A.C. Altamura

Clinical variables related to suicide attempts in schizophrenic patients: a retrospective study

In this study, we investigated the possible association between clinical or pharmacological variables and suicidal behavior in a sample of chronic schizophrenia or schizoaffective disorder patients. One hundred and three patients with a DSM-III-R diagnosis of chronic schizophrenia or schizoaffective disorder were studied. The sample was subdivided in two subsamples according to the presence/absence of suicidal attempts lifetime. The main demographic and clinical variables retrospectively collected were analyzed and compared between the two groups. Attempters had a significantly higher rate of nicotine abuse or dependence (chi-square=3.900, df=1, p<0.05, Odds Ratio (O.R.)=3.4), were more likely to have or have had lifetime major depressive episodes (chi-square=10.258, df=1, p<0.002, O.R.=6.5), were more likely to have a duration of untreated psychosis (DUP) > or =1 year (chi-square=6.228, df=1, p<0.02, O.R.=12.5), and were more frequently prescribed typical antipsychotics (chi-square=3.979, df=1, p<0.05, O.R.=6.5) than patients without suicidal attempts lifetime. Further investigations on larger samples and with prospective designs are warranted, particularly with respect to the role of early intervention and atypical antipsychotic treatment in reducing suicide risk in schizophrenic patients.

Venlafaxine in social phobia : a study in selective serotonin reuptake inhibitor non-responders

The study aimed to evaluate the clinical response to venlafaxine in social phobia in 12 patients who were non-responders to selective serotonin reuptake inhibitors, and to assess how the response could be influenced by the comorbidity in Axis II with avoidant personality disorder (APD). The duration of the study was of 15 weeks using open flexible doses regimen in individuals with or without concomitant APD. The venlafaxine dose ranged from 112.5 mg/day to 187.5 mg/day. Venlafaxine improves social phobia and/or APD symptomatology, as demonstrated by decreasing Liebowitz Social Anxiety Scale total scores (P < 0.05). In fact, venlafaxine significantly reduced the avoidant behaviour and specific sociophobic aspects, while notably improving the depression dimension and the basic anxiety symptoms. With regard to tolerability, the profile of venlafaxine was satisfactory with the main side-effects being nausea, headache and anxiety.

Interactions between transcranial direct current stimulation (tDCS) and pharmacological interventions in the Major Depressive Episode: Findings from a naturalistic study

BACKGROUND Transcranial direct current stimulation (tDCS) is a non-invasive, neuromodulatory technique with an emerging role for treating major depression. OBJECTIVE To investigate the interactions between tDCS and drug therapy in unipolar and bipolar depressed patients who were refractory for at least one pharmacological treatment. METHODS This was a naturalistic study using data from 54 female and 28 male patients (mean age of 54 years) that consecutively visited our psychiatric unit. They received active tDCS (five consecutive days, 2mA, anodal stimulation over the left and cathodal over the right dorsolateral prefrontal cortex, twice a day, 20minutes). The outcome variable (mood) was evaluated using the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS). Predictor variables were age, gender, disorder and pharmacological treatment (seven dummy variables). We performed univariate and multivariate analyses as to identify predictors associated to the outcome. RESULTS After 5 days of treatment, BDI and HDRS scores decreased significantly (29%±36%, 18%±9%, respectively, P<0.01 for both). Benzodiazepine use was independently associated with a worse outcome in both univariate (β=4.92, P<0.01) and multivariate (β=5.8, P<0.01) analyses; whereas use of dual-reuptake inhibitors positively changed tDCS effects in the multivariate model (β=-4.7, P=0.02). A similar trend was observed for tricyclics (β=-4, P=0.06) but not for antipsychotics, non-benzodiazepine anticonvulsants and other drugs. CONCLUSION tDCS over the DLPFC acutely improved depressive symptoms. Besides the inherent limitations of our naturalistic design, our results suggest that tDCS effects might vary according to prior pharmacological treatment, notably benzodiazepines and some antidepressant classes. This issue should be further explored in controlled studies.

