B. Dell’Osso

Do benzodiazepines still deserve a major role in the treatment of psychiatric disorders? A critical reappraisal

Discovered in the late 1950s by Leo Sternbach, the first benzodiazepine (BZD) chlordiazepoxide was followed by several congeners, which rapidly constituted one of the largest and most widely prescribed classes of psychotropic compounds. After 50 years, BZDs are still routinely utilized not only in psychiatry but, more generally, in the whole of medicine. Despite their high therapeutic index which makes BZDs safer than other compounds like barbiturates, as well as their rapidity of onset, psychiatrists and family physicians are well aware about the controversy that surrounds the wide use - often not adequately based on scientific evidence - of BZDs in many psychiatric disorders. In this overview of international treatment guidelines, systematic reviews and randomized clinical trials, the aim was to provide a critical appraisal of the current use and role of BZDs in psychiatric disorders and their disadvantages, with specific emphasis on anxiety and affective disorders, sleep disorders, alcohol withdrawal, violent and aggressive behaviours in psychoses, and neuroleptic-induced disorders. In addition, specific emphasis has been given to the extent of usage of BZDs and its appropriateness through the assessment of available international surveys. Finally, the entire spectrum of BZD-related adverse effects including psychomotor effects, use in the elderly, paradoxical reactions, tolerance and rebound, teratologic risk, dependence, withdrawal and abuse issues was examined in detail.

Transcranial direct current stimulation for the outpatient treatment of poor-responder depressed patients

Transcranial direct current stimulation (tDCS) is a selective, painless, brain stimulation technique that allows the electric stimulation of specific cortical regions. TDCS has been recently used as investigational intervention for major depression and treatment resistant depression (TRD) with encouraging results. The present study was aimed to investigate the efficacy and tolerability of tDCS in major depressives with poor response to pharmacological treatment. Twenty-three depressed patients, with a diagnosis of major depressive disorder or bipolar disorder, were treated with augmentative tDCS for 5 days, two sessions per day in a blind-rater trial. The course of depressive symptoms was analyzed using repeated measures ANOVA for HAM-D and MADRS total scores. A qualitative analysis on the basis of the HAM-D response was performed as well. Both analyses were conducted at three time-points: T0 (baseline), T1 (endpoint tDCS) and T2 (end of the first week of follow-up). All patients completed the trial without relevant side-effects. A significant reduction of HAM-D and MADRS total scores was observed during the study (P<0.0001). Treatment response (endpoint HAM-D reduction ≥50%) was obtained by four patients (17.4%) at T1 and by seven patients (30.4%) at T2 and remission (endpoint HAM-D<8) by three patients (13.0%) at T1 and by four subjects (17.4%) at T2. Present findings support the efficacy and good tolerability of tDCS in the acute treatment of patients with TRD with clinical benefit being progressive and extended to the first week of follow-up. Further sham-controlled trials with longer follow-up are needed to confirm present results.

EPA-0773 – Duration of untreated illness, duration of illness and severity of illness in obsessive compulsive disorder and main subtypes

Introduction Obsessive-compulsive disorder (OCD) symptoms are remarkably diverse, as regards both clinical presentation and severity 1 . Studies are conflicting about whether any specific phenotype of OCD is easier to treat or likely to benefit from a particular treatment. Duration of untreated illness (DUI) represents a modifiable parameter, whose reduction may positively influence the outcome and long-term course of specific psychiatric disorders 2 . The aim of this study was to evaluate possible differences concerning severity, duration of illness (DI) and DUI among OCD subtypes in a sample of OCD patients. Methods 114 OCD outpatients were recruited and assessed using the Y-BOCS. The main OCD phenotypes were identified through the YBOCS- Symptom Checklist. A one-way ANOVA test was performed to compare DUI, DI and Y-BOCS scores in the sample. Results Subjects were categorized into 4 clinical phenotypes,: aggressive/checking (n=31), contamination/cleaning (n=37), simmetry/ordering (n=32) and multiple phenotypes (n=14). DUI, DI and YBOCS scores were found significantly higher in aggressive/checking subgroup, compared to other subgroups (One Way ANOVA: F=3.58 p Conclusions DUI and DI resulted significantly higher in the aggressive/checking subgroup, compared to the other subgroups. YBOCS scores resulted significantly higher in the aggressive/checking subgroup compared to the others, showing that longer DUI and DI may condition a worse clinical outcome in this subgroup. Of note, within the total sample half of the whole DI was spent untreated.

