Adjustment disorder with anxiety in old age: comparing prevalence and clinical management in primary care and mental health care.

PURPOSE: Adjustment disorder with anxiety (AjD-A) is a common cause of severe anxiety symptoms, but little is known about its prevalence in old age. METHODS: This cross-sectional study examined the prevalence of AjD-A in outpatients over the age of 60 who consecutively consulted 34 general practitioners and 22 psychiatrists during a 2-week period. The diagnosis of AjD-A was obtained using the optional module for diagnostic of adjustment disorder of the Mini International Neuropsychiatric Interview (MINI). The study procedure also explored comorbid psychiatric conditions and documented recent past stressful life events, as well as social disability and current pharmacological and non-pharmacological management. RESULTS: Overall, 3651 consecutive subjects were screened (2937 in primary care and 714 in mental health care). The prevalence rate of AjD-A was 3.7% (n=136). Up to 39% (n=53) of AjD-A subjects had a comorbid psychiatric condition, mostly of the anxious type. The most frequently stressful life event reported to be associated with the onset of AjD-A was personal illness or health problem (29%). More than 50% of the AjD-A patients were markedly to extremely disabled by their symptoms. Compared to patients who consulted psychiatrists, patients who were seen by primary care physicians were older, had obtained lower scores at the Hamilton Anxiety Rating Scale, benefited less frequently from non-pharmacological management and received benzodiazepines more frequently. CONCLUSIONS: AjD-A appears to be a significantly disabling cause of anxiety symptoms in community dwelling elderly persons, in particular those presenting personal health related problems. Improvement of early diagnosis and non-pharmacological management of AjD-A would contribute to limit risks of benzodiazepine overuse, particularly in primary care settings.

[Adjustment disorders with anxiety. Clinical and psychometric characteristics in patients consulting a general practitioner]. / Le trouble de l'adaptation avec anxiété. Caractéristiques cliniques et psychométriques chez des patients consultant en médecine générale.

BACKGROUND: The DSM-IV and ICD-10 descriptions of adjustment disorders are broadly similar. Their main features are the following: the symptoms arise in response to a stressful event; the onset of symptoms is within 3 months (DSM-IV) or 1 month (ICD-10) of exposure to the stressor; the symptoms must be clinically significant, in that they are distressing and in excess of what would be expected by exposure to the stressor and/or there is significant impairment in social or occupational functioning (the latter is mandatory in ICD-10); the symptoms are not due to another axis I disorder (or bereavement in DSM-IV); the symptoms resolve within 6 months, once the stressor or its consequences are removed. Adjustment disorders are divided into subgroups based on the dominant symptoms of anxiety, depression or behaviour. Adjustment disorder with anxiety (ADA) is a very common diagnosis in primary care, liaison and general psychiatry services but we still lack data about its specificity as a clinical entity. Current classifications fail to provide guidance on distinguishing these disorders from normal adaptive reactions to stress. METHOD: Ninety-seven patients with ADA according DSM-IV were recruited in this primary care study and compared with 30 control subjects matched for age and sex. The diagnosis was made according to the MINI questionnaire completed with a standardized research of stressful events and an assessment of anxiety symptoms using different scales: the Hamilton Anxiety rating Scale (HAM-A), the Hospital Anxiety and Depression scale (HAD), The Penn-State Worry Questionnaire (PSWQ), the Positive and Negative Emotionality scale, 31 items (EPN-31 scale) and the State-Trait Anxiety Inventory (STAI-S). RESULTS: Life events in relation to work were the most frequent (43%). In terms of symptomatology, results showed that ADA is associated with a level of anxiety close to those obtained in other anxiety disorders, particularly GAD, in relation to general symptoms (physical and somatic) as well as anxious rumination and negative emotions. CONCLUSION: Further research is needed to better understand the disorder and clarify its frontiers, which still remain a controversial issue with regard to the homeostatic response to stress and other types of anxiety disorders. The results of our study suggest that this sub syndromic entity should be recognized and adequately treated, especially in general practice where it is very common.

Efficacy of etifoxine compared to lorazepam monotherapy in the treatment of patients with adjustment disorders with anxiety: a double-blind controlled study in general practice.