Meta-Review of Metanalytic Studies with Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Major Depression

Background: Major Depression (MD) and treatment-resistant depression (TRD) are worldwide leading causes of disability and therapeutic strategies for these impairing and prevalent conditions include pharmacological augmentation strategies and brain stimulation techniques. In this perspective, repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique with a favorable profile of tolerability which, despite being recently approved by the Food and Drug Administration (FDA) for the treatment of patients with medication-refractory unipolar depression, still raises some doubts about most effective parameters of stimulation. Methods: A literature search was performed using PubMed for the years 2001 through February 2011 in order to review meta-analytic studies assessing efficacy and safety issues for rTMS in depressive disorders. Fifteen meta-analyses were identified and critically discussed in order to provide an updated and comprehensive overview of the topic with specific emphasis on potentially optimal parameters of stimulation. Results: First meta-analyses on the efficacy of rTMS for the treatment of MD and TRD have shown mixed results. On the other hand, more recent meta-analytic studies seem to support the antidepressant efficacy of the technique to a greater extent, also in light of longer periods of stimulation (e.g. > 2 weeks). Conclusion: rTMS seems to be an effective and safe brain stimulation technique for the treatment of medication refractory depression. Nevertheless, further studies are needed to better define specific stimulation-related issues, such as duration of treatment as well as durability of effects and predictors of response.

Age at onset and latency to treatment (duration of untreated illness) in patients with mood and anxiety disorders: A naturalistic study

This study was designed to investigate and compare demographic and clinical features with specific emphasis on age at onset, age at first treatment and, in particular, on duration of untreated illness (DUI), in patients with different mood and anxiety disorders. Study sample included 729 outpatients with the following diagnoses: major depressive disorder (n=181), bipolar disorder type I (BD I, n=115) and II (BD II, n=186), generalized anxiety disorder (n=100), panic disorder (n=96), and obsessive–compulsive disorder (n=51). Main demographic and clinical variables of the sample were compared among the diagnostic groups using one-way analysis of variance or χ2 tests. The diagnostic groups showed significant differences in relation to age at onset and age at first pharmacological treatment and in relation to latency to treatment. In particular, patients with major depressive disorder showed the shortest DUI (39.08 months), whereas patient with BD II showed the longest DUI (97.2 months) in comparison with the other groups. Within the group with anxiety disorders (F=7.512, P<0.001), patients with panic disorder showed the shortest DUI (44.35 months), whereas patients with obsessive–compulsive disorder showed the longest DUI (90.57 months). The present findings suggest that patients with different mood and anxiety disorders show significant differences in terms of age at onset, age at first treatment and, consequently, DUI, which potentially reflect different reasons influencing treatment delay.

Efficacy and tolerability of quetiapine in the treatment of bipolar disorder: preliminary evidence from a 12-month open-label study

BACKGROUND The literature on the use of quetiapine for the treatment of bipolar disorder (BD) is limited to case reports, and there are no systematic studies on the efficacy of quetiapine in the prophylactic treatment of BD. The aim of the present study was to compare the efficacy of flexible doses of quetiapine and well established mood stabilizers in the maintenance treatment of BD. METHODS Twenty-eight DSM-IV BD outpatients were consecutively recruited into the study and were randomized to receive one of two open-label treatments, with quetiapine or classical mood stabilizers at flexible doses for 12 months. Clinical assessment was carried out using BPRS, CGI, YMRS and the 21-item HAM-D at baseline (T0) and every 2 months until the end of the study. ANOVAs with repeated measures were applied to the rating scale scores considering the time and the treatment group as main factors. RESULTS All patients experienced a significant improvement on the BPRS, CGI and HAM-D scores, with no significant side-effects and a good compliance. LIMITATIONS This study should be considered preliminary given the small sample size investigated and the open-label design. CONCLUSIONS If these results will be replicated on larger samples and in controlled studies, there could be relevant implications for the use of quetiapine as an alternative maintenance treatment for BD.

Clinical and psychosocial outcome of patients affected by panic disorder with or without agoraphobia: results from a naturalistic follow-up study

OBJECTIVE A clinical and psychosocial follow-up study of a cohort of 85 patients affected by panic disorder (PD) with or without agoraphobia was performed an average of 40 months after initial observation and following a mean duration of illness of 8 years. METHODS Eighty-five out of 130 patients affected by PDs with or without agoraphobia according to DSM-III R criteria, examined between 1990 and 1995 at an outpatient clinic were re-examined in 1997/1998 using the same standardized clinical evaluation performed on admission. Patients also underwent a structured diagnostic interview (Mini International Neuropsychiatric Interview, MINI) and psychosocial evaluation (Scale of Sheehans Disability Scale, DISS, Baker and Intagliatas Satisfaction with Life Domains Scale, SLDS). RESULTS At follow-up, the percentage of patients who had either improved or were in remission was considerably higher among those initially diagnosed as PD with respect to those diagnosed as panic disorder with agoraphobia (PDA): Thirty-eight percent of PD and 20.6% of PDA patients were in clinical remission. Mild panic symptoms and phobic avoidance were found in the majority of patients who were still symptomatic (respectively 71% and 57%). Approximately 60% of patients reported a significant difficulty in performing daily activities and 40% expressed dissatisfaction in at least 50% of life domains considered. Seventy-two percent of subjects examined were still undergoing pharmacological treatment at the time of follow-up. CONCLUSIONS The findings of the study are suggestive of a chronic illness with a significant impact on everyday quality of life of patients.

