Depression: Versiani M

Bauer M, Bschor T, Pfennig A, Whybrow PC, Angst J, Versiani M, Möller HJ, Anonymous00106. · University Hospital Carl Gustav Carus, Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany. · World J Biol Psychiatry. · Pubmed #17455102 No free full text.

Abstract: These practical guidelines for the biological treatment of unipolar depressive disorders in primary care settings were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). They embody the results of a systematic review of all available clinical and scientific evidence pertaining to the treatment of unipolar depressive disorders and offer practical recommendations for general practitioners encountering patients with these conditions. The guidelines cover disease definition, classification, epidemiology and course of unipolar depressive disorders, and the principles of management in the acute, continuation and maintenance phase. They deal primarily with biological treatment (including antidepressants, other psychopharmacological and hormonal medications, electroconvulsive therapy, light therapy).

Bauer M, Whybrow PC, Angst J, Versiani M, Möller HJ, Anonymous00267. · University of California Los Angeles (UCLA), Neuropsychiatric Institute & Hospital, Department of Psychiatry and Biobehavioral Sciences, Los Angeles, CA, USA. · World J Biol Psychiatry. · Pubmed #12479080 No free full text.

Abstract: These practice guidelines for the biological treatment of unipolar depressive disorders were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal for developing these guidelines was to systematically review all available evidence pertaining to the treatment of the complete spectrum of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating patients with these conditions. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for depressive disorders, as well as from meta-analyses and reviews on the efficacy of antidepressant medications and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and was then categorized into four levels of evidence (A-D). The first part of these WFSBP guidelines on unipolar depressive disorders covered the acute and continuation treatment of major depressive disorder (Bauer et al 2002). This second part of the guidelines covers the management of the maintenance-phase treatment of major depressive disorder, as well as the treatment of chronic and subthreshold depressive disorders (dysthymic disorder, double depression, minor depressive disorder and recurrent brief depression). These guidelines are primarily concerned with the biological treatment (including antidepressants, lithium, other psychopharmacological and hormonal medications, and electroconvulsive therapy) of young adults and also, albeit to a lesser extent, children, adolescents and older adults.

Möller HJ, Baldwin DS, Goodwin G, Kasper S, Okasha A, Stein DJ, Tandon R, Versiani M, Anonymous00012. · Department of Psychiatry, Ludwig-Maximilians-University München, Nussbaumstrasse 7, 80336 Munich, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #18668279 No free full text.

Abstract: In the past few years several papers have reported critically on the risk of suicidal thoughts and behaviour associated with antidepressants, primarily SSRIs. The risk-benefit ratio of antidepressant (AD) treatment has been questioned especially in children and adolescents. The critical publications led to warnings being issued by regulatory authorities such as the FDA, MHRA and EMEA and stimulated new research activity in this field. However, potential harmful effects of antidepressants on suicidality are difficult to investigate in empirical studies because these have several methodological limitations. Randomised controlled trials (RCTs) are the most reliable way to test the hypothesis that AD have such side effects. In addition to meta-analyses of RCTs, complementary research methods should be applied to obtain the most comprehensive information. We undertook a comprehensive review of publications related to the topics ADs, suicide, suicidality, suicidal behaviour and aggression. Based on this comprehensive review we conclude that ADs, including SSRIs, carry a small risk of inducing suicidal thoughts and suicide attempts, in age groups below 25 years, the risk reducing further at the age of about 30-40 years. This risk has to be balanced against the well-known beneficial effects of ADs on depressive and other symptoms (anxiety, panic, obsessive-compulsive symptoms), including suicidality and suicidal behaviour. According to the principles of good clinical practice, decision making should consider carefully the beneficial effects of AD treatment as well as potentially harmful effects and attempt to keep the potential risks of AD treatment to a minimum. It is the major problem facing efforts to identify the possible 'suicidal effects' of antidepressants.

Menezes GB, Fontenelle LF, Mululo S, Versiani M. · Programa de Ansiedade e Depressão, Instituto de Psiquiatria, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. · Rev Bras Psiquiatr. · Pubmed #18157434 links to  free full text

Abstract: OBJECTIVES: Anxiety disorders are common psychiatric conditions that cause significant disability, poor quality of life and enormous social cost. Although treatments with demonstrable efficacy are available a great number of patients fail to respond or remains with clinically significant residual symptoms after treatment. The objective of this study is to review aspects related to treatment resistance and pharmacological strategies to deal with anxiety disorders resistant to treatment. METHOD: Narrative review. RESULTS: We discuss conceptual aspects related to treatment resistance or refractoriness, predictors of poor treatment outcome, and finally, some strategies to deal with anxiety disorders (including social anxiety disorder, generalized anxiety disorder and panic disorder) that do not respond to standard therapeutic interventions. CONCLUSION: Treatment resistance in anxiety disorders remains a challenge to clinical practice going from non standardized concepts of response and resistance to a paucity of controlled studies concerning therapeutic strategies.

