A Unique Delusion with Depression in Early Stage of Neurocognitive Disorder Due to Vascular Disease: Considerations for Clinicians.

As global aging becomes more prominent, neurocognitive disorders (NCD) incidence has increased. Patients with NCD usually have an impairment in one or more cognitive domains, such as attention, planning, inhibition, learning, memory, language, visual perception, and spatial or social skills. Studies indicate that 50-80% of these adults will develop neuropsychiatric symptoms (NPS), such as apathy, depression, anxiety, disinhibition, delusions, hallucinations, and aberrant motor behavior. The progression of NCD and subsequent NPS requires tremendous care from trained medical professionals and family members. The behavioral symptoms are often more distressing than cognitive changes, causing caregiver distress/depression, more emergency room visits and hospitalizations, and even earlier institutionalization. This signifies the need for early identification of individuals at higher risk of NPS, understanding the trajectory of their NCD, and exploring treatment modalities. In this case report and review, we present an 82-year-old male admitted to our facility for new-onset symptoms of depression, anxiety, and persecutory delusions. He has no significant past psychiatric history, and his medical history is significant for extensive ischemic vascular disease requiring multiple surgeries and two episodes of cerebrovascular accident (CVA). On further evaluation, the patient was diagnosed with major NCD, vascular subtype. We discuss differential diagnoses and development of NPS from NCD in order to explain the significance of more thorough evaluation by clinicians for early detection and understanding of NCD prognosis.

What Should Be the Scope of Long-Term Care Organizations' Obligations to Offer Culturally and Linguistically Appropriate Services to Patients?

Limited access to health services, decreased quality of care, and worse health outcomes are well documented barriers people with limited English proficiency (LEP) face in US health care. Laws enacted since the 1964 Civil Rights Act recognize such barriers and have helped generate demand for culturally respectful health service provision, assessment of cross-cultural relations, and adaptation of services that fail to meet persons' needs and improve quality of life. Yet, as this commentary on a case considers, even with legal protections for language services for patients with LEP, long-term care facilities face limited resources and thus have limited capacity to offer such services.

Childhood adversity and adulthood major depressive disorder.

OBJECTIVE: Examine how specific types of childhood adversity are associated with clinical features and treatment in adults with Major Depressive Disorder (MDD). METHOD: This is a secondary analysis of the 35-site VA Augmentation and Switching Treatments for Improving Depression Outcomes study. A 10-item Adverse Childhood Events (ACE) survey was administered at baseline. RESULTS: 83% experienced at least one of the 10 ACEs and 20.7% experienced 6 or more. Participants with childhood adversities were more likely to be younger, female, unemployed, single or divorced, and to have had more severe depression and anxiety, more lifetime episodes, a younger age of first diagnosed MDD, more comorbid PTSD, worse quality of life, and more suicidal ideation than those no or fewer adversities. Neither the overall number nor any of the specific types of adversities were associated with lower remission rates after administration of standard "next-step" treatment strategies, while histories of different specific types were associated with lower depression severity, better quality of life, and less suicidal ideation post-treatment. CONCLUSIONS: Attention to different forms of childhood adversity and to diverse clinical outcomes beyond remission and relapse are important considerations when treating individuals with MDD with histories of childhood maltreatment. CLINICALTRIALS: gov identifier: NCT01421342.

Impact of Concurrent Posttraumatic Stress Disorder on Outcomes of Antipsychotic Augmentation for Major Depressive Disorder With a Prior Failed Treatment: VAST-D Randomized Clinical Trial.

OBJECTIVE: To determine whether concurrent posttraumatic stress disorder (PTSD) should affect whether to augment or switch medications when major depressive disorder (MDD) has not responded to a prior antidepressant trial. METHODS: Patients at 35 Veterans Health Administration medical centers from December 2012 to May 2015 with nonpsychotic MDD (N = 1,522) and a suboptimal response to adequate antidepressant treatment were randomly assigned to 3 "next step" treatments: switching to bupropion, augmenting the current antidepressant with bupropion, and augmenting with the antipsychotic aripiprazole. Blinded ratings with the 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C16) determined remission and response by 12 weeks and relapse after remission. Survival analyses compared treatment effects in patients with concurrent PTSD diagnosed with the Mini-International Neuropsychiatric Interview (n = 717, 47.1%) and those without PTSD (n = 805, 52.9%). RESULTS: Patients diagnosed with PTSD showed more severe depressive symptoms at baseline and were less likely to achieve either remission or response by 12 weeks. Augmentation with aripiprazole was associated with greater likelihood of achieving response (68.4%) than switching to bupropion (57.7%) in patients with PTSD (relative risk [RR] = 1.26; 95% CI, 1.01-1.59) as well as in patients without PTSD (RR = 1.29; 95% CI, 1.05-1.97) (78.9% response with aripiprazole augmentation vs 66.9% with switching to bupropion). Treatment comparisons with the group receiving augmentation with bupropion were not significant. There was no significant interaction between treatment group and PTSD on remission (P = .70), response (P = .98), or relapse (P = .15). CONCLUSIONS: Although PTSD was associated with poorer overall outcomes, the presence of concurrent PTSD among Veterans in this trial did not affect the comparative effectiveness of medications on response, remission, or relapse after initial remission. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01421342.

