Use of Pimavanserin in Combination with Selective Serotonin Reuptake Inhibitors (SSRIs)

Use of Pimavanserin in Combination with Selective Serotonin Reuptake Inhibitors (SSRIs)

2017 AAGP Annual Meeting Introduction: Impaired awareness of illness (anosognosia) means that a person does not recognize that he or she is sick. The ...

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2017 AAGP Annual Meeting Introduction: Impaired awareness of illness (anosognosia) means that a person does not recognize that he or she is sick. The term is used in neurology for impaired awareness of illness and comes from the Greek word for disease (nosos) and knowledge (gnosis). It literally means “to not know a disease.” In psychiatry, insight has been conceptualized as a broader multidimensional concept that may include awareness of mental disorder, understanding of the social consequences of disorder, awareness of the need for treatment, awareness of specific signs and symptoms of disorder and the attribution of symptoms to disorder. We believe that though this may bring more elucidation of the concept of insight, one of the more fundamental aspects of insight, is whether or not the person believes he/she suffers from an illness. Methods: The sample consisted of 250 New York City residents aged 55 and older with schizophrenia spectrum disorders; all patients developed the disorder prior to age 45. Data on 104 subjects followed for a mean time of 52.5 months are presented; there were no significant differences in demographic factors or insight at baseline between those in the follow-up group and those who did not complete the study. Mean age of the follow-up group was 61 years old; 55% were male, and 55% were white. There has been considerable debate as to what constitutes insight, and multi-dimensional scales have shown very high correlations with one item measures suggesting that a dichotomous variable of insight may be equally valid as a complex measures. Therefore, in this study, “insight” was considered present if persons acknowledged that they have a mental illness. This subjective measure of insight correlated highly with the rater assessment on the PANSS Insight and Judgment item (r = .60, p < .001). Results: We identified 16 predictor variables of insight at follow-up in bivariate analysis and used stepwise regression analysis to identify 6 significant variables. These variables were then entered in a logistic regression with 2 covariates: gender and time interval between baseline and follow-up. The six variable remained significant: Baseline insight: OR = 14.57; Dementia rating Scale conceptualization subscale: OR = 1.11; Education level: OR = 1.42; Number of physical disorders OR = 4.49; Age: OR = 0.82; Blunted affect: OR = 0.38. Thus, the initial 4 variables were positively associated with insight whereas the latter two were negatively associated. There were 8 potential T2 variables that were identified associated with T1 insight were assessed separately using ordinal regression analyses with baseline of the T2 variable, time interval between assessments, and age as covariates. Two variables at T2 retained significance: Number of confidantes (Wald = 27.82; p < .001); frequency of clinical services (Wald =8.44; p = .004). Conclusions: The findings suggest that there is fluidity in levels of insight over time, although about two-thirds of subjects maintained insight over both periods. Although many factors thought to be associated with of components of insight were predictors of insight at T2, only 8 variables retained significance in multivariable analysis. With respect to causal modeling, our data indicated that several demographic variables (greater age; lower education) and certain aspects of cognition (conceptualization) and negative symptoms (blunting of affect) predict diminished insight. Having more physical disorders predicted greater insight, perhaps because the former provided a causal explanation for having a mental illness. Greater insight was associated with more confidantes and greater use of clinical services on follow-up. Thus, even in this older population, insight is not fixed and there are modifiable predictor variables, thereby suggesting potential points of interventions.

Poster Number: NR 39

Use of Pimavanserin in Combination with Selective Serotonin Reuptake Inhibitors (SSRIs) James C. NortonJr., PhD; Doral Fredericks, PharmD, MBA; Kathy Chi-Burris, MPH; Randy Owen, MD ACADIA Pharmaceuticals Inc., San Diego, CA Introduction: Psychosis is common in Parkinson’s disease (PD) and increases in both frequency and severity with disease duration. It is associated with increased morbidity/mortality, complicates management of motor symptoms and often leads to long-term care placement. Pimavanserin is a potent, selective 5-HT2A inverse agonist/antagonist recently approved in the U.S. for treatment of hallucinations and delusions associated with Parkinson’s disease psychosis (PDP). In addition to psychosis, PD patients have other significant neuropsychiatric comorbidities and are frequently on numerous concomitant medications. Depression, specifically, affects up to 60% of PD patients and is frequently treated with SSRIs/SNRIs. Data in the literature support the potential for a synergistic effect between 5-HT2A receptor inverse agonist/antagonists and SSRIs in patients with neuropsychiatric disease. This post-hoc analysis evaluated a subgroup of patients from the pimavanserin clinical program to determine if there was any difference in antipsychotic response between the subjects receiving pimavanserin in combination with an SSRI versus those without. Methods: A pooled analysis of two 6-week randomized, double-blind, placebo-controlled Phase 3 studies of pimavanserin 34 mg (equivalent to 40 mg pimavanserin tartrate), consisting of the 020 data and the 012 North America (NA) data, was conducted to assess the overall treatment effect of pimavanserin 34 mg. The outside-NA region in Study 012 was not included due to a difference in methodology in the assessment of the primary endpoint. In Study 020 and Study 012 NA region the SAPS measure was assessed by central, independent raters over live video feed; this was not the case for sites in Study 012

