Jennifer D. Gottlieb

Comprehensive Versus Usual Community Care for First-Episode Psychosis: 2-Year Outcomes From the NIMH RAISE Early Treatment Program

OBJECTIVE The primary aim of this study was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first-episode psychosis designed for implementation in the U.S. health care system, with community care on quality of life. METHOD Thirty-four clinics in 21 states were randomly assigned to NAVIGATE or community care. Diagnosis, duration of untreated psychosis, and clinical outcomes were assessed via live, two-way video by remote, centralized raters masked to study design and treatment. Participants (mean age, 23) with schizophrenia and related disorders and ≤6 months of antipsychotic treatment (N=404) were enrolled and followed for ≥2 years. The primary outcome was the total score of the Heinrichs-Carpenter Quality of Life Scale, a measure that includes sense of purpose, motivation, emotional and social interactions, role functioning, and engagement in regular activities. RESULTS The 223 recipients of NAVIGATE remained in treatment longer, experienced greater improvement in quality of life and psychopathology, and experienced greater involvement in work and school compared with 181 participants in community care. The median duration of untreated psychosis was 74 weeks. NAVIGATE participants with duration of untreated psychosis of <74 weeks had greater improvement in quality of life and psychopathology compared with those with longer duration of untreated psychosis and those in community care. Rates of hospitalization were relatively low compared with other first-episode psychosis clinical trials and did not differ between groups. CONCLUSIONS Comprehensive care for first-episode psychosis can be implemented in U.S. community clinics and improves functional and clinical outcomes. Effects are more pronounced for those with shorter duration of untreated psychosis.

Once-weekly D-cycloserine effects on negative symptoms and cognition in schizophrenia: an exploratory study.

BACKGROUND Daily dosing with d-cycloserine has inconsistently improved negative symptoms in schizophrenia patients, whereas intermittent dosing significantly facilitated exposure-based therapy in two studies of patients with phobic anxiety. In animal models, single-dose administration enhances memory consolidation, but tachyphylaxis develops with repeated dosing. The objective of this exploratory study was to assess whether once-weekly dosing with d-cycloserine will produce persistent improvements in negative symptoms and cognition. METHODS Fifty stable adult schizophrenia outpatients treated with any antipsychotic except clozapine were enrolled and 38 were randomized, double-blind, in a parallel-group, eight-week add-on trial of d-cycloserine 50 mg or placebo administered once-weekly. Symptom rating scales and a cognitive battery were administered at baseline and week 8 before the dose of study drug. As an exploratory analysis of memory consolidation, the Logical Memory Test, modified to measure recall after 7 days, was administered at baseline and after the first weekly dose of d-cycloserine. The primary outcome measures were change from baseline to week 8 on the SANS total score and on a composite cognitive score. RESULTS Thirty-three subjects (87%) completed the trial. d-cycloserine significantly improved SANS total scores compared to placebo at week 8. Cognitive performance did not improve with d-cycloserine at 8 weeks. Delayed thematic recall on the Logical Memory Test was significantly improved with the first dose of d-cycloserine compared to placebo. Performance on immediate thematic recall and item recall on the Logical Memory Test did not differ between treatments. CONCLUSIONS Once-weekly dosing with d-cycloserine for 8 weeks produced persistent improvement of negative symptoms compared to placebo, although statistical significance was, in part, the result of worsening of negative symptoms with placebo. Consistent with animal models, a single dose of d-cycloserine facilitated memory consolidation tested after 7 days on a test of thematic recall. These results must be considered preliminary since a number of outcomes were examined without correction for multiple tests. These findings suggest that once-weekly dosing with d-cycloserine for the treatment of negative symptoms merits further study, as do d-cycloserine effects on memory consolidation.

The NAVIGATE Program for First-Episode Psychosis: Rationale, Overview, and Description of Psychosocial Components

Comprehensive coordinated specialty care programs for first-episode psychosis have been widely implemented in other countries but not in the United States. The National Institute of Mental Healths Recovery After an Initial Schizophrenia Episode (RAISE) initiative focused on the development and evaluation of first-episode treatment programs designed for the U.S. health care system. This article describes the background, rationale, and nature of the intervention developed by the RAISE Early Treatment Program project-known as the NAVIGATE program-with a particular focus on its psychosocial components. NAVIGATE is a team-based, multicomponent treatment program designed to be implemented in routine mental health treatment settings and aimed at guiding people with a first episode of psychosis (and their families) toward psychological and functional health. The core services provided in the NAVIGATE program include the family education program (FEP), individual resiliency training (IRT), supported employment and education (SEE), and individualized medication treatment. NAVIGATE embraces a shared decision-making approach with a focus on strengths and resiliency and on collaboration with clients and family members in treatment planning and reviews. The NAVIGATE program has the potential to fill an important gap in the U.S. health care system by providing a comprehensive intervention specially designed to meet the unique treatment needs of persons recovering from a first episode of psychosis. A cluster-randomized controlled trial comparing NAVIGATE with usual community care has recently been completed.

