Risperidone-Associated Hypocalcemia

Milovanovic, Dragan R.; Janjić, Vladimir; Zornić, Nenad; Dejanovic, Slavica Djukic; Janković, Slobodan

doi:10.1176/appi.ajp.2010.10071003

Cited by 8 publications

(10 citation statements)

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“…Psychotropic medications by themselves could cause sodium disturbances, primarily hyponatremia (16,17,40). Some psychotropics have also been associated with an increased risk for osteoporosis and bone fractures as well as hypocalcemia, either as a drug-class or individual medicines (15,19,59). Basic studies revealed the link between the activity of vitamin D receptor (VDR) and regulating enzymes (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Researchers proposed several pathogenic mechanisms and the effects of psychotropic drugs could be one of them (15). Hyponatremia is a rare but well-documented adverse effect of both antidepressant and antipsychotic agents while occasional reports revealed the disturbances of some other electrolytes in patients with serious mental conditions including drug-treated ones (16)(17)(18)(19). The regulation of vitamin D metabolism is interconnected with homeostatic regulations of bone minerals and certain major electrolytes get indirectly involved in them.…”

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confidence: 99%

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Vitamin D Deficiency and Associated Factors in Patients with Mental Disorders Treated in Routine Practice

Ristic

Živanović

Milovanovic

et al. 2017

J Nutr Sci Vitaminol

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SummaryThis research aimed to investigate factors associated with vitamin D deficiency and to provide data about its prevalence in patients suffering from different psychiatric illnesses. The study had a cross-sectional design and it included 220 patients of both genders, aged from 19-81 y, with a wide range of mental disorders (F00-F89), and treated in routine ambulatory and hospital practice. The researchers collected data from three sources: medical records, a study questionnaire and biochemical analysis of patients' serum samples (concentration of vitamin D measured as 25(OH)D, calcium, phosphorus, magnesium, sodium and potassium). Data were analyzed using descriptive statistics, methods for hypothesis testing and binary logistic regression, at the p#0.05 level. A total of 140 patients (64%) had a deficiency of vitamin D (,12 ng/mL), and 45 (20%) had inadequate vitamin D serum levels (12-20 ng/mL), while 35 (16%) had sufficient vitamin D serum concentrations (.20 ng/mL). Among variables related to demographics, life style habits, mental illness, comorbid disorders and drugs, two of them, female gender (odds ratio (OR)52.5, 95% confidence interval (CI)51.3-4.9, p50.006) and using clozapine (OR515.6, 95% CI 1.7-144.7, p50.02), were significantly associated with vitamin D deficiency. Physical activity (OR5 0.4, p50.02), exercising (OR50.2, 95% CI , p50.02) and offal in the diet (OR50.5, 95% CI 0.3-0.9, p50.03) significantly aggregated in the patients who had a 25(OH)D serum concentration above the deficiency cut-off level. Patients with mental disorders are at high risk for vitamin D deficiency, particularly females and clozapine users as well as those having no adequate physical activity or dietary habits.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Vitamin D Deficiency and Associated Factors in Patients with Mental Disorders Treated in Routine Practice

Ristic

Živanović

Milovanovic

et al. 2017

J Nutr Sci Vitaminol

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“…While the next level of investigation should involve binding studies using radiolabeled cinacalcet, we note that previously it has been shown that compounds that interact with neurotransmitter receptors may affect synthesis of calcium-binding proteins in the tissues, and alter calcium-dependent signaling pathways, which will affect calcium homeostasis and lead to a calcium-depleted state and/or trigger calcium redistribution within body compartments (el-Defrawi and Craig 1984;MacDonald et al 2005;Rushlow et al 2009). Risperidone, an atypical neuroleptic that antagonizes 5-HT1A and also different isoforms of dopamine receptors, has been associated with hypocalcemia (Smith et al 2006;Schatzberg and Nemeroff 2009;Milovanovic et al 2010). Our results provide an alternative explanation why cinacalcet causes hypocalcemia.…”

