[Drug treatments, from chlorpromazine to new molecules]. / Traitements médicamenteux, de la chlorpromazine aux nouvelles molécules.

The history of drug treatments, and particularly the discovery of certain molecules, led toan evolution in psychiatric practices. The discovery of the therapeutic properties of chlorpromazine in 1952 by Jean Delay and Pierre Deniker revolutionised the relational process between patients and caregivers.The perspectives are encouraging, notably in the areas of schizophrenia and mood disorders.

Deficit of inhibition motor control in untreated patients with schizophrenia: further support from visually guided saccade paradigms.

In addition to classical delusional, negative, and cognitive deficit, schizophrenia has consistently been associated with impairments in saccadic eye movements, e.g., an increased error rate in the antisaccade task. We hypothesized that a deficit in inhibitory control is a core defect in untreated patients with schizophrenia leading to impairment in different oculomotor paradigms. Ten drug-free or drug-naïve patients with schizophrenia were matched in age and gender to 11 healthy controls with no psychoactive substance use or abuse. They were explored using reflexive saccades with unpredictable targets with or without the gap procedure, predictive saccades and a fixation/distracter paradigm. Patients with schizophrenia displayed shorter latency in reflexive and predictive saccades. In the GAP condition, patients made more anticipatory saccades, fewer regular saccades, and had a shorter latency of express saccades than controls. In addition, patients had an increased error rate in the fixation/distracters task. Altogether, these results provide new evidence of reduced prefrontal inhibitory regulation of subcortical and brainstem systems involved in the control of saccades.

Leptin and ghrelin levels in patients with schizophrenia during different antipsychotics treatment: a review.

Energy homeostasis is achieved by the integration of peripheral metabolic signals by the neural circuits involving specific hypothalamic nuclei and brain stem regions. These neural circuits mediate many of the effects of the adipocyte-derived hormone leptin and gut-derived hormone ghrelin. The former is strongly anorexigenic while the latter is the only orexigenic agent active when administered by a peripheral route. Abnormal regulation of these 2 antagonistic regulatory peptides in patients with schizophrenia could play a role in the impairment in the regulation of food intake and energy balance. This bibliographical analysis aims to compare 27 prospective and cross-sectional studies published on circulating leptin and ghrelin levels during acute and chronic administration of antipsychotics treatment, especially atypical ones. Fasting morning leptin levels of schizophrenic patients increase rapidly in the first 2 weeks after atypical antipsychotic (AAP) treatment (mostly olanzapine and clozapine) and remain somehow elevated after that period up to several months. On the contrary, conventional antipsychotics (such as haloperidol) do not interfere with leptin levels. In contrast to leptin, fasting morning ghrelin levels decrease during the first few weeks after the beginning of AAPs treatment while they increase in the longer run. Surprisingly, body weight gain and correlations between the variation of these 2 peptides and adiposity and metabolism-related parameters such as the body mass index and abdominal perimeter were not systematically considered. Finally, an objective evaluation of feeding behavior during antipsychotic treatment remains to be determined.

Bipolar disorders and quality of life: the impact of attention deficit/hyperactivity disorder and substance abuse in euthymic patients.

Patients with bipolar disorders (BPD) display high rates of comorbidities, especially substance abuse (20-40%) and attention deficit/hyperactivity disorder (ADHD) (6%-20%). However, there are virtually no data evaluating the role of current ADHD on the global functioning of patients with BPD. The recent literature suggests that impairments in quality of life are a key prognostic feature for predicting the long course of BPD. The aim of this study was to investigate the intrinsic impact of adult ADHD and substance abuse in patients with BPD on levels of social adaptation, functioning and vitality. Seventy-three outpatients with BPD I or II, all euthymic and being treated with mood stabilizers, were evaluated using the following measures: 1) the Diagnostic Interview of Genetics Study for DSM-IV criteria; 2) the ADHD Self-Report Scale (ASRS) (screening of adult ADHD); 3) measures of quality of life: social adaptation (Social Adjustment Scale Self-Report (SAS-SR)), well-being (Short Form 36 (SF-36) Health Survey), and the Brief Psychiatric Rating Scale. In this clinical sample, 30% met the ADHD criteria and 22% were substance abusers. The results showed that the presence of ADHD in BPD patients significantly predicted a low social functioning and adaptation by comparison with BPD patients without ADHD. By contrast, we failed to detect a significant impact of substance abuse on those functional outcomes. This is the first step towards improved screening for comorbidities and an understanding of their crucial role in the prognosis of the disorder, as well as in defining new multilevel therapeutic strategies.