Adjustment Disorders With Anxiety (ADWA) account for almost 10% of psychologically motivated consultations in primary care. The aim of this double-blind randomised parallel group study was to compare (non-inferiority test) the efficacies of etifoxine, a non-benzodiazepine anxiolytic drug, and lorazepam, a benzodiazepine, for ADWA outpatients followed by general practitioners. 191 outpatients (mean age: 43, female: 66%) were assigned to receive etifoxine (50 mg tid) or lorazepam (0.5-0.5-1 mg /day) for 28 days. Efficacy was evaluated on days 7 and 28 of the treatment. The main efficacy assessment criterion was the Hamilton Rating Scale for Anxiety score (HAM-A) on Day 28 adjusted to Day 0. The anxiolytic effect of etifoxine was found not inferior to that of lorazepam (HAM-A score decrease: 54.6% vs 52.3%, respectively, p=0.0006). The two drugs were equivalent on Day 28. However, more etifoxine recipients responded to the treatment (HAM-A score decreased by >or=50%, p=0.03). Clinical improvement (based on Clinical Global Impression scale CGI, Social Adjustment Scale Self-Report SAS-SR, and Sheehan scores) was observed in both treatment arms, but more etifoxine patients improved markedly (p=0.03) and had a marked therapeutic effect without side effects as assessed by CGI, p=0.04. Moreover, 1 week after stopping treatment, fewer patients taking etifoxine experienced a rebound of anxiety, compared to lorazepam (1 and 8, respectively, p=0.034).

Randomized prospective study of the analgesic effect of nefopam after orthopaedic surgery.

BACKGROUND: Balanced postoperative analgesia combines non-narcotic drugs and opioids. We organized a large study to evaluate nefopam analgesia and tolerance in combination with morphine for patient-controlled analgesia (PCA) after orthopaedic surgery. METHODS: Two hundred and one patients scheduled to undergo hip arthroplasty were included in this multicentre (n=24), double-blind, randomized study comparing nefopam (20 mg every 4 h for 24 h) with placebo, the first dose being infused peroperatively. The primary outcome measure was the cumulative morphine dose received postoperatively by PCA over 24 h. Secondary outcome measures were the amount of morphine received as a loading dose in the postanaesthesia care unit (PACU) and during the 24-h observation period, and pain assessments using a visual analogue scale (VAS) and a verbal pain scale (VPS), patient's satisfaction with analgesia and treatment tolerance. RESULTS: The two groups were comparable with respect to their characteristics and preoperative pain assessment. PCA-administered morphine over 24 h was significantly less for the nefopam group than the control group (21.2 (15.3) and 27.3 (19.2) mg respectively; P=0.02). This morphine-sparing effect was greater (35.1%) for patients with severe preoperative pain (VAS>30/100). For the entire study period (loading dose and PCA), morphine use was less for the nefopam group (34.5 (19.6) vs 42.7 (23.6) mg; P=0.01). Pain VAS at PACU arrival and during the whole PACU period was significantly lower for the nefopam than for the placebo group (P=0.002 and 0.04 respectively). Patient satisfaction was similar for the nefopam and placebo groups. CONCLUSION: In combination with PCA morphine, nefopam gives significant morphine-sparing with lower immediate postoperative pain scores without major side-effects. This analgesic effect seems to be particularly notable for patients with intense preoperative pain.

Citrulline/malate promotes aerobic energy production in human exercising muscle.

BACKGROUND: Previous studies have shown an antiasthenic effect of citrulline/malate (CM) but the mechanism of action at the muscular level remains unknown. OBJECTIVE: To investigate the effects of CM supplementation on muscle energetics. METHODS: Eighteen men complaining of fatigue but with no documented disease were included in the study. A rest-exercise (finger flexions)-recovery protocol was performed twice before (D-7 and D0), three times during (D3, D8, D15), and once after (D22) 15 days of oral supplementation with 6 g/day CM. Metabolism of the flexor digitorum superficialis was analysed by (31)P magnetic resonance spectroscopy at 4.7 T. RESULTS: Metabolic variables measured twice before CM ingestion showed no differences, indicating good reproducibility of measurements and no learning effect from repeating the exercise protocol. CM ingestion resulted in a significant reduction in the sensation of fatigue, a 34% increase in the rate of oxidative ATP production during exercise, and a 20% increase in the rate of phosphocreatine recovery after exercise, indicating a larger contribution of oxidative ATP synthesis to energy production. Considering subjects individually and variables characterising aerobic function, extrema were measured after either eight or 15 days of treatment, indicating chronological heterogeneity of treatment induced changes. One way analysis of variance confirmed improved aerobic function, which may be the result of an enhanced malate supply activating ATP production from the tricarboxylic acid cycle through anaplerotic reactions. CONCLUSION: The changes in muscle metabolism produced by CM treatment indicate that CM may promote aerobic energy production.