Fontenelle LF, Nascimento AL, Mendlowicz MV, Shavitt RG, Versiani M. · Anxiety and Depression Research Program, Institute of Psychiatry, Universidade Federal of Rio de Janeiro (IPUB/UFRJ), Icaraí, Niterói, RJ, Brazil. · Expert Opin Pharmacother. · Pubmed #17376013 No free full text.

Abstract: The purpose of this article is to introduce the reader to an updated evidence-based drug treatment algorithm to be employed in patients with obsessive-compulsive disorder (OCD). Relevant studies were identified through a comprehensive review and classified according to the type of patients enrolled, the quality of the study design and the invasiveness, availability and complexity of the therapeutic approach. When ineffective, therapeutic trials with first-line strategies (such as the selective serotonin re-uptake inhibitors [SSRIs] and venlafaxine) should be followed by treatment approaches such as clomipramine, augmentation with antipsychotics or pindolol, SSRI megadoses or cognitive behavioral therapy. These therapeutic strategies are expected to help most patients with OCD. Additional approaches include intravenous clomipramine, oral morphine, 'heroic drug strategies', deep brain stimulation and functional neurosurgery. Independent studies are urgently needed to help identify the most promising drug treatment sequences for OCD.

Fontenelle LF, Mendlowicz MV, Versiani M. · Anxiety and Depression Research Program, Institute of Psychiatry, Federal University of Rio de Janeiro (IPUB/UFRJ), Rio de Janeiro, Brazil. · Prog Neuropsychopharmacol Biol Psychiatry. · Pubmed #16412548 No free full text.

Abstract: Since the early eighties, there has been a growing interest in the descriptive epidemiology of obsessive-compulsive disorder (OCD). In this narrative review, the authors describe the findings of a number of studies that employed selected instruments, such as the Diagnostic Interview Schedule, the Composite International Diagnostic Instrument, and the Schedule for Affective Disorders and Schizophrenia, to ascertain the prevalence and incidence rates for OCD in several different countries. We noted that there is a great heterogeneity of findings and that the potential reasons for this variability include not only the intrinsic characteristics of the population under study but also extrinsic factors (i.e., the several methodologically-informed decisions that are to be made before undertaking such investigations, such as the adoption of a specific diagnostic instrument). In order to further the knowledge on the epidemiology of OCD, it would be worthwhile to establish a global consensus regarding a standard assessment package for OCD, to produce more cross-culturally valid versions of the key research instruments, and to conduct studies specifically aimed at comparing the sociodemographic, clinical and prognostic aspects of OCD across different countries.

Fontenelle LF, Mendlowicz MV, Marques C, Versiani M. · The Anxiety and Depression Research Program, Institute of Psychiatry of the Federal University of Rio de Janeiro (IPUB/UFRJ), Rupa Lopes Trovão, 88, apt., 1501, Bloco A, Icaraí, Niterói, RJ, CEP: 24220-071, Brazil. · J Psychiatr Res. · Pubmed #15203292 No free full text.

Abstract: Little is known about the extent and the mechanisms through which culture may affect the clinical manifestations of obsessive-compulsive disorder (OCD). In this study, our objective was to identify culture-related symptomatological patterns in OCD. We described the socio-demographic and phenomenological characteristics of 101 adult patients with OCD seen at an university clinic for anxiety and depressive disorders in Rio de Janeiro, Brazil, and compared them with those reported in 15 clinical samples from North and Latin America, Europe, Africa, and Asia identified through a systematic review in MEDLINE, PsychINFO, and LILACS. Patients with OCD were almost universally characterized by: (1) a predominance of females, (2) a relatively early age of onset, and (3) a preponderance of mixed obsessions and compulsions. In contrast, a predominance of aggressive and religious obsessions was found only in Brazilian and Middle Eastern samples, respectively. The core features of OCD are probably relatively independent of cultural variations. The sole exception to this rule seems to be the content of the obsessions, in which cultural factors may play a significant role.

Bauer M, Whybrow PC, Angst J, Versiani M, Möller HJ, Anonymous00268. · Neuropsychiatric Institute & Hospital, Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles (ULCA), 300 UCLA Medical Plaza, Suite 2330, Los Angeles, CA 90095, USA. · World J Biol Psychiatry. · Pubmed #12479086 No free full text.

