Taijin kyofusho: a form of social anxiety disorder that responds to serotonin reuptake inhibitors?

Taijin kyofusho (TKS) has been categorized as a "culture-bound" illness that is unique to the East, although an alternative view holds that some TKS patients are best conceptualized as having a form of social anxiety disorder (SAD). However, pharmacotherapeutic interventions for TKS have not yet been rigorously investigated. A review was undertaken of 48 TKS patients initially treated with serotonin reuptake inhibitors (SRIs) in an outpatient setting of a Japanese hospital. Psychiatric diagnoses were determined according to DSM-IV, and a set of TKS diagnostic criteria based on a modification of DSM-IV SAD criteria. In addition, response to SRIs (clomipramine and fluvoxamine) was evaluated retrospectively using the Clinical Global Impressions (CGI) scale. All 48 patients met SAD-based TKS diagnostic criteria. In the pretreatment assessment, DSM-IV Axis I diagnoses included SAD (38%), major depressive episode (27%), and delusional disorder somatic type (15%). Sixteen (48%) of 33 patients treated with clomipramine or fluvoxamine for at least 6 months were categorized as responders (CGI = 1 or 2). Compared to responders, non-responders were significantly less likely to have pretreatment major depression, and significantly more likely to have comorbid cluster A personality disorders and to have received augmentation with antipsychotic drugs. Although TKS may be a heterogeneous condition with various comorbidities, patients invariably fulfilled diagnostic criteria for TKS based on SAD criteria. SRIs may be effective for a substantial number of TKS patients. Prospective controlled trials are necessary to confirm these findings and to delineate the pharmacotherapeutic profile of TKS.     

The demise of HRT? The long-term safety of hormone replacement therapy

The role of hormone replacement therapy (HRT) in the health of middle-aged women has come a full circle. HRT has been widely accepted as the treatment of choice for the management of menopausal symptoms. However, the Women's Health Initiative (WHI) and other recent randomised controlled trials have failed to confirm beliefs of other potential benefits in reducing the risk of coronary artery disease (CAD) and stroke. Indeed, early increases in cardiac event and stroke rate have been seen in women taking combination HRT. An increased risk of breast cancer diagnosis has also been confirmed in HRT users. The use of HRT now needs to be regarded as a short-term therapy for menopausal symptom management with treatment individualised for each woman.     

A model to measure anticipatory anxiety in mice?

Among animals from the same cage, mice removed last had a higher temperature compared to those removed first. This phenomenon a) persisted 2 and 24 h later; b) was present regardless of the number of the animals (5, 10, 15 and 20) in each cage, c) was independent of whether the number of animals was reduced or maintained constant in the cage and d) could even be observed by reversing the order of removal of the animals from the cage. In addition, the fewer the animals allocated to a cage the greater the percentage of those which became hyperthermic. This rise in rectal temperature of mice removed last was prevented by diazepam (2.5 and 5 mg/kg PO, 30 min), nitrazepam (2 and 4 mg/kg PO, 30 min) but not by imipramine (15 and 30 mg/kg PO, 30 min) or haloperidol (0.5 and 1 mg/kg PO, 60 min) and was observed in a greater opercentage of mice following subcutaneous yohimbine treatment (2 mg/kg, 60 min). This phenomenon does not seem to depend on physical exercise due to an attempt to escape, since no correlation appears to exist between motor activity (open-field) and rise in rectal temperature. These data would seem to indicate that hyperthermia in the last animals may represent a new tool for studying the neurobiology of anticipatory(?) anxiety.Preliminary results were presented at the XVI C.I.N.P. Congress and at the XXIV National Congress of the Italian Society of Pharmacology     

Do whole-food animal feeding studies have any value in the safety assessment of GM crops?

The use of whole-food (grain meal contained in feed) animal-feeding studies to support the safety assessment of genetically modified crops has been contentious. This may be, in part, a consequence of poorly agreed upon study objectives. Whole-food animal-feeding studies have been postulated to be useful in detecting both expected and unexpected effects on the composition of genetically modified crops. While the justification of animal feeding studies to detect unexpected effects may be inadequately supported, there may be better justification to conduct such studies in specific cases to investigate the consequences of expected compositional effects including expression of transgenic proteins. Such studies may be justified when (1) safety cannot reasonably be predicted from other evidence, (2) reasonable hypothesis for adverse effects are postulated, (3) the compositional component in question cannot be isolated or enriched in an active form for inclusion in animal feeding studies, and (4) reasonable multiples of exposure can be accomplished relative to human diets. The study design for whole-food animal-feeding studies should be hypotheses-driven, and the types of data collected should be consistent with adverse effects that are known to occur from dietary components of biological origin.     

The cost of asthma: can it be reduced?

