Twelve-month service use, suicidality and mental health problems of European adolescents after a school-based screening for current suicidality.

Suicide is one of the leading causes of death in adolescents and help-seeking behaviour for suicidal behaviour is low. School-based screenings can identify adolescents at risk for suicidal behaviour and might have the potential to facilitate service use and reduce suicidal behaviour. The aim of this study was to assess associations of a two-stage school-based screening with service use and suicidality in adolescents (aged 15 ± 0.9 years) from 11 European countries after one year. Students participating in the 'Saving and Empowering Young Lives in Europe' (SEYLE) study completed a self-report questionnaire including items on suicidal behaviour. Those screening positive for current suicidality (first screening stage) were invited to an interview with a mental health professional (second stage) who referred them for treatment, if necessary. At 12-month follow-up, students completed the same self-report questionnaire including questions on service use within the past year. Of the N = 12,395 SEYLE participants, 516 (4.2%) screened positive for current suicidality and were invited to the interview. Of these, 362 completed the 12-month follow-up with 136 (37.6%) self-selecting to attend the interview (screening completers). The majority of both screening completers (81.9%) and non-completers (91.6%) had not received professional treatment within one year, with completers being slightly more likely to receive it (χ2(1) = 8.948, V = 0.157, p ≤ 0.01). Screening completion was associated with higher service use (OR 2.695, se 1.017, p ≤ 0.01) and lower suicidality at follow-up (OR 0.505, se 0.114, p ≤ 0.01) after controlling for potential confounders. This school-based screening offered limited evidence for the improvement of service use for suicidality. Similar future programmes might improve interview attendance rate and address adolescents' barriers to care.

Lifestyle and biological factors influence the relationship between mental health and low-grade inflammation.

Mental health modulates the risk of common chronic conditions. Although inflammation is thought to partly explain this link, its relation with mental health is still unclear and largely unexplored. We investigated three scales assessing psychological resilience (CD-RISC), depression symptoms (PHQ9-6) and mental wellbeing (SF36-MCS) in an Italian adult population cohort (Nmax = 16,952). This showed a slightly higher frequency of men, more educated and younger participants, compared to samples with incomplete questionnaires. We performed stepwise generalized linear models to test the association between each scale and INFLA-score, a composite blood-based inflammation index. At each step, a class of potential mediators was included in the model, namely health conditions, lifestyle factors, or both (full model). Full model analysis was also conducted on single blood markers involved in the inflammatory process. In the baseline model, we observed significant associations of PHQ9-6 (standardized ß(SE) = 0.024(0.009), p = 8.9 × 10-3) and SF36-MCS (ß(SE) = -0.021(0.008), p = 7 × 10-3) with INFLA-score. These associations survived adjustment for health conditions but not for lifestyle factors, which explained 81% and 17% of the association with PHQ9-6 and SF36-MCS. Significant associations (p < 4.2 × 10-3) after mediator adjustment were observed for single low-grade inflammation markers, including platelet distribution width (with PHQ9-6 and CD-RISC), granulocyte- and neutrophil-to-lymphocyte ratios, monocyte and lymphocyte fractions (with SF36-MCS). After imputation of missing data, we observed substantially consistent associations. These findings suggest that the relationship between mental health and low-grade inflammation is largely influenced by lifestyle. However, the associations with specific biomarkers related to inflammation are partly independent and might be explained by biological factors.

Factors associated with different smoking status in European adolescents: results of the SEYLE study.

Early onset and long-term smoking are associated with physical and psychological health problems. The aim of the presented analysis was to investigate risk and influencing factors for different smoking status in a big sample of European adolescents. In the context of the "saving and empowering young lives in Europe" (SEYLE) study we surveyed 12,328 adolescents at the age of 13-17 from 11 countries. The survey took place in a school-based context using a questionnaire. Overall 58% reported the onset of ever-smoking under the age of 14 and 30.9% smoke on a daily basis. Multinomial logistic regression model showed significant positive associations between adolescent smoking and internalizing problems (suicidal behavior, direct self-injurious behavior, anxiety), externalizing problems (conduct problems, hyperactivity, substance consumption) and family problems (parental substance consumption, broken home). Our data show that smoking among adolescents is still a major public health problem and adolescents who smoke are at higher risk for mental problems. Further, adolescent smoking is associated with broken home families and parental behaviors. Therefore, early preventive measures are necessary not only for adolescents, but also for their parents.