Abstract: These practice guidelines for the biological treatment of unipolar depressive disorders were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal for developing these guidelines was to systematically review all available evidence pertaining to the treatment of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating patients with these conditions. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for depressive disorders, as well as from meta-analyses and reviews on the efficacy of antidepressant medications and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and was then categorized into four levels of evidence (A-D). This first part of the guidelines covers disease definition, classification, epidemiology and course of unipolar depressive disorders, as well as the management of the acute and continuation-phase treatment. These guidelines are primarily concerned with the biological treatment (including antidepressants, other psychopharmacological and hormonal medications, electroconvulsive therapy, light therapy, adjunctive and novel therapeutic strategies) of young adults and also, albeit to a lesser extent, children, adolescents and older adults.

Hirschfeld RM, Montgomery SA, Aguglia E, Amore M, Delgado PL, Gastpar M, Hawley C, Kasper S, Linden M, Massana J, Mendlewicz J, Möller HJ, Nemeroff CB, Saiz J, Such P, Torta R, Versiani M. · Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston 77555-0188, USA. · J Clin Psychiatry. · Pubmed #12363125 No free full text.

Abstract: BACKGROUND: Response to antidepressant drug therapy is less than optimal for a considerable proportion of depressed patients; at present, however, few data exist to guide their rational therapeutic management. This review describes general principles for the management of such patients. This review is the result of an expert roundtable meeting convened to review published clinical data and clinical experience and provide clinicians with evidence-based principles on the management of patients who fail to respond optimally to initial antidepressant therapy. ROUNDTABLE FINDINGS: Failure to respond may be defined as a < 25% decrease on an accepted symptom rating scale such as the Montgomery-Asberg Depression Rating Scale (MADRS) or the Hamilton Rating Scale for Depression (HAM-D) in a patient who has received an adequate dosage for 4 weeks. In these patients, a neuropharmacologic rationale exists to switch to an agent with a different mode of action or a dual action. Partial response may be defined as 6 to 8 weeks at an adequate dosage and 25% to 50% decrease in MADRS or HAM-D score. In these patients, dose escalation should be considered, followed by augmentation and switching strategies. For augmentation, knowledge of neuropharmacology may allow prediction of which second agent will potentiate or complement the action of the first agent; it may also permit the prediction of potential safety concerns. CONCLUSIONS OF THE PANEL: On the basis of a review of the medical literature and clinical experience regarding patients with partial response or nonresponse to antidepressant drug therapy, it appears that simultaneous targeting of both the noradrenergic and serotonergic systems is one of the most effective augmentation strategies. Switching to an agent of a different class is probably optimal for those patients who fail to respond to first-line therapy.

Brunello N, Mendlewicz J, Kasper S, Leonard B, Montgomery S, Nelson J, Paykel E, Versiani M, Racagni G. · Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, Modena, Italy. · Eur Neuropsychopharmacol. · Pubmed #12208564 No free full text.

Abstract: Depression is a common disorder that impacts on all aspects of a person's life. For the past 10 years, clinicians have focused on serotonin in their treatment of depression. This is largely due to the growing acceptance of the efficacy and safety of the selective serotonin reuptake inhibitors (SSRIs) in comparison with older tricyclic antidepressants (TCAs). However, evidence for a role of noradrenaline in depression has been accumulating for some time, beginning with the discovery that drugs which either caused or alleviated depression acted to alter noradrenaline metabolism. Until recently, the role of noradrenaline in depression was predicted from clinical experience with noradrenergic TCAs (desipramine, nortriptyline and protriptyline) and selective serotonin and noradrenaline reuptake inhibitors (venlafaxine, milnacipran). The licensing of reboxetine, a selective noradrenaline reuptake inhibitor now allows the role of noradrenaline in depression to be investigated directly. This review presents key data from the literature that support a role for noradrenaline in depression taking into account neurophysiology, psychopharmacology and clinical trial data.

Hirschfeld RM, Montgomery SA, Keller MB, Kasper S, Schatzberg AF, Möller HJ, Healy D, Baldwin D, Humble M, Versiani M, Montenegro R, Bourgeois M. · Department of Psychiatry & Behavioral Sciences, University of Texas Medical Branch, Galveston 77555-0188, USA. · J Clin Psychiatry. · Pubmed #10830147 No free full text.

Abstract: OBJECTIVE: This article reviews the available data on social functioning in depression and provides clinical guidelines and opinion on this important and expanding field. DATA SOURCES: A MEDLINE search was conducted to identify all English-language articles (1988-1999) using the search terms depression and social functioning, depression and social adjustment, depression and psychosocial functioning, and social functioning and antidepressant. Further articles were obtained from the bibliographies of relevant articles. DATA SYNTHESIS: Depressive disorders are frequently associated with significant and pervasive impairments in social functioning, often substantially worse than those experienced by patients with other chronic medical conditions. The enormous personal, social, and economic impact of depression, due in no small part to the associated impairments in social functioning, is often underappreciated. Both pharmacologic and psychotherapeutic approaches can improve social impairments, although there is a lack of extended, randomized controlled trials in this area using consistent assessment criteria. CONCLUSION: Despite this lack, it is becoming clear that not all treatments are equally effective in relieving the impaired social functioning associated with depressive disorders. Furthermore, efficacy in relieving the core symptoms of depression does not necessarily guarantee efficacy in relieving impaired social functioning.