A kinetic-pharmacodynamic model for clinical trial simulation of antidepressant action: application to clomipramine-lithium interaction.

A generic kinetic-pharmacodynamic (K-PD) model to describe the response to treatment assessed by a clinical score for depressed patients treated by antidepressants alone or combined with a drug that shortens the lag-time before effect was developed. The aims of this study were: (1) to verify model's ability to characterize clinical data, (2) to evaluate several statistics to summarize the clinical effect, (3) to compare the analysis based on these statistics to the conventional intent-to-treat analysis and (4) to determine the optimal dates of clinical assessment. The population K-PD model was fitted to the individual data from a randomized clinical trial assessing the efficacies of clomipramine and placebo or clomipramine and lithium to treat major depression in 141 patients. The K-PD model was able to fit the individual data even in the case of oscillating score profiles. The interindividual coefficient of variation of the model parameters ranged from 33 to 161%. The statistical analysis based on the secondary parameters yielded conclusions comparable to those of the conventional intent-to-treat analysis. The population model was then used for a clinical trial simulation. According to the simulation, the most sensitive summary statistics for detecting a difference between lithium and placebo were the fractional reduction of depression and the proportion of responders. The optimal dates to assess these parameters were day 9 and 11 respectively. The K-PD model might serve as a tool for clinical trial planning in the field of research on antidepressants and their facilitators.

Polymorphisms TaqI A of the DRD2, BalI of the DRD3, exon III repeat of the DRD4, and 3' UTR VNTR of the DAT: association with childhood ADHD in male African-Caribbean cocaine dependents?

The conflicting results reported by genetic studies with the variants of the genes coding for the dopaminergic system in cocaine addicts could be partially explained by the difficulties to constitute homogenous sample of patients. Childhood attention-deficit/hyperactivity disorder (ADHD), and/or impulsivity are frequently associated with cocaine addiction and could participate in the heterogeneity of the samples in cocaine addicts. Accordingly, it is hypothesized that cocaine addiction would be associated with the variants of the genes coding for the dopamine system in an homogenized sample of cocaine addicts, especially in individuals with childhood ADHD comorbidity, or with a high impulsivity score. The potential association of the variants TaqI A of the DRD2, BalI of the DRD3, exon III repeat of the DRD4, and 3' UTR VNTR of the DAT was examined in African-Caribbean males, smoked-cocaine dependents. All the subjects were assessed with the Diagnostic Interview of Genetic Studies, the Barratt's impulsivity scale, and the Wender Utah rating scale for childhood ADHD. A positive association was found with the DRD2 and DRD4 polymorphisms in the subgroups of patients with childhood ADHD, or with a high impulsivity score, which represented, respectively, 53.3 and 73.0% of the patients. Conversely, no positive association was found for any of the polymorphisms studied when the group of patients was examined as a whole. Therefore, our results suggest that the clinical dimensions of childhood ADHD and of impulsivity could be taken into account to homogenize the samples of patients in cocaine association studies.

Augmentation strategies of clozapine with antipsychotics in the treatment of ultraresistant schizophrenia.

BACKGROUND: Approximately 40% to 70% of neuroleptic-resistant schizophrenic patients are nonresponders to clozapine. Several clozapine augmentation strategies have come into clinical practice although often without evidence-based support. Among these strategies, the combined use of clozapine with another antipsychotic has been reported for up to 35% of patients receiving clozapine. OBJECTIVE: The purposes of the present work were to (1) review the available literature on the efficacy and safety of the clozapine augmentation with another antipsychotic using a MEDLINE search of the literature from 1978 to December 2005 and (2) to propose an operational definition of schizophrenia refractory to clozapine ("ultraresistant schizophrenia") for the implementation and homogenization of future therapeutic trials. CONCLUSION: Case controls and open clinical trials largely dominate the literature, and there are only 4 double-blind studies of clozapine augmentation with antipsychotics. The results of these studies are somewhat discrepant. Moreover, the heterogeneity of definitions of resistance to clozapine, of outcome measures and of dose and duration of pharmacological trials is a major limitation for drawing conclusions.

