Chiara Arici

Mood stabilizers for patients with bipolar disorder: the state of the art

Bipolar disorder (BD) is a prevalent and disabling condition, often comorbid with other medical and psychiatric conditions and frequently misdiagnosed. International treatment guidelines for BD recommend the use of mood stabilizers – either in monotherapy or in association – as the gold standard in both acute and long-term therapy. Commonly used in the clinical practice of BD, mood stabilizers have represented an evolving field over the last few years. The concept of stabilization, in fact, has been stressed as the ultimate objective of the treatment of BD, given the chronic and recurrent nature of the illness, which accounts for its significant levels of impairment and disability. To date, different compounds are included within the broad class of mood stabilizers, with lithium, anticonvulsants and, more recently, atypical antipsychotics being the most representative agents. This article is aimed at providing an updated review of the available literature in relation to the role of mood stabilizers in BD, with particular emphasis on their mechanism of action, main clinical aspects and specific use in the different phases of BD treatment, according to the most recently published international treatment guidelines.

Characterizing impulsivity profile in patients with obsessive-compulsive disorder

Abstract Objective. Impulsivity represents a key dimension in obsessive–compulsive disorder (OCD), in relation to outcome and course. It can be assessed through the Barratt Impulsiveness Scale (BIS), which explores three main areas: attentional, motor, and nonplanning. Present study was aimed to assess level of impulsivity in a sample of OCD patients, in comparison with healthy controls, using the BIS. Methods. Seventy-five OCD outpatients, 48 of them having psychiatric comorbidities and 70 healthy controls, were assessed through the BIS, and their scores were analyzed using Students t-test for independent samples, on the basis of demographic and clinical characteristics. Results. BIS total scores were significantly higher (P: 0.01) in patients compared to controls, with no difference between pure and comorbid patients. Attentional impulsivity scores were significantly higher than controls in patients with pure (P < 0.001) and comorbid OCD (P < 0.001), without differences among them. Patients with multiple OC phenotypes showed higher, though statistically non significant, total and attentional scores, compared to single phenotype patients. In addition, patients with comorbid major depressive disorder had higher, though statistically non significant, total and attentional scores, compared to patients with comorbid bipolar disorder, generalized anxiety disorder, and other disorders. Conclusions. Present findings showed higher impulsivity levels in OCD patients versus controls, particularly in the attentional area, and ultimately suggest a potential cognitive implication.

Augmentative transcranial direct current stimulation (tDCS) in poor responder depressed patients: a follow-up study.

OBJECTIVES Transcranial direct current stimulation (tDCS) is a non-invasive neurostimulation technique that has received increasing interest in the area of mood disorders over the last several years. While acute, double-blind, sham-controlled studies have already reported positive findings in terms of efficacy and safety for tDCS, follow-up data are lacking. This need prompted the present follow-up study, which assesses post-acute effects of tDCS (no maintenance stimulation was performed), in the mid-term, in a sample of major depressives. METHODS After completing an acute, open trial of tDCS, 23 outpatients with either major depressive disorder or bipolar disorder entered a naturalistic follow-up (T1) with clinical evaluations at one week (T2), 1 month (T3), and 3 months (T4). A quantitative analysis of Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS) total scores, through repeated measures analysis of variance (ANOVA) (T1-T4) and paired t-test for comparing specific time points (T1-T2, T2-T3, and T3-T4), was performed. In addition, a qualitative analysis on the basis of treatment response and remission (HAM-D) was performed. RESULTS Even though a progressive reduction of follow-up completers was observed from T2 to T4 (95.6% at T2, 65.2% at T3, and 47.8% at T4), the antidepressant effects of acute tDCS persisted over 3 months in almost half of the sample. Of note, no post-acute side effects emerged during the follow-up observation. The most frequent causes of drop-out from this study included major modifications in therapeutic regimen (30%) and poor adherence to follow-up visits (17%). CONCLUSIONS In this mid-term, open, follow-up study, tDCS showed mixed results. Further controlled studies are urgently needed to assess its effects beyond the acute phase.

