Objective To study predictors of non-stabilization (i. refractory mania/hypomania 15 versus 9% (OR = 1.87) but less likely due to refractory major depression 16% versus 25% (OR = 0.58) or adverse events 10 versus 19% (OR = 0.44). A history of recent SUDs early existence verbal abuse female gender and late onset of 1st depressive episode were associated with improved risk for non-stabilization with ORs of 1 1.85 1.74 1.1 Odanacatib and 1.04 respectively. Conclusions During open treatment with lithium and divalproex in individuals with RCBD a recent SUD a lifetime history of verbal misuse female gender and late onset of 1st depression independently expected non-stabilization. The non-stabilization for individuals with SUD was related to non-adherence and refractory mania/hypomania. Keywords: Bipolar disorder anxiety disorder substance use disorder mood stabilizer non-stabilization Introduction Lithium and divalproex are the two most commonly prescribed mood stabilizers.1-4 There has been a long history of interest in the combination of these two mood stabilizers in the treatment of bipolar disorders.5-14 One reason for the use of combination therapy is that patients with refractory bipolar disorder5-7 or rapid cycling bipolar disorder (RCBD)9 12 13 might respond better to combination therapy Odanacatib than lithium or divalproex monotherapy. Early studies revealed that rapid cycling15 and substance abuse16 were associated with lithium nonresponse. Open-label data also suggested that RCBD may respond better to divalproex than to lithium.15 17 In addition divalproex has shown efficacy in the acute treatment of bipolar mood episodes complicated by substance abuse.16 18 However two prior studies conducted by our group involving patients with RCBD have shown that combination therapy with lithium and divalproex was significantly less effective than previously recommended.21 22 Approximately Odanacatib only 20% of individuals met APO-1 the protocol-defined requirements for stabilization/randomization i.e. a 17-item HAM-D rating 20 YMRS rating ≤ 12 ≤.5 GAS rating ≥ 51 for at the least four weeks with lithium amounts ≥ 0.8 meq/L and valproate amounts 50 μg/ml ≥. Of the two research one was Odanacatib carried out in individuals with RCBD and a recently available background of SUDs22 and another was completed in individuals with RCBD but no latest background of SUDs.21 Furthermore a previous evaluation of the different band of our individuals with RCBD showed that degree of education ethnicity and legal history however not SUDs were connected with increased risk for non-adherence.23 Even though the clinical data are much less impressive than expected preclinical research show both lithium and divalproex to possess neuroprotective results through different intracellular systems.24 More both agents possess additive neuroprotective results importantly.25 Likely the combination therapy of the two agents will continue steadily to play a significant role in the treating individuals with bipolar disorder. With this report the reason why for non-stabilization in both research21 22 had been compared and 3rd party predictors of non-stabilization as an organization had been explored. Such info gets the potential to steer the use of the combination treatment of lithium and divalproex in patients with bipolar disorder. Method Patient Population The data for this study were derived from two studies previously conducted by our center among patients with RCBD.21 22 These studies were conducted to assess the efficacy of lithium and divalproex for managing the acute and maintenance treatment of RCBD with22 or without21 a “recent” history of SUD. A “recent” SUD was defined as having a diagnosis of substance dependence and continuing to meet abuse or dependence criteria for a substance(s) in the last 6 months at the initial assessment or having a diagnosis of substance abuse and continuing to abuse a substance(s) in the last 6 months. The study designs inclusion and exclusion criteria of these two studies have been summarized elsewhere.26 In addition to meeting psychiatric inclusion criteria patients who had acute medical conditions were excluded. Patients were also excluded from study participation if they had previous intolerance to documented lithium levels of 0.8 meq/L or divalproex levels of 50 μg/ml had been completely non-responsive to past lithium treatment had alcohol-related liver disease as reflected by diffuse elevations in liver function tests exceeding the upper limits of the normal range by 50% were pregnant or planning to become pregnant were taking.