Treatment patterns and costs in patients with generalised anxiety disorder: one-year retrospective analysis of data from national registers in Sweden.

PURPOSE: To investigate medication use, direct healthcare costs and comorbidities in patients with generalised anxiety disorder (GAD) within specialised care in Sweden 2006-2007. METHODS: A retrospective study was conducted using data from the National Patient Register and the Swedish Prescribed Drug Register. All patients with a primary GAD (ICD-10) diagnosis in 2006 were followed for 12 months to study medication use and health care consumption. Resource use was evaluated from the number of hospitalisation episodes, number of visits to outpatient care and medication dispensed. Costs were calculated by multiplying the number of visits and hospitalisation episodes with the corresponding unit costs. Descriptive statistics were used for all analyses. RESULTS: Three thousand seven hundred and one patients with a primary GAD diagnosis were included in the study. Thirty-four percent of the patients (n=1246) had at least one secondary comorbid diagnosis. SSRIs/SNRIs were the most commonly dispensed medications, followed by benzodiazepine-anxiolytics, hypnotics and antihistamines. The mean number of treatment days for all medications prescribed and dispensed was highest (1144 days) for elderly women aged 65 years or more (treatment days per patient could exceed 365 days due to multiple concomitant medication use). Elderly patients were frequently prescribed benzodiazepine-anxiolytics (n=92/117 men [79%]; n=238/284 women [84%]) and hypnotics (n=70 men [60%]; n=178 women [63%]) compared to the overall study population (n=612/1303 men [47%] and n=935/2398 women [39%], respectively). GAD-related direct costs accounted for 96% of all direct costs. Mean number of hospitalisation days and corresponding costs were high (19 days; SEK 92,156; n=358 [9.7%]) in relation to medication (SEK 5520; n=3352 [91%]) and outpatient costs (SEK 7698; n=3461 [94%]). CONCLUSIONS: The high rate of polypharmacy, significant psychiatric comorbidity and widespread use of benzodiazepine-anxiolytics and medications not indicated for GAD suggest that the disease burden is high. Total direct costs associated with the disease were high but still likely to be underestimated.

The size and burden of mental disorders and other disorders of the brain in Europe 2010.

AIMS: To provide 12-month prevalence and disability burden estimates of a broad range of mental and neurological disorders in the European Union (EU) and to compare these findings to previous estimates. Referring to our previous 2005 review, improved up-to-date data for the enlarged EU on a broader range of disorders than previously covered are needed for basic, clinical and public health research and policy decisions and to inform about the estimated number of persons affected in the EU. METHOD: Stepwise multi-method approach, consisting of systematic literature reviews, reanalyses of existing data sets, national surveys and expert consultations. Studies and data from all member states of the European Union (EU-27) plus Switzerland, Iceland and Norway were included. Supplementary information about neurological disorders is provided, although methodological constraints prohibited the derivation of overall prevalence estimates for mental and neurological disorders. Disease burden was measured by disability adjusted life years (DALY). RESULTS: Prevalence: It is estimated that each year 38.2% of the EU population suffers from a mental disorder. Adjusted for age and comorbidity, this corresponds to 164.8million persons affected. Compared to 2005 (27.4%) this higher estimate is entirely due to the inclusion of 14 new disorders also covering childhood/adolescence as well as the elderly. The estimated higher number of persons affected (2011: 165m vs. 2005: 82m) is due to coverage of childhood and old age populations, new disorders and of new EU membership states. The most frequent disorders are anxiety disorders (14.0%), insomnia (7.0%), major depression (6.9%), somatoform (6.3%), alcohol and drug dependence (>4%), ADHD (5%) in the young, and dementia (1-30%, depending on age). Except for substance use disorders and mental retardation, there were no substantial cultural or country variations. Although many sources, including national health insurance programs, reveal increases in sick leave, early retirement and treatment rates due to mental disorders, rates in the community have not increased with a few exceptions (i.e. dementia). There were also no consistent indications of improvements with regard to low treatment rates, delayed treatment provision and grossly inadequate treatment. Disability: Disorders of the brain and mental disorders in particular, contribute 26.6% of the total all cause burden, thus a greater proportion as compared to other regions of the world. The rank order of the most disabling diseases differs markedly by gender and age group; overall, the four most disabling single conditions were: depression, dementias, alcohol use disorders and stroke. CONCLUSION: In every year over a third of the total EU population suffers from mental disorders. The true size of "disorders of the brain" including neurological disorders is even considerably larger. Disorders of the brain are the largest contributor to the all cause morbidity burden as measured by DALY in the EU. No indications for increasing overall rates of mental disorders were found nor of improved care and treatment since 2005; less than one third of all cases receive any treatment, suggesting a considerable level of unmet needs. We conclude that the true size and burden of disorders of the brain in the EU was significantly underestimated in the past. Concerted priority action is needed at all levels, including substantially increased funding for basic, clinical and public health research in order to identify better strategies for improved prevention and treatment for disorders of the brain as the core health challenge of the 21st century.