Asthma is a major public health problem in developed countries, where it consumes a large and increasing share of scarce health resources. Ideally, medical management should be both optimal in terms of improving the patient's quality of life, and cost-effective for society. At present, there is very little information relating to costs and economic efficiency of current asthma management. Although the true total cost of asthma is unknown, current estimates suggest it is high. The main value of recent total cost estimates is that they identify the most expensive areas of asthma costs, and ideally, formal cost-effectiveness analyses should be concentrated on these areas. Asthma is still under- or inappropriately diagnosed, and undertreated. Several national and international consensus plans for the optimal management of asthma in children and adults have been published. If these inadequacies in asthma management were corrected, using current treatment recommendations, the overall cost of asthma from both the community and patient perspective should fall. The situation requires increased use of preventative medications {sodium cromoglycate (cromolyn sodium) or inhaled corticosteroids}, more widespread use of written crisis plans, more proactive medical consultations (rather than reactive or urgent consultations), further expansion of asthma education programmes, and further education of medical practitioners about the optimum management of both long term asthma and the acute exacerbation of asthma in the patient's home, the doctor's office, the hospital emergency room and the hospital inpatient setting. The increased costs associated with these measures would be more than offset by reduced expenditure on bronchodilator drugs, less widespread use of nebulisers at home and in hospitals, reduced antibiotic usage, reduced need for expensive emergency medical care and particularly reduced utilisation of hospital resources. To ensure that resources are being directed into the most cost-effective areas of asthma care, clinical trials of asthma should include utilisation of healthcare resources as an outcome measure, and estimates of the costs of the treatment under study. In addition, since the intangible cost (quality of life) is one of the most important effects of treatment from the patient's perspective, this should be more widely used as an outcome measure in clinical trials. Ultimately, prevention of asthma is the long term goal. If the hypothesis that sensitisation to house dust mite in early infancy is a major contributor to the subsequent development of asthma, then prevention may require drastic and expensive changes to current housing.     

Behavioral effects of betacarbolines in pigs:. anxiety or aversion?

Betacarbolines are often considered to be anxiogenic and may, therefore, have similar behavioral effects to those of corticotrophin releasing hormone (CRH); however, their actions have been little studied in pigs. This investigation was concerned with the effects of ethyl-beta-carboline-3-carboxylate (BCCE) and noreleagnine (NOR) on operant feeding, cortisol release, and overt behavior in swine, all of which are known to be affected by CRH in this species. Three experiments are described in which BCCE or NOR were given intravenously to prepubertal boars (n = 7). In Experiment 1, 400 microg/kg, but not 100 or 200 microg/kg, BCCE produced a rapid inhibition of ingestive activity whereas NOR (100, 200, or 400 microg/kg) was without effect. In Experiment 2, both BCCE and NOR increased plasma cortisol, but not growth hormone, concentrations. In Experiment 3, a high dose of BCCE (2 mg/kg) produced transient arousal and a sustained increase in respiration rate and plasma cortisol. These results indicate that although the responses of pigs to BCCE and CRH are similar in some respects, there are also marked behavioral differences. The possibility that BCCE has aversive rather than anxiogenic actions in this species is discussed.     

Communication barriers in counselling foreign-language patients in public pharmacies: threats to patient safety?

Background Foreign-language (FL) patients are at increased risk for adverse drug events. Evidence regarding communication barriers and the safety of pharmaceutical care of FL patients in European countries is scarce despite large migrant populations. Objective To investigate Swiss public pharmacists' experiences and current practices in counselling FL patients with a focus on patient safety. Method In a cross-sectional study heads of public pharmacies in Switzerland were surveyed using an electronic questionnaire. Main outcome measure The survey assessed the frequency of communication barriers encountered in medication counselling of FL patients, perceptions of risks for adverse drug events, satisfaction with the quality of counselling provided to FL patients, current strategies to reduce risks, and preferences towards tools to improve safety for FL patients. Results 498 pharmacists completed the survey (43?% response rate). More than every second pharmacist reported at least weekly encounters at which they cannot provide good medication counselling to FL patients in the regional Swiss language. Ad-hoc interpreting by minors is also common at a considerable number of pharmacies (26.5?% reported at least one weekly occurrence). Approximately 10?% of pharmacies reported that they fail at least weekly to explain the essentials of drug therapy (e.g. dosing of children's medications) to FL patients. 79.8?% perceived the risk of FL patients for adverse drug events to be somewhat or much higher compared to other patients. 22.5?% of pharmacists reported being concerned at least monthly about medication safety when FL patients leave their pharmacy. However, the majority of pharmacists were satisfied with the quality of care provided to FL patients in their pharmacy [78.6?% (very) satisfied]. The main strategy used to improve counselling for FL patients was the employment of multilingual staff. Participants would use software for printing foreign-language labels (41.2?%) and multilingual package inserts (42.0?%) if these were available. Conclusion Communication barriers with FL patients are frequent in Swiss pharmacies and pharmacists perceive FL patients to be at increased risk for adverse drug events. Development and dissemination of communication tools are needed to support pharmacists in counselling of a diverse migrant population.     

Effectiveness of adjunctive gabapentin in resistant bipolar disorder: is it due to anxious-alcohol abuse comorbidity?

