Anxiety Disorders: Bandelow B

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.

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.

Baldwin DS, Anderson IM, Nutt DJ, Bandelow B, Bond A, Davidson JR, den Boer JA, Fineberg NA, Knapp M, Scott J, Wittchen HU, Anonymous00170. · Division of Clinical Neurosciences, University of Southampton, Southampton, UK. · J Psychopharmacol. · Pubmed #16272179 No free full text.

Abstract: These British Association for Psychopharmacology guidelines cover the range and aims of treatment for anxiety disorders. They are based explicitly on the available evidence and are presented as recommendations to aid clinical decision making in primary and secondary medical care. They may also serve as a source of information for patients and their carers. The recommendations are presented together with a more detailed review of the available evidence. A consensus meeting involving experts in anxiety disorders reviewed the main subject areas and considered the strength of evidence and its clinical implications. The guidelines were constructed after extensive feedback from participants and interested parties. The strength of supporting evidence for recommendations was rated. The guidelines cover the diagnosis of anxiety disorders and key steps in clinical management, including acute treatment, relapse prevention and approaches for patients who do not respond to first-line treatments.

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.

Stein DJ, Bandelow B, Hollander E, Nutt DJ, Okasha A, Pollack MH, Swinson RP, Zohar J, Anonymous00173. · Medical Research Council Research Unit on Anxiety Disorder, University of Stellenbosch, Cape Town, Tygerberg, South Africa. · CNS Spectr. · Pubmed #14767396 No free full text.

Abstract: Posttraumatic stress disorder (PTSD) is a common and disabling condition. In addition to combat-related PTSD, the disorder occurs in civilians exposed to severe traumatic events, with the community prevalence rate for the combined populations reaching as high as 12%. If left untreated, PTSD may continue for years after the stressor event, resulting in severe functional and emotional impairment and a dramatic reduction in quality of life, with negative economic consequences for both the sufferer and society as a whole. Although PTSD is often overlooked, diagnosis is relatively straightforward once a triggering stressor event and the triad of persistent symptoms-reexperiencing the traumatic event, avoiding stimuli associated with the trauma, and hyperarousal have been identified. However, comorbid conditions of anxiety and depression frequently hamper accurate diagnosis. Treatment for PTSD includes psychotherapy and pharmacotherapy. The latter includes selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and monoamine oxidase inhibitors. Only SSRIs have been proven effective and safe in long-term randomized controlled trials. Current guidelines from the Expert Consensus Panel for PTSD recommend treatment of chronic PTSD for a minimum of 12-24 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.

Greist JH, Bandelow B, Hollander E, Marazziti D, Montgomery SA, Nutt DJ, Okasha A, Swinson RP, Zohar J, Anonymous00171. · Healthcare Technology Systems, Inc., Madison, Wisconsin 53717, USA. · CNS Spectr. · Pubmed #14767394 No free full text.

Abstract: What are the latest psychotherapeutic and pharmacotherapeutic treatment recommendations for obsessive-compulsive disorder (OCD)? OCD is a relatively common disorder with a lifetime prevalence of approximately 2% in the general population. It often has an early onset, usually in childhood or adolescence, and frequently becomes chronic and disabling if left untreated. High associated healthcare utilization and costs, and reduced productivity resulting in loss of earning, pose a huge economic burden to OCD patients and their families, employers, and society. OCD is characterized by the presence of obsessions and compulsions that are time-consuming, cause marked distress, or significantly interfere with a person's functioning. Most patients with OCD experience symptoms throughout their lives and benefit from long-term treatment. Both psychotherapy and pharmacotherapy are recommended, either alone or in combination, for the treatment of OCD. Cognitive-behavioral therapy is the psychotherapy of choice. Pharmacologic treatment options include the tricyclic antidepressant clomipramine and the selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. These have all shown benefit in acute treatment trials; clomipramine, fluvoxamine, fluoxetine, and sertraline have also demonstrated benefit in long-term treatment trials (at least 24 weeks), and clomipramine, sertraline, and fluvoxamine have United States Food and Drug Administration approvals for use in children and adolescents. Available treatment guidelines recommend first-line use of an SSRI (ie, fluoxetine, fluvoxamine, paroxetine, sertraline, or citalopram) in preference to clomipramine, due to the latter's less favorable adverse-event profile. Further, pharmacotherapy for a minimum of 1-2 years is recommended before very gradual withdrawal may be considered.