Section: Discussionmentioning

confidence: 63%

“…; Schatzberg and Nemeroff ; Milovanovic et al. ). Our results provide an alternative explanation why cinacalcet causes hypocalcemia.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic analysis for time-dependent effects of cinacalcet on serum calcium, phosphorus, and parathyroid hormone levels in 5/6 nephrectomized rats

et al. 2013

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This study investigates the time-dependent effects of cinacalcet on serum calcium, phosphorus, and parathyroid hormone (PTH) levels in 5/6 nephrectomized (NX) rats with experimental chronic renal insufficiency. In this study, 5/6 NX male, Sprague–Dawley rats were treated with vehicle or cinacalcet (10 mg/kg, oral, 1× daily). On Day 0 (before treatment), Day 12 and 13 after treatment (to approximate the clinical practice), and also at 0, 1, 4, 8, 16, and 24 hours after the last dosing, blood was collected for analysis. After 12 or 13 days of cinacalcet treatment, modest changes were observed in serum Ca and phosphorus (Pi), while PTH decreased by >45% to Sham levels (152 ± 15 pg/mL). Detailed mapping found that cinacalcet caused a significant time-dependent decrease in serum Ca following dosing, reaching a lowest point at 8 hours (decrease by 20% to 8.43 ± 0.37 mg/dL), and then returning to normal at 24 hours. Cinacalcet also caused a significant increase in serum Pi levels (by 18%). To investigate the potential mechanism of action, a broad approach was taken by testing cinacalcet in a panel of 77 protein-binding assays. Cinacalcet interacted with several channels, transporters, and neurotransmitter receptors, some of which are involved in brain and heart, and may impact Ca homeostasis. Cinacalcet dose-dependently increased brain natriuretic peptide (BNP) mRNA expression by 48% in cardiomyocytes, but had no significant effects on left ventricular hypertrophy and cardiac function. The results suggest that cinacalcet's hypocalcemic effect may be due to its nonspecific interaction with other receptors in brain and heart.

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“… 15 The recent studies found significant association between the use of risperidone and hypocalcemia, based on the evidence coming from investigations of different designs. 16 17 The latest review compiled sixteen studies investigating the link between schizophrenia, antipsychotic use and osteoporotic fractures. Important uncertainties still exists indicating the need for larger, prospective and more detailed research.…”

Section: Introductionmentioning

confidence: 99%

Parameters of Calcium Metabolism Fluctuated during Initiation or Changing of Antipsychotic Drugs

Milovanovic

Pirković

Zivancevic-Simonovic

et al. 2016

Psychiatry Investig

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ObjectiveSerum parameters of calcium homeostasis were measured based on previously published evidence linking osteoporotic fractures and/or bone/mineral loss with antipsychotics.MethodsProspective, four-week, time-series trial was conducted and study population consisted of patients of both genders, aged 35-85 years, admitted within the routine practice, with acute psychotic symptoms, to whom an antipsychotic drug was either introduced or substituted. Serial measurements of serum calcium, phosphorous, magnesium, 25(OH)D, parathyroid hormone, calcitonin, osteocalcin and C-telopeptide were made from patient venous blood samples.ResultsCalcium serum concentrations significantly decreased from baseline to the fourth week (2.42±0.12 vs. 2.33±0.16 mmol/L, p=0.022, n=25). The mean of all calcemia changes from the baseline was -2.6±5.7% (-24.1 to 7.7) with more decreases than increases (78 vs. 49, p=0.010) and more patents having negative sum of calcemia changes from baseline (n=28) than positive ones (n=10) (p=0.004). There were simultaneous falls of calcium and magnesium from baseline (63/15 vs. 23/26, p<0.001; OR=4.75, 95% CI 2.14-10.51), phosphorous (45/33 vs. 9/40, p<0.001; 6.06, 2.59-14.20) and 25(OH)D concentrations (57/21 vs. 13/35, p<0.001; 7.31, 3.25-16.42), respectively. Calcemia positively correlated with magnesemia, phosphatemia and 25(OH)D values. Parathyroid hormone and C-telopeptide showed only subtle oscillations of their absolute concentrations or changes from baseline; calcitonin and osteocalcin did not change. Adjustment of final calcemia trend (depletion/accumulation) for relevant risk factors, generally, did not change the results.ConclusionIn patients with psychotic disorders and several risks for bone metabolism disturbances antipsychotic treatment was associated with the decrease of calcemia and changes in levels of the associated ions.

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Risperidone-Associated Hypocalcemia

Cited by 8 publications

References 1 publication

Vitamin D Deficiency and Associated Factors in Patients with Mental Disorders Treated in Routine Practice

Vitamin D Deficiency and Associated Factors in Patients with Mental Disorders Treated in Routine Practice

Mechanistic analysis for time-dependent effects of cinacalcet on serum calcium, phosphorus, and parathyroid hormone levels in 5/6 nephrectomized rats

Parameters of Calcium Metabolism Fluctuated during Initiation or Changing of Antipsychotic Drugs

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