Anxiety Disorders: Altamura AC

Bareggi SR, Mundo E, Dell'Osso B, Altamura AC. · University of Milan, Department of Pharmacology, Via Vanvitelli 32, 20129 Milano, Italy. · Expert Opin Drug Metab Toxicol. · Pubmed #17916059 No free full text.

Abstract: Escitalopram, the active (S)-enantiomer of citalopram, has been approved in many countries throughout the world for the treatment of depression and anxiety disorders. It is more potent and selective than citalopram in inhibiting serotonin re-uptake in the CNS, and less potent than various other selective serotonin re-uptake inhibitors in relation to other transporter proteins and receptors: in particular, it is six times less potent than citalopram in binding to the histamine H1 and muscarinic receptors. Escitalopram has favourable pharmacokinetics: it is rapidly absorbed, has a bioavailability of 80% and is not affected by food intake. It has little potential for drug interactions: it has low protein binding and, as it is metabolised by three CYP isozymes, any impairment in the activity of one is unlikely to have a significant effect on metabolic clearance. Caution is necessary only when it is coadministered with drugs metabolised by CYP2D6, such as metoprolol, or administered to the elderly or patients with severe hepatic or renal impairment. The multiple-dose pharmacokinetics of oral escitalopram are proportional at a range of doses including its therapeutic doses. Escitalopram is approved for the treatment of a number of anxiety disorders. It seems to be well tolerated and induces few or no discontinuation symptoms, and may be considered a first-line agent for the pharmacotherapy of obsessive-compulsive disorder, generalised anxiety disorder, panic disorder and social phobia. Further studies are needed to define its activity in impulse control disorders.

Dell'Osso B, Altamura AC, Mundo E, Marazziti D, Hollander E. · Department of Psychiatry, Compulsive, Impulsive and Anxiety Disorders Program, Mount Sinai School of Medicine, New York, NY, USA. · Int J Clin Pract. · Pubmed #17229184 No free full text.

Abstract: Obsessive-compulsive disorder (OCD) is currently recognised as one of the most common psychiatric disorders as well as one of the most disabling of all medical disorders. Obsessive-compulsive related disorders (OCRDs), often comorbid with OCD, include many distinct psychiatric conditions (i.e. some somatoform disorders, eating disorders, impulse control disorders and some neurological conditions) which have overlapping symptoms and compulsive qualities with OCD. Although effective treatments exist, OCD and related disorders are often underdiagnosed and undertreated. Serotonin reuptake inhibitors (SRIs) and cognitive behavioural therapy (CBT) represent the first-line treatment for OCD and related disorders. However, the time and the doses of the medications used in the treatment of OCD and related disorders differ from those recommended in depressive disorders. In addition, remission is not common for patients with OCD and related disorders in clinical practice, and poor responders as well as refractory cases may benefit from different treatment strategies including integrated treatment, pharmacological augmentation and brain stimulation techniques.

Dell'Osso B, Altamura AC, Allen A, Marazziti D, Hollander E. · Compulsive, Impulsive and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1230, New York, NY 10029, USA. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #16960655 links to  free full text

Abstract: The article reviews the current knowledge about the impulse control disorders (ICDs) with specific emphasis on epidemiological and pharmacological advances. In addition to the traditional ICDs present in the DSM-IV-pathological gambling, trichotillomania, kleptomania, pyromania and intermittent explosive disorder-a brief description of the new proposed ICDs-compulsive-impulsive (C-I) Internet usage disorder, C-I sexual behaviors, C-I skin picking and C-I shopping-is provided. Specifically, the article summarizes the phenomenology, epidemiology and comorbidity of the ICDs. Particular attention is paid to the relationship between ICDs and obsessive-compulsive disorder (OCD). Finally, current pharmacological options for treating ICDs are presented and discussed.