Bandelow B. · Department of Psychiatry and Psychotherapy, University of Göttingen, Germany. · CNS Spectr. · Pubmed #18849910 No free full text.

Abstract: Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacotherapy treatments for obsessive-compulsive disorder (OCD). Clomipramine is effective in OCD but associated with more adverse events. Typically, higher doses of antidepressants are required for OCD. Up to 50% of patients do not respond to initial treatment of OCD. Treatment options for nonresponders include augmentation of antidepressants with atypical antipsychotics, among other strategies. First-line treatments for anxiety disorders include SSRIs, serotonin norepinephrine reuptake inhibitors, and pregabalin. Tricyclic antidepressants are equally effective as SSRIs, but are less well tolerated. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of dependency and tolerance. Other treatment options include irreversible and reversible monoamine oxidase inhibitors, the atypical antipsychotic quetiapine, and other medications. Cognitive-behavioral therapy has been sufficiently investigated in controlled studies of OCD and anxiety disorders and is recommended alone or in combination with the above medications.

Wedekind D, Engel K, Bandelow B. · Klinik für Psychiatrie und Psychotherapie der Georg-August-Universität Göttingen. · Fortschr Neurol Psychiatr. · Pubmed #18833508 No free full text.

This publication has no abstract.

Bandelow B, Wedekind D, Leon T. · University of Göttingen, Department of Psychiatry & Psychotherapy, von-Siebold-Str. 5, D-37075 Göttingen, Germany. · Expert Rev Neurother. · Pubmed #17610384 No free full text.

Abstract: Pregabalin is the first anxiolytic pharmacologic alternative for the treatment of generalized anxiety disorder (GAD) to be introduced in more than 10 years. GAD is a significant psychiatric condition with lifetime prevalence rates ranging between 5.7 and 6.4%. It causes significant impairment in quality of life and functional abilities equivalent to those associated with major depression. Randomized, controlled trials confirm that pregabalin is superior to placebo and comparable with lorazepam, alprazolam and venlafaxine for the treatment of patients with moderate-to-severe GAD. The onset of anxiolytic activity for pregabalin is apparent within 1 week following initiation of treatment, which is more rapid than that obtained with paroxetine and venlafaxine. Additionally, pregabalin has demonstrated potential for the prevention of relapse of GAD. Recently, the efficacy, safety and tolerability of pregabalin were also shown in a placebo-controlled study with elderly patients. Safety and tolerability profiles are favorable, with transient dizziness and somnolence of mild-to-moderate severity being the most commonly reported adverse events. Pregabalin has minimal potential for drug-drug interactions and does not provoke a clinically significant withdrawal response. Furthermore, pregabalin has low potential for abuse and dependence, unlike other classes of medications used for the treatment of GAD. Clinicians may consider the use of pregabalin in lieu of benzodiazepines as an alternative therapy for their patients with GAD.

Stein DJ, Baldwin DS, Dolberg OT, Despiegel N, Bandelow B. · Department of Psychiatry, University of Cape Town, South Africa. · J Clin Psychiatry. · Pubmed #17196054 No free full text.

Abstract: BACKGROUND: The placebo response rate has increased in several psychiatric disorders and is a major issue in the design and interpretation of clinical trials. The current investigation attempted to identify potential predictors of placebo response through examination of the placebo-controlled clinical trial database for escitalopram in 3 anxiety disorders and in major depressive disorder (MDD). METHOD: Raw data from placebo-controlled studies (conducted from 2002 through the end of 2004) of escitalopram in patients meeting DSM-IV criteria for MDD and anxiety disorders (generalized anxiety disorder [GAD], social anxiety disorder [SAD], panic disorder) were used. Potential predictors examined were type of disorder, location of study, dosing regimen, number of treatment arms, gender of patients, and duration and severity of disorder. RESULTS: Placebo response (defined as the percent decrease from baseline in the reference scale) was higher in GAD and MDD studies conducted in Europe (p < .0001 and p = .0006, respectively) and was not associated with gender or duration of episode. In GAD, the placebo response rate was higher in a European fixed-dose study, which also had more treatment arms. In SAD and in U.S. specialist-treated MDD, a higher placebo response rate was predicted by decreased baseline disorder severity. CONCLUSION: Additional work is needed before definitive recommendations can be made about whether standard exclusion criteria in clinical trials of antidepressants, such as mild severity of illness, maximize medication-to-placebo differences. This analysis in a range of anxiety disorders and MDD suggests that there may be instances in which the predictors of placebo response rate themselves vary across different conditions.

Bandelow B. · Department of Psychiatry and Psychotherapy, University of Gottingen, Gottingen, Germany. · CNS Spectr. · Pubmed #17008827 No free full text.

Abstract: Response and remission rates are commonly used to evaluate the efficacy of treatments for anxiety disorders and other psychiatric illnesses. Response is generally regarded as a clinically meaningful improvement in symptoms, while remission, the goal of treatment, is generally thought of as the absence or near absence of symptoms following illness, accompanied by a return to premorbid levels of functioning. Response and remission are often defined using psychiatric rating scales, based on score cutoffs or the magnitude of score changes from baseline. While no universally accepted criteria exist, a commonly used threshold for response is a >50% improvement in the total score, while for remission, various cutoff points have been used. Comparison of cutoffs or change scores for disease-specific scales with Clinical Global Impressions ratings is a useful way of evaluating response and remission criteria across disorders. To illustrate the use of disease-specific and global measures, this article summarizes data from randomized, placebo-controlled studies of adult patients with generalized anxiety disorder, social anxiety disorder, or panic disorder treated with the serotonin norepinephrine reuptake inhibitor venlafaxine extended release, for which acute-phase data are available (a total of 13 trials).

Bandelow B, Rüther E. · Department of Psychiatry and Psychotherapy, University of Göttingen, Germany. · CNS Spectr. · Pubmed #15448584 links to  free full text

Abstract: A substantial number of patients with panic disorder and agoraphobia may remain symptomatic after standard treatment (including selective serotonin reuptake inhibitors, tricyclic antidepressants, benzodiazepines, or irreversible monamine oxidase inhibitors). In this review, recommendations for the treatment of patients with panic disorder and agoraphobia who do not respond to these drugs are provided. Nonresponse to drug treatment could be defined as a failure to achieve a 50% reduction on a standard rating scale after a minimum of 6 weeks of treatment in adequate dose. When initial treatments have failed, the medication should be changed to other standard treatments. In further attempts at treatment, drugs should be used that have shown promising results in preliminary studies, such as venlafaxine. Combination treatments may be used, such as the combination of an selective serotonin reuptake inhibitor and a benzodiazepine. Psychological treatments such as cognitive-behavioral therapy have to be considered in all patients, regardless whether they are nonresponders or not. According to existing studies, a combination of pharmacologic treatment with cognitive-behavioral therapy can be recommended.

Bandelow B, Zohar J, Hollander E, Kasper S, Möller HJ, Anonymous00167. · Department of Psychiatry and Psychotherapy, University of Göttingen, Germany. · World J Biol Psychiatry. · Pubmed #12516310 No free full text.

Abstract: In this report, recommendations for the pharmacological treatment of anxiety and obsessive-compulsive disorders are presented, based on available randomized, placebo- or comparator-controlled clinical studies. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for panic disorder. Tri2-cyclic antidepressants (TCAs) are equally effective, but they are less well tolerated than the SSRIs. In treatment-resistant cases, benzodiazepines like alprazolam may be used when the patient does not have a history of dependency and tolerance. Due to possible serious side effects and interactions with other drugs and food components, the irreversible monamine oxidase inhibitor (MAOI) phenelzine should be used only when first-line drugs have failed. In generalised anxiety disorder, venlafaxine and SSRIs can be recommended, while buspirone and imipramine may be alternatives. For social phobia, SSRIs are recommended for the first line, and MAOIs, moclobemide and benzodiazepines as second line. Obsessive-compulsive disorder is best treated with SSRIs or clomipramine.

Kronenberg G, Berger P, Tauber RF, Bandelow B, Henkel V, Heuser I. · Psychiatric Department, Charité-CBF, Free University of Berlin, Germany. · Pharmacopsychiatry. · Pubmed #15706463 No free full text.

Abstract: OBJECTIVE: The present study was designed to examine the efficacy and tolerability of the non-peptide neurokinin-3 (NK3) receptor antagonist SR142801 in outpatients suffering from panic disorder. METHODS: In a pilot study, 52 patients who were responders to a cholecystokinin tetrapeptide (CCK-4) challenge were randomized to four weeks of treatment with SR142801 (n = 36) or placebo (n = 16). Panic symptoms were assessed on weekly visits and a second CCK-4 challenge was performed at the end of the double-blind placebo controlled treatment period. Tolerability of SR142801 was generally good. RESULTS: The proportion of patients who had at least one adverse event (AE) in the SR142801 group and the placebo group was similar (58.3 and 50 %, respectively). Independent of treatment group, patients' overall panic symptomatology was substantially improved at the end of the treatment. CONCLUSION: With regard to efficacy of outcome, the compound was not significantly different from placebo. However, post-CCK-4 plasma prolactin concentrations showed a significant difference between placebo and SR142801.

