Feasibility and success of cell-phone assisted remote observation of medication adherence (CAROMA) in clinical trials.

OBJECTIVE: Medication nonadherence is a serious issue in clinical trials, especially in studies of substance abuse disorders. Measuring and confirming adherence is critical to ensuring that collected data is accurate and interpretable. This study evaluated the feasibility and success of a smartphone-based approach (Cellphone Assisted Remote Observation of Medication Adherence [CAROMA]) to visually confirm medication adherence in a clinical trial. METHOD: Medication adherence was confirmed visually via smartphones provided to participants in a double-blind, randomized, placebo-controlled trial for cannabis dependence. Every morning, subjects (n=20) were video-called by staff who observed consumption of study medication. Adherence was also assessed with weekly face-to-face visits, pill counts and plasma drug levels. Subjects were paid for completing daily CAROMA visits, and for returning the smartphone at study completion. RESULTS: CAROMA confirmed 96.04% adherence to medication. Concordance between expected and actual remaining study medication counted at weekly study visits was 87.69%. Subjects assigned to active study medication had detectable plasma drug levels, while those assigned to placebo did not. CAROMA was estimated to cost approximately $100 per subject per week - a total of $300.24 per subject for the 3-week outpatient portion of the trial. CONCLUSION: This pilot study demonstrates the feasibility, success and cost-effectiveness of CAROMA to facilitate and confirm medication adherence in a clinical trial. Preliminary findings support larger and longer studies, and possibly applying this approach to clinical care - especially in other populations with high rates of medication nonadherence.

Efficacy of pimozide augmentation for clozapine partial responders with schizophrenia.

INTRODUCTION: A substantial number of patients with treatment-resistant schizophrenia respond only partially to clozapine. Therefore, it has been common practice to use augmentation strategies to maximize clozapine's effect. But the efficacy of this strategy remains poorly established. We have conducted a randomized double-blind placebo controlled clinical trial in patients with schizophrenia currently receiving clozapine with partial response, and tested the efficacy of pimozide augmentation on positive and negative symptoms and also on neurocognitive measures. METHODS: Thirty-two outpatients enrolled in the clinical trial and 28 completed. Patients with adequate blood levels of clozapine were randomized to pimozide vs placebo and participated in the trial for 12 weeks receiving monthly assessments for Brief Psychiatric Rating Scale (BPRS) and Schedule for Assessment of Negative Symptoms (SANS), and weekly assessments for electrocardiogram (EKG), and side effects. Neurocognitive tests measuring verbal fluency, working memory, motor and attention/executive function were obtained at study entry and end of the trial. RESULTS: We found no significant effect of pimozide on BPRS total, psychosis and depression subscale items, SANS scores or QTc interval. Neurocognitive measures did not show significant improvement either. DISCUSSION: In this well controlled clinical trial of patients with treatment-resistant schizophrenia currently receiving clozapine, pimozide augmentation was not an effective strategy to maximize the benefit for better control of positive and negative symptoms or improving neurocognitive function.

Enhanced sensitivity to the euphoric effects of alcohol in schizophrenia.

The purpose of this study was to determine whether schizophrenia was associated with alterations in alcohol response that might explain the elevated risk for AUDs in this population. In a randomized, double-blind, placebo-controlled, counter-balanced 3 test day laboratory study, the effects of alcohol were compared in 23 subjects with schizophrenia (without any previous alcohol use disorder (AUD) but with some alcohol exposure) and in 14 healthy subjects matched for age, gender, education, and lifetime exposure to alcohol. Standard alcohol drinks in a scheduled design were administered to produce blood alcohol levels of 0, 0.02-0.04 mg%, or 0.06-0.08 mg%. Schizophrenia symptoms, perceptual alterations, stimulant and depressant subjective effects of alcohol, and 'high' were measured before alcohol administration and at several post-drug time points. Verbal learning and recall, vigilance and distractibility, and motor function were assessed once per test day. Relative to healthy subjects, subjects with schizophrenia reported greater euphoria and stimulatory effects in response to alcohol. Alcohol produced small transient increases in positive psychotic symptoms and perceptual alterations without affecting negative symptoms. Alcohol also impaired several aspects of immediate and delayed recall, and vigilance, and distractibility. Schizophrenia patients showed increased euphoric and stimulatory responses to alcohol. These exaggerated positive responses to alcohol doses may contribute to the increased risk for AUDs associated with schizophrenia. The absence of 'beneficial' effects of alcohol does not support a self-medication hypothesis of alcohol use in schizophrenia.

Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction.

BACKGROUND: Recent advances in the neurobiology of cannabinoids have renewed interest in the association between cannabis and psychotic disorders. METHODS: In a 3-day, double-blind, randomized, placebo-controlled study, the behavioral, cognitive, motor, and endocrine effects of 0 mg, 2.5 mg, and 5 mg intravenous Delta-9-tetrahydrocannabinol (Delta-9-THC) were characterized in 13 stable, antipsychotic-treated schizophrenia patients. These data were compared with effects in healthy subjects reported elsewhere. RESULTS: Delta-9-tetrahydrocannabinol transiently increased 1) learning and recall deficits; 2) positive, negative, and general schizophrenia symptoms; 3) perceptual alterations; 4) akathisia, rigidity, and dyskinesia; 5) deficits in vigilance; and 6) plasma prolactin and cortisol. Schizophrenia patients were more vulnerable to Delta-9-THC effects on recall relative to control subjects. There were no serious short- or long-term adverse events associated with study participation. CONCLUSIONS: Delta-9-tetrahydrocannabinol is associated with transient exacerbation in core psychotic and cognitive deficits in schizophrenia. These data do not provide a reason to explain why schizophrenia patients use or misuse cannabis. Furthermore, Delta-9-THC might differentially affect schizophrenia patients relative to control subjects. Finally, the enhanced sensitivity to the cognitive effects of Delta-9-THC warrants further study into whether brain cannabinoid receptor dysfunction contributes to the pathophysiology of the cognitive deficits associated with schizophrenia.