The EPA guidance on suicide treatment and prevention needs to be adjusted to fight the epidemics of suicide at the North Pole area and other autochthonous communities.

More and more, youth suicide in the Inuit community is gaining importance, with a frequency in Greenland rising from 14.4 (1960-64) to 110.4 per 100,000 person-years (2010-11). The huge cultural/educational changes during the last 20 years and the role of globalization, especially of the occidental influence on this community may be at the origin of such an "epidemics" of suicide in this cultural region. Recently, a political organization representing the Inuit community in Canada (ITK for Inuit Tapiriit Kanatami) launched a National Inuit Suicide Prevention Strategy (NISP) based on the specificities of this community in comparison to the occidental civilization. In fact, not only the Canadian Inuit community is concerned by this epidemics of suicide, but also many other autochthonous groups. In this context, the European Psychiatric Association (EPA) guidance on suicide treatment and prevention needs to be adjusted to autochthonous individuals' needs.

Predictors for self-directed aggression in Italian prisoners include externalizing behaviors, childhood trauma and the serotonin transporter gene polymorphism 5-HTTLPR.

Suicidal behavior and self-mutilation can be regarded as the expression of self-directed aggression and both are common in prison populations. We investigated the influence of externalizing behaviors, depressive symptoms, childhood trauma, 5-HTTLPR variants on self-directed aggression (N = 145) in a group of 702 male Italian prisoners. Participants were comprehensively evaluated, including for psychiatric disorders, impulsive traits, lifetime aggressive behavior [Brown-Goodwin Lifetime History of Aggression (BGHA)], hostility, violent behavior during incarceration, depressive symptomatology [Hamilton Depression Rating Scale (HDRS)], childhood trauma [Childhood Trauma Questionnaire (CTQ)]. Logistic regression analysis showed false discovery rate corrected independent main effects of externalizing behaviors: BGHA (P = 0.001), violent behavior in jail (P = 0.007), extraversion (P = 0.015); HDRS (P = 0.0004), Axis I disorders (P = 0.015), CTQ (P = 0.004) and 5-HTTLPR genotype (P = 0.02). Carriers of 5-HTTLPR high (LA LA ), intermediate (LA LG , SLA ) activity variants were more likely to have exhibited self-directed aggression relative to the low activity (LG LG , SLG , SS) variant: high/low: odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.27-4.68, P = 0.007; intermediate/low: OR = 1.96, 95% CI 1.09-3.68, P = 0.025. The CTQ main effect was driven by physical abuse. There was no interactive effect of 5-HTTLPR and CTQ. Secondary logistic regression analyses in (1) all suicide attempters (N = 88) and (2) all self-mutilators (N = 104), compared with controls showed that in both groups, childhood trauma (P = 0.008-0.01), depression (P = 0.0004-0.001) were strong predictors. BGHA, violent behavior in jail predicted self-mutilation (P = 0.002) but not suicide attempts (P = 0.1). This study was able to distinguish differing influences on self-directed aggression between groups of closely related predictor variables within the externalizing behavioral domain. 5-HTTLPR had an independent, variant dosage effect.

Reasons for Attempted Suicide in Europe: Prevalence, Associated Factors, and Risk of Repetition.