[Cross-sectional study of the prevalence of adjustment disorder with anxiety in general practice]. / Etude transversale de la prévalence du trouble de l'adaptation avec anxiété en médecine générale.

Although Adjustment Disorder (AD) is considered a marginal diagnostic category by many clinicians and researchers, all the rare studies undertaken in the last decades indicate that the prevalence of this disorder is high in psychiatric settings, but has never been investigated in general practice. The purpose of this study was to evaluate the current prevalence of Adjustment Disorders With Anxiety (ADWA) in primary care settings and to describe the characteristics of the population, nature of the stressors and management of the disorder by General Practitioners (GPs). This French study involved 78 random liberal GPs, in 7 distinct regions (Paris, Lille, Bordeaux, Rouen, Dijon, Castres and Compiègne). GPs had to register all the consecutive attenders over 18 years old. For each physician, the registration period was over when 200 patients were registered, or 10 days of consultation were completed, or when 5 MINI had been performed. The average study period was 10 days per physician. At the first stage, they selected all the patients with psychological complaints, which were eventually associated to physical complaints. At the second stage, only the patients whose complaints were linked to a psychosocial stressor and without A1 and/or A2 DSM IV criteria for a Major Depressive Episode (MDE) were proposed the Mini International Neuropsychiatric Interview (MINI). The MINI is a brief structured clinical diagnostic interview that identifies the main axis-I DSM IV diagnoses in about 15 minutes. Before starting the study, all of the GPs participated in an intensive course on AD criteria recognition and were trained to use the MINI. The GPs registered a total of 7,759 consecutive patients. Twenty-two per cent (n = 1,719) of the patients reported psychological complaints, associated or not to physical complaints. Among them, 49% (n = 844) linked their complaints to identifiable psychosocial stressors. About half of the latter (n = 450) coded positive to A1 and/or A2 criteria for MDE. At the end, a total of 314 patients agreed to complete the MINI. Among the 1,719 patients with psychological complaints, the prevalence of ADWA eventually associated to other psychiatric disorders was 9.2%. The prevalence of "pure" ADWA was 4.5%. When considering the whole population of consecutive patients in primary care settings, the prevalence of pure ADWA was 1.0%. Patients suffering from pure ADWA were mostly women (66.7%), young patients (mean age: 42 years), with a professional activity. Patients had a psychiatric disorder history in 53.8% of the cases (mostly anxiety disorder). The main life events cited as being responsible for the disorder were work-associated problems (23.1%), followed by family illness (9.0%) and serious personal illness or accident (7.7%). The average duration of the disorder was 2.32 months. In 91% of the cases, GPs estimated that the patient required a pharmacological or psychological treatment. In most cases, they treated the patients with drug therapy (74.0%) associated with psychological support (counselling or psychotherapy, 76%). Anxiolytic agents were usually prescribed (64.9%), followed by antidepressants (10.8%) and hypnotics (8.1%). In conclusion, this first prevalence study of ADWA in general practice demonstrates that this disorder is frequent in primary care. It seems to be more present in patients who are of working age, especially women. ADWA would thus seem to preferentially affect active subjects. In most cases, GPs treat their patients with both psychological support and drug therapy. Anxiolytic is the elicited treatment of this disorder.

A double blind parallel group placebo controlled comparison of sedative and mnesic effects of etifoxine and lorazepam in healthy subjects [corrected].

