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

Ya-Wen Jen, Tzung-Jeng Hwang, Hung-Yu Chan, Ming H Hsieh, Chen-Chung Liu, Chih-Min Liu, Hai-Gwo Hwu, Ching-Hua Kuo, Yi-Ting Lin, Yi-Ling Chien, Wei J Chen, Ya-Wen Jen, Tzung-Jeng Hwang, Hung-Yu Chan, Ming H Hsieh, Chen-Chung Liu, Chih-Min Liu, Hai-Gwo Hwu, Ching-Hua Kuo, Yi-Ting Lin, Yi-Ling Chien, Wei J Chen

Abstract

Background: Switching to aripiprazole from other antipsychotics can avoid antipsychotic-induced hyperprolactinemia but may result in an abnormally low prolactin level. This study aimed to assess whether the aripiprazole-induced abnormally low prolactin level was a biomarker for subsequent rebound of positive symptoms in schizophrenia patients.

Methods: Participants were 63 patients in an 8-week trial of switching to aripiprazole, in which preswitching antipsychotics were maintained for the first 2 weeks and aripiprazole was fixed at 15 mg orally throughout the trial. A prolactin level of < 3.7 ng/ml was defined as abnormally low, and an increase of two or more points in the positive subscore of the Positive and Negative Syndrome Scale at two adjacent ratings was defined as a psychotic rebound.

Results: Among 63 patients, 25 (39.7%) had an abnormally low prolactin level and 21 (33.3%) had a psychotic rebound after switching to aripiprazole. In patients with abnormally low prolactin levels, 48.0% of them had a rebound in psychotic symptoms, whereas in those without abnormally low prolactin levels 23.7% did so. Multivariable logistic regression analysis with adjustment for sex, early age at onset, and preswitching medications revealed that abnormally low prolactin levels were associated with psychotic rebound (adjusted odds ratio = 3.55, 95% confidence interval = 1.02, 12.5). Furthermore, there was concurrency between the trend of the cumulative proportion of patients having an abnormally low prolactin level and that of the cumulative proportion of patients having a rebound in psychotic symptoms.

Conclusions: An abnormally low prolactin level after switching to aripiprazole in schizophrenia patients was a potential warning sign of a psychotic rebound. Hence, monitoring of prolactin levels after switching to aripiprazole may help avoid such rebound in schizophrenia.

Trial registration: NCT00545467 ; Date of registration: 17/10/2007.

Keywords: Aripiprazole; Biomarker; Prolactin; Psychotic rebound; Schizophrenia.

Conflict of interest statement

TJH received a research grant from AstraZeneca and honoraria from AstraZeneca, Taiwan Otsuka Pharmaceutical Co., and Eli Lilly and Company. HGH received honoraria from Taiwan Otsuka Pharmaceutical Co. YWJ, HYC, MHH, CCL, CML, CHK, YTL, YLC, and WJC report no other financial disclosures relevant to the subject of this article.

Figures

Fig. 1
Fig. 1
CONSORT flow diagram for the study
Fig. 2
Fig. 2
The cumulative proportion of patients with rebound in PANSS positive symptoms (▲) at follow-up measured time points, which are the 14th Day, 28th Day, and 56th Day, and of patients with abnormally low prolactin levels (●) at follow-up measured time points, which are the 14th Day and 56th Day. Concurrency of the two trends over time in the cumulative proportions is shown in a whole samples, N = 63, b male patients, N = 26, and c female patients, N = 37. The β coefficient presents the slope of the cumulated line. P value is from testing whether the β coefficient of positive rebound is different from that of low prolactin levels

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