Childhood trauma in adults with social anxiety disorder and panic disorder: a cross-national study.

OBJECTIVES: The influence of childhood trauma as a specific environmental factor on the development of adult psychopathology is far from being elucidated. As part of a collaborative project between research groups from South Africa (SA) and Sweden focusing on genetic and environmental factors contributing to anxiety disorders, this study specifically investigated rates of childhood trauma in South African and Swedish patients respectively, and whether, in the sample as a whole, different traumatic experiences in childhood are predictive of social anxiety (SAD) or panic disorder (PD) in adulthood. METHOD: Participants with SAD or PD (85 from SA, 135 from Sweden) completed the Childhood Trauma Questionnaire (CTQ). Logistic regression was performed with data from the two countries separately, and from the sample as a whole, with primary diagnoses as dependent variables, gender, age, and country as covariates, and the CTQ subscale totals as independent variables. The study also investigated the internal consistency (Cronbach alpha) of the CTQ subscales. RESULTS: SA patients showed higher levels of childhood trauma than Swedish patients. When data from both countries were combined, SAD patients reported higher rates of childhood emotional abuse compared to those with PD. Moreover, emotional abuse in childhood was found to play a predictive role in SAD/PD in adulthood in the Swedish and the combined samples, and the same trend was found in the SA sample. The psychometric qualities of the CTQ subscales were adequate, with the exception of the physical neglect subscale. CONCLUSION: Our findings suggest that anxiety disorder patients may differ across countries in terms of childhood trauma. Certain forms of childhood abuse may contribute specific vulnerability to different types of psychopathology. Longitudinal studies should focus on the potential sequential development of SAD/PD among individuals with childhood emotional abuse.

Childhood trauma in adults with social anxiety disorder and panic disorder: a cross-national study

Objectives: The influence of childhood trauma as a specific environmental factor on the development of adult psychopathology is far from being elucidated. As part of a collaborative project between research groups from South Africa (SA) and Sweden focusing on genetic and environmental factors contributing to anxiety disorders; this study specifically investigated rates of childhood trauma in South African and Swedish patients respectively; and whether; in the sample as a whole; different traumatic experiences in childhood are predictive of social anxiety (SAD) or panic disorder (PD) in adulthood. Method: Participants with SAD or PD (85 from SA; 135 from Sweden) completed the Childhood Trauma Questionnaire (CTQ). Logistic regression was performed with data from the two countries separately; and from the sample as a whole; with primary diagnoses as dependent variables; gender; age; and country as covariates; and the CTQ subscale totals as independent variables. The study also investigated the internal consistency (Cronbach alpha) of the CTQ subscales. Results: SA patients showed higher levels of childhood trauma than Swedish patients. When data from both countries were combined; SAD patients reported higher rates of childhood emotional abuse compared to those with PD. Moreover; emotional abuse in childhood was found to play a predictive role in SAD/PD in adulthood in the Swedish and the combined samples; and the same trend was found in the SA sample. The psychometric qualities of the CTQ subscales were adequate; with the exception of the physical neglect subscale. Conclusion: Our findings suggest that anxiety disorder patients may differ across countries in terms of childhood trauma. Certain forms of childhood abuse may contribute specific vulnerability to different types of psychopathology. Longitudinal studies should focus on the potential sequential development of SAD/PD among individuals with childhood emotional abuse

Psychiatric symptoms and disorders in HIV infected mine workers in South Africa. A retrospective descriptive study of acute first admissions.