Somatic augmentation strategies in clozapine resistance--what facts?

BACKGROUND: Polypharmacy without evidence-based support is sometimes needed for patients treated with 40% to 70% clozapine who are clozapine nonresponders. Several somatic augmentation strategies are proposed in the scientific literature, with different levels of evidence for safety and efficacy. OBJECTIVES: The purpose of the present study is to review the available literature on the efficacy and safety of clozapine augmentation with somatic agents other than antipsychotics. The following classes of agents are considered: (1) mood stabilizers, (2) antidepressants, (3) electroconvulsive therapy and repetitive transcranial magnetic stimulation, (4) glutamatergic agents, (5)fatty acids supplements, and (6) benzodiazepines. RESULTS: Case controls and small-size clinical trials largely dominate the literature, limiting the power to draw conclusions concerning safety issues and the meaning of negative studies. Moreover, variable definitions of clozapine resistance, heterogeneous outcome measures, and short duration of treatment trials are additional limitations. CONCLUSION: Generally, adjunctive strategies for clozapine-resistant patients remain based on scarce evidence of efficacy and significant safety concerns. Low-frequency repetitive transcranial magnetic stimulation, fatty acids supplements, and mirtazapine showed good tolerability and some efficacy, but the results need replication.

Cognitive dysfunctions in medicated and unmedicated patients with recent-onset schizophrenia.

Schizophrenia is associated with impairments in many cognitive domains on which the influence of antipsychotics, whether conventional or atypical, remains unclear. We conducted a study of recent-onset schizophrenic patients (DSM IV) that included unmedicated (n=19), and medicated (n=19) patients matched for age and IQ. Both groups of patients had comparably low extra-pyramidal symptoms (EPS). Cognitive tasks included attentional tasks (alertness and divided attention tests), a working memory task (a verbal n-back test) and the Wisconsin Card Sorting Test (WCST). After adjustment for the Total PANSS score, we found no significant difference between the two groups of patients in any of the cognitive tasks. When compared to a group of healthy controls (n=20) matched for IQ level, unmedicated patients performed significantly worse in all cognitive tasks, with significantly longer reaction times for alertness, divided attention and working memory. These results confirm the presence of cognitive impairments in attentional and executive functions in recent-onset patients whether or not they are medicated. There was no evidence that either conventional or atypical antipsychotics had an influence on patients when EPS were excluded. Altogether, our results further support the idea that cognitive deficits in schizophrenia are enduring features per se and cannot be considered as secondary to psychiatric symptoms or to the adverse effects of medication. In addition our results suggest that antipsychotics do not have a major effect on these impairments.

Prevalence of smoking in psychiatric patients.

Compelling evidence that tobacco-smoking is a form of drug addiction exists. The aim of this study is to determine the following: (1) prevalence of tobacco-smoking and of nicotine dependence in French psychiatric patients; (2) rates and patterns of tobacco smoking and of nicotine dependence according to diagnosis; (3) relationship between current smoking status and antipsychotic medications; and (4) relationship between cigarette smoking and neurological side effects induced by neuroleptics. A population of 711 psychiatric in- and outpatients was assessed using: (1) a detailed smoking self-questionnaire for smoking history and nicotine dependence; and (2) a questionnaire for staff covering treatments and DSMIII-R diagnoses. Data were analyzed using chi2 analysis of variance (ANOVA) tests (one factor) for quantitative comparisons between groups of patients, and analysis of covariance (ANCOVA) test with age covariate was performed for age-dependent variables. Prevalence of smoking in the population of psychiatric patients was significantly higher than in the French general population. Diagnoses among current smokers were mainly substance-related disorder and schizophrenia. The authors established correlations between prevalence of smoking and age, sex, marital and socioeconomic status, alcohol use, coffee consumption and other psychoactive substance use or abuse. The authors did not find relationship between smoking prevalence and institutionalization. Neuroleptic neurological side effects were significantly fewer among smokers compared to nonsmokers. However, the rate of smokers was significantly higher in psychiatric patients receiving neuroleptic drugs. Nicotine abuse in psychiatric patients, and especially in schizophrenic patients, could support the hypothesis that smoking is consistent with self-medication.

Clinical profile of responders to buprenorphine as a substitution treatment in heroin addicts: results of a multicenter study of 73 patients.

