The impact of prolactin-raising antipsychotics on bone mineral density in patients with schizophrenia: Findings from a longitudinal observational cohort

Takahashi, Tatsuichiro; Uchida, Hiroyuki; John, Majnu; Hirano, Jinichi; Watanabe, Koichiro; Mimura, Masaru; Correll, Christoph U.; Kishimoto, Toshifumi

doi:10.1016/j.schres.2013.04.015

Cited by 26 publications

(18 citation statements)

References 23 publications

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“…Hyperprolactinemia as an endocrinological dysfunction comes among main etiologies to secondary osteoporosis, due to its direct effect on bone mineralization on one side and decreasing sex hormones on the other side. Many authors, as in our study, highlighted such association between elevated prolactin level and poor bone density and subsequent pathological fractures [24,25].…”

Section: Discussionsupporting

confidence: 71%

Long Term Use of Antipsychotics and Adverse Effects on Bone Density

Rady¹,

Elsheshai²,

Elkholy³

et al. 2018

Neuropsychiatry

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Background and Objectives High incidence of osteoporosis and pathological fractures were observed in schizophrenic patients medicated by antipsychotics for long time. Hyperprolactinemia induced by antipsychotics may partially contribute to osteopenia. Though atypical antipsychotics cause less hyperprolactinemia than conventional antipsychotics, however, risperidone and amisulpride seem to have no advantage in this regard. Our study aims at assessing effect of long term use of antipsychotics on bone density. Methods 30 schizophrenic patients on antipsychotics for 2-10 yrs were recruited compared to control drug naïf schizophrenic group for bone mineral density Results: both groups were balanced for age and gender distribution. Significantly decreased bone mineral density was found among schizophrenic patients on long term use of antipsychotics (X 2 =3.25;p<0.05). This later had significantly higher serum prolactin (p<0.001) and lesser serum cortisol level (p<0.01). Conclusion Osteopenia and osteoporosis are common adverse effects among antipsychotics, though can easily be screened for, but it's often a forgotten side effect with impact on general health state.

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Section: Discussionsupporting

confidence: 71%

Long Term Use of Antipsychotics and Adverse Effects on Bone Density

Rady¹,

Elsheshai²,

Elkholy³

et al. 2018

Neuropsychiatry

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“…Some studies have demonstrated the beneficial effects of PS antipsychotics [58] and the association of PR antipsychotics with hip fractures [59] in both genders. Lin et al [60] have found dose-related bone-density protecting effect of clozapine in women with chronic schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Haloperidol affects bones while clozapine alters metabolic parameters - sex specific effects in rats perinatally treated with phencyclidine

Nikolić

Petronijević

Sopta

et al. 2017

BMC Pharmacol Toxicol

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BackgroundThe presentation of schizophrenia (SCH) symptoms differs between the sexes. Long-term treatment with antipsychotics is frequently associated with decreased bone mineral density, increased fracture risk and metabolic side effects. Perinatal phencyclidine (PCP) administration to rodents represents an animal model of SCH. The aim of this study was to assess the effects of chronic haloperidol and clozapine treatment on bone mass, body composition, corticosterone, IL-6 and TNF-α concentrations and metabolic parameters in male and female rats perinatally treated with PCP.MethodsSix groups of male and six groups of female rats (n = 6-12 per group) were subcutaneously treated on 2nd, 6th, 9th and 12th postnatal day (PN), with either PCP (10 mg/kg) or saline. At PN35, one NaCl and PCP group (NaCl-H and PCP-H) started receiving haloperidol (1 mg/kg/day) and one NaCl and PCP group (NaCl-C and PCP-C) started receiving clozapine (20 mg/kg/day) dissolved in drinking water. The remaining NaCl and PCP groups received water. Dual X-ray absorptiometry measurements were performed on PN60 and PN98. Animals were sacrificed on PN100. Femur was analysed by light microscopy. Concentrations of corticosterone, TNF-α and IL-6 were measured in serum samples using enzyme-linked immunosorbent assay (ELISA) commercially available kits. Glucose, cholesterol and triacylglycerol concentrations were measured in serum spectrophotometrically.ResultsOur results showed that perinatal PCP administration causes a significant decrease in bone mass and deterioration in bone quality in male and female rats. Haloperidol had deleterious, while clozapine had protective effect on bones. The effects of haloperidol on bones were more pronounced in male rats. It seems that the observed changes are not the consequence of the alterations of corticosterone, IL-6 and TNF-α concentration since no change of these factors was observed. Clozapine induced increase of body weight and retroperitoneal fat in male rats regardless of perinatal treatment. Furthermore, clozapine treatment caused sex specific increase in pro-inflammatory cytokines.ConclusionTaken together our findings confirm that antipsychotics have complex influence on bone and metabolism. Evaluation of potential markers for individual risk of antipsychotics induced adverse effects could be valuable for improvement of therapy of this life-long lasting disease.Electronic supplementary materialThe online version of this article (10.1186/s40360-017-0171-4) contains supplementary material, which is available to authorized users.

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“…However, it is well-established that the younger (<18 years of age) population is at an increased risk of experiencing adverse effects in the short-(<6 months) and medium-term (6-12 months), such as sedation, extrapyramidalism, weight gain, dyslipidemia and adverse effects related to prolactin (Correl CU, 2006;Merchán-Naranjo et al 2012), with an emphasis on the long-term (>12 months) effects of hyperprolactinemia, such as deleterious effects on bone. The latter could impede reaching peak bone mass, the maximum of which is reached at approximately 25 years, with the resulting future risk of osteoporosis and fracture (Colao et al 2003;Takahashi et al 2013).…”

Section: First Psychotic Episodes and The Pediatric-youth Populationmentioning

confidence: 99%

Multidisciplinary consensus on the therapeutic recommendations for iatrogenic hyperprolactinemia secondary to antipsychotics

Montejo

Arango

Bernardo

et al. 2017

Frontiers in Neuroendocrinology

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Hyperprolactinemia is an underappreciated/unknown adverse effects of antipsychotics. The consequences of hyperprolactinemia compromise therapeutic adherence and can be serious. We present the consensus recommendations made by a group of experts regarding the management of antipsychotic-induced hyperprolactinemia. The current consensus was developed in 3 phases: 1, review of the scientific literature; 2, subsequent round table discussion to attempt to reach a consensus among the experts; and 3, review by all of the authors of the final conclusions until reaching a complete consensus. We include recommendations on the appropriate time to act after hyperprolactinemia detection and discuss the evidence on available options: decreasing the dose of the antipsychotic drug, switching antipsychotics, adding aripiprazole, adding dopaminergic agonists, and other type of treatment. The consensus also included recommendations for some specific populations such as patients with a first psychotic episode and the pediatric-youth population, bipolar disorder, personality disorders and the elderly population.

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The impact of prolactin-raising antipsychotics on bone mineral density in patients with schizophrenia: Findings from a longitudinal observational cohort

Cited by 26 publications

References 23 publications

Long Term Use of Antipsychotics and Adverse Effects on Bone Density

Long Term Use of Antipsychotics and Adverse Effects on Bone Density

Haloperidol affects bones while clozapine alters metabolic parameters - sex specific effects in rats perinatally treated with phencyclidine

Multidisciplinary consensus on the therapeutic recommendations for iatrogenic hyperprolactinemia secondary to antipsychotics

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