Impact of opioid therapy on gonadal hormones: focus on buprenorphine.

Objective The USA is in the midst of an opioid crisis. Understanding the impact of opioids and commonly used treatments for opioid dependence is essential for clinicians and researchers in order to educate and treat the nation's growing population with opioid use disorders. As a relatively new treatment for opioid dependence, buprenorphine is gaining popularity to the extent of becoming not only a preferred approach to the maintenance of opiate addiction, but also an option for chronic pain management. The purpose of this report is to review the available evidence on the endocrine effects of buprenorphine, particularly as it relates to the hypothalamic-pituitary-gonadal (HPG) axis, which is controversial and not fully defined. Method We conducted a Pubmed search (2000-2017) for human studies in the English language for articles that were available as full length regarding buprenorphine, endocrinopathy, hypogonadism, bone density, opioids. Case reports were also reviewed, although prospective studies and randomized controlled trials received more weight. Results Opioid induced hypogonadism is well established. Most studies report that buprenorphine being a partial agonist/antagonist may not be impacting the pituitary trophic hormones as much. There are reports of sexual dysfunction in subjects maintained on buprenorphine, some without hormonal correlation. Thus with the understanding that pertinent clinical studies are limited in number, varied in methodology, mostly cross sectional, predominantly in men and small number of participants, more research in this area is warranted. Conclusion Based on a comprehensive review of the available literature, we conclude that despite its increasing popularity, buprenorphine has not been adequately studied in respect to its long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis. There is a great need for longitudinal systematic trials to define the potential buprenorphine-induced endocrine consequences.

Fat Distribution in Schizophrenia Patients: A Pilot Study Comparing First- and Second-Generation Antipsychotics.

BACKGROUND: Introduction of second-generation antipsychotics (SGAs) has reduced neurologic toxicity but are associated with increased weight gain and obesity. The objective of this pilot study is to compare the effects of first-generation antipsychotics (FGAs) and SGAs in patients with schizophrenia on body fat and presumed concomitant metabolic parameters. METHODS: Study compared schizophrenia nondiabetic men treated with FGAs (group 1, n = 5) and men treated with SGAs (group 2, n = 9). Each subject completed psychiatric and endocrine evaluation including severity of psychiatric symptoms, adverse effects, body weight, body composition, and measurements of glucose, insulin, adipokines, and inflammatory markers. Student t test was used for statistical analysis. RESULTS: Men treated with FGAs had a lower mean body mass index with a trend toward statistical significance (25.3 ± 1.4 vs 29.3 ± 1.7, P = 0.06). Treatment with FGAs was associated with lower waist/height ratio (0.55 ± 0.02 vs 0.62 ± 0.02, P = 0.036) and android fat mass index (0.62 ± 0.01 vs 0.96 ± 0.1, P = 0.03). Homeostasis Model Assessment for insulin resistance values were suggestive of significantly lower peripheral insulin resistance in men treated with FGAs (0.92 ± 0.15 vs 2.3 ± 0.34, P = 0.014). CONCLUSIONS: The results of this study are significant for decreased peripheral insulin resistance in men treated with SGAs in a setting of no significant age difference and only a trend toward higher body mass index, but consistent documentation of increased abdominal fat by 3 different methodologies. Future studies involving larger number of subjects are warranted to verify the present findings.

Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial.

IMPORTANCE: Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. OBJECTIVE: To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. DESIGN, SETTING, AND PARTICIPANTS: From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. INTERVENTIONS: Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). MAIN OUTCOMES AND MEASURES: The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. RESULTS: Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. CONCLUSIONS AND RELEVANCE: Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01421342.

Characteristics of U.S. Veteran Patients with Major Depressive Disorder who require "next-step" treatments: A VAST-D report.

