Lifetime presence of psychotic symptoms in bipolar disorder is associated with less favorable socio-demographic and certain clinical features.

BACKGROUND: The presence of psychotic symptoms in bipolar disorder (BD) is considered a feature of higher severity of illness and, in particular, of manic episodes in bipolar I disorder (BD I). However, the possibility to apply the "with psychotic features" specifier to major depressive episodes in either bipolar II disorder (BD II) or BD I highlights the need for additional research in this area. METHODS: The present study assessed the lifetime presence of psychotic symptoms and related socio-demographic and clinical features in a large sample of BD patients (N=360), with (BDPs, N=207) and without a lifetime history of psychosis (BDNPs, N=153). RESULTS: An overall less favorable socio-demographic profile was observed in BDPs vs BDNPs. In terms of clinical variables, BDPs vs BDNPs had: earlier age at onset (27.7±10.5 vs 30.1±12.3years; p=0.02), higher rates of BD I diagnosis (95.7% vs 45.8%; p<0.001), more elevated (manic/hypomanic/mixed) polarity of first (55.2% vs 24.4%; p<0.001) and most recent episode (69.8% vs 35.6%; p<0.001), more comorbid alcohol/substance use disorder (38.1% vs 21.9%; p=0.002), more lifetime hospitalizations (3.8±6.1 vs 2±3; p=0.002) and involuntary commitments (1±1.9 vs 0.1±0.4; p<0.001), more history of psychosocial rehabilitation (17.9% vs 5.7%; p=0.001), more current antipsychotic use (90.1% vs 70.9%; p<0.001), and lower GAF (62.3±14.2 vs 69.3±12.5; p<0.001), but shorter duration of most recent episode (34.1±45.4 vs 50.3±65.7days; p=0.04), lower rates of comorbid anxiety disorders (23.9% vs 38.2%; p=0.005), and antidepressant use (19.4% vs 56.6%; p<0.001). CONCLUSIONS: The present findings indicate an overall worse profile of socio-demographic and certain clinical characteristics associated with the lifetime presence of psychotic symptoms in bipolar patients.

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

BACKGROUND: 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. METHODS: An overall sample of 188 patients with MDD was assessed through a specific questionnaire investigating DUI and other variables related to the psychopathological onset and latency to first antidepressant treatment, after dividing them in two different subgroups on the basis of their epoch of onset. RESULTS: The whole sample showed a mean DUI of approximately 4.5 years, with patients with more recent onset showing a significantly shorter latency to treatment compared with the other group (27.1±42.6 vs 75.8±105.2 months, P<.05). Other significant differences emerged between the two subgroups, in terms of rates of onset-related stressful events and benzodiazepine prescription, respectively, higher and lower in patients with more recent onset. CONCLUSIONS: Our findings indicate a significant DUI reduction in MDD patients whose onset occurred after vs before 2000, along with other relevant differences in terms of onset-related correlates and first pharmacotherapy. Further studies with larger samples are warranted to confirm the present findings in Italy and other countries.

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

BACKGROUND: 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. METHODS: 101 SKZ or SSD patients were assessed with respect to DUI and related variables through clinical interview and questionnaire. RESULTS: Patients with SKZ showed earlier ages of onset, first diagnosis and first antipsychotic treatment compared with patients with other SSDs (F = 11.02, p < 0.001; F = 12.68, p < 0.001; F = 13.74, p < 0.001, respectively) who showed an earlier access to benzodiazepines than SKZ patients (F = 6.547; p < 0.05). Dividing the total sample by the epoch of onset (before 1978; between 1978-2000; after 2000) showed a significantly later age of onset in patients with onset within the two most recent epochs (F = 7.46; p < 0.001) and a reduced DUI across epochs (from 144 to 41 to 20 months, on average; F = 11.78, p < 0.001). CONCLUSION: Schizophrenic patients showed earlier onset and longer DUI compared with patients with other SSDs. Data on the total sample showed a later age of onset and a reduced DUI across epochs.

