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.

[Beneficial effect of a cognitive behavioral and multidisciplinary program in Alzheimer Disease on spouse caregiver anxiety: French study ELMMA]. / Bénéfice d'un programme cognitivo-comportemental et pluridisciplinaire de prise en charge de la maladie d'Alzheimer sur l'anxiété du conjoint : étude française ELMMA.

INTRODUCTION: Over the last decade, several programs have been developed for caregivers of Alzheimer disease patients. In France however, studies exploring their effects are still scarce. We conducted a study to compare two different interventions: a structured multidisciplinary program versus a classical intervention designed for Alzheimer disease patients and their spouses. METHODS: Sixteen couples (Alzheimer's disease patient and spouse) residing in our administrative district participated in this monocentric study. For at least two years, these couples participated in a multidisciplinary program (n=8 couples) or received usual care (n=8 couples). The multidisciplinary program involved biannual consultations with a neurologist, a neuropsychologist and a psychologist, in addition to an annual meeting, stratified on the patient's MMSE score, for spouses). Usual care involved biannual consultations with the neurologist. The multidisciplinary program included a psychological intervention based on cognitive behavioral theories and centered on psycho-education, problem solving, adaptation strategies and on prevention of depression and anxiety. The spouses and the patients evaluated the 2-year follow-up during clinical interviews, completed by questionnaires. Sociodemographic data were noted for the patients and their spouses. Levels of depression and anxiety (Mini International Neuropsychiatric Inventory, Montgomery and Asberg Depression Scale, State-Trait Anxiety Inventory), perceived stress (Perceived Stress Scale) and care burden (Zarit Burden Inventory) were evaluated in spouses. Levels of cognitive impairment (Mini Mental State Examination), autonomy (Instrumental Activities of Daily Living), psychological state (Montgomery and Asberg Depression Scale, Covi Anxiety Scale), and behavioral symptoms frequency (Neuropsychiatric Inventory) were assessed in patients. RESULTS: The main significant result showed that the spouses' state of anxiety was lower among participants in the multidisciplinary program, compared with the classical neurological intervention. It also was found that the spouses and the patients who participated in this multidisciplinary program were less depressed. CONCLUSION: This study shows that a multidisciplinary structured intervention, with only two annual consultations and one annual meeting for spouses, can contribute to decrease significantly the spouses' state of anxiety. Further studies including a larger number of subjects should be conducted to confirm these findings.

Prevention of progression to dementia in the elderly: rationale and proposal for a health-promoting memory consultation (an IANA Task Force).

Alzheimer's disease (AD) is the most frequent form of dementia and according to the most recent estimation it affects nearly 27 million people in the world. The onset of the disease is generally insidious. It is becoming increasingly evident that the underlying pathophysiological mechanisms are active long before the appearance of the clinical symptoms of the disease. In the current context, it is important to develop strategies to delay the onset of cognitive decline. Delaying the onset by 5 years would reduce the prevalence by half at term, and a delay of 10 years would reduce it by three-quarters. The effectiveness of currently suggested preventive approaches remains to be confirmed, but certain strategies could be applied straight away to at-risk subjects. We propose that a health-promoting memory consultation should be set up for elderly persons who have attended a specialized memory consultation and in whom the diagnosis of dementia and of AD in particular, has not been established by standardized tools. Through this consultation, they would be offered full multidimensional investigation of all aspects of their health status, follow-up could be organized, general practitioners in private practice could be made more conscious of this population and the elderly could be made more aware of the risk factors to which they are exposed. The development of an information policy for the elderly would meet a present need. In our reflection, we must take into account the question of how to give this preventive consultation its due place in the healthcare pathway of the elderly person in order to ensure coordinated follow-up with all the other health professionals involved. The principle of the health-promoting memory consultation is undergoing validation in a large French multicentre preventive trial in 1200 frail elderly persons aged 70 years followed for three years, the Multidomain Alzheimer Preventive Trial (MAPT).

VBM anticipates the rate of progression of Alzheimer disease: a 3-year longitudinal study.