Dell'Osso B, Altamura AC, Allen A, Hollander E. · Department of Psychiatry, Compulsive, Impulsive and Anxiety Disorders Program, Mount Sinai School of Medicine, New York, NY 10029, USA. · CNS Spectr. · Pubmed #16344833 links to  free full text

Abstract: Recent studies on the epidemiology of obsessive-compulsive disorder (OCD) estimate 50 million patients suffer from OCD worldwide, thus making it a global problem. The treatment of OCD has changed substantially over the last 2 decades following the introduction of selective serotonin reuptake inhibitors, which provide symptom improvement in approximately 60% of patients. However, some patients remain resistant to the standard pharmacologic and behavioral treatments. Although some treatment-resistant patients respond to pharmacologic augmentations, others do not, and there is evidence that some of the most severe cases benefit from treatment with neurosurgical interventions. Besides pharmacologic, behavioral, and neurosurgical approaches, different brain stimulation methods-transcranial magnetic stimulation, deep brain stimulation, and electroconvulsive therapy-have been investigated in treatment-resistant patients with OCD. However, available data about the use of these techniques in OCD treatment are quite limited in terms of sample size and study design, given the difficulty in conducting standard blinded trials for these procedures. In addition, none of the mentioned treatments have received Food and Drug Administration approval for the treatment of OCD. Nevertheless, promising findings regarding efficacy, tolerability, and non-invasiveness and/or reversibility of these techniques have increased interest in investigating their use in treatment-resistant OCD.

Altamura AC, Montresor C, Salvadori D, Mundo E. · Department of Psychiatry, Department of Clinical Sciences Luigi Sacco, University of Milan, Milan, Italy. · Int J Neuropsychopharmacol. · Pubmed #15469668 No free full text.

Abstract: The aim of this study was to evaluate the effects of comorbid subthreshold anxiety on the course and the treatment of Depressive Disorders. The sample studied comprised four groups defined by the DSM-IV Axis I diagnosis: (1) Patients with a Major Depressive Disorder (MDD) and an Anxiety Disorder (DA); (2) patients with MDD and a subthreshold Anxiety Disorder (Da); (3) patients with subthreshold depression and an Anxiety Disorder (dA); (4) patients with subthreshold depression and subthreshold anxiety (da). HAMD, HAMA and CGI rating scales were administered monthly for 12 months while patients were treated with different antidepressants. Significant differences were found among the four groups with respect to the baseline depressive symptoms: Da presented more frequently suicidal ideation (chi2=9.568, d.f.=3, p=0.023), psychomotor retardation (chi2=12.568, d.f.=3, p=0.006), sexual dysfunctions (chi2=7.761, d.f.=3, p=0.05), hypochondriacal ideation (chi2=13.633, d.f.=3, p=0.003), weight loss (chi2=9.520, d.f.=3, p=0.023), and diurnal variation of symptoms (chi2=13.258, d.f.=3, p=0.004). With respect to the treatment response Da patients showed an overall worse response to antidepressants, having a longer latency and a lower reduction of symptoms. These results suggest that patients with Major Depression and subthreshold anxiety present with a more severe baseline clinical picture and seem to have a less efficient response to antidepressants.

Altamura AC, Pioli R, Vitto M, Mannu P. · Department of Psychiatry, University of Milan, Istituto Scienze Biomediche, Italy. · Int Clin Psychopharmacol. · Pubmed #10468317 No free full text.

Abstract: 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.

Altamura AC, Dell'Osso B, Buoli M, Zanoni S, Mundo E. · Department of Psychiatry, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy. · J Clin Psychopharmacol. · Pubmed #18626267 No free full text.