To examine the prevalence of specific reasons for attempted suicide, factors associated with them, and whether reasons for attempted suicide influence risk of repetition. As part of the Monitoring Suicide in Europe (MONSUE) project, data on 4,683 suicide attempters from nine European countries were collected. Independence tests were used to study the influence of age, gender, and other factors on reported reasons. We examined risk of repetition using logistic regression analysis. Interpersonal conflict was common for all patients except those widowed, living alone, or retired. Mental health problems were prevalent among over 45 year-olds, patients unable to work, and patients with a history of at least three suicide attempts. Financial difficulties were cited more often by patients who were 45-64 years old, divorced or separated, living with children only, and unemployed. Close bereavement/serious illness and own physical illness were associated with those over 65 years of age. Two reasons for suicide attempt, interpersonal conflict and mental health problems, were associated with increased risk of repetition independent of other factors. Suicide attempters have a multitude of problems of varying prevalence depending on age, gender, and other factors. They present a range of clinical profiles that require a multidisciplinary response.

The interpersonal theory of suicide and adolescent suicidal behavior.

BACKGROUND: Joiner's interpersonal theory of suicide (IPTS) proposes that suicide results from the combination of a perception of burdening others, social alienation, and the capability for self-harm. The theory gained some empirical support, however the overall model has yet to be tested. This study aimed to test the main predictions of IPTS in a large community sample of Israeli adolescents. METHOD: 1196 Israeli Jewish and Arab high-school pupils participating in the SEYLE project completed a self-report questionnaire measuring perceived burdensomeness, thwarted belongingness, health risk behaviors, and non-suicidal self-injury (risk variables), and suicidal ideation and suicide attempts (outcome measures). The data were tested in cross-sectional regression models. RESULTS: Consistent with IPTS, perceived burdensomeness was found to interact with thwarted belongingness, predicting suicidal ideation. Depression mediated most of the effect of thwarted belongingness and perceived burdensomeness on suicidal ideation. Acquired capability for self-harm, as measured by health risk behaviors and direct non-suicidal self-injurious behaviors, predicted suicide attempt. However, this mechanism operated independently from ideation rather than in interaction with it, at variance with IPTS-based predictions. LIMITATIONS: The cross-sectional design precludes conclusions about causality and directionality. Proxy measures were used to test the interpersonal theory constructs. CONCLUSION: The findings support some of the IPTS predictions but not all, and imply two separate pathways for suicidal behavior in adolescents: one related to internalizing psychopathology and the other to self-harm behaviors. This conceptualization has clinical implications for the differential identification of adolescents at risk for suicidal behavior and for the development of prevention strategies.

The interactive effect of MAOA-LPR genotype and childhood physical neglect on aggressive behaviors in Italian male prisoners.

Aggressive disorders are moderately heritable; therefore, identification of genetic influences is important. The X-linked MAOA gene, encoding the MAOA enzyme, has a functional 30 bp repeat polymorphism in the promoter region (MAOA-LPR) that has been shown to influence aggression. Childhood trauma is a known risk factor for numerous psychopathologies in adulthood including aggressive behaviors. We investigated the interactive effect of MAOA-LPR genotype and a history of childhood trauma in predicting aggressive behaviors in a prisoner population. A total of 692 male prisoners were genotyped for MAOA-LPR with genotypes grouped into high and low transcriptional activity. Participant evaluations included measures of aggression (Brown-Goodwin Lifetime History of Aggression, BGHA), hostility (Buss-Durkee Hostility Inventory), impulsivity (Barratt Impulsiveness Scale), violence directed toward self and others, and childhood trauma [Childhood Trauma Questionnaire (CTQ)]. MAOA-LPR interacted with CTQ physical neglect (PN), the most common (47%) form of childhood trauma in this sample, to predict BGHA aggression (P = 0.002). Within the group not exposed to PN, carriers of the MAOA-LPR high-activity variant were more aggressive: (tR = 2.47, P < 0.014). We observed a crossover effect in that the increase in aggression scores with PN was greater in low-activity individuals (tR = 5.55, P < 0.0001) than in high-activity individuals (tR = 4.18, P < 0.0001). These findings suggest that childhood trauma and the functional MAOA-LPR polymorphism may interact to specifically increase risk for over aggressive behavior but not impulsivity or hostility. The MAOA-LPR low-activity variant may be protective against the development of aggressive behavior under low stress conditions, at least in this prisoner population.

Victimisation and psychosocial difficulties associated with sexual orientation concerns: a school-based study of adolescents.

