Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia. A Randomized Clinical Trial.

IMPORTANCE: Long-acting, injectable, second-generation antipsychotic medication has tremendous potential to bring clinical stability to persons with schizophrenia. However, long-acting medications are rarely used following a first episode of schizophrenia. OBJECTIVE: To compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial performed at a university-based research clinic, between 2005 and 2012. Eighty-six patients with recent onset of schizophrenia were randomized to receive long-acting injectable risperidone or oral risperidone. Half of each group was simultaneously randomized to receive cognitive remediation to improve cognitive functioning or healthy-behaviors training to improve lifestyle habits and well-being. An intent-to-treat analysis was performed between October 4, 2012, and November 12, 2014. INTERVENTIONS: A 12-month trial comparing the long-acting injectable vs oral risperidone and cognitive remediation vs healthy-behaviors training. MAIN OUTCOMES AND MEASURES: Psychotic relapse and control of breakthrough psychotic symptoms. RESULTS: Of the 86 patients randomized, 3 refused treatment in the long-acting injectable risperidone group. The psychotic exacerbation and/or relapse rate was lower for the long-acting risperidone group compared with the oral group (5% vs 33%; χ21 = 11.1; P < .001; relative risk reduction, 84.7%). Long-acting injectable risperidone better controlled mean levels of hallucinations and delusions throughout follow-up (ß = -0.30; t68 = -2.6, P = .01). The cognitive remediation and healthy-behaviors training groups did not differ significantly regarding psychotic relapse, psychotic symptom control, or hospitalization rates, and there were no significant interactions between the 2 medications and the 2 psychosocial treatments. Discontinuations owing to inadequate clinical response were more common in the oral group than in the long-acting risperidone group (χ21 = 6.1; P = .01). Adherence to oral risperidone did not appear to differ before randomization but was better for the long-acting risperidone group compared with the oral group (t80 = 5.3; P < .001). Medication adherence was associated with prevention of exacerbation and/or relapse (χ21 =11.1; P = .003) and control of breakthrough psychotic symptoms (ß = 0.2; t79 = 2.1; P = .04). CONCLUSIONS AND RELEVANCE: The use of long-acting injectable risperidone after a first episode of schizophrenia has notable advantages for clinical outcomes. The key clinical advantages are apparently owing to the more consistent administration of the long-acting injectable. Such formulations should be offered earlier in the course of illness. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00333177.

The impact of second-generation antipsychotic adherence on positive and negative symptoms in recent-onset schizophrenia.

OBJECTIVE: The aim of the study was to explore the extent to which initial severity of positive or negative symptoms in patients with recent-onset schizophrenia is related to medication nonadherence during the first outpatient year. METHODS: The study involved 64 first-episode schizophrenia patients treated with the second-generation oral antipsychotic medication, risperidone, for 12 months. Symptoms were evaluated using the SANS and SAPS completed every 3 months. Pearson correlations between medication adherence and symptoms were examined over each 3-month interval during 12 months of follow-through treatment. Possible causality was inferred from cross-lagged panel analyses. RESULTS: As expected, higher levels of adherence with antipsychotic medication were generally associated with lower levels of concurrent reality distortion (mean of SAPS delusions and hallucinations). Greater adherence during the 3-month baseline interval was generally associated with lower levels of avolition-apathy as well as alogia throughout the first outpatient year. However, medication adherence was not significantly associated with decreases in avolition-apathy or alogia over time. Cross-lagged panel analyses based on correlation coefficients are consistent with a causal relationship between initial medication adherence and lower levels of alogia. A test of mediation confirmed that an indirect path through reality distortion mediated the relationship between medication nonadherence and alogia. CONCLUSIONS: The associations between greater medication adherence and lower levels of negative symptoms appeared to be accounted for by the relationship of both variables to positive psychotic symptoms. The findings suggest that the impact of second-generation antipsychotic medication on suppression of negative symptoms might be mediated via a reduction in positive symptoms.

Impact on intracortical myelination trajectory of long acting injection versus oral risperidone in first-episode schizophrenia.