OBJECTIVE: To determine whether regional atrophy or neuropsychological factors can predict the rate of decline in patients with mild Alzheimer disease (AD). BACKGROUND: Despite important implications for planning the care and treatment strategy, few prognostic factors of severe AD progression are known. METHODS: Twenty-three patients with mild AD were followed up every 6 months over the course of 3 years. At baseline, patients with AD and 18 controls underwent a neuropsychological battery and a brain MRI. At the end of the 3 years, patients with AD were dichotomized into slow decliners (SLD) or fast decliners (FD) groups on the basis of their decline in Mini-Mental State Examination score over time. We compared baseline cognitive performance and imaging data using voxel-based morphometry (VBM). RESULTS: SLD and FD groups did not differ in age, gender, level of education, mean estimated duration of illness, and standard neuropsychological data at inclusion, except for the Attentional Battery of the Cambridge Neuropsychological Tests Automated Battery (speed processing in shifting condition). VBM comparison between SLD and FD groups demonstrated more gray matter tissue loss in the FD group in the medial occipitoparietal areas, especially in the precuneus, the lingual gyrus, the cuneus, and the surrounding cortex of the parieto-occipital sulcus bilaterally. CONCLUSION: Voxel-based morphometry analysis demonstrated that patients who will have a faster decline at 3 years already had a more extensive cortical atrophy than SLD patients, especially in the medial occipitoparietal areas, which was not yet detected by clinical and neuropsychological assessment.

[A strategy for therapy of depressive disorders and anxiety disorders by a health education intervention in medical consultations: the results of the APRAND program]. / Prévention des troubles anxieux et dépressifs par une action d'éducation pour la santé en consultation: résultats du programme APRAND.

BACKGROUND: Studies devoted to the detection and treatment of anxiety and depression in adult populations show that at least 10% meet ICD10 criteria for an anxiety or a depressive disorder, but only half are diagnosed as such and only one third of those receive appropriate treatment. The goal of the APRAND program was to explore the possibility of improving management strategies via health education during doctors' visits. METHODS: In 2001, EDF-GDF conducted an experimental program in which 21 physicians from its in-house health insurance program used the MINI mental state examination to screen for ICD10 criteria for anxiety and depressive disorders in 9743 employees on sick leave. A "here-elsewhere" epidemiologic study evaluated the program, recording the initial diagnoses and studying a year later the outcome of the persons identified with these disorders in 8 active centers (with prevention activities) and in 13 control centers (without prevention activities). The activities consisted of explanations of the disorders identified, delivery of the test results, delivery of leaflets based on the WHO guidelines, and strong recommendations to see a general practitioner, or a psychiatrist, or the occupational physician, if necessary. Logistic regressions compared the two groups, taking into account sex, age, geographic region, comorbidity, and medical care at screening. RESULTS: Preventive activities were significantly associated with the disappearance at 1 year of depressive episodes (OR=1.93; CI 95%; 1.3-2.84) and of phobic or panic disorders (OR=1.98; CI 95%; 1.14-3.44). The only other variables affecting prognosis were age and sex. The probability of recovery or remission increased by 10 to 20% at active centers, according to age, sex and disorder. Moreover, the physicians reported that they learned a great deal from the program, which thus also improved their practices. CONCLUSION: Diagnosis and prognosis of depressive episodes and phobic and panic disorders in adult populations can be improved by a preventive diagnostic and educational approach of the type used by APRAND during doctor's visits.

Moroccan colloquial Arabic version of the Mini International Neuropsychiatric Interview (MINI): qualitative and quantitative validation.

The validation of mini international neuropsychiatric interview (MINI) into Moroccan Colloquial Arabic language demonstrated good psychometric properties. The concordance between translated MINI's and expert diagnoses was good with kappa values greater than 0.80. The reliability inter-rater and test-retest were excellent with kappa values above 0.80 and 0.90, respectively.

[Diagnostic structured interviews in child and adolescent's psychiatry]. / Entretiens diagnostiques structurés en psychiatrie de l'enfant et de l'adolescent.

