Development and validation of a new instrument to measure perceived risks associated with the use of tobacco and nicotine-containing products.

BACKGROUND: Making tobacco products associated with lower risks available to smokers who would otherwise continue smoking is recognized as an important strategy towards addressing smoking-related harm. Predicting use behavior is an important major component of product risk assessment. In this context, risk perception is a possible factor driving tobacco product uptake and use. As prior to market launch real-world actual product use cannot be observed, assessing risk perception can provide predictive information. Considering the lack of suitable validated self-report instruments, the development of a new instrument was undertaken to quantify perceived risks of tobacco and nicotine-containing products by adult smokers, former smokers and never-smokers. METHODS: Initial items were constructed based on a literature review, focus groups and expert opinion. Data for scale formation and assessment were obtained through two successive US-based web surveys (n = 2020 and 1640 completers, respectively). Psychometric evaluation was based on Rasch Measurement Theory and Classical Test Theory. RESULTS: Psychometric evaluation supported the formation of an 18-item Perceived Health Risk scale and a 7-item Perceived Addiction Risk scale: item response option thresholds were ordered correctly for all items; item locations in each scale were spread out (coverage range 75-87%); scale reliability was supported by high person separation indices > 0.93, Cronbach's alpha > 0.98 and Corrected Item-Total Correlations > 0.88; and no differential item functioning was present. Construct validity evaluations met expectations through inter-scale correlations and findings from known-group comparisons. CONCLUSIONS: The Perceived Risk Instrument is a psychometrically robust instrument applicable for general and personal risk perception measurement, for use in different types of products (including cigarettes, nicotine replacement therapy, potential Modified Risk Tobacco Products), and for different smoking status groups (i.e., current smokers with and without intention to quit, former smokers, never smokers).

SSTR4, Childhood Adversity, Self-efficacy and Suicide Risk in Alcoholics.

BACKGROUND: Patients with alcohol dependence (AD) are known to develop poor social skills, to report a higher number of adverse childhood experiences (ACEs) and to attempt suicide more frequently than the general population. The background for the association between ACEs and a higher risk of suicide still remains understudied. SSTR4 rs2567608 is a functional polymorphism of the gene for somatostatin receptor subtype 4, predominantly found in the CA1 hippocampus area and involved in memory formation. We hypothesize that the functional polymorphism SSTR4 rs2567608, general self-efficacy, and adverse childhood experiences influence the risk of suicide attempt in patients with AD. METHODOLOGY: 176 patients with AD and 127 healthy controls were interviewed regarding 13 categories of ACEs and assessed with the General Self-Efficacy Scale. Genotyping for the SSTR4 rs2567608 polymorphism was performed according to the manufacturer's standard PCR protocol. RESULTS: Patients with AD and the controls did not differ significantly according to the SSTR4 rs2567608 genotype and allele frequencies. Lower general self-efficacy, higher number of ACEs, and the SSTR4 rs2567608 TT genotype increased the risk of suicide attempt in patients with AD, and it persisted significant only in male patients with AD. CONCLUSIONS: Our study supports previous findings on ACEs and general self-efficacy association with a risk for suicide. Additionally, we suggest that patients with AD of the SSTR4 rs2567608 TT genotype may be more vulnerable to ACEs and at a higher risk of suicide attempt.

Bipolar disorder: how far are we from a rigorous definition and effective management?

Bipolar disorder is a pathological disturbance of mood, characterized by waxing and waning manic, depressive and, sometimes distinctly mixed states. A diagnosis of bipolar disorder can only be made with certainty when the manic syndrome declares itself. Most individuals who are diagnosed with this disorder will experience both poles of the illness recurrently, but depressive episodes are the commonest cause of morbidity and, indeed, of death by suicide. Twin, adoption and epidemiological studies suggest a strongly genetic aetiology. It is a genetically and phenotypically complex disorder. Thus, the genes contributing are likely to be numerous and of small effect. Individuals with bipolar disorder also display deficits on a range of neuropsychological tasks in both the acute and euthymic phases of illness and correlations between number of affective episodes experienced and task performance are commonly reported. Current self-report and observer-rated scales are optimized for unipolar depression and hence limited in their ability to accurately assess bipolar depression. The development of a specific depression rating scale will improve the assessment of bipolar depression in both research and clinical settings. It will improve the development of better treatments and interventions. Guidelines support the use of antidepressants for bipolar depression. With regard to the adverse effects of antidepressants for bipolar depression, double-blind, placebo-controlled data suggest that antidepressant monotherapy or the addition of a tricyclic antidepressant may worsen the course of bipolar disorder. Importantly, adjunctive psychotherapies add significantly (both statistically and clinically) to the efficacy of pharmacological treatment regimens. The successful management of bipolar disorder clearly demands improved recognition of bipolar disorder and effective long-term treatment for bipolar depression as well as mania.

A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder.

To date, no large-scale, controlled trial comparing a serotonin-norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported. This double-blind study compares the efficacy of venlafaxine extended-release (ER) and paroxetine with placebo. A total of 664 nondepressed adult outpatients who met DSM-IV criteria for panic disorder (with or without agoraphobia) were randomly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER (75 mg/day or 150 mg/day), or paroxetine 40 mg/day. The primary measure was the percentage of patients free from full-symptom panic attacks, assessed with the Panic and Anticipatory Anxiety Scale (PAAS). Secondary measures included the Panic Disorder Severity Scale, Clinical Global Impressions--Severity (CGI-S) and--Improvement (CGI-I) scales; response (CGI-I rating of very much improved or much improved), remission (CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks); and measures of depression, anxiety, phobic fear and avoidance, anticipatory anxiety, functioning, and quality of life. Intent-to-treat, last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo. No significant differences were observed between active treatment groups. Panic-free rates at end point with active treatment ranged from 54% to 61%, compared with 35% for placebo. Approximately 75% of patients given active treatment were responders, and nearly 45% achieved remission. The placebo response rate was slightly above 55%, with remission near 25%. Adverse events were mild or moderate and similar between active treatment groups. Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder.

