Richardsonratliff0705

ophrenia. FUNDING ACKNOWLEDGEMENTS Supported by funding from Intra-Cellular Therapies, Inc.STUDY OBJECTIVES Depression is the leading cause of disability worldwide, with fewer than 50% of treated patients achieving full remission. This study ("CLARITY," ACP-103-042 NCT03018340) examined the 5-HT2A inverse agonist pimavanserin (PIM) as a potential adjunctive treatment for major depressive disorder (MDD). METHOD Adult female and male subjects with a DSM-5 primary diagnosis of a major depressive episode as part of MDD, inadequate response to ongoing SSRIs or SNRIs of adequate dose and duration as confirmed by the Massachusetts General Hospital Antidepressant Treatment History Questionnaire, and a MADRS total score >20 were randomized to PIM 34 mg/day or placebo (PBO) added to their SSRI/SNRI treatment. A sequential parallel comparison design was used, consisting of two 5-week stages. PBO nonresponders in Stage-1 who met prespecified criteria were re-randomized to PIM or PBO for the second period (Stage-2). The primary efficacy measure was the weighted average of Stage-1 and Stage-2 total scores of the to PBO on the key secondary endpoint, the Sheehan Disability Scale (LSM difference=-0.8, SE=0.3; P=0.004), and positive results were also seen on 7 of the 11 other secondary endpoints, including responder rate (≥50% reduction in HAMD-17 total; P=0.007), Massachusetts General Hospital Sexual Functioning Index (P less then 0.001), and Karolinska Sleepiness Scale for daytime sleepiness (P=0.02). Discontinuations due to adverse events were low (PIM 1.2%, PBO 3.2%). One serious adverse event was reported in each treatment group, deemed unrelated to treatment. No deaths were reported. Laboratory assessments, electrocardiography, and changes in vital signs were unremarkable, and no new safety signals were reported. CONCLUSIONS Study data provide evidence of the efficacy, safety, and tolerability of adjunctive PIM in treating MDD inadequately responsive to SSRI or SNRI therapy. Efforts to confirm these results are ongoing in a Phase 3 program. FUNDING ACKNOWLEDGEMENTS ACADIA Pharmaceuticals Inc.BACKGROUND Antidepressant-induced hyponatremia/syndrome of inappropriate antidiuretic hormone (SIADH) can cause significant morbidity and mortality. Antidiuretic hormone release due to stimulation of central serotonin 5HT1C, 5HT2 and α-1 adrenergic receptors is thought to cause this adverse effect (Spigset, 1995). Evidence on which antidepressants are more likely to cause hyponatremia is inconsistent (Coupland, 2011; Leth-Moller, 2016). Owing to its uncommon use, there is limited and conflicting data on the risk of hyponatremia with Moclobemide, a reversible inhibitor of monoamine oxidase A (Mercier, 1997; Mazhar, 2019). There are few reports of hyponatremia induced by multiple antidepressant classes in the same patient. OBJECTIVE To add to the literature on risk of hyponatremia with Moclobemide and other antidepressants. METHODS We report a case of hyponatremia sequentially induced by multiple different antidepressant classes who was treated with Moclobemide with no recurrence of hyponatremia. We review exisADH. He later developed hyponatremia after initiating the following antidepressants sequentially Fluvoxamine, Agomelatine, Nortriptyline, Bupropion. Hyponatremia resolved with fluid restriction and cessation of the implicated antidepressant each time before the next was initiated. He eventually tolerated Moclobemide 300mg/day with no recurrence of hyponatremia. CONCLUSIONS Agomelatine, Nortriptyline and Bupropion are reported to have a low risk of hyponatremia but were implicated in this case. Venlafaxine and Mirtazapine did not cause hyponatremia when first taken but were implicated when restarted after a period of cessation, underscoring the idiosyncratic nature of antidepressant-induced hyponatremia. Moclobemide can be considered for depressed patients with recurrent antidepressant-induced hyponatremia. Serum Na should be regularly monitored in patients taking antidepressants who are at high risk of hyponatremia.STUDY OBJECTIVES Depression occurs in ~50% of Parkinson's disease (PD) patients, increases in severity and duration as the disease progresses, and is associated with increased morbidity. Improvement of depression in PD patients is correlated with reduced physical disability and improved quality of life. We are assessing use of pimavanserin (PIM) for treatment of depression in adults with PD. click here METHOD A Phase-2, 8-week, open-label, single-arm study is being conducted to evaluate the safety and efficacy of PIM as an adjunct to SSRI/SNRI or as monotherapy in adults with both PD and symptoms of depression (baseline Hamilton Depression Scale [17-items] total score [HAMD-17] ≥15). The primary endpoint of the study is change from Baseline to Week 8 in the HAMD-17. Secondary measures included the Clinical Global Impression (CGI) scales (improvement and severity) and Scales of Outcomes in PD-Sleep (SCOPA). RESULTS Interim results based on the first 34 of 40 planned patients have been evaluated 55.9% of patients were malve completed the study to date, and another 7 are still continuing. Thirteen patients reported adverse events, the most common being falls, UTI, diarrhea, and nausea. CONCLUSIONS These interim data suggest that PIM as adjunctive treatment or monotherapy is associated with early improvement of depressive symptoms in patients with PD and is well tolerated. This is consistent with recently reported data of PIM in major depressive disorder. Final data will be shared at the time of this presentation. However, additional placebo-controlled data will be needed to determine fully the efficacy of PIM in patients with comorbid PD and depression. FUNDING ACKNOWLEDGEMENTS ACADIA Pharmaceuticals Inc.BACKGROUND The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial. METHODS Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm.