Anxiety Disorders: Allgulander C

Bandelow B, Zohar J, Hollander E, Kasper S, Möller HJ, Anonymous00037, Zohar J, Hollander E, Kasper S, Möller HJ, Bandelow B, Allgulander C, Ayuso-Gutierrez J, Baldwin DS, Buenvicius R, Cassano G, Fineberg N, Gabriels L, Hindmarch I, Kaiya H, Klein DF, Lader M, Lecrubier Y, Lépine JP, Liebowitz MR, Lopez-Ibor JJ, Marazziti D, Miguel EC, Oh KS, Preter M, Rupprecht R, Sato M, Starcevic V, Stein DJ, van Ameringen M, Vega J. · Department of Psychiatry and Psychotherapy, University of Gottingen, Gottingen, Germany. · World J Biol Psychiatry. · Pubmed #18949648 No free full text.

Abstract: In this report, which is an update of a guideline published in 2002 (Bandelow et al. 2002, World J Biol Psychiatry 3:171), recommendations for the pharmacological treatment of anxiety disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are presented. Since the publication of the first version of this guideline, a substantial number of new randomized controlled studies of anxiolytics have been published. In particular, more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs. The recommendations, developed by the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-traumatic Stress Disorders, a consensus panel of 30 international experts, are now based on 510 published randomized, placebo- or comparator-controlled clinical studies (RCTs) and 130 open studies and case reports. First-line treatments for these disorders are selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and the calcium channel modulator pregabalin. Tricyclic antidepressants (TCAs) are equally effective for some disorders, but many are less well tolerated than the SSRIs/SNRIs. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of substance abuse disorders. Potential treatment options for patients unresponsive to standard treatments are described in this overview. Although these guidelines focus on medications, non-pharmacological were also considered. Cognitive behavioural therapy (CBT) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders, OCD, and PTSD to support them being recommended either alone or in combination with the above medicines.

Allgulander C, Nutt D, Detke M, Erickson J, Spann M, Walker D, Ball SG, Russell JM. · Department of Clinical Neuroscience, Section of Psychiatry, Karolinska Institutet, Stockholm, Sweden. · J Psychopharmacol. · Pubmed #18635722 No free full text.

Abstract: 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.

Allgulander C, Bandelow B, Hollander E, Montgomery SA, Nutt DJ, Okasha A, Pollack MH, Stein DJ, Swinson RP, Anonymous00175. · Department of Psychiatry, Harvard University School of Medicine, Boston, Massachusetts, USA. · CNS Spectr. · Pubmed #14767398 No free full text.

Abstract: What are the current recommendations for the long-term treatment of generalized anxiety disorder (GAD)? GAD is a common disorder with a lifetime prevalence of 4% to 7% in the general population. GAD is characterized by excessive, uncontrollable worry or anxiety about a number of events or activities that the individual experiences on more days than not over a 6-month period. Onset of GAD symptoms usually occurs during an individual's early twenties; however, high rates of GAD have also been seen in children and adolescents. The clinical course of GAD is often chronic, with 40% of patients reporting illness lasting >5 years. GAD is associated with pronounced functional impairment, resulting in decreased vocational function and reduced quality of life. Patients with GAD tend to be high users of outpatient medical care, which contributes significantly to healthcare costs. Currently, benzodiazepines and buspirone are prescribed frequently to treat GAD. Although both show efficacy in acute treatment trials, few long-term studies have been performed. Benzodiazepines are not recommended for long-term treatment of GAD, due to associated development of tolerance, psychomotor impairment, cognitive and memory changes, physical dependence, and a withdrawal reaction on discontinuation. The antidepressant venlafaxine extended-release (XR) has received approval for the treatment of GAD in the United States and many other countries. Venlafaxine XR has demonstrated efficacy over placebo in two randomized treatment trials of 6 months' duration as well as in other acute trials. Paroxetine is the first of the selective serotonin reuptake inhibitors (SSRIs) to receive US approval for the treatment of GAD. Paroxetine demonstrated superiority to placebo in short-term trials, and investigations into the use of other SSRIs are ongoing. This suggests that other SSRIs, and serotonin and noradrenaline reuptake inhibitors, are likely to be effective in the treatment of GAD. Of the psychological therapies, cognitive-behavioral therapy (CBT) shows the greatest benefit in treating GAD patients. Treatment gains after a 12-week course of CBT may be maintained for up to 1 year. Currently, no guidelines exist for the long-term treatment of GAD.

Van Ameringen M, Allgulander C, Bandelow B, Greist JH, Hollander E, Montgomery SA, Nutt DJ, Okasha A, Pollack MH, Stein DJ, Swinson RP, Anonymous00174. · Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada. · CNS Spectr. · Pubmed #14767397 No free full text.

Abstract: What is the best approach for treating patients with social phobia (social anxiety disorder) over the long term? Social phobia is the most common anxiety disorder, with reported prevalence rates of up to 18.7%. Social phobia is characterized by a marked and persistent fear of being observed or evaluated by others in social performance or interaction situations and is associated with physical, cognitive, and behavioral (ie, avoidance) symptoms. The onset of social phobia typically occurs in childhood or adolescence and the clinical course, if left untreated, is usually chronic, unremitting, and associated with significant functional impairment. Social phobia exhibits a high degree of comorbidity with other psychiatric disorders, including mood disorders, anxiety disorders, and substance abuse/dependence. Few people with social phobia seek professional help despite the existence of beneficial treatment approaches. The efficacy, tolerability, and safety of the selective serotonin reuptake inhibitors (SSRIs), evidenced in randomized clinical trials, support these agents as first-line treatment. The benzodiazepine clonazepam and certain monoamine oxidase inhibitors (representing both reversible and nonreversible inhibitors) may also be of benefit. Treatment of social phobia may need to be continued for several months to consolidate response and achieve full remission. The SSRIs have shown benefit in long-term treatment trials, while long-term treatment data from clinical studies of clonazepam are limited but support the drug's efficacy. There is also evidence for the effectiveness of exposure-based strategies of cognitive-behavioral therapy, and controlled studies suggest that the effects of treatment are generally maintained at long-term follow-up. In light of the chronicity and disability associated with social phobia, as well as the high relapse rate after short-term therapy, it is recommended that effective treatment be continued for at least 12 months.

Pollack MH, Allgulander C, Bandelow B, Cassano GB, Greist JH, Hollander E, Nutt DJ, Okasha A, Swinson RP, Anonymous00172. · Division of Psychiatry, Huddinge University Hospital, Stockholm, Sweden. · CNS Spectr. · Pubmed #14767395 No free full text.

Abstract: What are the symptoms of panic disorder and how is the disorder most effectively treated? One of the most commonly encountered anxiety disorders in the primary care setting, panic disorder is a chronic and debilitating illness. The core symptoms are recurrent panic attacks coupled with anticipatory anxiety and phobic avoidance, which together impair the patient's professional, social, and familial functioning. Patients with panic disorder have medically unexplained symptoms that lead to overutilization of healthcare services. Panic disorder is often comorbid with agoraphobia and major depression, and patients may be at increased risk of cardiovascular disease and, possibly, suicide. Research into the optimal treatment of this disorder has been undertaken in the past 2 decades, and numerous randomized, controlled trials have been published. Selective serotonin reuptake inhibitors have emerged as the most favorable treatment, as they have a beneficial side-effect profile, are relatively safe (even if taken in overdose), and do not produce physical dependency. High-potency benzodiazepines, reversible monoamine oxidase inhibitors, and tricyclic antidepressants have also shown antipanic efficacy. In addition, cognitive-behavioral therapy has demonstrated efficacy in the acute and long-term treatment of panic disorder. An integrated treatment approach that combines pharmacotherapy with cognitive-behavioral therapy may provide the best treatment. Long-term efficacy and ease of use are important considerations in treatment selection, as maintenance treatment is recommended for at least 12-24 months, and in some cases, indefinitely.

Allgulander C, Nutt DJ. · No affiliation provided · J Psychopharmacol. · Pubmed #18635714 No free full text.

This publication has no abstract.

Allgulander C. · Instituto Karolinska, Departamento de Neurociência Clínica, Divisão de Psiquiatria, Estocolmo, Suécia. · Rev Bras Psiquiatr. · Pubmed #17650539 No free full text.

Abstract: Persons with generalized anxiety disorder often do not seek treatment, and if they do, it is more often for the somatic symptoms (muscle tension, insomnia) or for a secondary depression than because of the cardinal feature of generalized anxiety disorder: worry. The worry aspect becomes apparent when the patient is proposed to try anxiolytic medication. The physician will then need to be prepared to answer many questions regarding the potential hazards and benefits of such medication. These patients tend to have a sceptical attitude, having informed themselves on websites that display claims that are based on anything from evidence-based scientific guidelines to distorted, erroneous and unfounded allegations. Which are the frequent questions that worried patients pose to the physician before accepting anxiolytic pharmacotherapy? Having seen anxious patients in my practice during 25 years, and having conducted several clinical trials of anxiolytics I have put together evidence-based answers in plain language to these questions in this paper.

Allgulander C, Sheehan DV. · Karolinska Institute, Neurotec Department, Huddinge University Hospital, Stockholm. · Psychopharmacol Bull. · Pubmed #17450651 No free full text.

Abstract: Anxiety disorders are prevalent and associated with an increase in morbidity and mortality, particularly when present with additional psychiatric disorders. They represent a public health and economic burden, yet they are commonly underrecognized and undertreated. Benzodiazepines are effective anxiolytics, but they primarily treat the somatic symptoms of generalized anxiety disorder (GAD), and are not effective in treating the depressive symptoms that are often comorbid in chronic anxiety disorders like GAD. Some antidepressants may therefore offer the best choice of therapy. Their benefit in the treatment of GAD has been demonstrated using the tricyclic antidepressant, imipramine, and some selective serotonin reuptake inhibitors. The serotonin and norepinephrine reuptake inhibitor venlafaxine extended release (XR), has been indicated for GAD and has proven to be effective in both the short- and long-term treatment of patients with this disorder. Many patients treated with venlafaxine XR achieve and sustain remission from the symptoms of GAD, which is the goal of treatment.

Allgulander C. · Department of Clinical Neuroscience, Section of Psychiatry, Karolinska Institutet, Stockholm, Sweden. · Eur Neuropsychopharmacol. · Pubmed #16730165 No free full text.

Abstract: One of the most prevalent anxiety conditions seen in primary care is generalized anxiety disorder (GAD). Numerous physical ailments frequently accompany the psychic symptoms of anxiety, which often drive patients to ask for help. In spite of the high incidence of GAD, only 30% of sufferers are diagnosed. Furthermore, very few patients are prescribed medication or referred to a psychiatrist. The key aim is to ensure the early detection and management of these patients. Developing physician education programs may improve the identification of GAD. The use of simple diagnostic tools would also aid the early detection of sufferers. Physicians require more long-term data, including that on the influence of ethnicity and genetics, to assist them to better understand and more effectively manage GAD. By achieving early diagnosis and treatment of GAD, physicians can ensure that a lesser burden is inflicted upon sufferers, thus improving their quality of life.

Allgulander C, Kasper S. · Karolinska Institute, Neurotec Department, Huddinge University Hospital, Stockholm. · Psychopharmacol Bull. · Pubmed #12490826 links to  free full text

Abstract: Depression is increasingly being recognized as a common comorbid disorder in patients with severe and chronic medical conditions. However, patients with depression and anxiety frequently present with somatic complaints such as aches and pains, headache, and chronic fatigue. This leads to underrecognition and undertreatment of the psychiatric disorder in an attempt to identify the medical cause of the somatic complaint. Reports are demonstrating the efficacy of antidepressants in treating disorders other than depression and anxiety. Tricyclic antidepressants have shown their usefulness in the treatment of diabetic neuropathy, fibromyalgia, and headache. Controlled studies of several selective serotonin reuptake inhibitors have been shown to be efficacious in relieving the symptoms of premenstrual dysphoric disorder and fibromyalgia. Pilot studies have also been conducted with the serotonin and norepinephrine reuptake inhibitor venlafaxine for the treatment of diabetic neuropathy, fibromyalgia, migraine, premenstrual dysphoric disorder, and stroke. The results encourage further controlled studies.

Allgulander C, Hirschfeld RM, Nutt DJ. · Karolinska Institute, Neurotec Department, Huddinge University Hospital, Stockholm. · Psychopharmacol Bull. · Pubmed #12490824 links to  free full text

Abstract: Anxiety disorders are prevalent and associated with increased morbidity and mortality. Some chronic anxiety disorders, including generalized anxiety disorder (GAD), may be characterized by an underlying high level of anxiety on which exacerbations of symptoms are superimposed. Effective treatment of anxiety disorders should therefore strive to attain both an acute reduction in the symptoms of anxiety (a response) and sustained resolution of the symptoms of any underlying chronic anxiety (remission). This strategy may necessitate long-term treatment of these disorders by pharmacotherapy and/or psychotherapy. Studies using the serotonin and norepinephrine reuptake inhibitor (SNRI), venlafaxine extended release (XR), suggest that these aims may be achieved using this newer class of drugs. Studies with venlafaxine XR in patients with GAD have demonstrated robust anxiolytic efficacy over placebo, particularly regarding worry, cognitive dysfunction, and muscular tension, which are specific to GAD. Administration of venlafaxine XR over both short- (8-week) and long-term (6-month) periods resulted in a significantly greater number of patients achieving response and remission than obtained with placebo. Long-term treatment with venlafaxine XR in patients with GAD showed greater efficacy than that observed in short-term studies. This was achieved without any loss of short-term efficacy and patients' social functioning was also restored. While available data indicate that venlafaxine XR is an appropriate choice of agent in the long-term treatment of GAD, more studies are needed to determine how to further increase remission rates and to maintain remission beyond 6 months.

Dahl AA, Ravindran A, Allgulander C, Kutcher SP, Austin C, Burt T. · Department of Clinical Cancer Research, Rikshospitalet-Radiumhospitalet Trust, University of Oslo, Montebello, Oslo, Norway. · Acta Psychiatr Scand. · Pubmed #15877709 No free full text.

Abstract: 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.

Steiner M, Allgulander C, Ravindran A, Kosar H, Burt T, Austin C. · McMaster University, Department of Psychiatry and Behavioural Neurosciences, Women's Health Concerns Clinic, St Joseph's Hospital, Hamilton, Ontario, Canada. · Hum Psychopharmacol. · Pubmed #15551351 No free full text.

Abstract: OBJECTIVE: To evaluate gender differences in the clinical presentation of generalized anxiety disorder (GAD) and response to sertraline treatment. METHODS: Adult outpatients who met DSM-IV criteria for GAD with a minimum Hamilton rating scale for anxiety (HAM-A) total score>or=18 were randomized to 12 weeks of double-blind treatment with flexible doses (50-150 mg) of sertraline (n=182; female, 59%) or placebo (n=188; female, 51%). RESULTS: Clinical presentation of GAD was very similar in men and women in terms of the severity of the HAM-A psychic factor, severity of concomitant depression symptoms, duration of GAD, quality of life and impairment in physical health. Women had an earlier age of onset and higher HAM-A somatic factor scores compared with men. For both men and women, treatment with sertraline resulted in greater change from baseline to endpoint on the HAM-A compared with placebo (adjusted change+/-SE: men:-12.1+/-0.9 vs -8.8+/-0.9; women: -11.4+/-0.8 vs -7.1+/-0.9, p<0.001); the interaction between gender and treatment group was not significant, nor was there a significant difference between the average change from baseline for men compared with women. Similarly, responder rates based upon clinical global impression-improvement (CGI-I) scores at endpoint showed no significant interaction between gender and treatment, nor was there a significant difference in the response rates by gender; however, the response rate of sertraline compared with placebo was significantly different (p<0.0001) (men: 64% vs 40%; women: 62% vs 34%). Similar findings were evident at week 4 assessment and for completers (week 12). Overall, sertraline was well tolerated by both men and women. DISCUSSION: Women and men with GAD showed similar clinical presentations, with the exception that women had an earlier age of onset and reported more somatic anxiety symptoms. Sertraline was an effective and well tolerated treatment for GAD in both men and women.

Allgulander C, Dahl AA, Austin C, Morris PL, Sogaard JA, Fayyad R, Kutcher SP, Clary CM. · Karolinska Institutet, Neurotec Department, Section of Psychiatry at Huddinge, University Hospital, 141 86 Huddinge, Sweden. · Am J Psychiatry. · Pubmed #15337655 links to  free full text

Abstract: OBJECTIVE: Sertraline's efficacy and tolerability in treating generalized anxiety disorder were evaluated. METHOD: Adult outpatients with DSM-IV generalized anxiety disorder and a total score of 18 or higher on the Hamilton Anxiety Rating Scale were eligible. After a 1-week single-blind placebo lead-in, patients were randomly assigned to 12 weeks of double-blind treatment with placebo (N=188, mean baseline anxiety score=25) or flexible doses (50-150 mg/day) of sertraline (N=182, mean anxiety score=25). The primary outcome measure was baseline-to-endpoint change in the Hamilton anxiety scale total score. A secondary efficacy measure was the Clinical Global Impression (CGI) improvement score; response was defined as a score of 2 or less. RESULTS: Sertraline patients had significantly greater improvement than placebo patients on all efficacy measures at week 4. Analysis of covariance of the intent-to-treat group at endpoint (with the last observation carried forward) showed a significant difference in the decrease from baseline of the least-square mean total score on the Hamilton anxiety scale between sertraline (mean=11.7) and placebo (mean=8.0). Significantly greater endpoint improvement with sertraline than placebo was obtained for mean scores on the Hamilton anxiety scale psychic factor (6.7 versus 4.1) and somatic factor (5.0 versus 3.9). The rate of responders, based on CGI improvement and last observation carried forward, was significantly higher for sertraline (63%) than placebo (37%). Sertraline was well tolerated; 8% of patients versus 10% for placebo dropped out because of adverse events. CONCLUSIONS: Sertraline appears to be efficacious and well tolerated in the treatment of generalized anxiety disorder.

Allgulander C, Mangano R, Zhang J, Dahl AA, Lepola U, Sjödin I, Emilien G, Anonymous00251. · Karolinska Institutet, The Neurotec Department, Section of Psychiatry, Stockholm, Sweden. · Hum Psychopharmacol. · Pubmed #15303242 No free full text.

Abstract: This study evaluated the anxiolytic efficacy, safety and tolerability of a flexible dose of venlafaxine extended release (ER) compared with placebo and paroxetine in the short-term treatment of generalized social anxiety disorder (SAD). Adult outpatients with generalized SAD (n = 434) were randomized to receive capsules of venlafaxine ER 75 mg to 225 mg/day, paroxetine 20 mg to 50 mg/day, or placebo for 12 weeks. The primary efficacy variable was the Liebowitz social anxiety scale total score. Secondary efficacy variables included the patient-rated social phobia inventory and the proportion of responders in each group (a responder was defined as having a clinical global impression-improvement score of 1 or 2). Treatment with venlafaxine ER was associated with significantly greater improvement than treatment with placebo for all primary and secondary efficacy variables (p < 0.05). No significant differences in primary or secondary efficacy variables were observed between the venlafaxine ER and paroxetine groups. The week 12 response rates were 69%, 66% and 36% for the venlafaxine ER, paroxetine and placebo groups, respectively. Both active treatments were generally well tolerated and were associated with a similar incidence of adverse events. This study shows that venlafaxine ER is an effective, safe and well-tolerated drug treatment for SAD.

Ho HP, Westberg L, Annerbrink K, Olsson M, Melke J, Nilsson S, Baghaei F, Rosmond R, Holm G, Björntorp P, Andersch S, Allgulander C, Eriksson E. · Department of Pharmacology, Göteborg University, P.O.B. 431, SE 405 30 Göteborg, Sweden. · Psychoneuroendocrinology. · Pubmed #15219637 No free full text.

Abstract: Although genetic factors are known to be important risk factors for panic disorder there is as yet no conclusive data regarding specific gene variants. Prompted by evidence supporting progesterone to influence the pathophysiology of panic disorder, polymorphisms in the progesterone receptor gene, a single nucleotide polymorphism (G331A) and an insertion/deletion polymorphism (PROGINS) were investigated in 72 patients with panic disorder and 452 controls. The frequency of the A-allele of the G331A polymorphism was higher in panic disorder patients than in controls (p = 0.01). When male and female patients were analyzed separately, the association was observed in female patients only (p = 0.0009), with an odds ratio of 3.5. No differences between groups were observed for the PROGINS polymorphism. In conclusion, these data suggest that the G331A polymorphism in the progesterone receptor gene may influence the risk for panic disorder in women.

Michelson D, Allgulander C, Dantendorfer K, Knezevic A, Maierhofer D, Micev V, Paunovic VR, Timotijevic I, Sarkar N, Skoglund L, Pemberton SC. · Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. · Br J Psychiatry. · Pubmed #11731354 links to  free full text

Abstract: 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.

Allgulander C, Hackett D, Salinas E. · Neurotec/Psychiatry, Huddinge University Hospital, Huddinge, Sweden. · Br J Psychiatry. · Pubmed #11435263 links to  free full text

Abstract: 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.

Allgulander C, Nilsson B. · Neurotec/Psychiatry, Karolinska Institutet, Stockholm, Sweden. · Acta Psychiatr Scand. · Pubmed #11401659 No free full text.

Abstract: 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.

Allgulander C. · Karolinska Institutet, Neurotec, Division of Psychiatry at Huddinge University Hospital, Stockholm, Sweden. · Acta Psychiatr Scand. · Pubmed #10493085 No free full text.

Abstract: 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.

Owe-Larsson B, Säll L, Salamon E, Allgulander C. · Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry at Karolinska University Hospital Huddinge, Stockholm, Sweden. · Afr J Psychiatry (Johannesbg). · Pubmed #19582313 links to  free full text

Abstract: 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.

Gerdner A, Allgulander C. · Department of Social Work, Mid Sweden University, Ostersund, Sweden. · Nord J Psychiatry. · Pubmed #19021077 No free full text.

Abstract: Childhood maltreatment is delicate to assess both in clinical work and in research. There is a need for assessment tools that can be easily administered in an ethical and non-intrusive way that meets requirements of conceptual validity for various types of maltreatment and is sensitive to levels of severity. This study explores the psychometric properties of the Swedish translation of one such tool-the Childhood Trauma Questionnaire-Short Form (CTQ-SF; Bernstein and Fink, 1998). The CTQ-SF was administered to seven samples (total n=659)-five clinical samples and two non-clinical student samples. The factor structure supports the construct validity of the global maltreatment scale, four of the five maltreatment subscales (emotional abuse, physical abuse, sexual abuse and emotional neglect) and the minimization/denial (MD) scale, but not the physical neglect (PN) subscale. All items are highly correlated with their respective subscale. The discriminant validity is satisfactory. Highly significant correlation with social desirability gives further support for the MD-scale and to the recommendation of how to apply it. Internal consistency of PN is acceptable and for all other scales satisfactory. Swedish norm groups tend to score lower than similar American norm groups on abuse scales but higher on the neglect scales. Percentiles for seven gender-specific norm groups are presented. The weaknesses of the PN-scale are discussed and new constructs are proposed. The Swedish version of the CTQ-SF has the same construct validity and internal consistency as the original, including less homogeneity of the PN scale.