Structured diagnostic interviews, which evolved along the development of classification's systems, are now widely used in adult psychiatry, in the fields of clinical trials, epidemiological studies, academic research as well as, more recently, clinical practice. These instruments improved the reliability of the data collection and interrater reliability allowing greater homogenisation of the subjects taking part in clinical research, essential factor to ensure the reproducibility of the results. The diagnostic instruments, conversely to the clinical traditional diagnostic processes allow a systematic and exhaustive exploration of disorders, diagnostic criteria but also severity levels, and duration. The format of the data collection, including the order of exploration of the symptoms, is fixed. The formulation of the questions is tested to be univocal, in order to avoid confusions. In child and adolescent, researches in pharmacology and epidemiology increased a lot in the last decade and the standardisation of diagnostic procedures is becoming a key feature. This Article aims to make an assessment, a selection, and a description of the standardized instruments helping psychiatric diagnosis currently available in the field of child and adolescent's psychiatry. Medline and PsycINFO databases were exhaustively checked and the selection of the instruments was based on the review of four main criteria: i) compatibility with international diagnostic systems (DSM IV and/or ICD-10); ii) number of disorders explored; iii) peer reviewed Journals and iv) richness of psychometric data. After the analysis of the instruments described or mentioned in the literature, 2 structured interviews [the Diagnostic Interview Schedule for Children (DISC) and the Children's Interview for Psychiatric Syndromes (ChIPS)] and 4 diagnostic semi-structured interviews [the Schedule for Affective Disorders and Schizophrenia for School-Age Children (Kiddie-SADS), the Diagnostic Interview for Children and Adolescent (DICA), the Child and Adolescent Psychiatric Assessment (CAPA) and the Interview Schedule for Children and Adolescents ISCA)] were retained according to the 3 first criteria. All can be administered by clinicians, and x out of 6 can also be administered by lay-interviewers. All include a child/adolescent version and a parent version. Two instruments evaluate the presence of DSM IV axe II disorders: The ISCA explores the criteria of the Antisocial Personality Disorder. The CAPA evaluates Borderline, Obsessional-compulsive, Histrionic and Schizotypic Personality Disorders. Regarding the psychometric quality criterion, the selection was much more difficult because of the lack of data and the weakness of the samples studied in reliability studies. Interrater reliability appeared to be good for the 6 instruments, with kappas ranging from 0.5 to 1. This is usual in such instruments. The test-retest reliability was found to vary from bad to excellent depending on the instruments, the "informant" status (child/adolescent or parent), and the disorder explored, kappas ranging from 0.32 to 1. The worst results concerned face-to-face reliability studies which showed weak concordances for the diagnoses, whatever the procedure implemented: Diagnostic interview vs. i) Another diagnostic interview, vs. ii) An expert diagnosis or vs. iii) Scales and questionnaires. Overall, the K-SADS-PL appeared to be the instrument that has the best test-retest reliability for Anxious Disorders and Affective Disorders (the value kappa showing good to excellent reliabilities). Several important methodological observations emerged from this review. Firstly, the metrological data corresponding to the diagnoses according to DSM IV or ICD-10 criteria's were lacking. The face validity was globally satisfactory, but the data concerning their face-to-face validities and their test-retest reliability, although better than in the former versions, were limited because they were tested on small sample. In fact, it appeared that the agreements depend on the informant, the sample studied, the various diagnostic categories and the instrument used. Since the studies carried out by Cohen et al., with now obsolete versions of the DISC and K-SADS, no other study establishing a comparison between two EDS have been conducted. Consequently, the clinicians must be very careful before comparing DSM or ICD diagnoses generated by different instruments. The second point was the length of the interviews that appeared sometimes longer than instruments used in adults, considering the fact that diagnostic procedure implies two independent interviews, one with the child/adolescent and one with the adult referent. The minimum duration was found to be 1 h 30 for the Chips in clinical setting, while it could reach 4 h or more for the DISC IV or the ISCA. The interviews had to be often carried out in several sessions, so the assessment became very difficult in easily tired and/or distractible subjects. The third point referred to the necessity to consider multiple data sources in young patients during the diagnostic procedure, and the weakness of the levels of agreement generally reported between sources. Empirically, it was observed that the investigator granted more weight to the report of the children than to the parent's one, when the clinical judgement was necessary to synthesize the data. On another level, studies showed a high agreement on the factual contents or on the specific events (ex: hospitalization), like on the obvious symptoms (ex: enuresis). The parents report more problems of behaviour, school and relational difficulties, whereas the children report more fear, anxiety, obsessions and compulsions, or delusional ideas. In other words, it appeared that children were better informants in describing their mental states (internalised disorders), and that adults would bring more reliable information in describing externalised disorders. Like McClellan and Werry, we think that further researches are needed to clarify if and when this is the case. The last major point concerned the problem of language. These instruments must be used in the maternal language of the interviewees and they were developed for most of them into English only. For example, there is only one instrument available into French (the Kiddie SADS). Nowadays, it remains difficult to conduct international studies in child and adolescent psychiatry and/or to compare data is this domain. To conclude, the use of the EDS and EDSS brings many benefits, in academic researches as well as in clinical practice, but a more systematic use is limited by a certain number of parameters. The instruments currently available in child and adolescent are far from being optimal in terms of quality and quantity. It seems necessary and useful to contribute to their development and their improvement. In particular, the following points should be considered: drastic reduction of the length of the interviews; simplification in the use of these instruments, during the interviews, but also in the treatment of the data collected during the final phase of diagnosis generation, the clinician having to carry out ceaseless returns to check the presence or not of each diagnostic criterion; reduction of the duration of the highly necessary training, which can be easily solved by the global simplification of the instruments; quantitative and qualitative improvements of psychometric properties, in particular in terms of sensitivity, specificity and face-to-face validity. Finally, it is highly necessary to continue to develop structured diagnostic interviews adapted to the assessment of child and adolescent psychiatric diagnoses keeping in mind simplicity, feasibility and reliability. Developing this kind of instruments is hard, expensive, and sometimes tiresome but it remains the inescapable stage to produce high quality data in the future.