P-797 - Residual cognitive impairment in patients affected by bipolar disorder during euthymia: an assessment with functional magnetic resonance imaging (fMRI)

Introduction Bipolar Disorder (BD) is a chronic mood disorder with a prevalence estimated around 1–2%. Bipolar patients may experience social and working residual impairment even during euthymia. Furthermore, specific cognitive deficits, particularly involving working memory (WM), may persist during eythymia as well. Aim To evaluate the possible presence of cognitive and functional differences between euthymic bipolar subjects vs. healthy controls during euthymia by means of a WM task at fMRI associated with neuropsychological evaluations. Methods A sample of 30 subjects aged between 20 and 45 years (15 with BD and 15 controls) underwent fMRI examination at 3 Tesla with tasks of working memory (n-back). All participants received a neuropsychological evaluation, inlcuding Stroop Color-Word Interference test, Tower of London, Trail Making Test, Wisconsin Card Sorting Test and Verbal Fluency Test. Comparison tests were performed using statistical software SPSS and SPM5. Results The performance of the control group was significantly higher than both at the n-back task and at the neuropsychological tests. The full-factorial analysis of fMRI data showed a hypoactivation in bipolar patients in particular hippocampus and thalamus, associated with increased involvement of areas not involved in the frontal-parietal networks classically associated with WM. Conclusions The results seem to confirm the existence of a residual dysfunction during euthymia phase in BD, suggesting two distinct patterns of activation in the two groups studied, both from a neuropsychological point of view and from a neuroimaging perspective.

FC01-02 - Tanscranial direct current stimulation in depression: a comparison between therapeutic effects obtained in hospitalized vs non-hospitalized patients

Introduction Transcranial direct current stimulation (tDCS) is a novel somatic treatment proposed for depressive illness. Aims We aimed to assess the efficacy of tDCS in patients with severe, depression and whether hospitalized patients respond differently from non-hospitalized subjects. Methods 28 patients (aged 36-79 year) with drug-resistant Major Depressive Episode in major Depressive Disorder or in Bipolar Disorder, according to DSM IV-TR, were enrolled. Patients were divided into two groups: ‘outpatients’ (N=14) and ‘hospitalized patients’ (N=14).HAM-D (21 items) were administered as outcome measure, before and after tDCS, to assess treatment response. tDCS delivered by a Newronika stimulator (Milano, Italy) was delivered over the dorsolateral prefrontal cortex (anodal electrode was placed on the left DLPC and cathode electrode on the contralateral area) at the intensity of 2mA, for twenty minutes, twice a day for 5 consecutive days. Results All the patients well tolerated the treatment with no side effects. Despite the different severity at the baseline between the two groups (p=0.03), after five days of tDCS the mood scores improved in both groups, by 22% in outpatients group ([baseline vs post stimulation: mean± SE] HDRS: 20.3± 1.3 vs 15.9±1.8, p= 0.009) and by 32% in hospitalized patients (HDRS: 28.7± 2.7 vs 19.7±2.8, p= 0.0006). The improvement after tDCS did not differ between the two groups (p=0,3). Conclusions tDCS significantly improves patients with severe major depression after five days of treatment without significantly different effects in hospitalized and non hospitalized patients. Hence, tDCS treatment could be suitable also for non hospitalized patients at low suicidal risk.