Nutt D, Allgulander C, Lecrubier Y, Peters T, Wittchen U. · Psychopharmacology Unit, University of Bristol, Bristol, UK. · J Psychopharmacol. · Pubmed #18635721 No free full text.

Abstract: 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.

Davidson J, Allgulander C, Pollack MH, Hartford J, Erickson JS, Russell JM, Perahia D, Wohlreich MM, Carlson J, Raskin J. · Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA. · Hum Psychopharmacol. · Pubmed #18478624 No free full text.

Abstract: OBJECTIVE: To assess the efficacy and tolerability of duloxetine in elderly patients with generalized anxiety disorder (GAD). METHODS: Acute-phase data from a subset of patients (>or=65 years) with GAD were pooled from four randomized, double-blind, placebo-controlled trials of duloxetine (3 flexible, 1 fixed dosing). Patients were treated with duloxetine 60-120 mg once daily or placebo for 9-10 weeks. The primary outcome measure was the mean baseline-to-endpoint change in Hamilton anxiety scale (HAMA) total score. Secondary measures included the HAMA psychic and somatic anxiety subscales and the Hospital Anxiety Depression Scale (HADS). RESULTS: Of 1491 patients randomly assigned to treatment, 4.9% (duloxetine, n = 45; placebo, n = 28) were >or= 65 years old. Compared with placebo-treated patients, duloxetine-treated patients experienced significantly greater improvements on the HAMA-total (p = 0.029), the HAMA-psychic anxiety factor (p = 0.034), HADS-anxiety (p = 0.049) and -depression scales (p = 0.026), but not the HAMA somatic anxiety factor (p = 0.074). Nausea was reported significantly more often in duloxetine-treated patients (30.0% vs. 7.1%, p = 0.023); duloxetine-treated patients experienced greater weight loss (p = 0.018). More duloxetine-treated patients discontinued treatment due to an adverse event (22.2% vs. 0%; p = 0.006). CONCLUSION: Duloxetine was effective in an elderly patient subset with GAD, although there was a high rate of discontinuations due to adverse events.

Allgulander C, Jørgensen T, Wade A, François C, Despiegel N, Auquier P, Toumi M. · Karolinska Institutet, Stockholm, Sweden. · Curr Med Res Opin. · Pubmed #17825130 No free full text.

Abstract: 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 <or= 10) after 12 weeks of open-label treatment (10 mg/day escitalopram for Week 1 followed by 20 mg/day thereafter) were included. The study dataset comprised patients (n = 329) from French, Canadian, German and Swedish centres. HRQoL was assessed using the SF-36 scale, and data on sick leave and on-the-job productivity as measured by the Work Limitation Questionnaire and the work efficacy and work satisfaction visual analogue scales (VAS) scales were collected at baseline, randomization (Week 12), Weeks 36, 60 and at last assessment. For future health economic analysis, quality adjusted life years were calculated from the SF-36 results. RESULTS: At baseline, GAD patients reported significantly impaired quality of life compared with the general population. During the 12-week open-label treatment period, treatment responders reported significant improvements in HRQoL on all dimensions of the SF-36 (p < 0.001) and on-the-job productivity (p < 0.001), whereas sick leave decreased but did not reach statistical significance. After randomization, relapsed patients reported significantly lower QoL than non-relapsed patients on all 4 SF-36 mental health dimensions (p < 0.001). Relapsed patients reported slightly lower on-the-job productivity than non-relapsed patients and scored lower on the work efficacy and work satisfaction VAS scales. CONCLUSION: GAD adversely affects patient functioning and daily life. Short-term treatment with escitalopram reverses this impairment to population norms. GAD relapse is associated with a deterioration of HRQoL and work productivity.