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

AIMS: 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. METHODS: Two temporal cut-offs were established - the year 1978, when Law 180 (redefining standards for mental care) was introduced in Italy, and the year 2000 - in order to divide patients into three subgroups: onset before 1978, onset 1978-2000 and onset after 2000. RESULTS: A significant difference in terms of age at onset, age at first diagnosis and age at first treatment was observed in patients with onset 1978-2000 and in those with onset after 2000. In addition, a significant reduction of the DUI was found across epochs (onset before 1978: 192.25 ± 184.52 months; onset 1978-2000: 77.00 ± 96.63 months; and onset after 2000: 19.00 ± 31.67 months; P < 0.001). Furthermore, the proportion of patients with onset-related stressful events, use of benzodiazepines and neurological referral was found to be significantly different between the three epochs (χ(2) = 23.4, P < 0.001; χ(2) = 9.92, P = 0.007; χ(2) = 16.50, P = 0.011). CONCLUSIONS: Present data indicate a progressive, statistically significant reduction of latency to treatment and other related changes across subsequent epochs of onset in patients with different psychiatric disorders. Future studies will assess specific changes within homogeneous diagnostic subgroups.

Progranulin gene variability influences the risk for bipolar I disorder, but not bipolar II disorder.

OBJECTIVE: Recent data have shown that genetic variability in the progranulin (GRN) gene may contribute to the susceptibility to developing bipolar disorder (BD). However, in regard to patients with BD, no information is available on the role of genetic variability and plasma progranulin levels in different types of this disorder. METHODS: In this study, we performed an association analysis of GRN in an Italian population consisting of 134 patients with BD and 232 controls to evaluate progranulin plasma levels. RESULTS: The presence of the polymorphic variant of the rs5848 single nucleotide polymorphism is protective for the development of bipolar I disorder (BD-I) (odds ratio = 0.55, 95% confidence interval: 0.33-0.93; p = 0.024) but not bipolar II disorder (BD-II) (p > 0.05). In addition, plasma progranulin levels are significantly decreased in BD [mean ± standard deviation (SD) 112 ± 35 versus 183 ± 93 ng/mL in controls; p < 0.001]. CONCLUSIONS: Regarding the influence of GRN variability on BD susceptibility, the predisposing genetic background differs between BD-I and BD-II, possibly implying that pathogenic mechanisms differ between the two subtypes of BD.

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

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.

Duloxetine in affective disorders: a naturalistic study on psychiatric and medical comorbidity, use in association and tolerability across different age groups.

OBJECTIVE: Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor (SNRI), is currently approved in many countries for the treatment of Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD). The present naturalistic study was aimed to investigate tolerability of Duloxetine in a sample of patients with affective disorders and psychiatric/medical comorbidity, comparing tolerability in monotherapy versus polytherapy and across different age groups. METHODS: The sample included 165 patients, affected by anxiety and/or mood disorders with or without comorbidity, who had been taken Duloxetine for at least 1 month. Sample variables were collected through a retrospective chart review. RESULTS: Most common primary diagnoses were MDD (49.1 %), Bipolar Disorder (BD) (15.7 %) and GAD (5.5%). The 40 % of the sample had psychiatric comorbidity: in particular, anxiety disorders (15.8 %) (GAD 7.9%, Panic Disorder -PD- 7.3%) and personality disorders (9.1%) as the most frequent ones. With respect to medical comorbidities (68% of the sample), hypertension (12.1%) and diabetes (7.3%) were the most common ones. Mean duration of treatment and dosage of Duloxetine were, respectively, 11 months (± 9.1) and 70 mg/day (± 28.6). The 68 % of the sample received Duloxetine in association with other drugs. Minor side-effects, in particular drowsiness and gastrointestinal problems, were reported by 15 % of the sample. No difference in terms of tolerability across distinct groups, divided on the basis of mono- vs polytherapy as well as of different age, was found. CONCLUSION: Duloxetine, mostly administered in patients with affective disorders with psychiatric/ medical comorbidity and in association with other drugs, appeared to be well tolerated, showing limited rates of side effects of mild intensity. Further naturalistic studies are warranted to confirm present results.