Duration of untreated illness as a predictor of treatment response and clinical course in generalized anxiety disorder.

INTRODUCTION The aim of the present study was to investigate the impact of the duration of untreated illness (DUI)-defined as the time elapsing between the onset of generalized anxiety disorder (GAD) and the first adequate pharmacologic treatment-on treatment response and clinical course in a sample of subjects with GAD. METHODS One hundred patients with GAD, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria, were enrolled and their main demographic and clinical features collected. Patients were then treated with selective serotonin reuptake inhibitors or venlafaxine for 8 weeks in open-label conditions. Treatment response and other clinical variables were analyzed after dividing the sample into two groups according to DUI (DUI <or=12 months and DUI >12 months). RESULTS When the DUI was computed with respect to the first antidepressant treatment (DUI-AD), a higher improvement (Clinical Global Impressions-Severity of Illness scale) after the pharmacologic treatment was found in the group with a shorter DUI (analysis of variance with repeated measures: time effect F=654.975, P<.001; group effect: F=4.369, P=.039). When computed with respect to the first treatment with benzodiazepines (DUI-BDZ), the two groups did not show any significant difference in treatment response (time effect: F=652.183, P<.001; group effect: F=0.009, P=.924). In addition, patients with a longer DUI (DUI-BDZ or DUI-AD) showed an earlier age at onset, a longer duration of illness and a higher rate of comorbid psychiatric disorders with onset later than GAD. CONCLUSION Results from this preliminary study seem to suggest that a shorter DUI-AD may determine a better response to pharmacologic treatment in patients with GAD, and that a longer DUI (DUI-BDZ and DUI-AD) may be associated to a worse clinical course. Further investigation on the relationship between DUI and GAD is needed.

Neuropsychobiological aspects, comorbidity patterns and dimensional models in borderline personality disorder.

Borderline personality disorder (BPD) is a comorbid and disabling condition with high prevalence in psychiatric settings. The pathogenesis of BPD involves complex interactions among genetic, neurobiological and environmental factors, resulting in multiple core symptom domains such as emotional dysregulation, impulse dyscontrol, aggression, cognitive dysfunctions and dissociative states. Neurobiological studies show that symptoms and behaviors of BPD are partly associated with alterations in glutamatergic, dopaminergic and serotonergic systems. In addition, neuroimaging studies in BPD patients indicate differences in the volume and activity of specific brain regions related to emotion and impulse control, such as the prefrontal and cingulate cortex, amygdala and hippocampus. Neurobiological alterations are related to cognitive disturbances in patients with BPD and neuropsychological tests have shown abnormalities of memory, attention, language, and executive functions. The aim of the present review is to provide an updated overview of the main neuropsychobiological aspects of BPD and their relation to clinical symptoms, comorbidity patterns and dimensional models.

Understanding the pharmacokinetics of anxiolytic drugs

Introduction: Anxiety disorders are considered the most common mental disorders and they can increase the risk for comorbid mood and substance use disorders, significantly contributing to the global burden of disease. For this reason, anxiolytics are the most prescribed psychoactive drugs, particularly in the Western world. Areas covered: This review aims to analyze pharmacokinetic profile, plasma level variations so as the metabolism, interactions and possible relation to clinical effect of several drugs which are used primarily as anxiolytics. The drugs analyzed include benzodiazepines, anticonvulsants (pregabalin, gabapentin), buspirone, β-blockers and antihistamines (hydroxyzine). Regarding the most frequently used anxiolytic benzodiazepines, data on alprazolam, bromazepam, chlordesmethyldiazepam, chlordiazepoxide, clotiazepam, diazepam, etizolam, lorazepam, oxazepam, prazepam and clonazepam have been detailed. Expert opinion: There is a need for a more balanced assessment of the benefits and risks associated with benzodiazepine use, particularly considering pharmacokinetic profile of the drugs to ensure that patients, who would truly benefit from these agents, are not denied appropriate treatment. An optimal pharmacological approach involving an integrative pharmacokinetic and pharmacodynamic optimization strategy would ensure better treatment and personalization of anxiety disorders. So it would be desirable for the development of new anxiolytic drug(s) that are more selective, fast acting and free from the unwanted effects associated with the traditional benzodiazepines as tolerance or dependence.