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Am J Geriatr Psychiatry 25:3S, Supplement 1

2017 AAGP Annual Meeting outside of NA, where site-based raters conducted the assessments. Only sites using central, independent raters were pooled for this analysis. Subjects in both the 020 and 012 studies received 42 days of treatment, the end-of-treatment visit was referred to as Day 43 in 020 and Day 42 in 012. The mITT population included 268 subjects; with 135 in the pimavanserin 34 mg group and 133 in the placebo group. The full safety dataset included 433 subjects; with 202 in the pimavanserin 34 mg group and 231 in the placebo group. Of the 268 patients in the mITT population 189 patients did not take concomitant SSRIs while a total of 77 received concomitant therapy with SSRIs. A subgroup analysis was conducted to determine if there was any difference in response among the 77 subjects receiving pimavanserin in combination with an SSRI. Results: Overall, pimavanserin 34 mg demonstrated a 6.21-point improvement in psychosis at Week 6 as measured by blinded, independent raters using the PD-adapted Scale for Assessment of Positive Symptoms (SAPS-PD; primary change from baseline analysis [MMRM]). The treatment difference was 2.87 points over placebo (p < 0.001) and was clinically meaningful. Both subgroups (pimavanserin +/− SSRI) demonstrated a statistically significant improvement in the pimavanserin arm over placebo. Among patients taking concomitant SSRIs, the decrease in psychosis symptoms as measured by SAPS-PD at Day 43 was more prominent for both pimavanserin and placebo-treated subjects (−8.33 points and −4.01 points, respectively) compared to the 189 subjects not taking SSRIs (−5.36 points and −3.01 points, respectively); the treatment difference was of greater magnitude in the concomitant SSRI treated group (−4.32 vs. −2.34). A total of 10% (4/40) and 7.4% (12/162) of pimavanserin 34 mg treated patients, with and without SSRIs, respectively, discontinued because of adverse reactions. Conclusions: The results of this analysis further support findings that the combination of selective 5-HT2A agonist/antagonists and SSRIs may have additive beneficial effects, suggesting a possible enhancement of antipsychotic effect in patients treated with concomitant SSRIs. This research was funded by: ACADIA Pharmaceuticals Inc.

Poster Number: NR 40

Meeting Residents Halfway: The Geriatric Psychiatry Residency Track Susan M. Duffy, MD1; Susan K. Schultz, MD, MD2; Susan Maixner, MD3; Heba Gad, MD4; Nancy Williams, MD1; Faisal Tai, MD1 1

University of Iowa, Iowa City, IA University of Southern Florida, Tampa, FL 3 University of Michigan, Ann Arbor, MI 4 Dartmouth, Lebanon, NH 2

Introduction: The 2012 survey of Geriatric Psychiatry Fellowship Programs supported by the American Geriatrics Society and the Association of Directors of Geriatrics Academic Programs showed a decline in residents pursuing a fellowship as well as fewer total programs available. One reason for this decline is thought to be the additional year of training, which has led to requests to allow residents to commence the fellowship in their fourth year. Given that this request has not yet been successful, finding an alternative method of improving geriatric education is of utmost importance. One such method may be minifellowships within residency as a way of improving knowledge in a specific area but in a shortened timespan. We examined mini-fellowship programs offered in other residencies and used their format as a template to devise a Geriatric Psychiatry “track”. The Geriatric Psychiatry track is a 6 month 4th year elective that provides a cohesive clinical and didactic experience for residents who desire geriatric training but not the full fellowship. Methods: Residents were surveyed at different residency sites regarding their interest in a geriatric psychiatry fellowship as well as the elective geriatric psychiatry “track” within the residency. Specific questions focused on reasons for not pursing a fellowship in geriatrics as well as whether the track option would decrease the likelihood of applying for a fellowship. Basic demographic information was collected as well to assess correlation with responses. Results: A variety of factors contribute to life decisions during residency beyond academic interest in geriatric care. The demographics and social factors related to interest in pursuing a geriatric psychiatry fellowship and/or geriatric psychiatry elective track are described. Reasons for either choice are qualitatively presented along with the frequency of specific responses. Positive and negative attributes of each choice as voiced by the applicants and residents are qualitatively presented, including the perceived value of formal certification relative to advanced knowledge in the absence of certification. Conclusions: Data from this study provide essential information regarding whether a geriatric psychiatry track as a 4th year elective could add an alternative way of boosting geriatric knowledge in a manner that is acceptable to trainees and in line with their social, family and career needs. If effective, this would increase the number of providers with a higher level of geriatric psychiatry knowledge. Beyond our traditional training programs, innovative methods such as mini-fellowships may offer one solution to a highly complex problem.

Am J Geriatr Psychiatry 25:3S, Supplement 1

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