Francisco Lotufo-Neto

Meta-analysis of the reversible inhibitors of monoamine oxidase type A moclobemide and brofaromine for the treatment of depression.

The reversible inhibitors of monoamine oxidase type A (RIMAs) are a newer group of antidepressants that have had much less impact on clinical psychopharmacology than another contemporary class of medications, the selective serotonin reuptake-inhibitors (SSRIs). The RIMAs agents are distinguished from the older monoamine oxidase inhibitors (MAOIs) by their selectivity and reversibility. As a result, dietary restrictions are not required during RIMA therapy, and hypertensive crises are quite rare. In this article, we describe a series of meta-analyses of studies of the two most widely researched RIMAs, moclobemide (MOC; Aurorex) and brofaromine (BRO). Our findings confirm that both BRO and MOC are as effective as the tricyclic antidepressants, and they are better tolerated. However, BRO is not being studied at present for reasons unrelated to efficacy or side effects. MOC, which is available throughout much of the world (but not the United States), is significantly more effective than placebo and, at the least, comparable to the SSRIs in both efficacy and tolerability. For MOC, higher dosages may enhance efficacy for more severe depressions. We also found evidence that supports clinical impressions that MOC is somewhat less effective, albeit better tolerated, than older MAOIs, such as phenelzine or tranylcypromine. Little evidence has yet emerged to suggest that the RIMAs share older MAOIs’ utility for treatment of depressions characterized by prominent reverse neurovegetative features. Based on available evidence, the RIMAs appear to have a limited, but useful, role in the differential therapeutics of the depressive disorders.

Clomipramine, a better reference drug for panic/agoraphobia. I. Effectiveness comparison with imipramine

An 8-week, double-blind, flexible-dose trial comparing low doses of clomipramine (mean=50 mg) with moderate doses of imipramine (mean=113.8 mg and propanteline (active placebo), was carried out in 60 out-patients with panic disorder with or without agoraphobia. Efficacy evaluation included global, anxiety and depression rating scales, and the determination of rates of relapse over up to 10 weeks of single-blind placebo follow-up. Both tricyclics were significantly more effective than propanteline, but clomipramine tended to act faster and more consistently than imipramine on most measures. Given the degree of blindness achieved and the significantly lower doses of clomipramine, this seems a better reference drug than imipramine for clinical trials in panic/agoraphobia.

Mood improvement in 'normal' volunteers

To test the hypothesis that clomipramine is effective in improving subthreshold non-specific symptoms in subjects without any established psychopathology, we conducted a double-blind, cross-over controlled trial of clomipramine (oral doses of 10-40 mg/day) and propanteline (active placebo) for 5 weeks in nine normal volunteers. Four other subjects completed the first part of the trial. These subjects were selected from 275 respondents to newspaper and radio requests for subjects who considered themselves as normal but were unhappy about their usual moods. They did not reach cut-off scores in the Self-Report Questionnaire and did not meet diagnostic criteria for any lifetime or current ICD-10 or DSM-III-R condition, as assessed by an open psychiatric interview and the Schedules for Clinical Assessment in Neuropsychiatry. Despite the small sample and the low level of initial symptomatology, both subjects and observers consistently detected significant improvements with clomipramine in a number of assessments of mood, notably decreased irritability and anxiety. This controlled trial suggests that it is possible to improve subclinical complaints through psychopharmacological agents, raises questions about the mechanisms of their action and discusses their implications.