CONTEXT: Imaging and post-mortem studies suggest that frontal lobe intracortical myelination is dysregulated in schizophrenia (SZ). Prior MRI studies suggested that early in the treatment of SZ, antipsychotic medications initially increase frontal lobe intracortical myelin (ICM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of ICM decline in chronic SZ is due to medication non-adherence or pharmacokinetics, it may be modifiable by long acting injection (LAI) formulations. OBJECTIVES: Assess the effect of risperidone formulation on the ICM trajectory during a six-month randomized trial of LAI (RLAI) versus oral (RisO) in first-episode SZ subjects. DESIGN: Two groups of SZ subjects (RLAI, N=9; and RisO, N=13) matched on pre-randomization oral medication exposure were prospectively examined at baseline and 6 months later, along with 12 healthy controls (HCs). Frontal lobe ICM volume was assessed using inversion recovery (IR) and proton density (PD) MRI images. Medication adherence was tracked. MAIN OUTCOME MEASURE: ICM volume change scores were adjusted for the change in the HCs. RESULTS: ICM volume increased significantly (p=.005) in RLAI and non-significantly (p=.39) in the RisO groups compared with that of the healthy controls. A differential between-group treatment effect was at a trend level (p=.093). SZ subjects receiving RLAI had better medication adherence and more ICM increases (chi-square p<.05). CONCLUSIONS: The results suggest that RLAI may promote ICM development in first-episode SZ patients. Better adherence and/or pharmacokinetics provided by LAI may modify the ICM trajectory. In vivo MRI myelination measures can help clarify pharmacotherapeutic mechanisms of action.

Long acting injection versus oral risperidone in first-episode schizophrenia: differential impact on white matter myelination trajectory.

CONTEXT: Imaging and post-mortem studies provide converging evidence that subjects with schizophrenia (SZ) have a dysregulated trajectory of frontal lobe myelination. Prior MRI studies suggested that early in treatment of SZ, antipsychotic medications initially increase frontal lobe white matter (WM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of WM decline associated with chronic disease may be due to medication non-adherence, it may be modifiable by long acting injection (LAI) formulations. OBJECTIVES: Examine the impact of antipsychotic formulation on the myelination trajectory during a randomized six-month trial of LAI risperidone (RLAI) versus oral risperidone (RisO) in first-episode SZ subjects. DESIGN: Two groups of SZ subjects (RLAI, N=11; and RisO, N=13) that were matched in pre-randomization oral medication exposure and 14 healthy controls (HCs) were prospectively examined. Frontal lobe WM volume was estimated using inversion recovery (IR) MRI images. A brief neuropsychological battery that focused on reaction times was performed at the end of the study. MAIN OUTCOME MEASURE: WM volume change scores. RESULTS: WM volume remained stable in the RLAI and decreased significantly in the RisO groups resulting in a significant differential treatment effect, while the HC had a WM change intermediate and not significantly different from the two SZ groups. WM increase was associated with faster reaction times in tests involving frontal lobe function. CONCLUSIONS: The results suggest that RLAI may improve the trajectory of myelination in first-episode patients and have a beneficial impact on cognitive performance. Better adherence provided by LAI may underlie the modified trajectory of myelin development. In vivo MRI biomarkers of myelination can help clarify mechanisms of action of treatment interventions.

Diversity initiatives in academic psychiatry: applying cultural competence.

OBJECTIVE: This article describes the process of change in an academic department of psychiatry that has led to the development of a diversity initiative in teaching, research, recruitment, and services. METHODS: The authors performed a literature review of diversity initiatives using PubMed. The authors then wrote a case study of the development of a diversity initiative at UC Davis. RESULTS: Some articles on diversity initiatives were found, but none that detailed the administrative process, funding, or sustainability of such initiatives. In 1999, the UC Davis Department of Psychiatry and Behavioral Sciences recognized the importance of issues of diversity and established the Diversity Advisory Committee, a group of department faculty and residents that explores and addresses the diversity needs of the department. In our observations, there are at least three requirements for a successful diversity initiative: a diverse patient population, a "critical mass" of interested faculty, and support of the administration. With these three factors in place, the Diversity Advisory Committee produced four Continuing Medical Education symposia focused on diversity topics, developed a 4-year cultural psychiatry curriculum and a 4-year religion and spirituality curriculum within the residency, and supported nine residents who received awards from the APA's Minority Fellowships in 8 years. Future plans include department-wide and medical school faculty-wide diversity training, educational research, and a postgraduate fellowship in cultural psychiatry. CONCLUSION: This article shows that a diversity initiative can be undertaken with interested minority and nonminority faculty, administrative support, and a diverse patient population. The authors hope this article will provide assistance to other academic departments in developing diversity initiatives.

