Lucio Oldani

Augmentative repetitive Transcranial Magnetic Stimulation (rTMS) in the acute treatment of poor responder depressed patients: A comparison study between high and low frequency stimulation

BACKGROUND While the efficacy of repetitive transcranial magnetic stimulation (rTMS) in Major Depressive Disorder (MDD) is well established, the debate is still open in relation to bipolar depression and to a possible different effectiveness of high vs. low stimulation. The present study was aimed to assess and compare the efficacy and tolerability of different protocols of augmentative rTMS in a sample of patients with current Major Depressive Episode (MDE), poor drug response/treatment resistance and a diagnosis of MDD or bipolar disorder. METHODS Thirty-three patients were recruited in a 4-week, blind-rater, rTMS trial and randomised to the following three groups of stimulation: (1) (n=10) right dorsolateral prefrontal cortex (DLPFC) 1 HZ, 110% of the motor threshold (MT), 420 stimuli/day; (2) (n=10) right DLPFC, 1Hz, 110% MT, 900 stimuli/day; (3) (n=13) left DLPFC, 10Hz, 80% MT, 750 stimuli/day. RESULTS Twenty-nine patients completed the treatment, showing a significant reduction of primary outcome measures (HAM-D, MADRS and CGI-S total scores: t=8.1, P<0.001; t=8.6, P<0.001; t=4.6, P<0.001 respectively). No significant differences in terms of efficacy and tolerability were found between high vs. low frequency and between unipolar and bipolar patients. Side effects were reported by 21% of the sample. One of the 4 dropouts was caused by a hypomanic switch. CONCLUSIONS Augmentative rTMS appeared to be effective and well tolerated for the acute treatment of unipolar and bipolar depression with features of poor drug response/treatment resistance, showing a comparable effectiveness profile between protocols of high and low frequency stimulation.

A case of severe psychosis induced by novel recreational drugs

Introduction: The use of novel recreational drugs is becoming of public interest, especially after recent international alerts about their cardiovascular and neurological toxicity. Additionally, little is known about the psychiatric consequences of the long-term use of these compounds. Case presentation: We describe a case of severe psychotic episode likely induced by chronic use of a combination of new recreational drugs (methylenedioxypyrovalerone, mephedrone, butylone and alpha-pyrrolidinopentiophenone). The patient had no psychiatric history and showed poor response to conventional antipsychotic treatment (haloperidol). Conclusions: This case illustrates the potential negative effects of recreational drugs that cannot be limited to an acute psychotic episode but might determine a condition of prolonged paranoid psychosis. Although the use of these compounds is currently increasing, such molecules might often pass undetected in patients accessing the emergency room, leading to misdiagnosis (e.g. schizophrenic episode) and lack of appropriate treatment.

Brain stimulation treatments in bipolar disorder: A review of the current literature

Objectives. Brain stimulation techniques are non-pharmacologic strategies which offer additional therapeutic options for treatment-resistant depression (TRD). The purpose of this paper is to review the current literature regarding the use of brain stimulation in resistant bipolar disorder (BD), with particular reference to hypomanic/manic symptoms. Methods. Keywords pertaining to the brain simulation techniques used in the treatment of depression (either unipolar or bipolar) along with their role in regard to hypomanic/manic symptoms were used to conduct an electronic search of the literature. Pertinent findings were identified by the authors and reviewed. Results. Brain stimulation techniques represent a valid therapeutic option in TRD. They have been extensively studied in unipolar depression and, to a minor extent, in the depressive phase of BD, showing encouraging but often limited results. With exception of electroconvulsive therapy, the efficacy of brain stimulation in the treatment of manic symptoms of bipolar patients is still uncertain and needs to be fully evaluated. Conclusions. Brain stimulation in BD is derived from its use in unipolar depression. However, there are many important differences between these two disorders and more studies with a systematic approach need to be conducted on larger samples of bipolar patients with treatment-resistant characteristics.

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.

Differences in duration of untreated illness, duration, and severity of illness among clinical phenotypes of obsessive-compulsive disorder

INTRODUCTION Obsessive-compulsive disorder (OCD) is a prevalent, disabling, and comorbid condition that is frequently under-recognized and poorly treated. OCD phenotypes may differ in terms of clinical presentation and severity. However, few studies have investigated whether clinical phenotypes differ in terms of latency to treatment (ie, duration of untreated illness[DUI]), duration, and severity of illness. The present study was aimed to quantify the aforementioned variables in a sample of OCD patients. METHODS One hundred fourteen outpatients with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) diagnosis of OCD were recruited, and their main clinical features were collected. Severity of illness was assessed through the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and the main phenotypes were identified through the Y-BOCS Symptom Checklist. A one-way analysis of variance (ANOVA) test, followed by a Bonferroni post-hoc test, were performed to compare DUI, duration, and severity of illness across subgroups. RESULTS In the whole sample, the mean DUI exceeded 7 years (87.35±11.75 months), accounting for approximately half of the mean duration of illness (172.2±13.36 months). When subjects were categorized into 4 main clinical phenotypes, respectively, aggressive/checking (n=31), contamination/cleaning (n=37), symmetry/ordering (n=32), and multiple phenotypes (n=14), DUI, duration, and severity of illness resulted significantly higher in the aggressive/checking subgroup, compared to other subgroups (F=3.58, p<0.01; F=3.07, p<0.01; F=4.390, p<0.01). DISCUSSION In a sample of OCD patients, along with a mean latency to treatment of approximately 7 years, regardless of the phenotype, patients had spent half of their duration of illness (DI) without being treated. DUI, duration, and severity of illness resulted significantly higher in the aggressive/checking subgroup.