Venlafaxine extended-release capsules in panic disorder: flexible-dose, double-blind, placebo-controlled study.

BACKGROUND: Venlafaxine extended-release (ER) has proven efficacy in the treatment of anxiety symptoms in major depression, generalised anxiety disorder and social anxiety disorder. AIMS: To evaluate the efficacy, safety and tolerability of venlafaxine ER in treating panic disorder. METHOD: Adult out-patients (n=361) with panic disorder were randomly assigned to receive venlafaxine ER (75-225 mg/day) or placebo for up to 10 weeks in a double-blind study. RESULTS: Venlafaxine ER was not associated with a greater proportion of patients free from full-symptom panic attacks at the final on-therapy evaluation, but was associated with lower mean panic attack frequency and a higher proportion free from limited-symptom panic attacks, higher response and remission rates, and improvements in anticipatory anxiety, fear and avoidance. Adverse events were comparable with those of the drug in depression and anxiety disorders. CONCLUSIONS: Venlafaxine ER seems to be effective and well tolerated in the short-term treatment of panic disorder.

Efficacy of Venlafaxine ER in patients with social anxiety disorder: a double-blind, placebo-controlled, parallel-group comparison with paroxetine.

This study evaluated the anxiolytic efficacy, safety and tolerability of a flexible dose of venlafaxine extended release (ER) compared with placebo and paroxetine in the short-term treatment of generalized social anxiety disorder (SAD). Adult outpatients with generalized SAD (n = 434) were randomized to receive capsules of venlafaxine ER 75 mg to 225 mg/day, paroxetine 20 mg to 50 mg/day, or placebo for 12 weeks. The primary efficacy variable was the Liebowitz social anxiety scale total score. Secondary efficacy variables included the patient-rated social phobia inventory and the proportion of responders in each group (a responder was defined as having a clinical global impression-improvement score of 1 or 2). Treatment with venlafaxine ER was associated with significantly greater improvement than treatment with placebo for all primary and secondary efficacy variables (p < 0.05). No significant differences in primary or secondary efficacy variables were observed between the venlafaxine ER and paroxetine groups. The week 12 response rates were 69%, 66% and 36% for the venlafaxine ER, paroxetine and placebo groups, respectively. Both active treatments were generally well tolerated and were associated with a similar incidence of adverse events. This study shows that venlafaxine ER is an effective, safe and well-tolerated drug treatment for SAD.

Dopamine receptors and schizophrenia: contribution of molecular genetics and clinical neuropsychology.

Family, twin and adoption studies suggest that genetic factors play an important role in the aetiology of schizophrenia. The mode of inheritance, however, is complex and non-Mendelian. Although the aetiology of schizophrenia is unknown, it has been hypothesized that the necessary conditions for developing the disease are environmental stress and a vulnerability to psychosis. The implication of dopamine receptors to schizophrenia has been greatly studied. Several linkage and association studies have been performed in an attempt to establish the involvement of dopamine receptors in schizophrenia. However, although no conclusive evidence of linkage or association to any gene has been established, some results, suggestive of linkage for chromosomes 6, 22 and 13, await confirmation from other studies. Concerning association studies, it is also of interest that some studies support an association between schizophrenia and homozygosity at D(3). More work in larger samples is required before conclusive linkage hypothesis or association to a dopamine receptor may be established. Schizophrenic patients have been shown to have significant deficits in a wide range of cognitive processes, including memory, attention, reasoning ability and language. Since cognitive deficits are significant symptoms of schizophrenia which require effective treatment, their assessment in schizophrenic patients and during clinical trials of new potential antipsychotics is highlighted. Cognitive impairment in schizophrenia impedes psychosocial performance and is therefore an especially relevant target variable in the development of new therapeutic approaches. It is most prominent in tasks involving attention, memory and executive functions which are thought to reflect involvement of prefrontal and left-temporal brain areas. Semantic networks in schizophrenic patients with a younger age of onset are observed to be more disorganized and differ significantly to those of control subjects. The need to use broader approaches such as neuropsychological-related measures to identify pertinent phenotypes in non-affected subjects carrying vulnerability genes is also emphasized. Since dopamine receptors are the primary targets in the treatment of schizophrenia, improved therapy may be obtained by drugs that selectively target a particular subtype of dopamine receptor. In the development of novel antipsychotics, D(3) and D(4) receptors have received much attention and this is partly related to the fact that these receptors have a high abundance in brain areas associated with cognitive and emotional functions, such as parts of the limbic system and cortex. Recent studies suggest that atypical neuroleptics may significantly improve the cognitive deficits observed in schizophrenic patients and that atypical neuroleptics such as risperidone appear to improve memory and alertness suggesting that further clinical studies are needed to determine the precise influence of antipsychotics on the cognitive system of schizophrenic patients. Such studies could lead to useful insights as to the potential advantages of the newer antipsychotics which appear to have a sparing or beneficial effect on various components of cognitive function. However, the observation that cortical D(2) receptors are important sites of action for antipsychotics, that the cerebral cortex may harbour the common sites of actions of antipsychotics and that the balancing of the opposing actions of D(1) and D(2) receptor regulation may be an appropriate drug treatment suggests that the adjustment of D(1) receptor levels in the cortex may become an important goal of future antipsychotic generation. Such antipsychotics will be able to treat the positive, negative and cognitive deficits of schizophrenia.