Considerations in change management related to technology.

OBJECTIVE: The authors describe the complexity of social processes for implementing technological change. Once a new technology is available, information about its availability and benefits must be made available to the community of users, with opportunities to try the innovations and find them worthwhile, despite organizational resistances. METHOD: The authors reviewed the literature from psychiatry, psychology, sociology, business, and technology to distill common denominators for success and failure related to implementing technology. RESULTS: Beneficial technological innovations that are simple to use and obviously save everyone time and effort are easy to inaugurate. However, innovations that primarily serve management rather than subordinates or front-line utilizers may fail, despite considerable institutional effort. This article reviews and outlines several of the more prominent theoretical models governing successful institutional change. CONCLUSIONS: Successful implementation of difficult technological changes requires visionary leadership that has carefully considered the benefits, consulted with influence leaders at all organizational levels to spot unintended consequences and sources of resistance, and developed a detailed plan and continuous quality assurance process to foster implementation over time.

APA summit on medical student education task force on informatics and technology: steps to enhance the use of technology in education through faculty development, funding and change management.

OBJECTIVE: This article provides an overview of how trainees, faculty, and institutions use technology for acquiring knowledge, skills, and attitudes for practicing modern medicine. METHOD: The authors reviewed the literature on medical education, technology, and change, and identify the key themes and make recommendations for implementing technology in medical education. RESULTS: Administrators and faculty should initially assess their own competencies with technology and then develop a variety of teaching methods that use technology to improve their curricula. Programs should decrease the general knowledge-based content of curricula and increase the use of technology for learning skills. For programs to be successful, they must address faculty development, change management, and funding. CONCLUSIONS: Willingness for change, collaboration, and leadership at all levels are essential factors for successfully implementing technology.

Personal digital assistants in psychiatric education.

OBJECTIVE: This article describes the various administrative and clinical applications for PDA use in psychiatric care and review the process for implementation in an academic medical center. METHOD: The authors reviewed the psychiatric literature and tested various hardware and software products. RESULTS: The literature describes various uses of the PDA as a reference tool, in clinical care, and in training documentation. CONCLUSIONS: The PDA is capable of numerous vital roles in medical education.

APA Summit on Medical Student Education Task Force on Informatics and Technology: learning about computers and applying computer technology to education and practice.

OBJECTIVE: This article provides a brief overview of important issues for educators regarding medical education and technology. METHODS: The literature describes key concepts, prototypical technology tools, and model programs. A work group of psychiatric educators was convened three times by phone conference to discuss the literature. Findings were presented to and input was received from the 2005 Summit on Medical Student Education by APA and the American Directors of Medical Student Education in Psychiatry. RESULTS: Knowledge of, skills in, and attitudes toward medical informatics are important to life-long learning and modern medical practice. A needs assessment is a starting place, since student, faculty, institution, and societal factors bear consideration. Technology needs to "fit" into a curriculum in order to facilitate learning and teaching. CONCLUSION: Learning about computers and applying computer technology to education and clinical care are key steps in computer literacy for physicians.

Telepsychiatry: an overview for psychiatrists.

Telepsychiatry, in the form of videoconferencing and other modalities, brings enormous opportunities for clinical care, education, research and administration to the field of medicine. A comprehensive review of the literature related to telepsychiatry - specifically videoconferencing - was conducted using the MEDLINE, Embase, Science Citation Index, Social Sciences Citation Index and Telemedicine Information Exchange databases (1965 to June 2001). The keywords used were telepsychiatry, telemedicine, videoconferencing, Internet, primary care, education, personal digital assistant and handheld computers. Studies were selected for review if they discussed videoconferencing for patient care, satisfaction, outcomes, education and costs, and provided models of facilitating clinical service delivery. Literature on other technologies was also assessed and compared with telepsychiatry to provide an idea of future applications of technology. Published data indicate that telepsychiatry is successfully used for a variety of clinical services and educational initiatives. Telepsychiatry is generally feasible, offers a number of models of care and consultation, in general satisfies patients and providers, and has positive and negative effects on interpersonal behaviour. More quantitative and qualitative research is warranted with regard to the use of telepsychiatry in clinical and educational programmes and interventions.