[Pharmaco-epidemiological study on antipsychotic drug prescription in French Psychiatry: Patient characteristics, antipsychotic treatment, and care management for schizophrenia]. / Etude pharmaco-épidémiologique de la prescription des antipsychotiques en milieu psychiatrique en France -

UNLABELLED: In 2000, a one week national survey was conducted among 202 psychiatrists (129 participants) in France, from hospitals and clinics, private or public. The first 20 inpatients and 10 outpatients prescribed at least one antipsychotic drug (age range 18-65), were included. The diagnostic procedure was standardized with a structured interview: the Mini International Neuropsychiatric Interview (MINI). A total 2 068 patients were included, among whom 892 (43.1%) reached the criteria of schizophrenia according ICD-10. We present here data on these latter patients. Mean age was 38.8 years; with 38.8% females. Median duration of current antipsychotic treatment was 0.5 year in inpatients and 2 years in outpatients. Median duration of any antipsychotic treatment was 10 years, without difference between groups. Comorbid situations (anxiety disorder, depression and suicidal risk) were found in 33.1% of schizophrenic patients, with higher frequency among inpatients in private hospitals (54.8%) than in other groups. 46.8% patients were prescribed at least 2 neuroleptics, and 73.6% at least one non-neuroleptic drugs. Cyamemazine accounted for 16.6% of all neuroleptics drugs, and 56% of patients were prescribed an atypical antipsychotic (risperidone, olanzapine, amisulpride or clozapine). Atypical drugs accounted for 59.4% of patients who were prescribed only one neuroleptic drug. Inpatients had more neuroleptics coprescription than outpatients (mean 1.8 vs 1.4 drugs), with higher daily dose. In addition, inpatients had more other psychotropics prescribed (mean 1.5 vs 1.1 drugs). Overall, more other psychotropic drugs were prescribed among patients with -, than those without - comorbid situations (1.7 vs 1.2 drugs). Median time since admission, at the time of the study, were similar in private and public hospitals (107 vs 99 days) but maximal time since admission was respectively 2.8 and 48.9 years. Visit frequency for outpatients was more than one every two weeks for 43.1% in private and 24.7% in public clinics. Among inpatients only we found a difference between private and public hospitals for polypharmacy of non neuroleptics psychotropics, (mean 1.9 vs 1.5). In outpatients, long acting depot accounted for 26.6% of neuroleptics treatments in public clinics and 15.4% in private clinics. Finally, we found that polypharmacy among outpatients increased with duration of antipsychotic treatment. CONCLUSION: in France, important differences are reported in antipsychotic prescription for schizophrenia between in- and outpatients. Current antipsychotic prescription is more recent in inpatients than in outpatients, with similar duration of overall antipsychotic treatment. Inpatients have more drug prescription, antipsychotics and other psychotropics, than outpatients. Differences are less important between private and public providers. Inpatients in private hospitals receive more non neuroleptic drugs than in public hospitals, and depot antipsychotics are more used among patients of public clinics. Long term inpatients are found in public hospitals only. Outpatients follow up is more intensive in private than in public clinics.