Abstract: The aim of the present study was to evaluate the efficacy of short-term low-dose intravenous augmentative citalopram (10 mg/d) versus clomipramine (25 mg/d) versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors (SSRIs). Fifty-four patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, MDE and partial or no response to SSRIs per os (21-item Hamilton Depression Rating Scale [HAM-D21] score reduction, <50% or < or =25%, respectively, compared with pretreatment scores) were selected and randomized to citalopram (n = 18), clomipramine (n = 18), or placebo (n = 18) intravenous augmentation. The augmentation regimen lasted 5 days during which patients were maintained on their previous treatment with oral SSRIs. Analyses of variance with repeated measures on HAM-D(21), collected daily in blind-raters design, were performed to detect any change of depressive symptoms between the 3 groups. In addition, the number of responders and remitters was computed in the 3 groups of treatment. At end point, a significant treatment effect (F= 4.57; P = 0.015) and time-by-treatment effect (F = 11.22; P < 0.0001) were found on HAM-D21 total scores in favor of citalopram and clomipramine versus placebo, with a superiority of citalopram over clomipramine on overall symptoms (P = 0.05) as well as on anxiety-somatization symptoms (P = 0.027). The number of responders was significantly superior in the active treatment groups versus the placebo group ([chi](2)(2) = 16.36; P < 0.0001). The same result was found, considering the number of remitters ([chi](2)(2) = 13.50; P < 0.0001). Present findings suggest that both clomipramine and citalopram intravenous augmentation at low doses and for a short period are well tolerated and superior to placebo in major depressives with partial or no response to oral SSRIs with a possible superiority of citalopram over clomipramine with regard to anxiety-somatization symptoms. The lack of double-blind conditions and the limited sample size may limit the confidence in the reported results, and larger randomized controlled trials are warranted to confirm the present findings.

Altamura AC, Dell'osso B, D'Urso N, Russo M, Fumagalli S, Mundo E. · Department of Psychiatry, University of Milan, Milan, Italy. · CNS Spectr. · Pubmed #18496479 links to  free full text

Abstract: 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.

Pugliatti M, Sobocki P, Beghi E, Pini S, Cassano GB, Altamura AC, Pozzoli S, Rosati G, Anonymous00004. · Dipartimento di Neuroscienze e Scienze Materno-Infantili, Università di Sassari, Viale San Pietro 10, 07100, Sassari, Italy · Neurol Sci. · Pubmed #18483707 No free full text.

Abstract: The aim of this study was to estimate the cost of "brain" disorders in Italy. Country-specific prevalence and health-economic data on addiction, affective, anxiety and psychotic disorders, tumours, dementia, epilepsy, migraine/other headaches, multiple sclerosis, Parkinson's disease, stroke and head trauma were reviewed. Direct medical/non-medical and indirect costs were computed. Population-based samples and national or regional registries were used. The Italian population expected with a brain disorder was 12.4 million in 2004. The highest cost per case was for tumours and multiple sclerosis; the lowest was for anxiety disorders and migraine. Dementia (8.6 billion euros), psychotic and affective disorders (18.7 billion euros), migraine (3.5 billion euros) and stroke (3.4 billion euros) represented the highest total costs. Direct medical costs were predominant for psychiatric and neurosurgical disorders, direct non-medical costs for dementia, and indirect costs for neurological disorders. The total cost of brain disorders in Italy was 40.8 billion euros, 3% of the gross national product, and 706 euros per Italian citizen/year. This figure is however likely to be underestimated as it is based on retrospective methodology and samples of brain disorders, and does not include intangible costs.

Dell'osso B, Mundo E, Marazziti D, Altamura AC. · Department of Psychiatry, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Milan, Italy. · J Psychopharmacol. · Pubmed #18208931 No free full text.

Abstract: Obsessive compulsive disorder (OCD) is a chronic disorder, currently recognized as one of the most common psychiatric disorder as well as one of the most disabling of all medical disorders. OCD is characterized by high rates of partial and/or absent response to standard, recommended treatments (serotonin reuptake inhibitors and psychotherapy). Recent investigation showed that Venlafaxine, a dual serotonin and norepinephrine reuptake inhibitor (SNRI), may be a valid alternative for some treatment-refractory patients. We present the cases of four OCD patients with comorbid mood or anxiety disorders, who were treated with serotonin reuptake inhibitors (SRIs) at adequate doses for at least 12 weeks, showing partial/no response. Patients were then switched to Duloxetine up to 120 mg/day and followed up for 12 weeks. Three out of four patients showed a Yale-Brown Obsessive Compulsive Scale(Y-BOCS) score reduction >or=35%. Duloxetine may be helpful in patients with treatment-resistant OCD, although larger and controlled studies are warranted to confirm this preliminary observation.