D-cycloserine facilitation of cognitive behavioral therapy for delusions in schizophrenia☆

Glutamatergic N-methyl-D-aspartate (NMDA) receptor hypofunction has been proposed as a mechanism underlying psychosis. D-cycloserine, a partial agonist at the glycine site of the NMDA receptor, enhances learning in animal models, although tachyphylaxis develops with repeated dosing. Once-weekly dosing of D-cycloserine produces persistent improvement when combined with cognitive behavioral therapy (CBT) in anxiety disorders. Delusional beliefs can be conceptualized as a learning deficit, characterized by the failure to use contradictory evidence to modify the belief. CBT techniques have been developed with modest success to facilitate such reality-testing (or new learning) in delusional beliefs. The current study evaluated whether D-cycloserine could potentiate beneficial effects of CBT on delusional severity. Twenty-one outpatients with schizophrenia or schizoaffective disorder and moderately severe delusions were randomized in a double-blind cross-over design to receive a single-dose of either D-cycloserine 50mg or placebo in a counterbalanced order on two consecutive weeks 1h prior to a CBT intervention involving training in the generation of alternative beliefs. Assessments were completed at baseline, 7 days following the first study drug administration and 7 days following the second study drug administration. Contrary to prediction, there was no significant d-cycloserine treatment effect on delusional distress or severity as measured by the SAPS or PSYRATS. An unexpected finding was an order effect, whereby subjects who received D-cycloserine first had significantly reduced delusional severity, distress, and belief conviction on PSYRATS compared to subjects who received placebo first. However, this finding is consistent with animal models in which D-cycloserine enhances learning only when accompanying the first exposure to training.

A Randomized Controlled Trial of Family Intervention for Co-occurring Substance Use and Severe Psychiatric Disorders

Substance use disorders have a profound impact on the course of severe mental illnesses and on the family, but little research has evaluated the impact of family intervention for this population. To address this question, a randomized controlled trial was conducted comparing a brief (2-3 mo) Family Education (ED) program with a longer-term (9-18 mo) program that combined education with teaching communication and problem-solving skills, Family Intervention for Dual Disorders (FIDD). A total of 108 clients (77% schizophrenia-spectrum) and a key relative were randomized to either ED or FIDD and assessed at baseline and every 6 months for 3 years. Rates of retention of families in both programs were moderate. Intent-to-treat analyses indicated that clients in both programs improved in psychiatric, substance abuse, and functional outcomes, as did key relatives in knowledge of co-occurring disorders, burden, and mental health functioning. Clients in FIDD had significantly less severe overall psychiatric symptoms and psychotic symptoms and tended to improve more in functioning. Relatives in FIDD improved more in mental health functioning and knowledge of co-occurring disorders. There were no consistent differences between the programs in substance abuse severity or family burden. The findings support the utility of family intervention for co-occurring disorders, and the added benefits of communication and problem-solving training, but also suggest the need to modify these programs to retain more families in treatment in order to provide them with the information and skills they need to overcome the effects of these disorders.

Therapeutic Factors Contributing to Change in Cognitive-Behavioral Group Therapy for Older Persons with Schizophrenia

The contributions of homework, therapy participation, cognitive insight, and skills acquisition to treatment outcomes in group CBT for schizophrenia were examined. Increased cognitive insight was associated with reduced positive, negative and total symptoms, but not improved psychosocial functioning. Greater participation was associated with increased cognitive insight, reduction in total and negative symptoms, and a trend was found for positive symptoms. Greater homework adherence was associated with greater skill acquisition, but skill acquisition was not significantly associated with change in any outcome. The therapeutic factors contributing to change in CBT for schizophrenia appear different for symptom and psychosocial functioning outcomes.

Evaluation of cognitive restructuring for post-traumatic stress disorder in people with severe mental illness

BACKGROUND A cognitive-behavioural therapy (CBT) programme designed for post-traumatic stress disorder (PTSD) in people with severe mental illness, including breathing retraining, education and cognitive restructuring, was shown to be more effective than usual services. AIMS To evaluate the incremental benefit of adding cognitive restructuring to the breathing retraining and education components of the CBT programme (trial registration: clinicaltrials.gov identifier: NCT00494650). METHOD In all, 201 people with severe mental illness and PTSD were randomised to 12- to 16-session CBT or a 3-session brief treatment programme (breathing retraining and education). The primary outcome was PTSD symptom severity. Secondary outcomes were PTSD diagnosis, other symptoms, functioning and quality of life. RESULTS There was greater improvement in PTSD symptoms and functioning in the CBT group than in the brief treatment group, with both groups improving on other outcomes and effects maintained 1-year post-treatment. CONCLUSIONS Cognitive restructuring has a significant impact beyond breathing retraining and education in the CBT programme, reducing PTSD symptoms and improving functioning in people with severe mental illness.

