It is thought that both selective serotonin reuptake inhibitors (SSRIs) and non-steroidal anti-inflammatory drugs (NSAIDs) can cause the adverse reaction of upper gastrointestinal hemorrhage (UGIH). To evaluate differences in the probability of UGIH occurring when SSRIs, NSAIDs, or both combined are administered, the authors performed a systematic review of related articles and a meta-analysis of data in those articles, which were identified by searching the literature published between 1999 and 2012 using PubMed, Scirus, and Google Scholar. The odds ratios were calculated using the Mantel-Haenszel method. The integrated odds ratios for SSRIs only, NSAIDs only, and the combination were 1.73 (0.65-2.82), 2.55 (1.51-3.59), and 4.02 (2.89-5.15), respectively. Use of the combination resulted in an odds ratio 2.32 times higher than use of either alone. Since the combination of SSRIs and NSAIDs resulted in a significantly higher risk of UGIH than either type of drug alone, clinicians should avoid use of the combination as much as possible. If it is necessary to administer both kinds of drugs, the minimum dosage should be prescribed for the shortest time period possible, and patients, particularly elderly patients, should be closely monitored for development of UGIH and other complications.Key words meta-analyses; epidemiology; combination use; non-steroidal anti-inflammatory drug (NSAID); selective serotonin reuptake inhibitor (SSRI); upper gastrointestinal hemorrhage (UGIH) Selective serotonin reuptake inhibitors (SSRIs) are widely used in the treatment of panic and obsessive compulsive disorders in many countries, and the effects have been confirmed. Usage of SSRIs is increasing because of their low toxicity compared with classical antidepressants, which have a different mode of action.1) Thus, among the many kinds of antidepressants available, SSRIs are currently the most commonly prescribed, and their usage has steadily increased in elderly patients with depression in particular.2) However, SSRIs are reported to have some specific adverse reactions, such as upper gastrointestinal hemorrhage (UGIH). 3)Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used over-the-counter drugs, have also been shown to be associated with a risk of UGIH.1) Although SSRIs and NSAIDs are sometimes administered in combination, 4) the harmful effects of this combination have not been clarified, as the Food and Drug Administration (FDA) has not accurately analyzed the risk of UGIH resulting from combination use of SSRIs and NSAIDs. 3)Therefore, we collected data for cases of UGIH resulting from the administration of SSRIs alone, NSAIDs alone, and combination use reported between 1999 and 2012, and performed a meta-analysis in order to analyze the risk of UGIH associated with combination use of SSRIs and NSAIDs. METHODS Literature SearchWe searched the literature through PubMed, Scirus, and Google Scholar for articles published between 1999 and 2012 using the following terms: "NSAIDs other drug interaction," "adverse intera...

The adverse events induced by drugs have been complicated, when two or more drugs are administrated for a patient. We selected "Stevens-Johnson Syndrome (SJS)" as a research object, which is one of the severe skin manifestations. The data source is a database constructed by the Food and Drug Administration (FDA). FDA's post-marketing safety surveillance program is supported by the Adverse Event Reporting System (AERS). AERS is designed with a computerized information database. To analyze the relationships between the concurrent medication and SJS in this study, we applied association rule learning. Our purpose is to propose an efficient procedure that enables the detection of signals for drugs related to an adverse event, without assuming the involvement of a specific drug. We defined new value K for the evaluation of existing signal detection. Association rule was evaluated according to criterion K value. As a result, it was suggested to obtain a strong signal by combining two concomitant drugs. Association rule learning in this study was applicable for the analysis of the relationships between adverse events and pairs of drugs.

This study aimed to determine the potentially severe chemical properties of drugs that can cause adverse drug reactions (ADRs) such as erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) by using a data mining method. The study data were extracted from the Adverse Event Reporting System database of the FDA. EM was considered a mild reaction, and SJS and TEN were considered severe reactions. In this study, a new concept termed the "risk of aggravation" (ROA) was defined as whether a certain drug is more likely to cause severe adverse reactions than mild ones. Partial least squares and logistic regression analysis were applied using binary response variable ROAs. These analyses correctly predicted 50 of the 72 drugs associated with SJS and/or TEN and 28 of the 38 drugs associated with EM using binary chemical descriptors that are the same as those using the metric chemical descriptors.

Comparative Molecular Field Analysis (CoMFA) is most widely used as one of the 3-dimensional QSAR (3D-QSAR) methods to identify the relationship between chemical structure and biological activity. Conventional CoMFA requires at least 3 orders of experimental data, such as IC50 and Ki, to obtain a good model, although practically there are many screening assays where biological activity is measured only by a rating scale. Hence, rating classification-oriented CoMFA coupled with ordinal logistic regression has been developed, and its predictive ability and 3D graphical analysis ability have been investigated. As a result, this novel CoMFA (Logistic CoMFA) has been found to be more robust than conventional CoMFAs in both predictive and 3D graphical analysis abilities. Furthermore, Logistic CoMFA is useful since it can provide the probability of each rank.