Fontenelle LF, Mendlowicz MV, Ribeiro P, Piedade RA, Versiani M. · Anxiety and Depression Research Programme, Institute of Psychiatry of the Federal University of Rio de Janeiro (IPUB/UFRJ), Brazil. · Int J Neuropsychopharmacol. · Pubmed #15941492 No free full text.

Abstract: We investigated whether findings from pretreatment low-resolution electromagnetic tomography (LORETA) predicted response to drug treatment in patients with obsessive-compulsive disorder (OCD). The 3D intra-cerebral distribution of neuronal electrical activity from the scalp-recorded potential distribution of 17 drug-free patients with OCD was assessed with LORETA. They were treated with antidepressants in the maximum tolerated doses for at least 12 wk. Individuals were considered to be treatment responders if they displayed a reduction of at least 35% on the initial YBOCS scores and had a final CGI score of 1 or 2. The SPM-99 t test for independent samples was employed to compare, voxel-by-voxel, the brain electrical activities of responders (n = 10) and non-responders (n = 7). Responders exhibited significantly lower activities in beta band in the rostral anterior cingulate [Brodmann's area (BA) 24 and 32] (p = 0.002) and the medial frontal gyrus (BA 10) (p = 0.002), suggesting that a distinctive pattern of activity within the medial surface of the frontal lobe predicts therapeutic response in OCD.

Versiani M, Moreno R, Ramakers-van Moorsel CJ, Schutte AJ, Anonymous00197. · Institute of Psychiatry, Federal University of Rio de Janeiro, Botafogo, Rio de Janeiro, Brazil. · CNS Drugs. · Pubmed #15697327 No free full text.

Abstract: INTRODUCTION: Depression is a major global problem associated with large medical, sociological and economic burdens. Mirtazapine (Remeron, Organon NV, The Netherlands) is an antidepressant with a unique mechanism of action that has similar or superior efficacy to TCAs and SSRIs in moderate-to-severe depression. However, this agent has not yet been tested in patients with severe depression alone. OBJECTIVE: To compare the antidepressant efficacy and tolerability of mirtazapine and fluoxetine and their effects on anxiety and quality of life in patients with severe depression (> or = 25 points on the first 17 items of the Hamilton Depression Rating Scale [HDRS-17]). METHODS: In this double-blind study, 297 severely depressed patients were randomised to receive mirtazapine 15-60 mg/day (n = 147) or fluoxetine 20-40 mg/day (n = 152) for 8 weeks. 294 subjects were actually treated and 292 included in the intent-to-treat population. Symptom severity was measured by the HDRS-17, Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) rating scale. Quality of life was self-assessed by patients using the Leeds Sleep Evaluation Questionnaire and the Quality of Life, Enjoyment and Satisfaction Questionnaire. Adverse events were recorded throughout the study. RESULTS: No statistically significant differences were noted between the two groups in change from baseline HDRS-17 score at any time point; both treatments were associated with large (approximately 15 points) decreases by study end. However, more mirtazapine-treated patients tended to exhibit a > or = 50% decrease in HDRS score (significant at day 7; 9.0% vs 0.7%, p = 0.002). Significant differences in favour of mirtazapine were also observed at day 14 for changes in MADRS scores (-10.9 vs -8.5, p = 0.006) and the proportion of patients with > or = 50% decrease in MADRS score (21.4% vs 10.9%, p = 0.031). On the CGI, the proportion of 'much/very much improved' patients tended to be greater with mirtazapine (significant at day 7; 9.7% vs 3.4%, p = 0.032). No significant between-group differences were observed for the majority of quality-of-life measures. However, mirtazapine produced significantly better improvements on 'sleeping assessment 1' (14.9 +/- 5.2 vs 13.7 +/- 5.4, p = 0.028) and 'sleeping assessment 2' (p = 0.013) than fluoxetine. Both agents were generally well tolerated but mirtazapine-treated patients experienced a mean weight gain of 0.8 +/- 2.7 kg compared with a mean decrease in weight of 0.4 +/- 2.1 kg for fluoxetine-treated patients (p < 0.001). CONCLUSIONS: Mirtazapine is as effective and well tolerated as fluoxetine in the treatment of patients with severe depression.