[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.

[Use of a structured diagnostic interview to identify depressive episodes in an epidemiologic study: a posteriori internal validation]. / Utilisation d'un entretien diagnostique structuré pour identifier les épisodes dépressifs dans une étude épidémiologique: validation interne a posteriori.

BACKGROUND: During these last years, many structured and standardized diagnostic interviews have been developed in order to identify psychiatric disorders in a standardized way. These tools enable a systematic investigation of these disorders according to international classifications. Their main drawback is to be long. To assess the care of depression, we used a shorter and more simple tool: the Mini International Neuropsychiatric Interview (MINI) to identify depressive subjects. METHOD: The study was conducted in the Gazel cohort from the French National Electricity and Gas Company. A stratified sample of 2394 civil servants selected in order to over-represent depressive subjects was asked to answer to the MINI interview through a phone interview. An epidemiological and statistical analysis was performed to test the MINI internal validity: prevalence of depressive disorders using different threshold of diagnosis (number of symptoms required to identify someone as depressive), frequency of different symptoms, variability between investigators and potential biases. RESULTS: Respondents to the phone interview (1108 civil servants) had more often presented depression markers for the last 5 years. Prevalence of depressive episodes changed little when we varied the threshold of diagnosis and did not stress any threshold problem. The variability between investigators was important, but the estimation of prevalence remained stable when we excluded extreme rates of prevalence. The choice of a classification system affected the prevalence estimation. Using the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) from the American Psychiatric Association, the prevalence of depressive episodes was lower and closer to the estimations shown in the literature than using the International Classification of Disease (ICD 10). Moreover, the stratification assigned very unbalanced weights to the stratification strata. By excluding depressive episodes observed in the stratum "control" (no depression "marker" from 1989 to 1994 in the database), the prevalence was very lower, whatever the classification was. Finally, factors which appeared linked to care of depression with the ICD definition remained the same when the DSM diagnosis definition was used, and relative risks were quite similar. CONCLUSION: The MINI appears to be a short and simple tool, suited to the epidemiological studies. This analysis does not highlight any failure in the internal consistency of the MINI. The remaining question is what the MINI really measures, particularly comparing to a psychiatrist's diagnosis.

Differences between prescription and consumption of antidepressants and anxiolytics.

The rate of detection of depressed patients by general practitioners (GPs) is generally reported to be lower than 50%, with some studies giving a value as low as 14%. In addition, GPs tend to overdiagnose anxiety and underdiagnose depression. Patients are not necessarily aware of the psychological nature of the disorder and only one-fifth list psychological complaints as the reason for contact. We collected information on the prescription and consumption of drugs in order to assess the influence of recognition of depression by GPs and of other factors on the treatment received by patients. Our results, which are particularly important in the context of current discussions on the cost of mental healthcare treatments, indicate not only a need for GPs to improve their identification rates but also a need to make patients more aware of the nature of their psychological diagnoses. When spontaneous psychological complaints are presented, the identification rate increases very substantially, and when patients are well aware of their conditions, compliance increases. It is clear from our results that greater specific recognition of psychiatric patients accompanied by the prescription of a specific treatment would not substantially alter the direct costs of drug prescription. On the contrary, it would very probably lower many costs, since the proportion of specific treatment given to properly identified patients is very low at present.

The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.

The Mini-International Neuropsychiatric Interview (M.I.N.I.) is a short structured diagnostic interview, developed jointly by psychiatrists and clinicians in the United States and Europe, for DSM-IV and ICD-10 psychiatric disorders. With an administration time of approximately 15 minutes, it was designed to meet the need for a short but accurate structured psychiatric interview for multicenter clinical trials and epidemiology studies and to be used as a first step in outcome tracking in nonresearch clinical settings. The authors describe the development of the M.I.N.I. and its family of interviews: the M.I.N.I.-Screen, the M.I.N.I.-Plus, and the M.I.N.I.-Kid. They report on validation of the M.I.N.I. in relation to the Structured Clinical Interview for DSM-III-R, Patient Version, the Composite International Diagnostic Interview, and expert professional opinion, and they comment on potential applications for this interview.

