Off Ranges for TSH Based on the Clinical Picture, Results of Neuroimaging and Laboratory Tests in Unsupervised Cluster Analysis as Individualized Diagnosis of Early Schizophrenia

“…There are data that show that, for example, chlorpromazine (a typical neuroleptic D2 receptor antagonist) causes a significant decrease in TSH levels after discontinuation. The use of aripiprazole (D2 partial agonist and 5-HT2A antagonist) may therefore have a similar effect to chlorpromazine withdrawal, i.e., it may reduce TSH levels [77]. On the other hand, other studies show that there are no significant changes in TSH and FT4 levels for aripiprazole.…”