mHealth for Schizophrenia: Patient Engagement With a Mobile Phone Intervention Following Hospital Discharge

Background mHealth interventions that use mobile phones as instruments for illness management are gaining popularity. Research examining mobile phone‒based mHealth programs for people with psychosis has shown that these approaches are feasible, acceptable, and clinically promising. However, most mHealth initiatives involving people with schizophrenia have spanned periods ranging from a few days to several weeks and have typically involved participants who were clinically stable. Objective Our aim was to evaluate the viability of extended mHealth interventions for people with schizophrenia-spectrum disorders following hospital discharge. Specifically, we set out to examine the following: (1) Can individuals be engaged with a mobile phone intervention program during this high-risk period?, (2) Are age, gender, racial background, or hospitalization history associated with their engagement or persistence in using a mobile phone intervention over time?, and (3) Does engagement differ by characteristics of the mHealth intervention itself (ie, pre-programmed vs on-demand functions)? Methods We examined mHealth intervention use and demographic and clinical predictors of engagement in 342 individuals with schizophrenia-spectrum disorders who were given the FOCUS mobile phone intervention as part of a technology-assisted relapse prevention program during the 6-month high-risk period following hospitalization. Results On average, participants engaged with FOCUS for 82% of the weeks they had the mobile phone. People who used FOCUS more often continued using it over longer periods: 44% used the intervention over 5-6 months, on average 4.3 days a week. Gender, race, age, and number of past psychiatric hospitalizations were associated with engagement. Females used FOCUS on average 0.4 more days a week than males. White participants engaged on average 0.7 days more a week than African-Americans and responded to prompts on 0.7 days more a week than Hispanic participants. Younger participants (age 18-29) had 0.4 fewer days of on-demand use a week than individuals who were 30-45 years old and 0.5 fewer days a week than older participants (age 46-60). Participants with fewer past hospitalizations (1-6) engaged on average 0.2 more days a week than those with seven or more. mHealth program functions were associated with engagement. Participants responded to prompts more often than they self-initiated on-demand tools, but both FOCUS functions were used regularly. Both types of intervention use declined over time (on-demand use had a steeper decline). Although mHealth use declined, the majority of individuals used both on-demand and system-prompted functions regularly throughout their participation. Therefore, neither function is extraneous. Conclusions The findings demonstrated that individuals with schizophrenia-spectrum disorders can actively engage with a clinically supported mobile phone intervention for up to 6 months following hospital discharge. mHealth may be useful in reaching a clinical population that is typically difficult to engage during high-risk periods.

Public Mental Health Clients with Severe Mental Illness and Probable Posttraumatic Stress Disorder: Trauma Exposure and Correlates of Symptom Severity

Individuals with severe mental illness (SMI) are at greatly increased risk for trauma exposure and for the development of posttraumatic stress disorder (PTSD). This study reports findings from a large, comprehensive screening of trauma and PTSD symptoms among public mental health clients in a statewide community mental health system. In 851 individuals with SMI and probable PTSD, childhood sexual abuse was the most commonly endorsed index trauma, followed closely by the sudden death of a loved one. Participants had typically experienced an average of 7 types of traumatic events in their lifetime. The number of types of traumatic events experienced and Hispanic ethnicity were significantly associated with PTSD symptom severity. Clients reported experiencing PTSD in relation to events that occurred on average 20 years earlier, suggesting the clinical need to address trauma and loss throughout the lifespan, including their prolonged after-effects.

Antisocial personality disorder in people with co-occurring severe mental illness and substance use disorders: clinical, functional, and family relationship correlates

Antisocial personality disorder (ASPD) is an important correlate of substance abuse severity in the addiction population and in people with co-occurring serious mental illness and addiction. Because family members often provide vital supports to relatives with co-occurring disorders, this study explored the correlates of ASPD in 103 people with co-occurring disorders (79% schizophrenia-schizoaffective, 21% bipolar disorder) in high contact with relatives participating in a family intervention study. Clients with ASPD were more likely to have bipolar disorder and to have been married, but less likely to have graduated from high school. ASPD was associated with more severe drug abuse and depression, worse functioning, and less planning-based social problem solving. The relatives of clients with ASPD also reported less planning-based problem solving, worse attitudes towards the client, and worse mental health functioning. Client ASPD was associated with less long-term exposure to family intervention. The findings suggest that clients with ASPD in addition to co-occurring disorders are a particularly disadvantaged group with greater illness severity, more impaired functioning, and more strained family relationships. These difficulties may pose special challenges to delivering family intervention for this group.