DSM-IH-R Psychotic Disorders: procedural validity of the Mini International Neuropsychiatric Interview (MINI). Concordance and causes for discordance with the CIDI.

OBJECTIVES: the Mini International Neuropsychiatric Interview (MINI) is a short diagnostic structured interview (DSI) designed to generate positive diagnosis for the main Diagnostic and Statistical Manual (DSM)-III-R/IV Axis I disorders and to explore the symptoms of Criterion A for Schizophrenia (Sc) to rule out the presence of Psychotic Disorders. The procedural validity of the MINI was investigated in psychiatric patients using the Composite International Diagnostic Interview (CIDI) as a gold standard in Europe and the Structured Clinical Interview for DSM-III-R (SCID-P)in the US. This paper presents the concordance and the reasons for discordance between the MINI and the CIDI for DSM-III-R Psychotic and Mood Disorders. No study had systematically analysed the sources of disagreement between DSI based on the same operational criteria in psychotic patients. METHODS: 256 consecutively recruited psychiatric patients and 50 non-psychiatric subjects passed the MINI and the CIDI. RESULTS: concordance was good for the presence of Major Depressive Episode (MDE), Manic Episode, Psychotic Disorders, syndromes or symptoms (0.65 to 0.82). Inconsistencies in evaluation of the disorder recency accounted for 25 to 40% of discordance for current diagnoses. Fifty-three percent of discordance for lifetime Manic Episode resulted from inconsistencies in the severity of the index episode. Fifty percent of discordance for the diagnosis of Psychotic Disorders was due to algorithmic differences between the two DSI. CONCLUSION: the MINI yields reliable DSM-III-R diagnoses within a short time frame (22 minutes). Depending on the quantitative and the qualitative analyses of discrepancies between the MINI and the CIDI for Psychotic Disorders and Mood Episodes, we proposed and tested modifications leading to improvements in both interviews. The procedural validity of the modified MINI according to the modified CIDI was found to be very good.

Lack of amnestic, psychotomimetic or impairing effect on psychomotor performance of eliprodil, a new NMDA antagonist.

The possible effects on memory, psychomotor performance and mood of eliprodil, a new non-competitive NMDA receptor antagonist acting through the polyamine modulatory site, was assessed in a randomized, double-blind, cross-over, placebo-controlled study involving 11 healthy young male volunteers. Eliprodil 30 mg, a placebo and midazolam 15 mg, a positive control, were administered as a single oral dose at 1 week wash-out intervals. Objective tests evaluated both memory (Sternberg memory scanning and paired words for short-term memory, delayed free recall of pictures for long-term memory) and psychomotor functions and arousal (critical flicker fusion threshold, choice reaction time, body sway). Mood was assessed using self-ratings (LARS, POMS, ARCI). Statistical analysis was performed using an ANOVA with pairwise comparisons using Tukey's method. A single dose of eliprodil 30 mg was free of any detrimental effect on memory and skilled performance and did not produce either subjective sedation or excitation or psychotomimetic effects in comparison with placebo. In contrast, a single dose of midazolam 15 mg induced a marked impairment in psychomotor performance and cognitive functions (significant reduction in CFF, increase in CRT and body sway, disruption of short- and long-term memory). The potent sedative activity of midazolam, peaking 1 to 3 h post-dose, was confirmed by subjective evaluation and had disappeared 8 h post-dose.

Comparison of the effects of zolpidem and triazolam on memory functions, psychomotor performances, and postural sway in healthy subjects.

