Fracture Risk From Psychotropic Medications
ABSTRACT Selective serotonin reuptake inhibitors (SSRIs), benzodiazepines, and antipsychotics have each been associated with an increased risk of fracture in older individuals. The aim of this study was to better define the magnitude of fracture risk with psychotropic medications and to determine whether a dose-effect relationship exists.
Population-based administrative databases were used to examine psychotropic medication exposure and fractures in persons aged 50 years and older in Manitoba between 1996 and 2004. Persons with osteoporotic fractures (vertebral, wrist, or hip [n = 15,792]) were compared with controls (3 controls for each case matched for age, sex, ethnicity, and comorbidity [n = 47,289]). Medications examined included antidepressants (SSRIs vs other monoamines), antipsychotics, lithium, and benzodiazepines.
Selective serotonin reuptake inhibitors were associated with the highest adjusted odds of osteoporotic fractures (odds ratio [OR] = 1.45; 95% confidence interval [CI], 1.32-1.59). Other monoamine antidepressants (OR = 1.15; 95% CI, 1.07-1.24) and benzodiazepines (OR = 1.10; 95% CI, 1.04-1.16) were also associated with greater fracture risk, although the relationship was weaker. Lithium was associated with lower fracture risk (OR = 0.63; 95% CI, 0.43-0.93), whereas the relationship with antipsychotics was not significant in the models that adjusted for diagnoses. A dose-effect relationship was seen with SSRIs and benzodiazepines.
This study provides novel insight into the relationship between fractures and psychotropic medications in the elderly. Selective serotonin reuptake inhibitors seem to have a greater risk than other psychotropic classes, and higher doses may further increase that risk. Lithium seems to be protective against fractures.
- SourceAvailable from: Holger J Sørensen
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- "In a sample with schizophrenia, current and prior use of antipsychotics increased the risk of hip fracture but no significant associations with dose or degree of blockade of the alpha-1 receptor or histamine-1 receptor were found (Hugenholtz et al., 2005). Bolton et al. found osteoporotic fracture to be associated with schizophrenia, but observed no independent effect of antipsychotics (Bolton et al., 2008). Pouwels et al. found a 1.76 fold increased risk of hip fracture in elderly people treated with conventional but not atypical antipsychotics (Pouwels et al., 2009). "
ABSTRACT: In a nationwide study using linkage of Danish hospital registers we examined predictors of hip fracture (ICD-10: S72) in 15,431 patients with schizophrenia (ICD-10: F20 or ICD-8: 295) and 3,807,597 population controls. Shorter education, disability pension, lifetime alcohol abuse, somatic co-morbidity, antipsychotics (IRR=1.19; 95% CI 1.15-1.24), antidepressant (IRR=1.18; 95% CI 1.16-1.20), anticholinergics (IRR=1.29; 95% CI 1.22-1.36), benzodiazepines (IRR=1.06; 95% CI 1.04-1.08) and corticosteroids (IRR=1.44; 95% CI 1.36-1.53) were significant predictors. In 556 persons with schizophrenia and hip fracture (matched to 1:3 to schizophrenia controls without hip fracture), antipsychotic polypharmacy predicted hip fracture. Analyses among antipsychotic monotherapy patients showed no differential effect of individual antipsychotics. A dose-response relationship of hip fracture and lifetime antipsychotics consumption was found (IRR=1.13 95% CI 1.07-1.19) and both prolactin-increasing and non-prolactin-increasing antipsychotics contributed to the effect. In conclusion, several factors, including complex psychopharmacological treatment, contribute in the prediction of hip fracture in large populations. Preventive strategies should focus attention to severely ill patients with high likelihood of a receiving complex psychopharmacologic treatment and high doses of antipsychotics.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 05/2013; 23. DOI:10.1016/j.euroneuro.2013.04.002 · 5.40 Impact Factor
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- "3 Abrahamsen et al., 2009 (15) Denmark Case-control Men !50 years Any/hip/spine fracture Cases: NR/15,716 1995– 2000 Age, fracture history, modified Charlson comorbidity index Controls: NR/47,149 4 Bolton et al., 2008 "