OBJECTIVE: The social and living conditions of mine workers in South Africa contribute to a rapid transmission of human immunodeficiency virus (HIV) and other sexually transmitted infections. HIV-associated dementia is a serious condition during HIV disease. Several other psychiatric symptoms and disorders, such as psychosis, secondary mania and depression, have also been associated with clinical HIV infection. We describe the onset of psychiatric symptoms and signs in a group of untreated, HIV infected male mine workers first admitted for psychiatric treatment at the Rand Mutual Hospital in Johannesburg. METHOD: Between 1987 and 1997, 38 consecutive cases were admitted, and their files were retrieved for study in 2006. The subjects were 38 black male mine workers admitted acutely for psychiatric care due to psychiatric symptoms, and subsequently diagnosed with HIV infection. The presenting psychiatric symptoms on admission and diagnoses at discharge were compiled for all patients, not to infer causality but to establish the range of symptoms that the clinician has to deal with. RESULTS: The 38 patients presented with a wide range of psychiatric symptoms. The dominating symptoms were those of cognitive deficits, and different psychotic manifestations. 12 of the patients, almost one third of the individuals, were diagnosed with dementia. The patients with dementia exhibited cognitive deficits, and in addition often abnormal behaviour and psychotic symptoms, and several also had symptoms of secondary mania. 5 of the patients presented with delirium. Psychosis, without concurrent dementia, was diagnosed in 5 patients. Bipolar disorder with mania, without concurrent dementia, and major depression was present in 2 patients, respectively. Screening for substance abuse showed that 9 of the patients had ongoing cannabis abuse and 10 had alcohol abuse. Cannabis-induced psychotic disorder was present in 5 patients. CONCLUSION: The findings confirm that patients with a new diagnosis of HIV may present with disorders of thought and/or cognition as well as gross behavioural disturbance, and that psychotic symptoms and secondary mania could be manifestations of the clinical onset of HIV/acquired immune deficiency syndrome (AIDS) infection.

HIV infection and psychiatric illness.

OBJECTIVE: To review the clinical features and current knowledge on the treatment of psychiatric symptoms and disorders in patients with human immunodeficiency virus (HIV) infection. METHOD: We searched the PubMed database combining HIV/AIDS with different keywords for psychiatric diagnoses and symptoms (e.g. depression, mania, anxiety, psychosis, dementia, substance abuse) and for psychopharmacological treatment. The years covered by these searches included 1980 to 2008. RESULTS: Patients with HIV infection are at an increased risk of psychiatric illness. Major depressive disorder and subsyndromal depressive symptoms, as well as anxiety disorder and substance abuse are more prevalent among HIV infected individuals than among the general population. HIV-associated neurocognitive disorders (HAND) are common among HIV patients, and HIV-associated dementia (HAD) is a serious condition during the acquired immune deficiency syndrome (AIDS) stage of HIV disease. Secondary mania and psychosis might be the first clinical symptom of HIV dementia. The introduction of highly active anti-retroviral therapy (HAART) has resulted in significant decreases in morbidity and mortality for HIV infected patients. HAART has also decreased the incidence of HAD, but does not give complete protection from this condition. The utility of psychotropic medications in HIV patients has not been studied sufficiently as a basis for guidelines, and more controlled trials are needed. CONCLUSION: Psychiatric illness is common in HIV infected individuals, and underlines the importance for screening not only for cognitive impairment but also for co morbid mental disease in HIV-positive patients. Further studies of the neuropsychiatric complications during HIV disease and the use of psychotropics under these circumstances are clearly needed. A better understanding of the pathogenesis of HAD is essential to identify additional therapeutic strategies for prevention and treatment of this neurodegenerative disease. Studies are also needed for optimizing effective utilization of antiretrovirals into the CNS. Mania and psychosis secondary to HAD may be used as an indicator to initiate HAART, irrespective of CD4 count. Further research on the utility of HAART in the treatment of such acute neuropsychiatric symptoms associated with HIV infection should be initiated.

Establishing non-inferiority in treatment trials in psychiatry: guidelines from an Expert Consensus Meeting.

Comparing the efficacy of different treatments in psychiatry is difficult for many reasons, even when they are investigated in "head-to-head" studies. A consensus meeting was, therefore, held to produce best practice guidelines for such studies. This article presents the conclusions of this consensus and illustrates it using published data in the field of antidepressant treatment of generalized anxiety disorder.

A non-inferiority comparison of duloxetine and venlafaxine in the treatment of adult patients with generalized anxiety disorder.

The present study is a non-inferiority comparison of duloxetine 60-120 mg/day and venlafaxine extended-release (XR) 75-225 mg/day for the treatment of adults with generalized anxiety disorder (GAD). The non-inferiority test was a prespecified plan to pool data from two nearly identical 10-week, multicentre, randomized, placebo-controlled, double-blind studies of duloxetine 60-120 mg/day and venlafaxine 75-225 mg/ day for the treatment of GAD. An independent expert consensus panel provided six statistical and clinical criteria for determining non-inferiority between treatments. Response was defined as > or =50% reduction in Hamilton Anxiety Rating Scale (HAMA) total score. In the pooled sample, patients were randomly assigned to duloxetine (n = 320), venlafaxine XR (n = 333) or placebo (n = 331). For the non-inferiority analysis, the per-protocol patients who were treated with duloxetine (n = 239) or venlafaxine XR (n = 262) improved significantly more (mean HAMA reductions were -15.4 and -15.2, respectively) than placebo-treated patients (n = 267; -11.6, P < or = 0.001, both comparisons). Response rates were 56%, 58% and 40%, respectively. Discontinuation rate because of AEs was significantly higher for duloxetine (13.4%, P < or = 0.001) and venlafaxine XR (11.4%, P < or = 0.01) groups compared with placebo (5.4%). Duloxetine 60-120 mg/day met all statistical and clinical criteria for non-inferiority and exhibited a similar tolerability profile compared with venlafaxine XR 75-225 mg/day for the treatment of adults with GAD.

Health-related quality of life (HRQOL) among patients with Generalised Anxiety Disorder: evaluation conducted alongside an escitalopram relapse prevention trial.

BACKGROUND: Improving health-related quality of life (HRQoL) should be a treatment goal for patients with Generalised Anxiety Disorder (GAD). OBJECTIVES: To assess the impact of treatment with escitalopram on HRQoL as well as the effect of relapse on HRQoL and work productivity. METHODS: This study was conducted alongside a double-blind, placebo-controlled, relapse prevention multinational clinical trial. Relapse was defined as a Hamilton Anxiety Scale (HAMA) >or= 15. Treatment responders (HAMA

Sertraline in generalized anxiety disorder: efficacy in treating the psychic and somatic anxiety factors.

OBJECTIVE: The objective was to study the efficacy of sertraline on symptoms of psychic and somatic anxiety in patients suffering from moderate-to-severe generalized anxiety disorder (GAD). METHOD: Out-patients with DSM-IV GAD were randomized to 12 weeks of double-blind treatment with placebo. The psychic and somatic anxiety factors of the Hamilton Anxiety Rating Scale (HAM-A) and the Quality of Life, Enjoyment, and Satisfaction Questionnaire were analyzed. RESULTS: Treatment with sertraline resulted in significantly greater last observation carried forward (LOCF)-endpoint improvement than placebo on both the HAM-A psychic and somatic anxiety factors. At LOCF-endpoint, all items on the HAM-A psychic factor were more improved on sertraline than placebo, as were three of seven items on the somatic factor. Reduction of secondary depressive symptoms was more correlated with endpoint improvement in quality of life than either psychic- or somatic anxiety. CONCLUSION: Sertraline treatment demonstrated efficacy for both the psychic and somatic anxiety symptoms of GAD.

Efficacy of usual antidepressant dosing regimens of fluoxetine in panic disorder: randomised, placebo-controlled trial.

BACKGROUND: Although serotonin reuptake inhibitors are effective in panic disorder, questions concerning whether doses associated with antidepressant efficacy are also effective for panic disorder remain. AIMS: To assess the efficacy of the usual antidepressant dose of fluoxetine in treating full panic attacks. METHOD: Patients with panic disorder were randomised to placebo or to fluoxetine initiated at 10 mg daily for 1 week and then increased to 20 mg daily. The trial lasted 12 weeks, but after 6 weeks patients who had failed to achieve a satisfactory response were eligible for dose escalation to a maximum of 60 mg of fluoxetine daily. RESULTS: Fluoxetine was associated with a statistically significantly greater proportion of panic-free patients compared with placebo after 6 weeks and at end-point. CONCLUSIONS: Fluoxetine at a dose of 20 mg daily is safe and efficacious in reducing symptoms of panic disorder. Patients who fail to obtain a satisfactory response at 20 mg daily may benefit from further dose increases.

Venlafaxine extended release (ER) in the treatment of generalised anxiety disorder: twenty-four-week placebo-controlled dose-ranging study.

BACKGROUND: Generalised anxiety disorder (GAD) has received less study than other anxiety disorders, particularly its long-term treatment. AIMS: To assess the efficacy and safety of venlafaxine extended release (ER) in patients with GAD. METHOD: A total of 541 out-patients, 18-86 years old, were recruited to this 24-week, placebo-controlled, double-blind study of three fixed doses (37.5, 75 and 150 mg/day) of venlafaxine ER. RESULTS: All doses of venlafaxine ER showed efficacy superior to placebo, apparent from week 2, that was sustained throughout the 24-week study for the two higher doses. The discontinuation rate did not differ significantly among the treatment groups. CONCLUSIONS: Venlafaxine ER is an effective and safe treatment for GAD for up to 6 months.

A prospective study of 86 new patients with social anxiety disorder.

OBJECTIVE: To determine the prognosis in 86 new patients with social anxiety disorder. METHOD: Untreated subjects with social anxiety were recruited by advertising in Stockholm, randomized to 3 months treatment with paroxetine or placebo, and then offered continued specialist care. Metabolizing capacity was determined by genotyping CYP2D6 in the subjects on paroxetine. After a mean 32 months all were contacted for a personal interview. RESULTS: Of the 92 evaluable subjects, 86 (93%) were interviewed. A favourable prognosis was seen in the subjects randomized to paroxetine who chose to continue with serotonergic medication. The least favourable prognosis was in those given placebo who chose not to be treated after the trial. Twenty-four subjects were still symptomatic and dysfunctional and had not sought treatment. Drug-induced adverse effects caused treatment termination in six subjects, one of whom had a poor metabolizing genotype. CONCLUSION: Due to their condition, some subjects with social anxiety refrain from effective treatments. The efficacy of serotonergic medication was maintained and augmented after a mean period of 32 months.

Victims of criminal homicide in Sweden: a matched case-control study of health and social risk factors among all 1,739 cases during 1978-1994.

OBJECTIVE: The psychiatric and medical characteristics of victims of homicide have not been systematically studied and are often confounded by race. This study was undertaken to determine health and social factors contributing to the risk of being murdered in the Swedish, predominantly Caucasian population. METHOD: All 1,739 homicides between 1978 and 1994 in Sweden were studied in terms of variables in national case registers regarding health, crimes, immigration, and marital status. The same data were extracted for matched comparison persons in the general population, with controls for time of exposure. The data were analyzed by conditional logistic regression on matched pairs. RESULTS: Traumatic brain injury, physical abuse, alcohol dependence, and criminal recidivism conferred risk of being murdered. CONCLUSIONS: To the authors' knowledge, this is the first report of traumatic brain injury, in both men and women, as a risk factor for being murdered. Brain injury may mark risk-taking behavior in general or may cause provocative behavior.

Paroxetine in social anxiety disorder: a randomized placebo-controlled study.

OBJECTIVE: The aim of this study was to evaluate the utility of paroxetine treatment in social anxiety disorder. METHOD: Previously undiagnosed and untreated subjects with social anxiety disorder (generalized social phobia) were selected from among responders to a newspaper advertisement. They were randomized to double-blind treatment with paroxetine 20-50 mg daily or placebo for 3 months. Outcome measures were self-rated social anxiety and avoidance behaviour, and clinician-rated global assessment of improvement. RESULTS: Significant differences in efficacy between treatments (intent-to-treat analysis: 44 subjects on paroxetine and 48 subjects on placebo) were noted after 4-6 weeks, increasing through the treatment period in the paroxetine group. Nine subjects on paroxetine and 3 subjects on placebo discontinued the treatment due to adverse events. Sexual side-effects were noted by 18 subjects on paroxetine and 4 subjects on placebo. CONCLUSION: Paroxetine was effective in alleviating symptoms and avoidance behaviour in social anxiety disorder.

[Documented effects of SSRI preparations in anxiety]. / Dokumenterade effekter av SSRI-preparat vid ångest.

The article consists in a review of the clinical evidence for treating anxiety disorders with selective serotonin re-uptake inhibitors (SSRIs). Sufficient documentation now exists to support the use of SSRIs in treating panic and obsessive-compulsive disorders, and in Sweden moclobemide is now approved for use in treating social phobia, and buspirone for use in treating generalised anxiety disorder. Further documentation of the treatment of post-traumatic stress disorder with SSRIs is probably to be expected. Benzodiazepines remain the most commonly used anxiolytics. Although persistent adverse sexual reactions, and withdrawal symptoms upon abrupt termination of medication, are notable side effects of SSRIs, patients become measurably more self-confident and focused, and manage risks more adequately. This underscores the need of further research into the interrelationship of personality traits and anxiety symptoms.