Dell'Osso B, Mundo E, Altamura AC. · Department of Psychiatry and Clinical Sciences "Luigi Sacco", University of Milan, Milano, Italy. bernardo.dell' · CNS Spectr. · Pubmed #17075559 links to  free full text

Abstract: Obsessive-compulsive disorder (OCD) is a relatively common, often chronic and disabling disorder with high rates of partial and/or absent response to standard, recommended treatments, such as selective serotonin reuptake inhibitors (SSRIs) and psychotherapy. This article presents the cases of four patients suffering from OCD and comorbid mood or anxiety disorders, who were treated with SSRIs at adequate doses for at least 12 weeks, showing a partial response. Quetiapine treatment was added to SSRIs at a dose of 25 mg/day and titrated up to 200 mg/day. Patients were followed up for 6 months. After 12 weeks, all the patients were classified as "much improved" on the Clinical Global Impression-Improvement scale and showed a Yale-Brown Obsessive-Compulsive Scale score reduction > or =35%. After 6 months of follow-up, all the patients maintained the same level of improvement. Although quetiapine augmentation to SSRIs has shown mixed results in published controlled trials in the acute treatment (12 weeks) of patients with treatment-resistant OCD, this case series indicates that patients who benefit from this pharmacologic regimen in the acute phase tend to maintain such an improvement. Larger follow-up studies are warranted to confirm our findings.

Altamura AC, Bassetti R, Santini A, Frisoni GB, Mundo E. · Department of Psychiatry and Clinical Sciences Luigi Sacco, University of Milan, Via G.B. Grassi 74, Milan 20157, Italy. · Prog Neuropsychopharmacol Biol Psychiatry. · Pubmed #14751432 No free full text.

Abstract: In this study, the authors investigated if CNS degenerative abnormalities could correlate with depressive symptoms in elderly patients, if the presence of mild/moderate cognitive impairment could be related to the response to treatment and the role of peculiar clinical features in influencing the response to treatment. Fifty-three patients (60-75 years) diagnosed as affected by late onset (after 60 years) Major Depressive Episodes according to DSM-IV criteria were studied. Brain vascular and degenerative markers were assessed by computed tomography (CT) through measurements of a lateralized version of the bifrontal index and a rating scale addressing subcortical disease. The presence of mild/moderate cognitive impairment [(24-28 total score at the Mini-Mental State Examination (MMSE)], and of specific symptoms were assessed at baseline and evaluated with respect to the antidepressant response. Patients with CT abnormalities showed higher baseline scores on Hamilton Rating Scale for Depression (HAM-D) items "late insomnia" (t=-2.674, P=.002), "somatic symptoms" (t=-3.355 P=.002), and Brief Psychiatric Rating Scale (BPRS) item "emotional withdrawal" (t=-3.355, P=.002). No significant correlation was found between the vascular index and baseline clinical symptoms, while the HAM-D "depressed mood" item was negatively correlated to the right frontal index (R=-0.692, P=.006). Patients with CT abnormalities showed a lower reduction of HAM-D total scores than patients with normal CT (time effect: F=29.277, P<.0001; group effect: F=5.154, P<.03), while a significant reduction of symptoms in time (time effect: F=33.33, P<.0001) but no differences between groups were found on Hamilton Rating Scale for Anxiety (HAM-A). Both patients with and without mild cognitive impairment improved on the HAM-D (time effect: F=19.668, P<.0001), BPRS (time effect: F=18.345, P<.0001), and HAM-A (time effect: F=17.959, P<.0001) total scores. Patients with emotional withdrawal showed lower improvement on BPRS total scores (time effect: F=26.946, P<.0001; group effect: F=5.121, P<.03). The results from this study showed that patients with baseline emotional withdrawal and CT abnormalities have poorer outcome. Further investigations on larger samples are needed to confirm these findings.

Carpiniello B, Baita A, Carta MG, Sitzia R, Macciardi AM, Murgia S, Altamura AC. · Department of Public Health-Section of Psychiatry, University of Cagliari, Via Liguria, 13-09127, Cagliari, Italy. · Eur Psychiatry. · Pubmed #12547305 No free full text.

Abstract: 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 Sheehan's Disability Scale, DISS, Baker and Intagliata's 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.