Tolerability and use in co-administration of pregabalin in affective patients: a 6-month prospective naturalistic study

Objective: The aims of the present study were to investigate the main demographic and clinical characteristics, comorbidity patterns, use in association and tolerability of pregabalin in a sample of patients with affective disorders, and to compare demographic and clinical variables of the groups divided, according to the treatment pregabalin was associated with. Methods: One hundred and fourteen consecutive outpatients, with anxiety and/or depressive disorders with or without comorbidity, were started on pregabalin, assessed and interviewed and their demographic data, associated therapy, tolerability and side effects collected over an observational period of 6 months. Results: The most frequent primary diagnoses were mood disorders (49.1%) and generalized anxiety disorder (21.9%). The most commonly associated treatments were antidepressants (66.7%) and mood stabilizers (15.8%). The most frequent side effects were sedation (3.4%), dizziness (0.9%), nausea (0.9%), diarrhea (0.9%), cough (0.9%) and peripheral edema (0.9%). When patients were divided according to the co-treatments, subgroups differed in terms of prescription of benzodiazepines (χ2 = 15.25, df = 6, p = 0.013, phi = 0.37), with the most frequent use of these molecules in patients co-treated with tricyclic antidepressants and minor use in the selective serotonin reuptake inhibitors group. Conclusions: Differences in the co-administration of benzodiazepines might suggest a stronger anxiolytic effect when pregabalin is combined with specific psychotropic drugs (e.g., SSRIs).

Factors characterizing access and latency to first pharmacological treatment in Italian patients with schizophrenia, mood, and anxiety spectrum disorders

Latency to first pharmacological treatment [duration of untreated illness (DUI)] in psychiatric disorders can be measured in years, with differences across diagnostic areas and relevant consequences in terms of socio-occupational functioning and outcome. Within the psychopathological onset of a specific disorder, many factors influence access and latency to first pharmacotherapy and the present study aimed to investigate such factors, through an ad-hoc developed questionnaire, in a sample of 538 patients with diagnoses of schizophrenia-spectrum disorder (SZ), mood disorder (MD), and anxiety disorder (AD). Patients with SZs showed earlier ages at onset, first diagnosis and treatment, as well as shorter DUI compared with other patients (43.17 months vs. 58.64 and 80.43 months in MD and AD; F=3.813, P=0.02). Patients with MD and AD reported more frequently onset-related stressful events, benzodiazepines as first treatment, and autonomous help seeking compared with patients with SZs. In terms of first therapist, psychiatrist referral accounted for 43.6% of the cases, progressively decreasing from SZ to MD and AD (57.6, 41.8, and 38.3%, respectively). The opposite phenomenon was observed for nonpsychiatrist clinician referrals, whereas psychologist referrals remained constant. The present findings confirm the presence of a relevant DUI in a large sample of Italian patients with different psychiatric disorders (5 years, on average), pointing out specific differences, in terms of treatment access and latency, between psychotic and affective patients. Such aspects are relevant for detection of at-risk patients and implement early intervention programs.

Efficacy, tolerability, compliance, and quality of life of patients with mood disorders switched from Quetiapine immediate release to extended release

The present study aimed to assess switch from immediate-release (IR) to extended-release (XR) Quetiapine in terms of efficacy, tolerability, compliance, and quality of life in a sample of patients with mood disorders. Thirty patients, 10 with major depressive disorder and 20 with bipolar disorder, with residual depressive symptoms, who had switched from Quetiapine IR (mean 365 mg/day) to XR (mean 373 mg/day), were recruited and evaluated using different psychometric scales, administered at T0 (switch), T1, and T2 (1 and 6 weeks after the switch, respectively). A significant reduction from T0 to T2 of the total scores on the Hamilton Depression Rating Scale (t=2.15; P=0.04), Hamilton Anxiety Scale (t=3.04; P=0.006), and Clinical Global Impression-Severity Item (t=2.8; P=0.01) was found. No differences were found in terms of compliance and quality of life. The switch was well tolerated by 2/3 of patients. Most reported side effects were early/central insomnia with day drowsiness (16.7%), increased appetite and weight (8.4%), mild asthenia (4.2%), and constipation (4.2%), which, in two cases, led to switch interruption. Strategies to relieve side effects, including gradual cross-switch, improved switch feasibility. Switch from Quetiapine IR to XR seems to be associated with clinical improvement in major depressives with residual symptoms, although some patients may report side effects because of the different pharmacokinetics.