Fontenelle LF, Mendlowicz MV, Versiani M. · Anxiety and Depression Research Program, Institute of Psychiatry of the Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. · Psychiatry Clin Neurosci. · Pubmed #15679537 No free full text.

Abstract: The purpose of the present paper was to identify the rate of prevalence of impulse control disorders (ICD) in patients with obsessive-compulsive disorder (OCD) and to compare patients with OCD with and without ICD with regard to sociodemographic, clinical and prognostic characteristics. Forty-five patients with OCD were assessed by means of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (4th edn, DSM-IV) plus additional modules for the assessment of ICD and examined using the Yale-Brown Obsessive-Compulsive Scale, the Clinical Global Impression, the Beck Depression Inventory, the Hamilton Depression Rating Scale, and the Global Assessment of Functioning. These patients were treated with serotonin re-uptake inhibitors (SRI) and followed for a variable period of time. Individuals with ICD (here defined as including not only the impulse control disorders not elsewhere classified of the DSM-IV, but also other disorders in which impulse control is a prominent feature such as alcohol and drug dependence, paraphilias and bulimia nervosa/binge eating disorder) were compared to those without ICD using the Mann-Whitney U-test and the Pearson's goodness of fit chi2 test. Sixteen patients with OCD (35.5%) displayed comorbid ICD. Patients with ICD were characterized by a significantly earlier age at OCD onset (P=0.04), a more insidious appearance of OCD symptoms (P=0.04), a higher rate of comorbid anxiety disorders (P=0.03), a greater number (P=0.02) and severity of compulsive symptoms (P=0.04), an increased rate of counting compulsions (P=0.02), and a higher number of required SRI trials (P=0.01). When OCD is found in association with ICD, the clinical picture is characterized by a greater severity of the obsessive-compulsive symptoms at presentation and by the requirement of a greater number of therapeutic attempts during follow up.

Valença AM, Nardi AE, Mezzasalma MA, Nascimento I, Zin WA, Lopes FL, Versiani M. · Laboratory of Panic and Respiration, Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Brazil. · Sao Paulo Med J. · Pubmed #12870055 links to  free full text

Abstract: CONTEXT: This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam, a benzodiazepine. OBJECTIVES: To evaluate the clinical efficacy of clonazepam in a fixed dosage (2 mg/day), compared to placebo, in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes. TYPE OF STUDY: Randomized study with clonazepam and placebo. SETTING: Outpatient Anxiety and Depression Unit of the Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. PARTICIPANTS: 34 patients with a diagnosis of panic disorder with agoraphobia, between 18 and 55 years old. PROCEDURES: Administration of clonazepam or placebo for 6 weeks, in panic disorder patients, after they were classified within two subtypes of panic disorder: respiratory and non-respiratory. MAIN MEASUREMENTS: Changes in the number of panic attacks in comparison with the period before the beginning of the study; Hamilton Anxiety Scale; Global Clinical Impression Scale; and Patient's Global Impression scale. RESULTS: In the group that received clonazepam, by the end of the 6th week there was a statistically significant clinical improvement, shown by the remission of panic attacks (p < 0.001) and decrease in anxiety (p = 0.024). In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder, regarding the therapeutic response to clonazepam. CONCLUSION: Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder, suggesting there is no difference in the therapeutic response between the two subtypes.

Fontenelle LF, Mendlowicz MV, Marques C, Versiani M. · Anxiety and Depression Research Program, Institute of Psychiatry of the Federal University of Rio de Janeiro (IPUB/UFRJ), Brazil. · J Psychiatr Res. · Pubmed #12842166 No free full text.

Abstract: It has been suggested that early- and late-onset forms of obsessive-compulsive disorder (OCD) may stem from different neurobiological substrates manifesting themselves through particular phenotypic profiles. Our study aimed to assess the existence of clinical and therapeutic differences between adult patients with early- and late-onset OCD (EOCD and LOCD, respectively). Sixty-six patients with OCD were consecutively recruited among individuals seeking treatment in a university hospital clinic for anxiety and depressive disorders. Patients with EOCD (n=33) and LOCD (n=33) were compared and contrasted with regard to clinical and therapeutic characteristics using the two tailed t test for continuous variables and the Pearson's goodness of fit Chi-square test for categorical ones; Fisher's exact test was employed when indicated. We found that, compared to their LOCD counterparts, adult patients with EOCD were characterized by (1) male gender predominance, (2) greater number of clinically significant obsessions and compulsions, (3) higher frequency of rituals repetition, (4) increased severity of obsessive-compulsive symptoms at baseline, and (5) greater number of required therapeutic trials during the follow-up. However, no significant differences between groups were noted in the final treatment outcome. Our results are consistent with previous studies suggesting that EOCD may represent a more severe subtype of this disorder.