This paper describes the psychomotor and mnesic effects of single oral doses of etifoxine (50 and 100 mg) and lorazepam (2 mg) in healthy subjects. Forty-eight healthy subjects were included in this randomized double blind, placebo controlled parallel group study [corrected]. The effects of drugs were assessed by using a battery of subjective and objective tests that explored mood and vigilance (Visual Analog Scale), attention (Barrage test), psychomotor performance (Choice Reaction Time) and memory (digit span, immediate and delayed free recall of a word list). Whereas vigilance, psychomotor performance and free recall were significantly impaired by lorazepam, neither dosage of etifoxine (50 and 100 mg) produced such effects. These results suggest that 50 and 100 mg single dose of etifoxine do not induce amnesia and sedation as compared to lorazepam.

Nefopam enantiomers: preclinical pharmacology/toxicology and pharmacokinetic characteristics in healthy subjects after intravenous administration.

Nefopam (NEF) is a potent analgesic compound administered as a racemic mixture. Previous in vitro and in vivo studies with nefopam enantiomers have shown that (+)nefopam [(+)NEF] is substantially more potent than (-)nefopam [(-)NEF]. Differences between enantiomers have also been suggested in metabolic studies in vitro. The impact of these differences in vivo is not known because there is little or no information on the relative plasma concentrations of the enantiomers or on their kinetics. In this study, individual enantiomers of nefopam were synthesized and examined for acute toxicity in male and female rats and mice. Pharmacologic properties of enantiomers were examined using in vitro binding assays and antinociceptive tests in rats and mice. Additionally, a pharmacokinetic study was conducted in human volunteers. Subjects were administered 20 mg nefopam as Acupan(R) either as a 5- or 20-min intravenous infusion. In a control phase, subjects were administered only vehicle. Blood samples were collected through the following 24 h. Plasma samples were analyzed for individual enantiomers using a chiral assay developed for this purpose. The pharmacologic differences of previous studies were confirmed in receptor binding assays and in the hot plate and the formalin tests in mice. Neither enantiomer demonstrated substantial activity in the tail flick test in rats. No significant differences were revealed between LD(50) values of nefopam enantiomers after oral or intravenous administration in male and female rats or mice. There were no significant differences in AUC(0-infinity), C(max), or half-life between enantiomers following intravenous administration. Based on these findings, there is currently no compelling rationale to justify administering or monitoring individual enantiomers.

Prevalence and pathogenicity of Clostridium difficile in hospitalized patients. A French multicenter study.

BACKGROUND: Although Clostridium difficile is the main agent responsible for nosocomial diarrhea in adults, its prevalence in stool cultures sent to hospital microbiology laboratories is not clearly established. OBJECTIVES: To determine the prevalence of C difficile in inpatient stools sent to hospital microbiology laboratories and to assess the relationship between serotypes and toxigenicity of the strains isolated and the clinical data. METHODS: From January 18, 1993, to July 31, 1993, the presence of C difficile was systematically investigated in a case-control study on 3921 stool samples sent for stool culture to 11 French hospital microbiology laboratories. The prevalence of C difficile in this population (cases) was compared with that of a group of 229 random hospital controls matched for age, department, and length of stay (controls). Stool culture from controls was requested by the laboratory although not prescribed by the clinical staff. Serotype and toxigenesis of the strains isolated were compared. RESULTS: The overall prevalence of C difficile in the cases was twice the prevalence in the controls (9.7% vs 4.8%; P < .001) and was approximately 4 times as high in diarrheal stools (ie, soft or liquid) as in normally formed stools from controls (11.5% vs 3.3%; P < .001). The strains isolated from diarrheal stools were more frequently toxigenic than those isolated from normally formed stools. Serogroup D was never toxigenic, and its proportion was statistically greater in the controls than in the cases (45% vs 18%; chi 2 = 5.2; P < .05). Conversely, serogroup C was isolated only from the cases. Clostridium difficile was mainly found in older patients ( > 65 years), suffering from a severe disabling disease, who had been treated with antibiotics and hospitalized for more than 1 week in long-stay wards or in intensive care. CONCLUSIONS: This multicenter period prevalence study clearly supports the hypothesis of a common role of C difficile in infectious diarrhea in hospitalized patients. Disease associated with C difficile should therefore be systematically evaluated in diarrheal stools from inpatients.