This study examined victimisation, substance misuse, relationships, sexual activity, mental health difficulties and suicidal behaviour among adolescents with sexual orientation concerns in comparison to those without such concerns. 1112 Irish students (mean age 14 yrs) in 17 mixed-gender secondary schools completed a self-report questionnaire with standardised scales and measures of psychosocial difficulties. 58 students (5%) reported having concerns regarding their sexual orientation. Compared with their peers, they had higher levels of mental health difficulties and a markedly-increased prevalence of attempted suicide (29% vs. 2%), physical assault (40% vs. 8%), sexual assault (16%vs. 1%) and substance misuse. Almost all those (90%) with sexual orientation concerns reported having had sex compared to just 4% of their peers. These results highlight the significant difficulties associated with sexual orientation concerns in adolescents in Ireland. Early and targeted interventions are essential to address their needs.

The association between pathological internet use and comorbid psychopathology: a systematic review.

BACKGROUND: Pathological Internet use (PIU) has been conceptualized as an impulse-control disorder that shares characteristics with behavioral addiction. Research has indicated a potential link between PIU and psychopathology; however, the significance of the correlation remains ambiguous. The primary objective of this systematic review was to identify and evaluate studies performed on the correlation between PIU and comorbid psychopathology; the secondary aims were to map the geographical distribution of studies, present a current synthesis of the evidence, and assess the quality of available research. SAMPLING AND METHODS: An electronic literature search was conducted using the following databases: MEDLINE, PsycARTICLES, PsychINFO, Global Health, and Web of Science. PIU and known synonyms were included in the search. Data were extracted based on PIU and psychopathology, including depression, anxiety, symptoms of attention deficit and hyperactivity disorder (ADHD), obsessive-compulsive symptoms, social phobia and hostility/aggression. Effect sizes for the correlations observed were identified from either the respective publication or calculated using Cohen's d or R(2). The potential effect of publication bias was assessed using a funnel plot model and evaluated by Egger's test based on a linear regression. RESULTS: The majority of research was conducted in Asia and comprised cross-sectional designs. Only one prospective study was identified. Twenty articles met the preset inclusion and exclusion criteria; 75% reported significant correlations of PIU with depression, 57% with anxiety, 100% with symptoms of ADHD, 60% with obsessive-compulsive symptoms, and 66% with hostility/aggression. No study reported associations between PIU and social phobia. The majority of studies reported a higher rate of PIU among males than females. The relative risks ranged from an OR of 1.02 to an OR of 11.66. The strongest correlations were observed between PIU and depression; the weakest was hostility/aggression. CONCLUSIONS: Depression and symptoms of ADHD appeared to have the most significant and consistent correlation with PIU. Associations were reported to be higher among males in all age groups. Limitations included heterogeneity in the definition and diagnosis of PIU. More studies with prospective designs in Western countries are critically needed.

The European Psychiatric Association (EPA) guidance on suicide treatment and prevention.

