Objective Observational studies report that selective serotonin reuptake inhibitor (SSRI) antidepressants are connected with an increased threat of falls in older people but these research may over-estimate drug-specific risk due to confounding. 60 years or old). Involvement 12 weeks of randomized double-blind treatment with olanzapine plus olanzapine or sertraline plus placebo. Measurements Percentage of individuals who fell at least one time. Results Older participants were significantly more likely than younger participants to fall. Among older participants the odds ratio of falling with olanzapine plus sertraline versus olanzapine plus placebo was 1.56 (95% CI 0.63-3.83). There was not a statistically significant treatment effect or treatment × age interaction with respect to the proportion of participants falling. These negative results may have been due to low statistical power. Conclusion Evaluating the association between SSRIs and falls in a RCT is limited by the large sample size that is required. An alternative approach is to examine the ON-01910 effect of an SSRI ON-01910 on measures of postural stability and gait that are valid markers of risk of falling. designed to examine the risk of falling we calculated the sample size that would have been required to detect a statistically significant difference between the two treatment groups in the proportion of persons falling: given a two-tailed alpha of 0.05 and statistical power of 0.8 a sample size of 3 361 would have been required for analyses that included both age groups and a sample size of 858 would have been required for analyses confined to the older age group. Table 3 Number and Percentage of Participants Who Fell in STOP-PD DISCUSSION Falls and their prevention are of great public health importance. Given the potential biases of observational studies reporting the risk of falls with SSRIs and the absence of RCT data pertaining to this question we performed this exploratory analysis in an attempt to move the field forward. Strengths of this study include its 12-week duration that allows for a longer period of observation of falling than the more traditional 6-8 week antidepressant RCT the double-blind randomized design the adult lifespan approach that allows for a comparison of younger and older adults the inclusion of persons with chronic medical conditions who are more representative of ‘real world’ older patients than more physically healthy patients typically selected for regulatory studies of antidepressants the standardized approach to the dosing of sertraline and olanzapine and the prospective and systematic collection of falls data on all participants. Conversely limitations of the study include the absence of sertraline and placebo monotherapies the fact that the study was not designed to examine risk of falls and the focus on individuals with psychotic depression which potentially limits generalizability of the findings. We found that the study was not sufficiently powered to detect a statistically significant difference between the two treatment arms in the proportion of participants falling either for the study group as a whole or for older participants only. Therefore the negative statistical findings pertaining to the treatment effect and the treatment × age interaction do not necessarily mean that the addition of sertraline to olanzapine was not associated with an increased risk of falls. In fact notwithstanding the relatively wide confidence interval the the odds ratio of old individuals dropping when treated with olanzapine and sertraline versus olanzapine plus placebo is related to chances ON-01910 ratios reported by observational research for the association of SSRIs and falls.3 This research demonstrates BSG the limitation of looking to assess falls in colaboration with an SSRI inside a placebo-controlled RCT that’s primarily designed and powered to judge treatment efficacy. It really is unlikely a placebo-controlled RCT of adequate length and power will become carried out to definitively address the query of whether SSRIs raise the threat of falls. A meta-analysis of many RCTs could address this query but published SSRI tests never have reported falls data unfortunately. An alternative type of study can be to examine the result of antidepressants on actions of postural balance and gait that are valid markers of improved threat of falls.9 10 These RCTs wouldn’t normally only take into account potential confounding variables (such as for example vascular shifts in ON-01910 the mind and executive dysfunction11) but would also explore the interaction between your antidepressant and these variables. Acknowledgments Way to obtain Financing: The STOP-PD medical trial was funded by USPHS.