In France, high-dosage buprenorphine (HDB) is the main substitution treatment for narcotic addiction. Few data have been published concerning clinical factors predicting a good response to this treatment in a daily practice. A hospital-based multicenter clinical research program (PHRC) was undertaken in heroin-addicted patients, diagnosed according to DSM-III-R, to detect clinical criteria susceptible of predicting a good response to HDB administered during a 3-month treatment period. At the inclusion time in the study, a diagnostic structured interview (DIGS) was performed, and the Addiction Severity Index (ASI), Zuckerman scale, depression scale from Jouvent, and CGI were scored. MMPI was also administered. Good response was defined as an ongoing participation in the study, with absence of opiate detected in 75% of urine collected during the last month of treatment. Only subjects treated for at least 1 month were eligible for analyses. One hundred fifteen patients were recruited and 73 were analyzed. Patients received 8.5+/-2.6 mg (m+/-S.D.) of buprenorphine for 1 to 3 months. A forward stepwise logistic regression showed that six clinical parameters may predict a good response to treatment: probability to respond to buprenorphine was higher in subjects having a high psychopathology (ASI) subscore, low disinhibition and boredom susceptibility factor scores (Zuckerman scale), no alcohol dependence, no family history of addiction or mood disorder, and duration of opiate dependence less than 10 years. Only the MMPI D subscale was a psychological pattern correlated to a good response to substitution treatment. These findings are important to consider when making the decision to prescribe HDB substitution treatment in opiate addiction.

Multicenter double-blind randomized parallel-group clinical trial of efficacy of the combination clomipramine (150 mg/day) plus lithium carbonate (750 mg/day) versus clomipramine (150 mg/day) plus placebo in the treatment of unipolar major depression.

BACKGROUND: The therapeutic efficacy of adding lithium to an ongoing antidepressant in resistant depression is well known. However there is less data concerning the efficacy of giving lithium and antidepressant concurrently from the start of treatment. METHODOLOGY: The primary objective of this study was to compare the efficacy of a combination of clomipramine+lithium (C+L) with that of clomipramine+placebo (C+P) in-patients with unipolar major depression, during the first 11 days of treatment. Secondary objectives were the assessment of effectiveness after 6 weeks and assessment of the safety of the combination clomipramine and lithium carbonate. C+L and C+P groups were compared for 6 weeks in a multicenter randomized trial of 141 patients hospitalized with a DSM-IV diagnosis of major depression. Efficacy was evaluated using the standard MADRS and CGI scales. RESULTS: Analysis of the 'as treatment ITT' population showed: the percentage reduction in MADRS scores between D0 and D11 in this population was better in the C+L group but not statistically significant (C+L: 32.1 vs. C+P: 27.4, P=0.07). Nevertheless, the comparison of mean MADRS scores showed a significant difference in the C+L group on days 4 (C+L: 25.1 vs. C+P: 27.8) and 7 (C+L: 18.6 vs. C+P: 21.5), P<0.05, and approaching significance on day 11 (C+L: 14.6 vs. C+P 17.2, P=0.054). On day 7, the number of patients in total remission was threefold higher in the C+L group than in the C+P group (15 vs. 4%, P<0.05) and twofold on day 11 (29 vs. 14%, P<0.05). CGI severity score showed C+L was superior to C+P on days 4, 7 and 11 and CGI improvement score was better in C+L group on day 11 (P<0.05). After 6 weeks of treatment no statistical difference was found between the two groups from the clinical point of view. Safety based upon clinical and laboratory parameters was satisfactory in both groups during the 6 weeks of the study. LIMITATIONS: Patients with bipolar disorder, previously treated with clomipramine or with any other mood stabilizers during the previous week; or with suicide attempt during the current episode with a score > or =3 for item 10 of the MADRS were excluded from the study. CONCLUSION: The results of this study suggests that lithium slightly to moderately potentiates antidepressant treatment in unipolar non-refractory patients with severe major depression in the first days of treatment but not as significantly as for the bipolar population.

Interaction of lithium with 5-HT(1B) receptors in depressed unipolar patients treated with clomipramine and lithium versus clomipramine and placebo: preliminary results.

