Ritanserin in the treatment of alcohol dependence – a multi-center clinical trial

Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled study to determine the safety and efficacy of the 5-HT₂ receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1 week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received weekly individual sessions of manual-guided cognitive-behavioral therapy. Comparing the single-blind period with endpoint, there was approximately a 23% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in drinks/drinking day; and a 37% diminution in alcohol craving for all treatment groups. All treatment groups experienced a beneficial clinical outcome as assessed by the Clinical Global Impression Scale. There was, however, no significant difference between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome. Subjects were of relatively high social functioning at baseline, and this did not change significantly during treatment. Treatment groups did not differ significantly on either medication compliance or reported adverse events. Ritanserin treatment was associated with a dose-related prolongation of subjects’ QTc interval recording on the electrocardiogram. These results suggest that alcohol dependent subjects can show marked clinical improvement within a structured alcohol treatment program. These findings do not support an important role for ritanserin in the treatment of alcohol dependence. Received: 30 April 1996/Final version: 3 July 1996     

Staircase bioassay: the up-and-down method

Experiments are conducted to estimate the threshold for an all-or-none response. Threshold is defined to be a point above which 50% of the subjects will respond and below which 50% of the subjects will not respond. Examples are death, death in a fixed time period, shock, fibrillation, emesis. Staircase designs, in particular up-and-down trials, produce median (ED50) estimates of given standard error with as few as one-fifth the number of subjects as the traditional designs with preset numbers of tests at each of several levels of stimulus. We discuss these estimates and their efficiency as well as procedures to estimate standard deviation and its use in designing up-and-down trails. The advantages in using several short series in factorial experiments are presented. Suggestions are given for minimizing the complications of sequential designs. Case studies indicate the efficiency of the design for various applications.     

Effects of omalizumab, a humanized monoclonal anti-IgE antibody, on nasal reactivity to allergen and local IgE synthesis.

BACKGROUND: Treatment with omalizumab has been shown to reduce serum free IgE concentrations and to have beneficial effects on allergic airway disease. However, its effect on IgE synthesis is unknown. OBJECTIVE: To determine whether omalizumab therapy affects nasal reactivity to allergen and local IgE production. METHODS: Nineteen patients with perennial allergic rhinitis were treated with intravenous omalizumab every 2 weeks for 26 weeks in an open-label study. Serum free and total IgE concentrations were measured at baseline and every 2 weeks throughout the study. Nasal challenge to dust mite allergen was performed at baseline and after 12 and 24 weeks of treatment. Nasal lavage fluid obtained before and after each nasal challenge was evaluated for mite-specific antibodies, plaque-forming cells, and productive epsilon messenger RNA (mRNA). RESULTS: During treatment, serum free IgE concentrations were decreased by 97% to 99%, and the nasal response to allergen challenge was significantly reduced on days 80 and 164. The postchallenge increase in nasal lavage mite specific IgE was significantly reduced by treatment with omalizumab on day 168. IgE plaque-forming cells and productive epsilon mRNA were not significantly affected by omalizumab treatment. CONCLUSIONS: Omalizumab treatment markedly reduced serum free IgE and the clinical response to nasal allergen challenge. However, the absence of an effect on IgE-secreting B cells and epsilon mRNA in nasal lavage fluid suggests that omalizumab treatment for 6 months does not significantly modulate synthesis of nasal IgE.     

Women who stop smoking spontaneously prior to prenatal care and predictors of relapse before delivery

This study explores the experience of pregnant women who quit smoking prior to initiating prenatal care. These "spontaneous quitters" comprised 41% of a socioeconomically and ethnically diverse population of prepregnancy smokers enrolled in a health maintenance organization. Compared to women who were smoking at the start of prenatal care, spontaneous quitters had been lighter smokers, were less likely to have another smoker in their household, indicated a stronger belief in the harmful effect of maternal smoking, had a history of fewer miscarriages, and entered prenatal care earlier. Biochemical validation of smoking status over the course of pregnancy found that 21% of the spontaneous quitters relapsed prior to delivery. Characteristics reported at the first prenatal visit that were associated with maintenance included having achieved cessation for a longer period of time without smoking even a puff, higher self-efficacy for maintenance, stronger belief in the harmful effect of maternal smoking, primigravida, and greater frequency of nausea. The identification of spontaneous quitters and selected intervention for those at greatest risk of relapse is recommended for inclusion in routine prenatal care.     

