Psychotropic-Related Hip Fractures: Meta-Analysis of First-Generation and Second-Generation Antidepressant and Antipsychotic Drugs

BACKGROUND: In 2007, more than 18,000 adults aged 65 or older died from injuries related to falls, with up to 30% experiencing severe injuries such as hip fracture or head trauma. The economic impact of falls and fractures among older people is substantial, with direct economic consequences totaling $19 billion in 2000. OBJECTIVE: To evaluate the association between antipsychotic and antidepressant agents and the risk of hip fracture in older adults, across multiple studies. METHODS: An English-language PubMed/MEDLINE search for studies from January 1966 to January 2011 was conducted, using key words including aged, hip fracture, fractures, antidepressive agents, and antipsychotic agents, as well as individual drug names. Criteria for study inclusion were mean subject age greater than or equal to 65 years, adjusted for age and sex, hip fracture-specific results provided, data specific to a drug class, subclass, or single agents, and cohort or case-controlled study design. Two authors reviewed all studies for inclusion/exclusion. A random effects model was used to calculate summary odds ratios. RESULTS: A total of 166 studies were identified in the initial search. Ten antipsychotic-related and 14 antidepressant-related studies, representing more than 70,000 hip fracture cases and approximately 270,000 subjects from 4 continents, met the inclusion criteria. Summary odds ratios (95% CI) were first-generation (conventional) antipsychotics 1.68 (1.43 to 1.99), second-generation (atypical) antipsychotics 1.30 (1.14 to 1.49), first-generation (tricyclic) antidepressants 1.71 (1.43 to 2.04), and second-generation (selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and unique agents such as bupropion, mirtazapine, and trazodone) antidepressants 1.94 (1.37 to 2.76). Clear evidence of heterogeneity was noted among all antidepressant study analyses (I-2>87%; Q statistic p < 0.05). CONCLUSIONS: All drug classes studied first-and second-generation antipsychotics and antidepressants were associated with an increased risk of hip fracture in predominantly older adult populations.