We evaluated effectiveness and predictors of response of gabapentin (GBP) as adjunctive treatment in a sample of 43 subjects with DSM-III-R bipolar disorder who were resistant to standard mood stabilizers. Diagnostic evaluation was performed by means of the Semistructured Interview for Mood Disorder. Clinical evaluation was performed at the beginning and end of the observation period by means of the Hamilton Rating Scale for Depression (HAM-D), the Young Mania Rating Scale, and the Clinical Global Impression Scale. GBP was administered as an adjunctive treatment for an 8-week period in combination with other mood stabilizers, benzodiazepines, antidepressants, and neuroleptics. Mean dosage +/- SD at week 8 was 1270 +/- 561.4 mg (range, 600-2400 mg). Adjunctive treatment with GBP was well tolerated by almost all the subjects; only three patients had to interrupt treatment before week 8, two because of inefficacy and one because of the appearance of side effects (ataxia and irritability); in other patients, the most frequent side effects were sedation, irritability, tremor, ataxia or motor instability, and nausea. Eighteen (41.9%) of 43 patients who began treatment were considered responders. Mean total HAM-D score showed a significant reduction during the 8 weeks of treatment. Analysis of the various HAM-D dimensions showed that the anxiety-somatization factor was the one with the greatest change. Seventeen of the 18 responder patients remained in remission for a period ranging from 4 to 12 months without clinically significant side effects or adverse events. One patient had to interrupt GBP treatment and be administered neuroleptics because of the reappearance of manic symptoms. Regarding response predictors, logistical regression analysis showed that the presence of panic disorder and alcohol abuse was associated with positive response. The results of the present study replicate prior studies indicating that GBP is an effective and well tolerated treatment in a large proportion of bipolar patients who are resistant to traditional mood stabilizers. More specifically, this drug appears to have antidepressant and anxiolytic properties. What is new in the present report is the suggestion that the utility of GBP in resistant bipolar disorder resides in its effectiveness against comorbid panic disorder and alcohol abuse.     

The safety of atypical antipsychotics: does QTc provide all the answers?

Drug safety of atypical antipsychotics is important due to the increasing mortality gap between patients with schizophrenia and the general population. This editorial discusses the safety evaluation of ziprasidone with a focus on the risk of the potentially fatal cardiac arrhythmia, torsades de pointes (TdP). The exact incidence of antipsychotic-induced TdP remains unknown because capturing TdP warrants continuous monitoring and tens of thousands of patient-years due to the rarity of TdP. For this reason, surrogate markers such as the QTc interval are used despite their limitations. New surrogate markers Tpeak-Tend and T-wave morphology have seen the light of day but their validity remain unknown. Large pragmatic trials have been conducted, but their contributions to drug safety evaluations are controversial. Finally, psychiatrists should have in mind that safety evaluation should include more than the risk of TdP. Some atypical antipsychotics are associated with life-shortening side effects, such as severe weight gain and type 2 diabetes, which may contribute more to the overall mortality than TdP. In addition to this, suboptimal treatment may result in life-shortening behaviors such as suicide. A shared decision including a thorough discussion of risks and benefits with the patients is essential.     

GABAA receptor subtypes: any clues to the mechanism of benzodiazepine dependence?

Chronic use of benzodiazepines for the treatment of anxiety has revealed that these drugs can lead to dependence as indicated by withdrawal symptoms following cessation and tolerance to the drugs effects. Together with their reinforcing properties, this has led to them being labelled as scheduled drugs. Our new knowledge regarding the molecular structure of the benzodiazepine binding site and the growing ability to differentiate GABA(A) receptor subtypes, either by genetic manipulation or subtype selective compounds, have begun to facilitate our understanding of what underlies the mechanism of benzodiazepine dependence. In addition, the involvement of GABA(A) receptors in this phenomenon is leading to a greater understanding of other drugs such as alcohol and opiates.     

The depressed borderline: one disorder or two?

Depression in the borderline patient may present as a reactive mood state, an expression of character, or an independent comorbid affective disorder. The symptom picture is most often heterogeneous, "atypical," and chronic. Pharmacologic trials with tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) produce modest improvement on a variety of symptoms, though not always on depression. Medication effects on depressed mood in borderline personality disorder (BPD) are independent of comorbid diagnoses of major depression, atypical depression, or hysteroid dysphoria. Residual symptoms are the rule. A literature review, including studies of comorbidity, longitudinal followup, family history, and laboratory and pharmacotherapy studies, suggests that the borderline patient has both a core biologic affective dysregulation and a pathologic personality organization. The combination of constitutional and psychodynamic etiologies for borderline pathology requires consideration of both pharmacotherapy and psychotherapy in any comprehensive treatment.     

The right to remain in ignorance about genetic information--can such a right be defended in the name of autonomy?

Within the field of medicine, it has become widely accepted that respecting the autonomy of individuals justifies their right to know. More recently, commentators have asked whether such respect also justifies an individual's right not to know; that is, their right to remain in ignorance. In this paper, I examine what the concept of autonomy entails and whether one is justified in exercising a right not to know genetic information about oneself in the name of autonomy. An important distinction is drawn between autonomous choices generally and autonomous choices about how we shall conduct our lives. Against this theoretical discussion, I consider two hypothetical cases. I conclude by claiming that ignorance cannot be justified in the name of autonomy, and furthermore that where genetic information is pertinent to one's future autonomy, one cannot exercise a right not to know.