Lithium is commonly used in combination with antidepressant drugs as a treatment for refractory depression; less often, it is used in non-resistant depression. The aim of this study was to examine the interaction of lithium with 5-HT(1B) receptors in 10 non-resistant unipolar depressed patients treated with clomipramine+lithium (C+L) vs. clomipramine+placebo (C+P). A mediation of the serotonergic system has been proposed in the literature to explain the clinical effect of lithium. Indeed, in a previous study of healthy human blood platelets, we demonstrated the interaction of lithium with adenylate cyclase activity coupled to 5-HT(1B) receptors. The functional activity of these receptors was measured by studying the inhibitory effect of L694,247, a 5-HT(1B) receptor agonist, on the adenylate cyclase activity determined by the production of cAMP. Using the same technique in the present study, we found that lithium significantly reduced the inhibition of adenylate cyclase activity induced by 5-HT(1B) receptor activation. This result confirms the specific interaction of lithium with 5-HT(1B) receptors. Moreover, a correlation between the percentage of 5-HT(1B) receptor-dependent adenylate cyclase inhibition and the clinical benefit of lithium was established, suggesting 5-HT(1B) receptors may be a target for the therapeutic effect of lithium.

Cerebellum development and schizophrenia: an association study of the human homeogene Engrailed 2.

Epidemiological data and family studies in schizophrenia show that genetic factors contribute to the vulnerability to this disorder. The homeogene Engrailed 2 (EN2) is specifically involved in patterning the region that gives rise to the cerebellum and controls the plasticity of midbrain dopaminergic neurons. We carried out an association study for a CA repeat polymorphism located in the 3' region of the homeogene EN2. The subjects consisted of 165 patients with schizophrenia and 97 controls matched for age and ethnicity from a French Caucasian population. We found no significant association of schizophrenia with this bi-nucleotide repeat polymorphism of the EN2 gene.

Correlation between clinical syndromes and neuropsychological tasks in unmedicated patients with recent onset schizophrenia.

The aim of this study is to circumscribe the cognitive deficits according to schizophrenic syndromes in a population of sub-acute untreated patients. We have studied the cross-sectional correlation between cognitive deficits and schizophrenic symptoms, in a group of 24 untreated patients (including 17 neuroleptic-naive patients) with recent onset of the disease. A task of alertness, a working memory (WM) test (including two levels of difficulty) and an abbreviated version of the Wisconsin Card Sorting Test (WCST) were selected. WM deficits and poor performance on the WCST were highly correlated with disorganized symptoms, modestly with the positive syndrome and not with the negative syndrome. Thus, disorganized symptoms, more than any other, appear to be related to the impairment of executive function and WM in recent onset unmedicated patients with schizophrenia.

Milnacipran and venlafaxine at flexible doses (up to 200 mg/day) in the outpatient treatment of adults with moderate-to-severe major depressive disorder: a 24-week randomized, double-blind exploratory study.

The objective of this exploratory, multicenter, randomized, double-blind study, was to evaluate the efficacy and safety/tolerability of milnacipran and venlafaxine administered at flexible doses (100, 150 or 200 mg/day, bid administration) for 24 weeks (including 4 weeks up titration period) in the outpatient treatment of adults presenting with a moderate or severe episode of major depressive disorder (MDD) without high suicidal risk (MINI-DSM IV-TR). Of the 195 patients included, 134 (68.7%) completed the study. At baseline the two groups were similar, except there was a higher proportion of patients whose episode was severe-DSM IV in the milnacipran group (63.3% versus 54.0% in the venlafaxine group). The initial MADRS score (mean 31.0) decreased progressively during the study, and this decrease was in the two treatment groups (n = 177: 90 milnacipran; 87 venlafaxine) at week 24 (observed case/OC, mean change -23.1 milnacipran; -22.4 venlafaxine). The rate of MADRS response (reduction >/= 50%) at week 8 and week 24-last observation carried forward/LOCF was similar in the two groups (week 8: 64.4% milnacipran; 65.5% venlafaxine; week 24: 70% milnacipran; 77% venlafaxine), as was the rate of MADRS remission (score

Balneotherapy versus paroxetine in the treatment of generalized anxiety disorder.