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.

[Understanding the role of the duration of untreated illness in psychiatric disorders: a narrative review]. / Una revisione critica sul ruolo della durata di malattia non trattata nei disturbi psichiatrici.

INTRODUCTION: The duration of untreated illness (DUI) is defined as the interval between the onset of a psychiatric disorder and the administration of the first pharmacological treatment. AIM: The aim of the present article is to analyze the relationship between the DUI or the duration of untreated psychosis (DUP) and some clinical parameters in different psychiatric disorders, like major psychoses, mood disorders and anxiety disorders. Another objective is to analyze - according to the available literature - the relationship between a long DUI and neurobiological modifications occurring with the progression of the disorder and related to the clinical outcome. Finally, given that the DUI is a modifiable prognostic factor, different intervention programs aimed to reduce this variable are presented and discussed. MATERIALS AND METHODS: An updated review of the current literature was conducted through PubMed in order to compare different studies focused on DUI in major psychoses, depressive and anxiety disorders. RESULTS: A significant body of evidence shows that a prolonged DUI represents a negative prognostic factor particularly in schizophrenia. Nevertheless, an increasing number of studies points toward a similar conclusion in mood and anxiety disorders as well, even though fewer studies have been published in this field. CONCLUSIONS: Given the relationship between a longer DUI and a worse outcome--not only in major psychoses but also in mood and anxiety disorders--specific intervention programs aimed to reduce the latency to treatment are definitely envisaged.

Regulation of gene transcription in bipolar disorders: Role of DNA methylation in the relationship between prodynorphin and brain derived neurotrophic factor.

Bipolar Disorder (BD) is a prevalent and disabling condition, determined by gene-environment interactions, possibly mediated by epigenetic mechanisms. The present study aimed at investigating the transcriptional regulation of BD selected target genes by DNA methylation in peripheral blood mononuclear cells of patients with a DSM-5 diagnosis of type I (BD-I) and type II (BD-II) Bipolar Disorders (n=99), as well as of healthy controls (CT, n=42). The analysis of gene expression revealed prodynorphin (PDYN) mRNA levels significantly reduced in subjects with BD-II but not in those with BD-I, when compared to CT. Other target genes (i.e. catechol-O-methyltransferase (COMT), glutamate decarboxylase (GAD67), serotonin transporter (SERT) mRNA levels remained unaltered. Consistently, an increase in DNA methylation at PDYN gene promoter was observed in BD-II patients vs CT. After stratifying data on the basis of pharmacotherapy, patients on mood-stabilizers (i.e., lithium and anticonvulsants) were found to have lower DNA methylation at PDYN gene promoter. A significantly positive correlation in promoter DNA methylation was observed in all subjects between PDYN and brain derived neurotrophic factor (BDNF), whose methylation status had been previously found altered in BD. Moreover, among key genes relevant for DNA methylation establishment here analysed, an up-regulation of DNA Methyl Transferases 3b (DNMT3b) and of the methyl binding protein MeCP2 (methyl CpG binding protein 2) mRNA levels was also observed again just in BD-II subjects. A clear selective role of DNA methylation involvement in BD-II is shown here, further supporting a role for BDNF and its possible interaction with PDYN. These data might be relevant in the pathophysiology of BD, both in relation to BDNF and for the improvement of available treatments and development of novel ones that modulate epigenetic signatures.

Continued versus discontinued cannabis use in patients with psychosis: a systematic review and meta-analysis.

BACKGROUND: Although the link between cannabis use and development of psychosis is well established, less is known about the effect of continued versus discontinued cannabis use after the onset of psychosis. We aimed to summarise available evidence focusing on the relationship between continued and discontinued cannabis use after onset of psychosis and its relapse. METHODS: In this systematic review and meta-analysis, we searched MEDLINE for articles published in any language from the database inception date up until April 21, 2015 that included a sample of patients with a pre-existing psychotic disorder with a follow-up duration of at least 6 months. We used a combination of search terms for describing cannabis, the outcome of interest (relapse of psychosis), and the study population. We excluded studies if continued cannabis use or discontinued cannabis use could not be established. We compared relapse outcomes between those who continued (CC) or discontinued (DC) cannabis use or were non-users (NC). We used summary data (individual patient data were not sought out) to estimate Cohen's d, which was entered into random effects models (REM) to compare CC with NC, CC with DC, and DC with NC. Meta-regression and sensitivity analyses were used to address the issue of heterogeneity. FINDINGS: Of 1903 citations identified, 24 studies (16 565 participants) met the inclusion criteria. Independent of the stage of illness, continued cannabis users had a greater increase in relapse of psychosis than did both non-users (dCC-NC=0·36, 95% CI 0·22-0·50, p<0·0001) and discontinued users (dCC-DC=0·28, 0·12-0·44, p=0·0005), as well as longer hospital admissions than non-users (dCC-NC=0·36, 0·13 to 0·58, p=0·02). By contrast, cannabis discontinuation was not associated with relapse (dDC-NC=0·02, -0·12 to 0·15; p=0·82). Meta-regression suggested greater effects of continued cannabis use than discontinued use on relapse (dCC-NC=0·36 vs dDC-NC=0·02, p=0·04), positive symptoms (dCC-NC=0·15 vs dDC-NC=-0·30, p=0·05) and level of functioning (dCC-NC=0·04 vs dDC-NC=-0·49, p=0·008) but not on negative symptoms (dCC-NC=-0·09 vs dDC-NC=-0·31, p=0·41). INTERPRETATION: Continued cannabis use after onset of psychosis predicts adverse outcome, including higher relapse rates, longer hospital admissions, and more severe positive symptoms than for individuals who discontinue cannabis use and those who are non-users. These findings point to reductions in cannabis use as a crucial interventional target to improve outcome in patients with psychosis. FUNDING: UK National Institute of Health Research.

Which factors influence onset and latency to treatment in generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder?

Anxiety disorders are common, comorbid, and disabling conditions, often underdiagnosed and under-treated, typically with an early onset, chronic course, and prolonged duration of untreated illness. The present study aimed to explore the influence of sociodemographic and clinical factors in relation to onset and latency to treatment in patients with generalized anxiety disorder (GAD), panic disorder (PD), and obsessive-compulsive disorder (OCD). A total of 157 patients with a Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Text Revision (DSM-IV-TR) diagnosis of PD (n=49), GAD (n=68), and OCD (n=40) were recruited, and epidemiological and clinical variables were collected through a specific questionnaire. Statistical analyses were carried out to compare variables across diagnostic groups. PD, GAD, and OCD patients showed a duration of untreated illness of 53.9±81.5, 77.47±95.76, and 90.6±112.1 months, respectively. Significant differences between groups were found with respect to age, age of first diagnosis, age of first treatment, family history of psychiatric illness, onset-related stressful events, benzodiazepine prescription as first treatment, antidepressant prescription as first treatment, and help-seeking (self-initiated vs. initiated by others). Patients with GAD, PD, and OCD showed significant differences in factors influencing onset and latency to treatment, which may, in turn, affect condition-related outcome and overall prognosis. Further studies with larger samples are warranted in the field.

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.

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.

Epigenetic modulation of BDNF gene: differences in DNA methylation between unipolar and bipolar patients.