Structural and metabolic differentiation between bipolar disorder with psychosis and substance-induced psychosis: An integrated MRI/PET study

BACKGROUND Bipolar disorder (BD) may be characterized by the presence of psychotic symptoms and comorbid substance abuse. In this context, structural and metabolic dysfunctions have been reported in both BD with psychosis and addiction, separately. In this study, we aimed at identifying neural substrates differentiating psychotic BD, with or without substance abuse, versus substance-induced psychosis (SIP) by coupling, for the first time, magnetic resonance imaging (MRI) and positron emission tomography (PET). METHODS Twenty-seven BD type I psychotic patients with (n=10) or without (n=17) substance abuse, 16 SIP patients and 54 healthy controls were enrolled in this study. 3T MRI and 18-FDG-PET scanning were acquired. RESULTS Gray matter (GM) volume and cerebral metabolism reductions in temporal cortices were observed in all patients compared to healthy controls. Moreover, a distinct pattern of fronto-limbic alterations were found in patients with substance abuse. Specifically, BD patients with substance abuse showed volume reductions in ventrolateral prefrontal cortex, anterior cingulate, insula and thalamus, whereas SIP patients in dorsolateral prefrontal cortex and posterior cingulate. Common alterations in cerebellum, parahippocampus and posterior cingulate were found in both BD with substance abuse and SIP. Finally, a unique pattern of GM volumes reduction, with concomitant increased of striatal metabolism, were observed in SIP patients. CONCLUSIONS These findings contribute to shed light on the identification of common and distinct neural markers associated with bipolar psychosis and substance abuse. Future longitudinal studies should explore the effect of single substances of abuse in patients at the first-episode of BD and substance-induced psychosis.

Reduced duration of untreated illness over time in patients with schizophrenia spectrum, mood and anxiety disorders.

Psychiatric disorders represent highly impairing conditions, often underdiagnosed and undertreated, with a conspicuous duration of untreated illness (DUI). Given that social and cultural factors influence the DUI and assuming that progress in diagnosis and treatment determines a reduced latency to pharmacotherapy, we assessed and compared DUI and related variables in a large sample of psychiatric patients (n = 562) whose onset occurred within three different a priori‐defined epochs.

Neuroimaging procedures and related acquisitions in bipolar disorder: state of the art.

Bipolar disorder (BD) is a chronic and disabling mood disorder, with significant suicide rates among psychiatric disorders. Although the pathophysiological bases of BD have not been fully elucidated yet, over the last two decades, neuroimaging research has documented specific neuroanatomic and functional abnormalities in bipolar patients. The present review was aimed to provide an updated and comprehensive overview about currently available evidence on main structural and functional alterations documented in BD by neuroimaging procedures, through a Medline research. Among the structural alterations, the most consistent ones seem to be at the level of frontal, temporal and insular cortices, amygdala and basal ganglia, having been ventriculomegaly reported as well. Magnetic resonance spectroscopy findings showed, in turn, biochemical alterations in several neurotransmitter systems. Functional neuroimaging data are quite heterogeneous with positron emission tomography and single photon emission computed tomography studies showing phase-specific abnormalities of blood flow and glucose metabolism, as well as modifications of serotonin transporter density and binding. Functional magnetic resonance imaging data documented impaired neural networks involved in emotional regulation, including anterior limbic, ventral and dorsal prefrontal regions. Taken as a whole, neuroimaging data are strongly advancing the understanding of the neural bases of BD as described in the present review.

Prevalence of suicide attempt and clinical characteristics of suicide attempters with obsessive-compulsive disorder: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS)

OBJECTIVE Obsessive-compulsive disorder (OCD) is associated with variable risk of suicide and prevalence of suicide attempt (SA). The present study aimed to assess the prevalence of SA and associated sociodemographic and clinical features in a large international sample of OCD patients. METHODS A total of 425 OCD outpatients, recruited through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network, were assessed and categorized in groups with or without a history of SA, and their sociodemographic and clinical features compared through Pearsons chi-squared and t tests. Logistic regression was performed to assess the impact of the collected data on the SA variable. RESULTS 14.6% of our sample reported at least one SA during their lifetime. Patients with an SA had significantly higher rates of comorbid psychiatric disorders (60 vs. 17%, p<0.001; particularly tic disorder), medical disorders (51 vs. 15%, p<0.001), and previous hospitalizations (62 vs. 11%, p<0.001) than patients with no history of SA. With respect to geographical differences, European and South African patients showed significantly higher rates of SA history (40 and 39%, respectively) compared to North American and Middle-Eastern individuals (13 and 8%, respectively) (χ2=11.4, p<0.001). The logistic regression did not show any statistically significant predictor of SA among selected independent variables. CONCLUSIONS Our international study found a history of SA prevalence of ~15% in OCD patients, with higher rates of psychiatric and medical comorbidities and previous hospitalizations in patients with a previous SA. Along with potential geographical influences, the presence of the abovementioned features should recommend additional caution in the assessment of suicide risk in OCD patients.