Physical health of patients with bipolar disorder

Bipolar disorder is a chronic, typically early onsetting group of mental disorders with a lifelong risk of relapse. It is characterized by recurrent periods of depression and pathologically elevated mood consisting of increased energy and activity during which patients may experience sleep loss, over-confidence, impaired concentration, extreme talkativeness, and engage in irresponsible risk-taking behavior. As a result, it is often problematic to undertake usual activities and maintain interpersonal relationships (World Health Organization [WHO], 2001). An estimated 2.4% of the world’s population suffer from some form of bipolar disorder, with a lifetime prevalence of 0.6% for bipolar I disorder and 0.4% for bipolar II disorder, while 1.4% of the total population has a lifetime prevalence of subsyndromal bipolar disorder (Merikangas et al., 2011). Bipolar disorders are categorized into bipolar I and bipolar II depending on a patient history of major depressive and hypomanic episodes only (bipolar II), or depressive and manic episodes in addition to hypomanic and mixed episodes (bipolar I). Subsyndromal symptoms may be diagnosed as bipolar disorder not otherwise specified. Patients with bipolar disorder encounter many difficulties in leading a normal lifestyle, even with the support of family, friends and carers, and therefore tend to have a low quality of life (QoL), which is powerfully influenced by two factors: the nature of mental illness itself and treatment-related comorbidities. Features of social disability that may trouble patients with bipolar disorder include problems in developing and sustaining friendships and difficulties in maintaining intimate relationships with a partner. Furthermore, the inability to manage money, housework, and coping with an emergency (Kai and Crosland, 2001) impedes a normal lifestyle. Possibly as a consequence of poor QoL, “self

Access and latency to first antipsychotic treatment in Italian patients with schizophrenia and other schizophrenic spectrum disorders across different epochs.

The duration of untreated illness (DUI) is a measure to express the latency to first psychopharmacological treatment: it differs among psychiatric disorders, being influenced by several illness‐intrinsic and environmental factors. The present study aimed to assess differences in DUI and related variables in patients with schizophrenia (SKZ) versus other schizophrenic spectrum disorders (SSDs) across different epochs.

Prevalence and disability of comorbid social phobia and obsessive–compulsive disorder in patients with panic disorder and generalized anxiety disorder

Abstract Objective. Generalized anxiety disorder (GAD) and panic disorder (PD) are disabling conditions, often comorbid with other anxiety disorders. The present study was aimed to assess prevalence and related disability of comorbid social phobia (SP) and obsessive–compulsive disorder (OCD) in 115 patients with GAD (57) or PD (58). Methods. Patients were classified as having threshold, subthreshold, or no comorbidity, and related prevalence rates, as well as disability (Sheehan Disability Scale, SDS), were compared across diagnostic subgroups. Results. SP and OCD comorbidities were present in 30.4% of the sample, with subthreshold comorbidities present at twice the rate of threshold ones (22.6% vs. 11.3%). Compared with GAD patients, PD patients showed significantly higher subthreshold and threshold comorbidity rates (27.6% and 13.8% vs. 17.5% and 8.8%, respectively). Comorbid PD patients had higher SDS scores than the comorbid and non-comorbid GAD subjects. The presence of threshold SP comorbidity was associated with the highest SDS scores. Conclusions. SP and OCD comorbidities were found to be prevalent and disabling among GAD and PD patients, with higher subthreshold than threshold rates, and a negative impact on quality of life. Present findings stress the importance of a dimensional approach to anxiety disorders, the presence of threshold and subthreshold comorbidity being the rule rather than the exception.

Italian patients with more recent onset of Major Depressive Disorder have a shorter duration of untreated illness

Previous investigation on the duration of untreated illness (DUI) in patients with Major Depressive Disorder (MDD) revealed a different latency to first antidepressant treatment, with adverse consequences in terms of outcome for individuals with a longer DUI. Recent reports, moreover, documented a reduced DUI, as observed with the passage of time, in patients with different psychiatric disorders. Hence, the present study was aimed to assess DUI and related variables in a sample of Italian patients with MDD as well as to investigate potential differences in subjects with onset before and after 2000.