Andreoli V, Caillard V, Deo RS, Rybakowski JK, Versiani M. · Primario Servizi Psychiatri, Ospedale di Soave, Soave, Italy. · J Clin Psychopharmacol. · Pubmed #12172339 No free full text.

Abstract: The clinical profile of reboxetine, a selective noradrenaline reuptake inhibitor, was compared with that of the selective serotonin reuptake inhibitor fluoxetine and placebo in a double-blind, multicenter, parallel-group clinical trial of patients with major depression. Among the 381 patients treated with reboxetine 8 to 10 mg/day, fluoxetine 20 to 40 mg/day, or placebo for up to 8 weeks, a statistically significant greater reduction in the mean Hamilton Rating Scale for Depression (21-item HAM-D) total score (the primary efficacy variable) was seen for both active treatment groups compared with placebo (p < 0.024). A significantly greater proportion of patients treated with either reboxetine or fluoxetine also achieved a response (>or=50% reduction in HAM-D) or remission (HAM-D <or=10 points) than those who received placebo (p < 0.01 for both analyses). Similar findings were recorded in a subpopulation of severely ill patients, with statistically significantly greater decreases in the mean HAM-D total score between both active treatment groups compared with placebo (p < 0.024). Additional efficacy assessments (Montgomery-Asberg Depression Rating Scale, Clinical Global Impression) reflected the primary efficacy analysis, with both active treatments offering comparable efficacy that was superior to that of placebo.Reboxetine and fluoxetine are more effective than placebo in the treatment of major depression. Futhermore, both antidepressants are well tolerated but possess different adverse event profiles.

Versiani M, Cassano G, Perugi G, Benedetti A, Mastalli L, Nardi A, Savino M. · Institute of Psychiatry, Federal University of Rio de Janeiro, Brazil. · J Clin Psychiatry. · Pubmed #11838623 No free full text.

Abstract: BACKGROUND: Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) as well as benzodiazepines have been shown to be effective for the treatment of panic disorder. The introduction of SSRIs has enabled a greater understanding of the role of serotonin in the etiology of panic disorder; however, the role of norepinephrine has been more challenging to ascertain. The aim of this study was to determine the efficacy and tolerability of reboxetine, a novel selective norepinephrine reuptake inhibitor, in patients with panic disorder with and without agoraphobia. METHOD: Eighty-two patients (aged 18-65 years) with DSM-III-R panic disorder, with or without agoraphobia, were randomly assigned to receive 6 to 8 mg/day of reboxetine (42 patients) or placebo (40 patients) for 8 weeks in this placebo-controlled, parallel-group, double-blind clinical trial. RESULTS: Of the 82 patients enrolled in the trial, 75 were considered in the analysis (37 patients in the reboxetine group and 38 patients in the placebo group). At last assessment, there was a significant reduction in the mean number of panic attacks (range, 9.3-1.2) and phobic symptoms (range, 8.1-3.2) in the reboxetine group compared with the placebo group (ranges, 8.5-5.8 and 7.7-5.2, respectively; p < .05). Improvement in Hamilton Rating Scale for Depression, Hopkins Symptom Checklist-90, and Sheehan Disability Scale scores were also greater in the reboxetine group compared with the placebo group. Adverse events reported more frequently with reboxetine than placebo included dry mouth (36% vs. 16%), constipation (27% vs. 22%), and insomnia (26% vs. 22%). CONCLUSION: Reboxetine was effective and well tolerated in the treatment of panic disorder.

Versiani M, Amin M, Chouinard G. · Federal University, Rio de Janeiro, Ipanema, Brazil. · J Clin Psychopharmacol. · Pubmed #10653205 No free full text.

Abstract: The efficacy and tolerability of reboxetine, a unique selective noradrenaline reuptake inhibitor, were compared with those of placebo in a 6-week, randomized, double-blind study of hospitalized patients with a DSM-III-R diagnosis of major depressive disorder. Fifty-two patients (25 in the placebo group, 27 in the reboxetine group) were included in the efficacy analysis. Sixteen (64%) of those in the placebo group and four (15%) in the reboxetine group were withdrawn during the study because of lack of efficacy. Improvement in the mean Hamilton Rating Scale for Depression (HAM-D) total score at last assessment was significantly greater in the reboxetine group than in the placebo group (p < 0.001). Similarly, the response rate to treatment, defined as > or =50% reduction in HAM-D total score, was 74% for patients who received reboxetine compared with 20% for those who received placebo (p < 0.001). A significantly greater response with reboxetine than with placebo was seen as early as day 10 of treatment (p = 0.006). The therapeutic efficacy of reboxetine was substantiated by improvement in mean scores on the Zung Self-Rating Scale and on the Clinical Global Impression Severity of Illness and Global Improvement scales. Reboxetine was well tolerated, and only one patient in each group withdrew because of adverse events. Dry mouth, insomnia, blurred vision, sweating, and constipation were recorded more frequently in the reboxetine group than in the placebo group. There was a tendency toward orthostatic changes in the systolic blood pressure, but this was not clinically significant. This study demonstrated that reboxetine is significantly more effective than placebo in the treatment of hospitalized patients with severe major depressive disorder and is well tolerated.

