Jared P. Walsh

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.

Risperidone augmentation for schizophrenia partially responsive to clozapine: A double-blind, placebo-controlled trial

RATIONALE Risperidone augmentation of clozapine in refractory schizophrenia has theoretical but only inconsistent support from clinical trials. OBJECTIVES To examine if adding risperidone to stable yet symptomatic schizophrenia outpatients on optimized clozapine monotherapy improves psychopathology. METHODS We conducted a double-blind placebo-controlled parallel-group trial of a fixed dose of 4 mg/day risperidone added for 6 weeks in 24 outpatients with schizophrenia. RESULTS Subjects who received risperidone showed a non-significant decrease in PANSS total score. The PANSS disorganized thought subscale improved significantly (beta=-3.3079, p=0.047). CONCLUSIONS Our trial does not support the routine addition of risperidone to clozapine in refractory schizophrenia patients. However, much larger trials are needed to conclusively settle the question of added efficacy from this combination.

Modafinil for clozapine-treated schizophrenia patients: a double-blind, placebo-controlled pilot trial.

BACKGROUND Patients with schizophrenia often suffer from cognitive deficits and negative symptoms that are poorly responsive to antipsychotics including clozapine. Clozapine-induced sedation can worsen cognition and impair social and occupational functioning. OBJECTIVES To evaluate the efficacy, tolerability, and safety of modafinil for negative symptoms, cognition, and wakefulness/fatigue in DSM-IV-diagnosed schizophrenia patients treated with clozapine. METHOD A double-blind, placebo-controlled, flexible-dosed 8-week pilot trial was conducted between September 2003 and September 2007, adding modafinil up to 300 mg/d to stabilized schizophrenia outpatients receiving clozapine. Psychopathology, cognition, and wakefulness/fatigue were assessed with standard rating scales. RESULTS Thirty-five patients were randomly assigned to treatment with study drug and included in the analysis. Modafinil did not reduce negative symptoms or wakefulness/fatigue or improve cognition compared to placebo. Modafinil was well tolerated and did not worsen psychosis. CONCLUSIONS Results of this pilot trial do not support routine use of modafinil to treat negative symptoms, cognitive deficits, or wakefulness/fatigue in patients on clozapine. However, given our limited power to detect a treatment effect and the clear possibility of a type II error, larger trials are needed to resolve or refute a potential therapeutic effect of uncertain magnitude. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00573417.

Knowledge, attitudes, and beliefs regarding HPV vaccination: ethnic and cultural differences between African-American and Haitian immigrant women.

BACKGROUND Black women have higher rates of cervical cancer and lower rates of HPV vaccination than White women in the United States, and Haitians may be an especially vulnerable subgroup of Black women. To reduce these disparities, understanding differences among subgroups of Black women is crucial. METHODS The objective of our study was to assess similarities and differences in the knowledge, attitudes, beliefs, and practices toward HPV vaccination and actual vaccination rates among African-American and Haitian immigrant women and their daughters. We used validated surveys of HPV knowledge, trust in physicians, acculturation, and constructs of the health belief model: Perceived susceptibility, severity, and barriers. We probed womens thought processes about vaccination using open-ended questions. We then reviewed medical records to determine vaccination rates. RESULTS Nineteen African Americans and 51 Haitians participated. Although 75% of Haitians and 63% of African Americans intended to vaccinate their daughters, only 47% of African-American and 31% of Haitian daughters were vaccinated. African Americans were more knowledgeable than Haitians and had more prior experience with HPV disease. Most African Americans felt that vaccination fell within the parental role, whereas many Haitians felt uncomfortable vaccinating against sexually transmitted infections because they felt children should not be having sex. Both ethnic groups wanted more information about HPV vaccines. CONCLUSION Cultural differences between African-American and Haitian immigrant mothers revealed distinct barriers for vaccine acceptance. Improving HPV vaccine rates in Black women may require culturally competent and sensitive approaches that address ethnic-specific barriers.