A dose-finding and discontinuation study of clomipramine in panic disorder

Eighty-one panic disorder patients with or without agoraphobia were treated with flexible doses of clomipramine under single-blind conditions. Fifty-seven (70.3%) reached operational criteria for full remission in 16.2 ± 6.5 weeks, with a mean dose of 89.1 ± 8.2 mg/day. Fifty-four (81%) of them received a continuous post-remission maintenance treatment at full doses of clomipramine for 4–6 months. No patient relapsed during the clomipramine maintenance phase. Their medication was then tappered and discontinued with placebo substitution under double-blind conditions. Fifty-one (63%) patients were followed-up until relapse or recurrence for up to 3 years, with periodic assessments. Three different outcome groups were identified: the first (n = 19, 19; 37.2%) experienced an early/immediate relapse (5.2 ± 4.9 weeks after drug discontinuation); the second group (n= 22, 22; 43.1%) experienced recurrence after 42.9 ± 35 weeks following discontinuation; and the third group (n = 10, 10; 19.6%) remained assymptomatic and functionally well throughout the follow-up. Predictors of early relapse were: (1) higher baseline score in the Beck Depression Inventory; (2) higher global score on the phobic avoidance scale after the full remission criteria; and (3) the need for higher clomipramine doses to reach full remission. The need for long-term or intermittent maintenance for most patients is emphasized.

Substance Use and Misuse in Brazilian Movies (2000-2008)

Considering the absence of data on the appearance of drugs other than alcohol and tobacco in movie scenes, we decided to study the prevalence of portrayal of illicit drug use in a convenience sample of 50 Brazilian Movies. A total of 192 scenes (12h49′03″) meeting the inclusion criteria were identified and assessed in a structured manner. Despite several limitations regarding the nature of this comparison, we found that scenes show substance use and misuse almost similar to that in the general population, mainly alcohol (especially among people of low socioeconomic status), cannabis and inhalants. Main differences were found in cocaine and tranquilizers (over- and underexposure in movies, respectively).

Virtual reality exposure using three-dimensional images for the treatment of social phobia

Objective: To test a potential treatment for social phobia, which provides exposure to phobia-inducing situations via computer-generated, three-dimensional images, using an open clinical trial design. Methods: Twenty-one patients with a DSM-IV diagnosis of social phobia took part in the trial. Treatment consisted of up to 12 sessions of exposure to relevant images, each session lasting 50 minutes. Results: Improvements in social anxiety were seen in all scales and instruments used, including at follow-up 6 months after the end of treatment. The average number of sessions was seven, as the participants habituated rapidly to the process. Only one participant dropped out. Conclusion: This study provides evidence that exposure to computer-generated three-dimensional images is relatively inexpensive, leads to greater treatment adherence, and can reduce social anxiety. Further studies are needed to corroborate these findings.

DSM-5 Alcohol Use Disorder Criteria in “Crazy Heart” (2009)—A Media Content Analysis with Teaching Purposes

ObjectiveThe movie Crazy Heart (2009) draws our attention to alcohol disorders as it has a large number of scenes which portray alcohol consumption and fulfill the new DSM-5 Alcohol Use Disorder (DSM-5-AUD) criteria. In view of the recent launch of DSM-5, this is an appropriate opportunity to explore alcohol consumption in a large number of scenes employing the DSM-5-AUD criteria to study this.MethodsWe use media content analysis to identify DSM-5 AUD criteria as portrayed by the main protagonist of the movie Bad Blake in a structured manner. We studied his behavior and attitudes in the context of the film structure and storyline.ResultsThe severity continuum of DSM-5 AUD can be demonstrated through the trajectory of the character Bad Blake. In the course of the movie, there is some reference to all the DSM-5-AUD criteria, which can be applied to this character within the 21 scenes selected for this study.ConclusionThis film can therefore be helpful and used to introduce students and trainees to the DSM-5-AUD criteria. It also allows teachers to discuss with their students and trainees the options of treatment including decision to quit drinking (total abstinence) and the recovery and relapse of this chronic condition.

Gender differences in aggressiveness in children and adolescents at risk for schizophrenia

OBJECTIVE This study aimed to investigate whether differences in aggression-related behavioral problems occur between boys and girls at high risk for schizophrenia living in the city of São Paulo, Brazil. METHOD Using the Child Behavior Checklist, we compared the prevalence of behavioral problems between genders for the offspring (6-18 years) of mothers with diagnosis of schizophrenia and a comparison group of children born to women with no severe mental disorders recruited at the gynecology outpatient clinic of the same hospital. The Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition was applied for the evaluation of diagnostic status of mothers. RESULTS Male children of women with schizophrenia had a lower prevalence of aggressive behavior compared to females (4% vs. 36%; p = 0.005), whereas no gender differences regarding aggression were detected in the comparison group (24% vs. 32%; p = 0.53). Logistic regression analyses showed that male gender and being a child of women with schizophrenia interacted so as to favor lower prevalence of aggressive behavior (p = 0.03). CONCLUSION These findings reinforce the notion that behavioral gender differences related to schizophrenia are already detectable in childhood.