OBJECTIVE: Finding effective and lasting treatments for patients with Major Depressive Disorder (MDD) that fail to respond optimally to initial standard treatment is a critical public health imperative. Understanding the nature and characteristics of patients prior to initiating "next-step" treatment is an important component of identifying which specific treatments are best suited for individual patients. We describe clinical features and demographic characteristics of a sample of Veterans who enrolled in a "next-step" clinical trial after failing to achieve an optimal outcome from at least one well-delivered antidepressant trial. METHODS: 1522 Veteran outpatients with nonpsychotic MDD completed assessments prior to being randomized to study treatment. Data is summarized and presented in terms of demographic, social, historical and clinical features and compared to a similar, non-Veteran sample. RESULTS: Participants were largely male and white, with about half unmarried and half unemployed. They were moderately severely depressed, with about one-third reporting recent suicidal ideation. More than half had chronic and/or recurrent depression. General medical and psychiatric comorbidities were highly prevalent, particularly PTSD. Many had histories of childhood adversity and bereavement. Participants were impaired in multiple domains of their lives and had negative self-worth. LIMITATIONS: These results may not be generalizable to females, and some characteristics may be specific to Veterans of US military service. There was insufficient data on age of clinical onset and depression subtypes, and three novel measures were not psychometrically validated. CONCLUSIONS: Characterizing VAST-D participants provides important information to help clinicians understand features that may optimize "next-step" MDD treatments.

Adiposity-independent hypoadiponectinemia as a potential marker of insulin resistance and inflammation in schizophrenia patients treated with second generation antipsychotics.

OBJECTIVE: The purpose of this study was to explore body fat independent effect of second generation antipsychotics (SGAs) on measures of glucose and adipokine homeostasis, and markers of inflammation. METHOD: Eight non-diabetic men with schizophrenia (age: 55±3years, BMI: 29.7±1.2kg/m(2)) on SGAs were studied after an overnight fast. DXA and single-cut CT of abdomen were respectively used for the assessment of total body and abdominal fat. Blood samples were collected for measurements of glucose, insulin, leptin, adiponectin, C-reactive protein (CRP), and TNF-α. Data in schizophrenic subjects were compared to eight age (55±2.8years) and BMI (29.6±1.1kg/m(2)) matched healthy men. RESULTS: The results were significant for markedly decreased serum adiponectin in schizophrenia patients (4.6±0.9 vs 11.1±1.5ng/mL, p=0.001). Lower levels of adiponectin in schizophrenia men were associated with significant increases in insulin resistance (4.2±0.7 vs 1.7±0.4, p=0.004), CRP (3.5±1.2 vs 1.2±0.3, p=0.037), and leptin (12±1.4 vs 8.5±1.4ng/mL, p=0.05). Various measures of adiposity, including fat mass index (FMI) and abdominal fat were not different in the two study groups. CONCLUSIONS: These findings in the context of comparable age and total body/abdominal fat mass are assumed to be either disease specific, and/or treatment inflicted. The definitive invoking etiology and a presumptive role of hypoadiponectinemia in the development of insulin resistance and increased risk of inflammation warrant future investigation.

Reasons for adherence and nonadherence: a pilot study comparing first- and multi-episode schizophrenia patients.

RATIONALE: Most first-episode schizophrenia patients will stop their medication after their acute symptoms improve. Understanding the salient motivations and attitudes that drive adherence--as well as nonadherence--is an important part of developing strategies to prevent or delay nonadherence during the early phases of the illness. METHODS: Self-reported reasons for adherence and nonadherence among first-episode and multi-episode patients with schizophrenia were obtained from cross-sectional adherence interviews from two prospective adherence studies: one composed of a first-episode sample (n=33) and the other with recently relapsing multi-episode patients (n=16). Both groups received the Rating of Medication Influences (ROMI) Scale at approximately 16 to 20 weeks after an acute psychotic episode. The specific ROMI items were ranked in order of percentage (%) strong, and were compared both within each patient group for rank order of importance, and also compared between groups to determine the differences in specific adherence and nonadherence influences. RESULTS: The doctor-patient relationship was more likely to be endorsed as a strong adherence influence in the first-episode sample (74%) than in the multi-episode sample (13%, X²=18.07, p<.01). Change in physical appearance attributed to medication was a more commonly endorsed nonadherence influence for the multi-episode sample (25%) relative to the first-episode sample (0%, X²=9.2, p<.01). CONCLUSIONS: The doctor-patient relationship stands out as being the major reason for ongoing adherence for first-episode schizophrenia patients. Our post hoc interpretation is that lack of prior experience with medication and treatment elevates the importance of the relationship with the treating clinician for first-episode patients.