ABSTRACT: Previous studies have reported inconsistent findings regarding the association between the use of selective serotonin reuptake inhibitors (SSRIs) and the risk of fracture. We identified relevant studies by searching three electronic databases (MEDLINE, EMBASE, and the Cochrane Library) from their inception to October 20, 2010. Two evaluators independently extracted data. Because of heterogeneity, we used random-effects meta-analysis to obtain pooled estimates of effect. We identified 12 studies: seven case-control studies and five cohort studies. A meta-analysis of these 12 observational studies showed that the overall risk of fracture was higher among people using SSRIs (adjusted odds ratio [OR] = 1.69, 95% confidence interval [CI] 1.51-1.90, I(2 ) = 89.9%). Subgroup analysis by adjusted number of key risk factors for osteoporotic fracture showed a greater increased fracture risk in those adjusted for fewer than four variables (adjusted OR = 1.83, 95% CI 1.57-2.13, I(2) = 88.0%) than those adjusted for four or more variables (adjusted OR = 1.38, 95% CI 1.27-1.49, I(2) = 46.1%). The pooled ORs anatomical site of fracture in the hip/femur, spine, and wrist/forearm were 2.06 (95% CI 1.84-2.30, I(2 ) = 62.3%), 1.34 (95% CI 1.13-1.59, I(2 ) = 48.5%), and 1.51 (95% CI 1.26-1.82, I(2 ) = 76.6%), respectively. Subgroup analysis by exposure duration revealed that the strength of the association decreased with a longer window of SSRI administration before the index date. The risk of fracture was greater within 6 weeks before the index date (adjusted OR = 3.83, 95% CI 1.96-7.49, I(2 ) = 41.5%) than 6 weeks or more (adjusted OR = 1.60, 95% CI 0.93-2.76, I(2 ) = 63.1%). Fracture risk associated with SSRI use may have a significant clinical impact. Clinicians should carefully consider bone mineral density screening before prescribing SSRIs and proper management for high-risk populations.Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 05/2012; 27(5):1186-95. DOI:10.1002/jbmr.1554 · 6.59 Impact Factor
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- "These effects are greater in magnitude and more consistent than observed in users of TCAs    . In terms of lithium, there is preliminary evidence that it improves femoral neck and spine BMD , and decreases fracture risk  . "
ABSTRACT: Popular psychotropic drugs, like the antidepressant selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), and the mood stabilizer lithium, may have skeletal effects. In particular, preclinical observations suggest a direct negative effect of SSRIs on the skeleton. A potential caveat in studies of the skeletal effects of psychotropic drugs is the hypoactive (skeletal unloading) phenotype they induce. The aim of this study was to investigate the contribution of physical inactivity to the skeletal effects of psychotropic drugs by studying bone changes in cage control and tail suspended mice treated with either vehicle, SSRI, TCA or lithium. Tail suspension was used to control for drug differences on physical activity levels by normalizing skeletal loading between groups. The psychotropic drugs were found to have contrasting skeletal effects which were independent of drug effects on animal physical activity levels. The latter was evident by an absence of statistical interactions between the activity and drug groups. Pharmacological inhibition of the 5-hydroxytryptamine (5-HT) transporter (5-HTT) using a SSRI reduced in vivo gains in lower extremity BMD, and negatively altered ex vivo measures of femoral and spinal bone density, architecture and mechanical properties. These effects were mediated by a decrease in bone formation without a change in bone resorption suggesting that the SSRI had anti-anabolic skeletal effects. In contrast, glycogen synthase kinase-3[beta] (GSK-3[beta]) inhibition using lithium had anabolic effects improving in vivo gains in BMD via an increase in bone formation, while TCA-mediated inhibition of the norepinephrine transporter had minimal skeletal effect. The observed negative skeletal effect of 5-HTT inhibition, combined with recent findings of direct and indirect effects of 5-HT on bone formation, are of interest given the frequent prescription of SSRIs for the treatment of depression and other affective disorders. Likewise, the anabolic effect of GSK-3[beta] inhibition using lithium reconfirms the importance of Wnt/beta-catenin signaling in the skeleton and it's targeting by recent drug discovery efforts. In conclusion, the current study demonstrates that different psychotropic drugs with differing underlying mechanisms of action have contrasting skeletal effects and that these effects do not result indirectly via the generation of animal physical inactivity.Bone 04/2010; 46(4):985-92. DOI:10.1016/j.bone.2009.12.031 · 4.46 Impact Factor