BACKGROUND: The brain derived neurotrophic factor (BDNF) gene and its epigenetic regulation have been repeatedly implicated in the pathophysiology of mood disorders. Following previous investigation in the field, we further investigated differences in BDNF promoter gene methylation in patients with mood disorders, comparing unipolar and bipolar subjects, on the basis of illness phase, gender, age and psychotropic prescription. METHODS: 154 patients (43 MDD; 61 BD I; 50 BD II), on stable pharmacological treatment, and 44 age-matched, healthy controls were recruited. BDNF methylation levels from peripheral blood mononuclear cells (PBMCs) were compared by analysis of variance followed by Bonferroni׳s post-hoc test. RESULTS: Similar, higher levels of BDNF gene promoter methylation were found in BD II and MDD patients, compared to BD I subjects (P<0.01). When stratified on the basis of mood status, methylation levels of depressed patients were significantly higher, compared to the levels of manic/mixed patients (P<0.01). While gender and age did not seem to influence methylation levels of BDNF gene promoter, patients on lithium and valproate showed overall lower levels. LIMITATIONS: Cross-sectional analysis using PBMCs with further investigation with larger samples, including drug-naïve patients, needed to replicate findings in neuronal cells. CONCLUSIONS: Present data confirm our previous results of higher methylation levels in BD II (compared to BD I) and MDD patients (compared to controls). A closer relationship between BD II and MDD, compared to BD I patients as well an association of lower methylation levels with the presence of mania/mixed state, compared to the depressive phase, was observed.

Duration of untreated illness and duration of illness in anxiety disorders: assessment and influence on outcome.

Anxiety disorders are disabling and generally chronic conditions, with a lifetime prevalence of 15-20% in the general population. These disorders are usually associated with early onset and often remain untreated for several years with important consequences on patients' functioning and quality of life. From this perspective, recent literature has considered duration of illness (DI) and duration of untreated illness (DUI), two important variables influencing outcome in many psychiatric conditions including anxiety disorders. The DUI has been defined as the interval between the onset of a specific psychiatric disorder and the subsequent administration of the first adequate pharmacological treatment given at standard dosages and for an adequate period of time in compliant subjects. The DI can be defined as the time elapsing between the onset of a psychiatric disorder and the recovery from the illness. The two variables are likely interrelated, with a longer DUI being a major contributor to a longer DI. A significant body of evidence has shown that prolonged DI and DUI are associated with structural and functional brain abnormalities as well as with poor treatment response, particularly in schizophrenia. More recently, an increasing number of studies have been pointing toward a similar conclusion in affective disorders. As a consequence, the assessment of the latency to treatment (DUI) may represent one of the first steps in order to plan early interventions and reduce the overall DI. The present chapter highlights the role of the DI and latency to treatment in anxiety disorders, focusing on epidemiologic, neuropathological, clinical and prognostic issues.

Differences in latency to first pharmacological treatment (duration of untreated illness) in anxiety disorders: a study on patients with panic disorder, generalized anxiety disorder and obsessive-compulsive disorder.

AIM: The latency to first pharmacological treatment (duration of untreated illness or 'DUI') is supposed to play a major role in terms of outcome in psychotic conditions. Interest in the field of affective disorders and, in particular, of duration of untreated anxiety, has been recently registered as well. However, a preliminary epidemiologic investigation of the phenomenon is necessary. The present study was aimed to investigate and compare age at onset, age at first pharmacological treatment and DUI in a sample of patients affected by different anxiety disorders. DUI was defined as the interval between the onset of the specific anxiety disorder and the administration of the first adequate pharmacological treatment in compliant subjects. METHODS: Study sample included 350 patients, of both sexes, with a DSM-IV-TR diagnosis of panic disorder (n = 138), generalized anxiety disorder (n = 127) and obsessive-compulsive disorder (n = 85). RESULTS: Panic disorder was associated with the shortest DUI (39.5 months), whereas obsessive-compulsive disorder was associated with the longest latency to treatment (94.5 months) (F = 13.333; P < 0.0001). Patients with generalized anxiety disorder showed a mean DUI of 81.6 months. CONCLUSION: Present results indicate that patients with different anxiety disorders may wait for years (from 3 up to 8) before receiving a first adequate pharmacological treatment. Differences in terms of age at onset, age at the first pharmacological treatment and, ultimately, in DUI in specific anxiety disorders may depend on multiple clinical and environmental factors. Latency to non-pharmacological interventions (e.g. psychoeducation and different forms of psychotherapy) needs to be addressed and correlated with DUI in future studies.