Morbidity persistence and comorbidity of mood, anxiety, and eating disorders among preoperative bariatric patients

The current study investigates the patterns of disease persistence and comorbidity of psychiatric disorders among patients with class III obesity in pre-operative period. For 393 treatment-seeking patients with severe obesity recruited from a bariatric center, we ascertained their psychiatric diagnosis through Structured Clinical Interview for DSM-IV (SCID-I). Following, the frequency, persistence and comorbidity pattern of psychiatric disorders in this sample were determined. Current psychiatric disorders were observed in over half of patients during preoperative period, being anxiety disorders the most frequent diagnosis. For lifetime disorders, mood disorders were the most frequent diagnosis. Most of the sample presented 2 or more concurrent lifetime psychiatric disorders. While mood and eating disorders were frequent conditions, anxiety disorders were the most persistent conditions (the highest one month-to-lifetime prevalence ratio) and were significantly correlated with bipolar, depressive and eating disorders. Psychiatric disorders are frequent and enduring conditions among patients looking for bariatric surgery. Comorbid anxiety, mood, and eating disorders are remarkable features in treatment-seeking patients with obesity. Prognostic implications of preoperative psychiatric disorders on surgery outcome should be demonstrated prospectively in intervention studies.

DSM-5 Post-Traumatic Stress Disorder Criteria in “Precious” (2009): Media Content Analysis for Educational Purposes

Films and other audio-visual materials are excellent sources for teaching psychopathology and depicting psychiatric interventions. Documentaries and institutional films are commonly used as auxiliary tools in education, whereas feature films are still gaining more recognition [2–6]. When utilized as psycho-pedagogic tools, movies endorse a broad comprehension of human interactions, individuals displaying signs of a psychiatric disorder or negative responses to certain stimuli and ultimately the capacity to feel empathy toward the characters and situations presented, that can intimately resemble real life in many ways [2–6]. It is well know that “art imitates life, as life imitates art” [2–6] and, thus, many of the films that fascinate audiences around the world and win prizes for their cinematographic quality are important depictions of what our culture is experiencing on a given era [2–6]. When a motion picture comes as a result of excellent screenplay, direction, acting—better if all together—it becomes an even more effective tool for teaching, helping audiences, and health professionals alike to comprehend psychopathology and the portrayal of the responses of others to these disorders [3–6]. Cinema is a useful pedagogic medium in many fields of medicine [2–4] and psychiatry is certainly one of the pioneering and most engaged areas in endorsing movies as teaching/learning instruments, at both undergraduate and graduate levels [2–6]. We studied the depiction of mental health issues in mainstream movies [3–5, 7, 8] released between years 2008 and 2013. To narrow our selections, due to time and financial constraints, we looked at films that contained one (or more) scenes featuring psychiatric and/or substance abuse disorders and that had received at least one Academy Award® nomination (in any category). Since 1929, the Academy Awards have had a major role to play in the success of films internationally. We were chiefly interested in whether or not the celebrated films depicted psychiatric and/or drug abuse disorders in a manner that met the current Diagnostic and Statistical Manual of Mental Disorders—5th Edition (DSM5) [2–6, 9]. Movies such as “There Will Be Blood” (2007), “Rachel Getting Married” (2008), and “Crazy Heart” (2009) comprised the list obtained by our research group. Among the selection, the film “Precious: Based On The Novel Push, by Sapphire” (2009), whose director Lee Daniels has other stunning pieces in his curriculum, like “Monster’s Ball” (2001) and “The Butler” (2013), stands out for its vivid and realistic portrayal of post-traumatic stress disorder (PTSD). The film is about a 16-year-old, morbidly obese girl that suffers, early in life, severe parental mistreatment and sexual abuse, followed by subsequent educational and relational difficulties. * João Maurício Castaldelli-Maia jmcmaia2@gmail.com