Observations on Increased CPK Levels in "Asymptomatic" Cocaine Abusers

Summary

Systematic efforts by NIDA and NIAAA to develop new medications for drug and alcohol dependence have resulted in recent FDA approval of LAAM for opiate dependence, naltrexone for alcohol dependence and, more recently, a nasal spray for nicotine dependence. This article reviews the current strategies that guide these development efforts, including further examination of the interactions between potential pharmacotherapeutic agents and the drugs of abuse, the enhancement of pharmacotherapeutic efficacy with non‐pharmacological interventions, and the development of more precise and meaningful measures of research outcome.     

Violence among comorbid and noncomorbid severely mentally ill adults: A pilot study

This pilot study examined the relationship between substance dependence and violence in a sample of severely mentally ill adults. Subjects were 42 psychiatric outpatients enrolled in a clinical case management program in San Francisco, California. Almost 40% of the participants reported perpetrating at least one violent act in the past 12 months. Comorbid participants were over 4% times more likely to commit a violent act in the past 12 months than noncomorbid participants. Substance dependence was also more frequently associated with perpetration of a violent act by female than by male participants and by Caucasian than by African American participants. Comorbid mentally ill participants appear more likely to perpetrate violent acts than those with mental illness alone. The dangers of substance dependence in terms of the perpetration of violence may not be in mental illness or substance dependence alone but in their co‐occurrence. Further investigation is needed to assess risk factors for violence and victimization in multiple environmental and situational domains. It will be important to explore the moderating effects of gender and race on the co‐occurrence of mental illness, substance dependence, and the perpetration of violent acts.     

What is the link between migraine and psychiatric disorders? From epidemiology to therapeutics

The association between migraine and psychiatric disorders is well documented through numerous population-based studies. The results of these studies are coherent and show an increased risk of suffering from depression, bipolar disorders, numerous anxiety disorders, especially post-traumatic stress disorder. This raises the question of stress as a precipitating factor for migraine illness. Psychiatric comorbidity is even more frequent in chronic migraine than in episodic migraine patients. Many prospective studies have shown that psychiatric comorbidity could be considered as a risk factor for migraine chronicization. Psychiatric comorbidity is also responsible for an increase of the frequency of anti-migraine drug intake, a worsening of quality of life and a worsening of functional impairment. It is also responsible for an increase in the direct and indirect costs of migraine. The reason why psychiatric comorbidity is so high in migraineurs is not unambiguous. Multiple causal relationships and common etiological factors are linked. Recently, genome-wide association studies gave leads to a genetic common heritability between major depressive disorder and migraine. For clinicians, an important topic remains how to treat migraineurs with psychiatric comorbidity. These patients suffer frequently from severe migraine or refractory migraine. Antidepressant and anti-convulsive drugs can be useful, as well as psychological therapies. But moreover, it is of utmost importance to propose an integrated multidisciplinary approach to these difficult patients.     

Validation and utilisation of a digital version of the survey instrument for natural history,Aetiology and Prevalence of Patellofemoral pain studies (eSNAPPS)

ObjectiveThis study validated the newly adapted electronic SNAPPS (eSNAPPS) against the original paper SNAPPS. Subsequently, the study estimated the prevalence of PFP in running participants and spectators attending three mass-participant running events in the United Kingdom by using the eSNAPPS tool.DesignThis study had two parts. Firstly, a validation of the original paper version of the SNAPPS tool. Secondly, if validation was achieved, eSNAPPS was used in a prevalence study.ParticipantsA convenience sample of running participants and spectators aged 18–40 years attending the mass participation running events.Main outcome measureThe 12-month prevalence of PFP.Results: eSNAPPS was valid in identifying those with PFP (ICC 0.99 for Overall agreement, p < 0.0001). In the prevalence study, a total of 1080 running participants and spectators completed the eSNAPPS. The overall prevalence of PFP was 17.4% (95%CI: 15.2%, 19.8%); 20.5% of males (16.5, 24.9) and 15.7% of females (13.1, 18.7) had PFP. Prevalence was 17.4% (15.2, 19.8) in spectators and 16.7% in running participants (14.5, 19.0).ConclusionThe overall PFP prevalence in this study was slightly smaller than those previously reported in the literature. Findings also show that there were similar prevalence estimates in spectators and running participants.