Katona C, Bercoff E, Chiu E, Tack P, Versiani M, Woelk H. · Department of Psychiatry and Behavioural Sciences, Middlesex Hospital, London, UK. · J Affect Disord. · Pubmed #10628889 No free full text.

Abstract: BACKGROUND: Depression in older people is often unrecognised and untreated or under-treated. Antidepressant treatment may itself exacerbate a pre-existing illness, interact with concomitant medications or produce undesirable cognitive and sedative side effects. Newer antidepressants may offer advantages in terms of a lesser burden of adverse effects. METHODS: The comparative tolerability of the unique selective noradrenaline reuptake inhibitor (selective NRI) reboxetine (4-6 mg/day; n = 176) and that of imipramine (50-100 mg/day; n = 171) was assessed in an elderly ( > 65 years) cohort of depressed or dysthymic patients in an 8-week, double-blind, multicentre trial. Comparative efficacy was also assessed. RESULTS: Overall, 68% of patients in the reboxetine group experienced adverse events compared with 71% in the imipramine group. Reboxetine-treated patients were less likely to develop hypotension and related symptoms (7% vs. imipramine 16%) or cardiovascular disorders (12.5% vs. imipramine 21.1%), while those treated with imipramine were less likely to experience insomnia (6.3% vs. 2.9%). Adverse events were more often assessed as related to treatment (43%) and moderate to severe in intensity (73%) with imipramine than with reboxetine (33% and 65%, respectively). Furthermore, there were fewer serious adverse events in the reboxetine-treated group (P = 0.019). The reduction in the Hamilton Rating Scale for Depression (HAM-D) was comparable between the treatment groups in the total population. At the last assessment, the majority of patients in both treatment groups were assessed as normal to borderline or mildly ill using the Clinical Global Impression (CGI) scale. In a subanalysis of the dysthymic patients a modest but significant difference in favour of imipramine was observed for both HAM-D and CGI assessments. This may have been a reflection of a trend towards more severe depressive symptoms at baseline in the reboxetine group. CONCLUSIONS: Reboxetine is as effective as imipramine in the treatment of depression in elderly patients but is at least as well tolerated with a lower risk of hypotension and related symptoms, fewer serious adverse events, adverse event-related withdrawals and treatment-related adverse events.

Versiani M, Ontiveros A, Mazzotti G, Ospina J, Dávila J, Mata S, Pacheco A, Plewes J, Tamura R, Palacios M. · Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. · Int Clin Psychopharmacol. · Pubmed #10565798 No free full text.

Abstract: Although common in clinical settings, major depressive disorder with associated anxious symptoms ('anxious depression') has not been well studied in antidepressant clinical trials. The aim of this study was to compare the effects of fluoxetine versus amitriptyline in this group of patients. After a single-blind placebo run-in period of 2 weeks, patients were treated on a double-blind basis with fluoxetine or amitriptyline for 8 weeks. Assessment instruments included: 21-item Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Clinical Global Impressions, Raskin Depression Scale and Covi Anxiety Scale. A total of 157 patients were randomized to either fluoxetine or amitriptyline. Fluoxetine was given at a fixed dose of 20 mg/day and amitriptyline was given in a range of 50-250 mg/day (mean of 138.1 mg/day). Fluoxetine was comparable to amitriptyline in all efficacy measures except the HAMD sleep factor. Unwanted effects were more frequent and more severe in the amitriptyline-treated patients. Fluoxetine was comparably efficacious to amitriptyline in the treatment of major depression with associated anxiety. Since fluoxetine was far better tolerated, it is a promising alternative for this frequent and disabling condition.

Versiani M, Mehilane L, Gaszner P, Arnaud-Castiglioni R. · Institute of Psychiatry, Federal University, Rio de Janeiro, Brazil. · J Clin Psychiatry. · Pubmed #10401920 No free full text.