Escitalopram tolerability as mono- versus augmentative therapy in patients with affective disorders: a naturalistic study.

BACKGROUND: Escitalopram is a selective serotonin reuptake inhibitor, widely used in the treatment of affective disorders. The purpose of this study was to examine its safety and tolerability, as mono- versus augmentative therapy, in a group of patients with affective disorders. MATERIALS AND METHODS: The sample consisted of 131 patients suffering from different affective disorders, including major depressive disorder, bipolar disorder, and generalized anxiety disorder, who received escitalopram for at least 4 weeks. Data were analyzed on the basis of mono- versus augmentative therapy, as well as age, gender, mean daily dosage, and patterns of combination therapy. RESULTS: Sixty-seven (51.1%) patients were treated with monotherapy (mean dose of 11.76 mg/day) and 64 (48.9%) with augmentative escitalopram (mean dose of 12.81 mg/day). The mean duration of escitalopram treatment was 14 months. The most frequently combined compounds were: other antidepressants (36.5%), mood stabilizers (33.4%), and atypical antipsychotics (30.1%). Side effects were reported in 5.3% of the total sample and the most common were insomnia (2.3%), nausea (2.3%), and dizziness (0.8%). No significant difference, in terms of tolerability, in mono- versus augmentative therapy groups was found. In addition, neither age nor gender was significantly correlated with a greater presence of side effects. Finally, no significant correlation between dosage and side effects was observed. CONCLUSION: Over a 14-month observation period, escitalopram, either as monotherapy or an augmentative treatment, was found to be well tolerated in a large sample of patients with affective disorders, with an overall low rate of side effects.

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 (χ(2) = 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).

Patterns of Axis I comorbidity in relation to age in patients with Bipolar Disorder: a cross-sectional analysis.

BACKGROUND: Several data indicate that the clinical course and treatment response of Bipolar Disorder (BD) is influenced by comorbidity. However, whether differences in comorbidity patterns exist in relation to classes of age remains debated. The present study was aimed to evaluate differences in terms of cross-sectional Axis I comorbidity among young (≤30 years), adult (>30 and ≤45 years) and older adult patients with BD (>45 years). METHODS: Study sample included 508 patients with BD, subdivided into 3 groups of age: ≤30 years (n=52), >30 and ≤45 years (n=186) and >45 years (n=270). Demographic and clinical variables, with specific emphasis on Axis I comorbidity, were compared across the different groups using chi-square tests. Furthermore, a binary logistic regression was performed. RESULTS: Two-hundred eleven patients (41.5%) showed at least another concomitant Axis I disorder. The 3 groups were homogenous in terms of type of diagnosis (type 1 or 2 BD) and gender. However, they were different in terms of cross-sectional Axis I comorbidity (p=0.001) with a higher frequency of substance abuse (p=0.04) and Anorexia (p=0.014) in young patients, and of Obsessive Compulsive Disorder in adult patients (p=0.001). In addition, young patients showed more frequently the presence of a second comorbid Axis I condition compared to the other sub-groups (p=0.05). With regard to the type of abuse, young subjects were more frequently cannabis (p<0.001) and cocaine abusers (p<0.001) compared to the other subgroups. LIMITATIONS: Lifetime Axis I and Axis II and cross-sectional Axis II comorbidity patterns were not analyzed. CONCLUSIONS: Preliminary results from the present exploratory study seem to suggest different profiles of cross-sectional Axis I comorbidity and abuse in bipolar patients in relation to age. This aspect should be taken into account for the choice of pharmacological treatments and global management in clinical practice.