Bandelow B, Behnke K, Lenoir S, Hendriks GJ, Alkin T, Goebel C, Clary CM. · Department of Psychiatry and Psychotherapy, University of Göttingen, von-Siebold-Strasse 5, D-37505 Göttingen, Germany. · J Clin Psychiatry. · Pubmed #15096081 No free full text.

Abstract: OBJECTIVE: Several classes of medications have demonstrated efficacy in panic disorder, but direct comparison of 2 proven treatments is still uncommon. The purpose of this study was to compare sertraline and paroxetine in the acute treatment of panic disorder. METHOD: Adult outpatients with panic disorder with or without agoraphobia (DSM-IV and ICD-10 criteria) were randomly assigned in double-blind fashion to 12 weeks of treatment with flexible doses of sertraline (titrated up to 50-150 mg/day; N = 112) or paroxetine (titrated up to 40-60 mg/day; N = 113). Patients were then tapered off medication over 3 weeks. The primary analysis was a noninferiority analysis of Panic and Agoraphobia Scale (PAS) scores. Secondary measures included panic attack frequency and the Clinical Global Impressions-Improvement scale (CGI-I) (with responders defined as those with a CGI-I score < or = 2). Data were collected from January 2000 to June 2001. RESULTS: Sertraline and paroxetine were associated with equivalent levels of improvement on the PAS total score, as well as on all secondary outcome measures. Eighty-two percent of patients taking sertraline versus 78% of those taking paroxetine were CGI-I responders at endpoint. Numerically more patients on paroxetine treatment compared with sertraline treatment discontinued due to adverse events (18% vs. 12%; NS), and a significantly higher proportion of paroxetine patients showed > or = 7% weight gain (7% vs. < 1%; p <.05). During the taper period, the proportion of panic-free patients increased by 4% with sertraline but decreased by 11% with paroxetine (p <.05). CONCLUSION: Sertraline and paroxetine had equivalent efficacy in panic disorder, but sertraline was significantly better tolerated and was associated with significantly less clinical worsening during taper than paroxetine.

Broocks A, Meyer T, Opitz M, Bartmann U, Hillmer-Vogel U, George A, Pekrun G, Wedekind D, Rüther E, Bandelow B. · Department of Psychiatry and Psychotherapy, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. · Eur Neuropsychopharmacol. · Pubmed #12729940 No free full text.

Abstract: Blunted neuroendocrine and physiological responses to the selective 5-HT(1A) receptor agonist, ipsapirone, have been observed in patients with panic disorder and/or agoraphobia (PDA). In order to examine whether this hyporesponsiveness to ipsapirone is modified by pharmacological or non-pharmacological therapeutic interventions, challenges with an oral dose of ipsapirone (0.3 mg/kg) and placebo were performed in patients with PDA before and after 10 weeks of treatment with clomipramine, aerobic exercise and placebo. Before treatment, administration of ipsapirone was followed by significant increases of cortisol, anxiety and other psychopathological symptoms in comparison to the placebo challenge. In addition, a significant decrease of body temperature was observed. After the 10-week treatment period, the psychological responses to ipsapirone were significantly reduced in the clomipramine and the exercise group. In contrast, there was a non-significant trend towards higher cortisol responses after clomipramine and exercise treatment. The hypothermic response to ipsapirone was significantly reduced by clomipramine treatment. In conclusion, our results demonstrate that effective treatment of panic disorder has divergent effects on the psychological, neuroendocrine and temperature responses to ipsapirone.

Broocks A, Bandelow B, Koch K, Bartmann U, Kinkelbur J, Schweiger U, Hohagen F, Hajak G. · Department of Psychiatry and Psychotherapy, University of Lübeck, 23538 Lübeck, Germany. · Neuropsychopharmacology. · Pubmed #12093600 links to  free full text