Abstract: BACKGROUND: The long-term efficacy and tolerability of the antidepressant reboxetine, a unique selective norepinephrine reuptake inhibitor (selective NRI), were assessed in an international study. METHOD: Two hundred eighty-three patients with recurrent DSM-III-R major depression who responded to 6 weeks of reboxetine treatment (> or =50% decrease in Hamilton Rating Scale for Depression [HAM-D] total score) were randomly assigned to receive reboxetine or placebo for 46 weeks in a double-blind phase. Relapse (> or =50% increase in HAM-D total score and/or a HAM-D total score > or =18) rate was the principal assessment criterion and included patients who experienced relapse or recurrence. Only patients who remained relapse-free at the end of the first 6-month treatment period were included in the relapse rate assessment at the end of the second 6-month treatment period. RESULTS: Reboxetine was associated with a markedly lower relapse rate than placebo (22% vs. 56%; p<.001) and a greater cumulative probability of a maintained response (p = .0001) during long-term treatment. Patients in remission (HAM-D total score < or =10) at the time of random assignment were less likely to relapse (16% reboxetine, 48% placebo; p<.001). The proportion of patients who were relapse-free and therefore remained in the study was significantly (p< or =.001) higher among those on reboxetine treatment than on placebo at the end of the first (61% vs. 40%) and second (88% vs. 59%) 6 months of treatment. Additional efficacy measures supported these findings. The incidence of adverse events with reboxetine was low and comparable with that for placebo. Discontinuation due to adverse events occurred infrequently. CONCLUSION: Reboxetine treatment over 1 year is more effective than placebo in the prevention of relapse in patients with recurrent depression. The low relapse rates at the end of the second 6 months of treatment further suggest that reboxetine effectively prevents recurrence of depressive symptoms following episode resolution. Reboxetine is well tolerated in long-term treatment of depression, a finding that bodes well for long-term patient compliance.

Menezes GB, Fontenelle LF, Versiani M. · Program of Anxiety and Depression, Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. · Rev Bras Psiquiatr. · Pubmed #17639267 links to  free full text

This publication has no abstract.

Nardi AE, Nascimento I, Freire RC, Veras AB, de-Melo-Neto VL, Valença AM, Lopes FL, Soares-Filho GL, Levitan MN, de Carvalho MR, da Costa RT, King AL, Mezzasalma MA, Grivet LO, Rassi A, Versiani M. · Laboratory of Panic & Respiration, Federal University of Rio de Janeiro, Brazil. · J Affect Disord. · Pubmed #17604118 No free full text.

Abstract: BACKGROUND: Mood disorders are considered related to anxiety disorders and their association may determine clinical course and prognosis. We aimed to describe with retrospective methodology the demographic, clinical, and treatment features in a group of panic disorder comorbid with bipolar I disorder (PD-BI) patients who were been treated for at least 3 year-period and compare them with bipolar I (BI) patients who were treated during the same period. METHOD: We compared the demographic and clinical data of 26 PD-BI, 28 BI, and 25 panic disorder (PD) outpatients without history of comorbidity with mood disorder were diagnosed and treated for at least 3 years in the Federal University of Rio de Janeiro. RESULTS: PD group have a higher educational level, are more married, and are more economically active. In the PD-BI and BI patients the disorders started earlier. They also turn out to have an equivalent pattern in the presence of drug abuse episodes, moderate or severe depressive episodes, psychotic episodes, suicide attempts, maniac episodes, mixed episodes, use of fewer days of antidepressants and benzodiazepines, and use of more days of antipsychotics and mood stabilizers. The PD-BI and the BI groups had a higher frequency of depressive episodes and psychotic episodes. LIMITATIONS: It is a retrospective data description based on a naturalistic treatment. The sample has a small size and the some data could be different in a large sample. CONCLUSION: PD-BI patients have demographic, clinical and therapeutic features similar to BI and the data support its validation as a special severe bipolar I disorder subgroup.

Fontenelle LF, de Souza WF, de Menezes GB, Mendlowicz MV, Miotto RR, Falcão R, Versiani M, Figueira IL. · Anxiety and Depression Research Program, Institute of Psychiatry, Universidade Federal of Rio de Janeiro, Rio de Janeiro, Brazil. · J Nerv Ment Dis. · Pubmed #17468686 No free full text.

Abstract: We compared the history, the profile, and the severity of sexual symptoms of 31 patients with obsessive-compulsive disorder (OCD) to those of 26 patients with social anxiety disorder (SAD) by means of the Sexual Inventory of the Institute of Psychiatry of the Federal University of Rio de Janeiro, the Clinical Interview for the Diagnosis of DSM-IV Sexual Disorders, the Female Sexual Function Index, the International Index of Erectile Function, the Arizona Sexual Experience Scale, and the Sexual Behavior Inventory. Patients with OCD reported more difficulties to reach orgasm (p = 0.009), less frequent effective erections (p = 0.05), and a positive history of sexual abuse (p = 0.006) significantly more often than patients with SAD. Male patients with SAD reported not using contraceptive methods significantly more frequently than male patients with OCD (p = 0.007). Patients with OCD and patients with SAD exhibit different profiles of sexual behavior.