Abstract
BackgroundSwitching 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.MethodsParticipants 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.ResultsAmong 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.ConclusionsAn 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 registrationNCT00545467; Date of registration: 17/10/2007.
Highlights
Switching to aripiprazole from other antipsychotics can avoid antipsychotic-induced hyperprolactinemia but may result in an abnormally low prolactin level
For model 1, after adjustment for sex, early age at onset, and preswitching medication, having an abnormally low prolactin level (PRL) at follow-up was significantly associated with a rebound in psychotic symptoms, with an adjusted odds ratios (aORs) of 3.55
For model 2, with further adjustment for baseline prolactin levels and Positive and Negative Syndrome Scale (PANSS) positive subscore, the association remained significant
Summary
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. The partial agonism of aripiprazole on the dopaminergic neurons in the mesolimbic system might be too intense for those patients who had increased postsynaptic D2 receptor density in response to previous antipsychotics’ blocking [12, 13]. This may lead to a worsening in psychotic symptoms and to a lowering of prolactin level (PRL) through inhibition by dopamine in the tuberoinfundibular pathway [14]. Case reports and retrospective studies among adult schizophrenia patients receiving aripiprazole showed abnormally low PRL, with varying thresholds [16,17,18,19]
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