Panic-attack-induced transient leukocytosis in a healthy male: a case report.

The lifetime prevalence of panic attacks is 28.3% in American adults 18 years and older. The age of onset of panic attack extends throughout adulthood; however, it typically develops in early adulthood, with median age of onset of 22 years [Kessler R.C., Chiu W.T., Jin R., Ruscio A.M., Shear K., Walters E.E. The epidemiology of panic attacks, panic disorder, and agoraphobia in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2006 Apr;63(4):415-24.]. As reported in our case, panic attacks could induce transient leukocytosis in healthy adults. If practitioners recognize this association, expensive investigations and extensive hospital stays may be prevented, although prudent practice would likely still require some type of investigations.

Anti-amyloid treatments in Alzheimer's disease.

Alzheimer's disease is one of the most challenging threats to the healthcare system in society. One of the main characteristic of Alzheimer's disease (AD) pathology is formation of amyloid plaques from accumulation of amyloid beta peptide. The therapeutic agents that are currently available for AD including acetylcholinesterase inhibitors (AchEIs) and the N-methyl-D-aspartate (NMDA) antagonist are focused on improving the symptoms and do not revert the progression of the disease. This limitation coupled with the burgeoning increase in the prevalence of AD and resultant impact on healthcare economics calls for more substantial treatments for AD. According to the leading amyloid hypothesis, cleavage of amyloid precursor protein to release amyloid beta peptide is the critical event in pathogenesis of Alzheimer's disease. Recently treatment strategies have been focused on modifying the formation, clearance and accumulation of neurotoxic amyloid beta peptide. This article reviews different therapeutic approaches that have been investigated to target amyloid beta ranging from secretase modulators, antiaggregation agents to amyloid immunotherapy. Authors review the different novel drugs which are in clinical trials.

Symptomatic remission in a multiracial urban population of older adults with schizophrenia.

OBJECTIVE: Symptomatic remission has been reported in younger patients with schizophrenia. This study aims to determine the prevalence of symptomatic remission in older adults with schizophrenia. METHODS: The Schizophrenia Group consisted of 198 persons aged 55+ years living in the community who developed schizophrenia before age 45 years. Our definition of remission was adapted from the criteria of the Remission in Schizophrenia Working Group. To attain remission, persons had to have scores of <3 on eight domains of the Positive and Negative Symptom Scale and no hospitalizations within the previous year. Using George's Social Antecedent Model, we examined the association of remission with 18 predictor variables. RESULTS: Forty-nine percent of the sample met the criteria for symptomatic remission. In logistic regression analysis, four variables--fewer total network contacts, greater proportion of intimates, fewer lifetime traumatic events, and higher Dementia Rating Scale scores--were significantly associated with remission. CONCLUSIONS: Remission rates were consistent with those reported in younger samples. Our findings suggest that symptomatic remission is an attainable goal and that treatments focused on those variables associated with remission may augment outcomes in older persons with schizophrenia.

Subjective reasons for adherence to psychotropic medication and associated factors among older adults with schizophrenia.

RATIONALE: There are limited data examining subjective influences on medication adherence among older persons with schizophrenia. The subjective reasons for adherence to antipsychotic medication and associated clinical and psychosocial factors in this population are examined. METHODS: The sample consisted of 198 community dwelling persons aged >or=55 who developed schizophrenia before age 45. Using the Rating of Medication Influences Scale (ROMI), a principal component factor analysis with varimax rotation yielded three subscales: Medication Affinity and Prevention, Influence of Others, and Impact of Authority. These subscales were dichotomized into high and low based on a median split. We also created an ordinal High Adherence measure based on the summed scores of each person's three dichotomized ROMI subscales. A modified Health Belief Model was used to examine the association between 18 predictor variables and the ROMI subscales and the adherence scale. RESULTS: The mean subscale rankings were Medication Affinity and Prevention > Impact of Authority > Influence of Others. In logistic regression, lower education, more side effects, higher depression scores, and more mental health services were associated with higher scores on Influence of Others subscale. More side effects and more entitlements were associated with higher scores on the Medication Affinity and Prevention subscale. The Impact of Authority subscale had no significant associations. More side effects and higher depression scores were associated with higher scores on High Adherence measure. CONCLUSION: We identified a three-dimensional model for explaining the subjective reasons for medication adherence in older persons with schizophrenia. Our findings suggest that cognitive approaches and use of authority figures may be useful for promoting adherence in older adults. Independent variables associated with these subscales may provide guidance for improving adherence in this population.