Abstract: Reduced 5-HT1A-receptor responsiveness has been reported in patients with panic disorder(PD) and/or agoraphobia (PDA). Although many of these patients are regular smokers, it has not been examined whether psychological or neurobiological effects induced by the selective 5-HT1A-receptor agonist, ipsapirone, are affected by the smoking status of the patients.In order to clarify this question neuroendocrine challenges with oral doses of ipsapirone (0.3 mg/kg) and placebo were performed in 39 patients with PDA, and results were compared between patients who smoked (>10 cigarettes per day, n = 17) and patients who had been non-smokers for at least two years (n = 22).Patients who were smokers (but did not smoke during the challenge procedure) had significantly reduced baseline concentrations of cortisol and a significantly lower body temperature. In comparison to placebo, administration of ipsapirone was associated with significant increases of various psychological symptoms and plasma cortisol concentrations. The subgroup of PD patients who were smokers showed significantly higher cortisol responses to ipsapirone than non-smokers.In conclusion, smoking status has to be taken into account when assessing the responsiveness of 5-HT1A receptors in patients with psychiatric disorders. The prevention of smoking during challenge sessions might not be the ideal approach in heavy smokers, since sudden abstinence from smoking is likely to affect neurobiological and possibly psychological responses to ipsapirone.

Bandelow B, Broocks A, Pekrun G, George A, Meyer T, Pralle L, Bartmann U, Hillmer-Vogel U, Rüther E. · Department of Psychiatry, University of Göttingen, Germany. · Pharmacopsychiatry. · Pubmed #11071019 No free full text.

Abstract: BACKGROUND: A new 13-item scale has been developed for measuring severity of illness in patients with panic disorder and agoraphobia, the Panic and Agoraphobia Scale (P & A). The scale has five subscales covering the main factors that reduce quality of life in panic disorder patients (panic attacks, avoidance, anticipatory anxiety, disability and worries about health). The application of this scale in a double-blind placebo-controlled panic disorder trial is described. At the same time, the aim of the study was to compare the therapeutic effects of aerobic exercise with a treatment of well-documented efficacy. METHODS: Patients with Panic disorder (DSM-IV) were randomly assigned to three treatment modalities: running (n=45), clomipramine (n=15) or placebo (n=15). Treatment efficacy was measured with the Panic and Agoraphobia Scale (P & A) and other rating scales. RESULTS: According to the P & A and other scales, both exercise and clomipramine led to a significant decrease of symptoms in comparison to placebo treatment. Clomipramine was significantly more effective and improved anxiety symptoms significantly earlier than exercise. The evaluation of the P & A subscales revealed that exercise exerted its effect mainly reducing anticipatory anxiew and panic-related disability. CONCLUSIONS: The new Panic and Agoraphobia Scale was shown to be sensitive to differences between different panic treatments. Analysis of the scales five subscores may help to understand mechanisms of action of panic disorder treatments.

Bandelow B, Brunner E, Beinroth D, Pralle L, Broocks A, Hajak G, Rüther E. · Department of Psychiatry, University of Göttingen, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #10195340 No free full text.

Abstract: In clinical trials in psychiatry, changes in severity are usually measured with ordinal level scales which are applied repeatedly during the trial, showing a constant decline in psychopathology scores as treatment leads to improvement. Previous non-parametric tests for repeated measures in factorial designs did not test the hypothesis that scale scores decrease constantly during the trial. A recently developed "rank test for ordered alternatives in a mixed model" was developed and applied to the data of a clinical trial in panic disorder. Thirty-seven outpatients with panic disorder and agoraphobia (PDA) were treated with imipramine (75-150 mg/day) in an 8-week open, prospective trial. Patients with intercurrent agoraphobia were instructed in practising self-exposure in their agoraphobic situations. The total score on the Panic and Agoraphobia Scale, the Hamilton Anxiety Scale (HAMA) and the Clinical Global Impression Scale (CGI) were used as the main efficacy measures. The new rank test showed significant treatment results in all scales applied. Treatment results were excellent, as was shown by a decrease in the average Panic and Agoraphobia Scale severity scores from 28.9 (range 14-45) to 13.3 (range 0-37; rank statistic Tn = 6.7; p < 0.0001). The largest effect size r(w) of all clinician-rated scales was seen with the observer-rated version of the Panic and Agoraphobia Scale, although closely followed by the CGI and the HAMA. Among the self-rated scales, the Panic and Agoraphobia Scale also showed the largest effect size. All five subscores of the Panic and Agoraphobia Scale showed significant improvements. The highest treatment effect sizes were seen in the "panic attacks" subscore, followed by the "anticipatory anxiety" subscore. The new statistical test applied in this study, which has some advantages in comparison with previously applied tests, is suitable for psychiatric treatment evaluations since it can also be applied in the case of discrete repeated measurements.

Bandelow B, Engel K, Wedekind D. · Klinik für Psychiatrie und Psychotherapie der Universität Göttingen. · MMW Fortschr Med. · Pubmed #19504830 No free full text.