UNLABELLED: Suicide is a major public health problem in the WHO European Region accounting for over 150,000 deaths per year. SUICIDAL CRISIS: Acute intervention should start immediately in order to keep the patient alive. DIAGNOSIS: An underlying psychiatric disorder is present in up to 90% of people who completed suicide. Comorbidity with depression, anxiety, substance abuse and personality disorders is high. In order to achieve successful prevention of suicidality, adequate diagnostic procedures and appropriate treatment for the underlying disorder are essential. TREATMENT: Existing evidence supports the efficacy of pharmacological treatment and cognitive behavioural therapy (CBT) in preventing suicidal behaviour. Some other psychological treatments are promising, but the supporting evidence is currently insufficient. Studies show that antidepressant treatment decreases the risk for suicidality among depressed patients. However, the risk of suicidal behaviour in depressed patients treated with antidepressants exists during the first 10-14 days of treatment, which requires careful monitoring. Short-term supplementary medication with anxiolytics and hypnotics in the case of anxiety and insomnia is recommended. Treatment with antidepressants of children and adolescents should only be given under supervision of a specialist. Long-term treatment with lithium has been shown to be effective in preventing both suicide and attempted suicide in patients with unipolar and bipolar depression. Treatment with clozapine is effective in reducing suicidal behaviour in patients with schizophrenia. Other atypical antipsychotics are promising but more evidence is required. TREATMENT TEAM: Multidisciplinary treatment teams including psychiatrist and other professionals such as psychologist, social worker, and occupational therapist are always preferable, as integration of pharmacological, psychological and social rehabilitation is recommended especially for patients with chronic suicidality. FAMILY: The suicidal person independently of age should always be motivated to involve family in the treatment. SOCIAL SUPPORT: Psychosocial treatment and support is recommended, as the majority of suicidal patients have problems with relationships, work, school and lack functioning social networks. SAFETY: A secure home, public and hospital environment, without access to suicidal means is a necessary strategy in suicide prevention. Each treatment option, prescription of medication and discharge of the patient from hospital should be carefully evaluated against the involved risks. TRAINING OF PERSONNEL: Training of general practitioners (GPs) is effective in the prevention of suicide. It improves treatment of depression and anxiety, quality of the provided care and attitudes towards suicide. Continuous training including discussions about ethical and legal issues is necessary for psychiatrists and other mental health professionals.

A protective genetic variant for adverse environments? The role of childhood traumas and serotonin transporter gene on resilience and depressive severity in a high-risk population.

Genetic aspects may influence the effect of early adverse events on psychological well being in adulthood. In particular, a common polymorphism within the serotonin transporter gene (5-HTTLPR short/long) has been associated to the risk for stress-induced psychopathology. In the present study we investigated the role of childhood traumas and 5-HTTLPR on measures of psychological resilience and depression in a sample of individuals at a high risk for psychological distress (763 male prisoners). The 5-HTTLPR genotype did not influence resilience and depressive severity. However, a significant interaction was observed between 5-HTTLPR and childhood traumas on both resilience and depressive severity. In particular, among subjects exposed to severe childhood trauma only, the long-allele was associated to lower resilience scores and increased current depressive severity as compared to short/short homozygous. Sex specific effects, difference in type and duration of stressors and the specific composition of the sample may explain discrepancy with many studies reporting the short-allele as a vulnerability factor for reactivity to stress. We here speculated that in males the long-allele may confer lower resilience and therefore higher vulnerability for depressive symptoms in subjects exposed to early stress and currently living in stressful environments.

Pregabalin in outpatient detoxification of subjects with mild-to-moderate alcohol withdrawal syndrome.

OBJECTIVE: In this open, prospective study we aimed to investigate the efficacy, medical safety and practicability of pregabalin in outpatient detoxification of alcohol-dependent patients with mild-to-moderate alcohol withdrawal syndrome (AWS). Craving reduction, improvement of psychiatric symptoms and quality of life were the secondary endpoints. METHODS: Forty alcohol dependent patients (DSM-IV) were detoxified receiving 200-450 mg of pregabalin. Withdrawal (Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar)) and craving (Visual Analogue Scale (VAS); Obsessive and Compulsive Drinking Scale (OCDS)) rating scales were applied; psychiatric symptoms and quality of life were evaluated using the Symptom Check List-90 Revised (SCL-90-R) and the QL-Index, respectively. Relapsed and abstinent patients in the post-detoxification evaluation have been compared. RESULTS: Alcohol withdrawal symptoms and craving for alcohol resulted significantly reduced (p < 0.001) over time after pregabalin treatment. Pregabalin also resulted in a favourable improvement in psychiatric symptoms and quality of life (p < 0.001). CONCLUSIONS: To our knowledge, this is the first open, prospective study, about the possible use of pregabalin as an outpatient detoxification agent. These preliminary data show its efficacy and safety in the management of patients with mild-to-moderate AWS.

Mono- and polysubstance dependent subjects differ on social factors, childhood trauma, personality, suicidal behaviour, and comorbid Axis I diagnoses.