Zolpidem is a rapid-onset, short-duration imidazopyridine hypnotic drug and is specific agonist of the omega-1 (BZD1) receptors. Its hypnotic characteristics resemble those of triazolam. The aims of this study were to assess the effects of zolpidem on memory (the main objective), psychomotor performances, and postural sway (secondary objectives) in 18 healthy subjects and to compare them with those of triazolam and placebo. Short- and long-term memory (paired words associate and pictures test), psychomotor performances (critical flicker fusion frequency, choice reaction time, digit symbol substitution test), and postural sway were evaluated before and 1.5, 4, 6, and 8 h after the administration of a single dose of zolpidem (10 mg), triazolam (0.25 mg), and placebo. For each assessment, the maximal effect for both hypnotic drugs occurred 1.5 hour after intake. Both drugs decreased psychomotor performance, impaired memory, and increased postural sway. The effects of both hypnotic agents were short lasting, and no alterations were found 6 and 8 hours, respectively, after drug intake. No clinically relevant differences were found between zolpidem and triazolam for memory, psychomotor performance, postural sway, or adverse effects. It may be concluded that zolpidem, like triazolam, impairs short- and long-term memory, psychomotor performances, and postural sway and that these effects are of short duration.

Comparative study of the psychomotor and antistress effects of ritanserin, alprazolam and diazepam in healthy subjects: some trait anxiety-independent responses.

The new potential anxiolytic ritanserin was studied in a double-blind manner vs. alprazolam, diazepam and placebo in 23 healthy subjects. The subjects belonged either to a high anxiety level group or a low anxiety level group, in order to study the effect of the anxiety level on the pharmacodynamic responses. The assessments included cognitive function (memory tests), psychomotor performance [Critical Flicker Fusion (CFF), Choice Reaction Time (CRT)], subjective ratings of alertness and overnight sleep and stress paradigm. Ritanserin (10 mg), alprazolam (0.75 mg), diazepam (10 mg) and placebo were given as single oral doses following a latin square design. Groups were well contrasted on the Cattell anxiety scale and were not overlapping. On no psychometric variable have there been any interactions between the anxiety level and the drug factor. At baseline an anxiety-related difference between the two groups was observed: lower CFF value in the high anxiety group (-1.4 Hz). Both benzodiazepines impaired psychomotor assessment and memory function and increased sleepiness. Ritanserin decreased CFF values without significantly affecting CRT on which nevertheless a trend to impairment was observed. Memory tests, and subjective ratings of alertness were unaffected by ritanserin. A trend to an antistress effect was observed on electrodermogram after ritanserin. Both benzodiazepines decreased central nervous system arousal and memory while ritanserin was inactive except on CFF. Recent data support the hypothesis that 5-HT2 blockers decrease pupil diameter which is a well known covariate of flicker frequency.

Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase-A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects.

1. The effects of two reversible, predominantly monoamine oxidase-A (MAO-A) inhibitors, moclobemide (150 mg three times daily) and toloxatone (400-200-400 mg day-1) on monoamine metabolites and psychometric performance were compared in a double-blind placebo controlled crossover study in 12 healthy subjects. 2. After 7 days of moclobemide/toloxatone/placebo administration subjects were hospitalized for 24 h on day 8. Blood samples were drawn every 2 h for determination of plasma noradrenaline (NA), 3,4-dihydroxyphenylglycol (DHPG), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA). Urine was collected for measurements of normetanephrine and 3-methoxytyramine excretion. Psychometric performance (short- and long-term memory, critical flicker fusion frequency, choice reaction time) and subjective feelings were assessed before each drug intake (in the morning, at noon, in the evening). 3. Compared with placebo, both reversible monoamine oxidase inhibitors decreased the plasma concentration of DHPG and HVA. The overall fall in DHPG (AUC from 0 to 24 h) was 44% during moclobemide and 12% during toloxatone (P less than 0.001) and the overall decrease in HVA was 38% and 20% (P less than 0.005) on moclobemide and toloxatone, respectively. 4. Before the next drug intake, MAO-A inhibition, as judged by the decrease of plasma DHPG concentration, was significantly different from placebo with moclobemide but not with toloxatone. 5. Moclobemide, but not toloxatone, exerted a moderate, but significant inhibition of the deamination of 5-hydroxytryptamine (5-HT) as judged by the fall in plasma 5-HIAA concentration. Neither drug influenced plasma NA concentration. 6. A significant rise in urinary excretion of normetanephrine was observed on moclobemide and to a lesser extent on toloxatone. The urinary excretion of 3-methoxytyramine was significantly raised by moclobemide but not by toloxatone. 7. Neither moclobemide nor toloxatone altered memory function, vigilance, subjective feelings or sleep characteristics of the subjects.