This publication has no abstract.

Stein DJ, Bandelow B, Dolberg OT, Andersen HF, Baldwin DS. · Department of Psychiatry, University of Cape Town, Groote Schuur Hospital (J-2), Anzio Rd., Observatory 7925, Cape Town, South Africa. · Ann Clin Psychiatry. · Pubmed #19439157 No free full text.

Abstract: BACKGROUND: Anxiety disorders are associated with significant disability. There is growing interest in the question of whether pharmacotherapy that effectively reduces symptoms can also restore function. Recovery could potentially be defined as a lack of disability, with an associated reduction in symptom severity. Conversely, relapse could potentially be defined in terms of either increased disability or increased symptoms. METHODS: We analyzed a database of randomized controlled trials of escitalopram in generalized anxiety disorder (GAD) and social anxiety disorder (SAD), focusing on the relationship between disorder-specific severity scales, and the Sheehan Disability Scale (SDS). In short-term studies, cut-points on symptom scales were derived for recovered function. In relapse prevention studies, the effects of defining relapse in terms of increased disability scores were examined. RESULTS: In GAD and SAD, there is a close correlation between primary symptom severity scales and the SDS, both in the short term and during relapse prevention. Thus, functional recovery is associated with relatively low symptom severity scores, and rates of relapse-defined in terms of increased disability-are significantly lower on escitalopram than on placebo. CONCLUSIONS: These data indicate that recovery and relapse can potentially be defined either in terms of symptom severity or functioning. Thus, the concept of functional recovery and relapse may be useful in defining treatment outcomes. Longer-term treatment of anxiety disorders is needed to ensure functional recovery.

Wedekind D, Sprute A, Broocks A, Hüther G, Engel K, Falkai P, Bandelow B. · Department of Psychiatry and Psychotherapy, University of Goettingen, Von-Siebold-Strasse 5, D-37075 Goettingen, Germany. · Curr Pharm Des. · Pubmed #19075728 No free full text.

Abstract: INTRODUCTION: Data on basal hypothalamo-pituitary-adrenomedullary (HPA) function over controlled treatment trials with serotonergic drugs in anxiety disorders are still rare. METHODS: 29 patients with panic disorder participating in a 10 week randomized, controlled trial (paroxetine vs. placebo with exercise or relaxation; N=60) collected urine for cortisol excretion over 3 consecutive nights before start and before termination of the treatment episode. Urinary cortisol was measured by radioimmunoassay. Efficacy measures were the Clinical Global Impression Scale (CGI) and the Panic and Agoraphobia Scale (P&A). 83% were female (p<.05 vs. males). 55% received additional aerobic exercise, and 45% relaxation. 55% received paroxetine treatment, and 45% placebo. Significantly fewer males received placebo treatment (p<.05). RESULTS: All subjects improved significantly. Cortisol excretion did not differ between treatment groups or at pre-/post measurements. Females showed a significantly higher variability of cortisol excretion compared to males, at pre-(p<.005) and post (p=.015) assessments. Males displayed a trend to lower basal HPA function at end of treatment (p=.08). HPA variability after treatment showed a trend to be higher in the paroxetine (p=.052) -who clinically improved significantly better- compared to the placebo group. No relationship between HPA activity and treatment response or with exercise was detected. DISCUSSION: HPA function shows significant gender differences, with females having a higher HPA function variability. Future studies on HPA function in treatment trials should address gender and medication effects.

Engel K, Bandelow B, Gruber O, Wedekind D. · Department of Psychiatry and Psychotherapy, Anxiety Research Unit, University of Goettingen, von-Siebold-Strasse 5, 37075 Goettingen, Germany. · J Neural Transm. · Pubmed #18568288 links to  free full text

Abstract: Neuroimaging studies have gained increasing importance in validating neurobiological network hypotheses for anxiety disorders. Functional imaging procedures and radioligand binding studies in healthy subjects and in patients with anxiety disorders provide growing evidence of the existence of a complex anxiety network, including limbic, brainstem, temporal, and prefrontal cortical regions. Obviously, "normal anxiety" does not equal "pathological anxiety" although many phenomena are evident in healthy subjects, however to a lower extent. Differential effects of distinct brain regions and lateralization phenomena in different anxiety disorders are mentioned. An overview of neuroimaging investigations in anxiety disorders is given after a brief summary of results from healthy volunteers. Concluding implications for future research are made by the authors.