BACKGROUND: The study aimed to examine the clinical correlates of polysubstance dependence. SUBJECTS AND METHODS: Seven hundred and fifty two substance-dependent subjects were interviewed with the Mini-International Neuropsychiatric Interview, the Brown-Goodwin Assessment for Lifetime History of Aggression (BGLHA), and the Hamilton Depression Rating Scale (HDRS). Subjects completed the Childhood Trauma Questionnaire (CTQ), Eysenck Personality Questionnaire (EPQ), and Barratt Impulsivity Scale (BIS). Subjects found to have polysubstance dependence were compared with subjects with monosubstance dependence. RESULTS: Polysubstance dependence was found in 48.3% of the subjects. Subjects with polysubstance dependence were significantly younger, more were separated/divorced and unemployed, and they had significantly higher CTQ scores for childhood emotional and physical neglect, higher EPQ psychoticism scores, higher BGLHA aggression scores, and higher BIS impulsivity scores. Significantly more of the polysubstance dependent subjects had attempted suicide, self-mutilated, and exhibited aggressive behavior. Significantly more monosubstance dependent subjects had an Axis I psychiatric disorder and they had higher HDRS depression scores. CONCLUSIONS: Polysubstance dependence is common among the groups studied and may be associated with certain socio-demographic, developmental, and personality factors.

Childhood trauma as a correlative factor of suicidal behavior - via aggression traits. Similar results in an Italian and in a French sample.

BACKGROUND AND OBJECTIVE: Childhood trauma and aggressive traits are considered risk factors for suicidal behavior. The hypothesis we aimed to test in this study was the existence of an association between childhood trauma and aggression in two distinct samples of Italian and French suicide attempters. METHOD: Study participants comprise 587 subjects with different psychiatric diagnoses according to DSM-IV-TR criteria. Three different samples were analyzed and compared: a group of French suicide attempters (N=396; mean age 40.47 SD=13.52; M/F: 110/286); a group of Italian suicide attempters (N=103; mean age 38.60 SD=12.04; M/F 27/76) and an Italian psychiatric comparison group (N=88; mean age: 41.49 SD=12.05; M/F; 37/51). Patients were interviewed with the Brown-Goodwin Assessment for Lifetime History of Aggression (BGLHA) and the Childhood Trauma Questionnaire (CTQ) 34-items for Italian data and 28-items for French data. RESULTS: When compared with the comparison group, Italian suicide attempters had significantly higher scores on the BGLHA scale and reported higher scores on the CTQ scores for physical abuse, sexual abuse and emotional abuse. Significant correlations between childhood trauma and aggression were found in both groups, Italian and French, of suicide attempters. CONCLUSION: The hypothesis tested was supported as psychiatric patients who had attempted suicide reported significantly more childhood trauma and aggression. Significant correlations were found between aggressive behavior, and childhood trauma in suicidal patients. This finding was replicated in two independently recruited samples in two countries with different prevalence of suicidal behavior.

Quetiapine decreases alcohol consumption, craving, and psychiatric symptoms in dually diagnosed alcoholics.

AIMS: Patients with dual diagnosis are often excluded from clinical trials although more than half of all individuals with Bipolar Disorder have a substance abuse problem at some point in their lifetime, representing a high-risk clinical population. The purpose of this study was to investigate the safety and efficacy of quetiapine in the treatment of alcohol dependence comorbid with disorders characterized by high levels of mood and behavioral instability. METHODS: Twenty-eight subjects, after a detoxification period, were orally treated with flexible doses of quetiapine for 16 weeks. At each assessment patients were evaluated through the Obsessive Compulsive Drinking Scale (OCDS), the Visual Analogue Scale (VAS) for craving, the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), the Brief Psychiatric Rating Scale (BPRS), the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression (CGI) scale. RESULTS: Forty-three percent of patients remained totally alcohol free, 32% patients relapsed, with an average of 15.4 drinking days in the period of the study (112 days) and 25% dropped-out. Significant reductions from baseline to exit were observed in the OCDS, VAS, BPRS, HDRS, and number of drinking days per week. Changes in alcohol craving correlated with psychiatric symptoms as to BPRS and HDRS, with the highest level of correlation evidenced for the HDRS items of insomnia. DISCUSSION: In this open-label study, quetiapine decreased alcohol consumption, craving for alcohol, and psychiatric symptoms intensity, maintaining a good level of tolerance. A strength of this study is that the use of quetiapine was not adjunctive with other pharmacological and non-pharmacological treatment. Double-blind placebo-controlled studies are required with a larger study population to confirm these data. In the meantime, for a select group of psychiatric patients, quetiapine may offer some advantages in preventing relapse.