INTRODUCTION: Preliminary studies have suggested that balneotherapy (BT) is an effective and well-tolerated treatment for generalized anxiety disorder (GAD) and psychotropic medication withdrawal syndrome. We carried out a study in 4 spa resorts to assess the efficacy of BT in GAD. METHOD: We compared BT to paroxetine in terms of efficacy and safety in a randomized multicentre study lasting 8 weeks. Patients meeting the diagnostic criteria of GAD (DSM-IV) were recruited. Assessments were conducted using the Hamilton Rating Scale for Anxiety (HAM-A) and other scales, by a specifically trained and independent physician. The primary outcome measure was the change in the total HAM-A score between baseline and week 8. RESULTS: A total of 237 outpatients were enrolled in four centres; 117 were assigned randomly to BT and 120 to paroxetine. The mean change in HAM-A scores showed an improvement in both groups with a significant advantage of BT compared to paroxetine (-12.0 vs -8.7; p<0.001). Remission and sustained response rates were also significantly higher in the BT group (respectively 19% vs 7% and 51% vs 28%). CONCLUSION: BT is an interesting way of treating GAD. Due to its safety profile it could also be tested in resistant forms of generalized anxiety and in patients who do not tolerate or are reluctant to use pharmacotherapies.

Effects of atypical neuroleptics on alertness and visual orienting in stabilized schizophrenic patients: a preliminary study.

It has been shown that schizophrenic patients treated with conventional neuroleptics display a general slowness in latency in simple reaction-time tasks and a disengagement deficit in visual-orienting tasks. Yet, the influence of atypical neuroleptics on attention is still controversial. The purpose of our study was to investigate the effect of atypical neuroleptics in tasks requiring alertness, selective attention or visual orienting. Thirteen stabilized schizophrenic patients receiving atypical neuroleptics were compared to 13 healthy controls matched for age, gender, and study level, in a choice reaction time (CRT) task and a visual-orienting task cued target detection (CTD) task. The results showed that patients and controls obtained comparable reaction times (RTs) in the CRT task. In the CTD task, both groups had comparable RTs but the presence of invalid cues caused a greater attentional cost in both visual fields for patients compared to controls, indicating a symmetrical disengagement deficit. To conclude, patients treated with atypical neuroleptics had a phasic alertness ability similar to controls. By contrast, an impairment of disengagement was present in those patients. Thus, atypical neuroleptics could have a positive influence on certain but not all attentional domains.

Association between the dopamine receptor D4 (DRD4) gene and obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a frequent and disabling anxiety disorder. Dopamine (DA) might be involved in its pathophysiology, therefore DA receptors are candidate genes in OCD. A 48-base pairs (bp) polymorphism located in the third exon of the dopamine receptor type 4 (DRD4) gene has been described. Previous case control studies, however, have reported inconclusive results in OCD. The aim of the study was to study this polymorphism in a family-based association study of 55 trios. Extended transmission-disequilibrium test (ETDT) for preferential allele transmission in this group showed an absence of transmission of the allele 2 for the 48 bp repeat polymorphism of the DRD4 gene (P = 0.005). Moreover, in a population-based association study, we found a significantly lower frequency of the allele 2 in patients suffering from OCD compared to ethnically-matched controls (P = 0.02). We found no association of DRD4 48 bp polymorphism with OCD in the subgroup of patients with comorbid tics. This study is the first to report on a significant association of variants of the DRD4 gene in OCD, found on both family- and population-based studies. The results suggest that the 2 allele or a nearby genetic variation could have a protective effect against OCD symptoms.

Aplicaçäo da versäo em pórtuguês de um guia para entrevista semi-estruturada adaptada a quatro escalas de depressäo / Application of the Portuguese version of a structuredinterview guide for four depression rating scales

Os autores apresentam o desenvolvimento e aplicaçäo de um guia para uma entreveista semi-estruturada adaptada a quatroescalas para avaliaçäo da depressäo:escala de avaliaçäo de depressäo de Hamilton - 17 itens (HDRS-17), escala de avaliaçäo da depressäo de Montgomery-Asberg (MADRS), escla de lentificaçäo depressiva de Wildlocher (ERD), bem como de uma escala "complementar" de apreciaçäo da sintomatologia depressiva (EC) centrada nos sintomas que näo fazem parte do núcleo depressivo e que näo säo pesquisadas pelas escalas clássicas (baseada na escala de apreciaçäo da depressäo e da mania - EADM 1 - de P. Pichot). A versäo final em português foi testada em 66 pacientes deprimidos brasileiros hospitalizados. Esta entrevista se mostrou eficaz para a coleta de dados suficientes para poder preencher as 4 escalas com uma duraçäo de aplicaçäo de aproximadamente 45 minutos