A comparative study of the efficacy of long-term treatment with escitalopram and paroxetine in severely depressed patients.

OBJECTIVE: This randomised, double-blind, fixed-dose study evaluated the efficacy of escitalopram and paroxetine in the long-term treatment of severely depressed patients with major depressive disorder (MDD). RESEARCH DESIGN AND METHODS: Patients with a primary diagnosis of MDD and baseline Montgomery-Asberg Depression Rating Scale (MADRS) >or= 30 were randomised to 24 weeks of double-blind treatment with fixed doses of either escitalopram (20 mg) (n = 232) or paroxetine (40 mg) (n = 227). The primary analysis of efficacy was an analysis of covariance (ANCOVA) of change from baseline to endpoint (Week 24) in MADRS total score (last observation carried forward, LOCF). MAIN OUTCOME MEASURES; RESULTS: At endpoint (24 weeks), the mean change from baseline in MADRS total score was -25.2 for patients treated with escitalopram (n = 228) and -23.1 for patients with paroxetine (n = 223), resulting in a difference of 2.1 points (p < 0.05). The difference in the change in the MADRS total score (LOCF) was significantly in favour of escitalopram from Week 8 onwards. The proportion of remitters (MADRS or= 35), there was a difference of 3.4 points at endpoint in the MADRS total score in favour of escitalopram (p < 0.05). The overall withdrawal rate for patients treated with escitalopram (19%) was significantly lower than with paroxetine (32%) (p < 0.01). The withdrawal rate due to adverse events was significantly lower for escitalopram (8%) compared to paroxetine (16%) (p < 0.05). There were no significant differences in the incidence of individual adverse events during treatment. CONCLUSION: Escitalopram is significantly more effective than paroxetine in the long-term treatment of severely depressed patients.

Mirtazapine in the treatment of panic disorder: an open-label trial.

The aim of this open label trial was to evaluate mirtazapine tolerability and effectiveness in controlling symptomatology of patients with panic disorder. Forty-five patients with panic disorder, with or without agoraphobia, 11 of them with a comorbid diagnosis of major depression, were included. Patients were assessed with a structured psychiatric interview and their symptomatology evaluated with specific psychometric scales. Three study participants dropped out due to adverse events. Mirtazapine was administered at an established dose of 30 mg daily for 3 months. Patients were assessed at weeks 2 and 4, and then at monthly intervals. All psychometric measures showed statistically significant reductions in total scores at the rated time points, with a pronounced decline in number and intensity of panic attacks and anticipatory anxiety throughout the study. Mirtazapine was well tolerated as signified by the low discontinuation rate (6.3%), and all patients showed a significant symptomatic improvement. The improvement did not appear to be linked to the concurrent presence of a depressive illness.

Cholesterol and serotonin indices in depressed and suicidal patients.

BACKGROUND: Prolactin and cortisol responses to d-fenfluramine challenge of central serotonin are reduced in depressed and suicidal patients. Low serum cholesterol levels are also reported in suicidal behavior. Thus, we examined for a relationship between serum cholesterol and fenfluramine challenge responses in patients with depression and/or attempted suicide. METHODS: We studied 12 patients and six controls. Blood was drawn for baseline serum cholesterol and the d-fenfluramine challenge test performed. RESULTS: Serum cholesterol levels were significantly lower in suicidal patients than in either non-suicidal patients or controls. However, neither the prolactin nor cortisol responses to d-fenfluramine correlated significantly with serum cholesterol levels. CONCLUSION: No relationship was found between serum cholesterol and these peripheral indices of serotonergic function.