Anxiety Disorders: Möller HJ

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.

Müller N, Schennach R, Riedel M, Möller HJ. · Hospital for Psychiatry & Psychotherapy, Ludwig-Maximilians-University, 80336 Munich, Germany. · Expert Rev Neurother. · Pubmed #18416656 No free full text.

Abstract: Major depressive disorder (MDD) is one of the most disabling disorders. Antidepressant pharmacotherapy is currently effective in approximately 70% of all treated cases; the potential superiority of a dual mechanism of pharmacological action (e.g., inhibiting the reuptake of serotonin and norepinephrine) is widely known. Duloxetine, a novel dual acting, selective serotonin and norepinephrine reuptake inhibitor, has demonstrated clinical efficacy in the treatment of MDD and general anxiety disorder (GAD). Duloxetine has been found to be safe and well tolerated, with mild-to-moderate adverse events, a favorable cardiovascular and sexual dysfunction profile, and minor influence on weight gain. The efficacy of duloxetine in the treatment of MDD has been established in randomized, double-blind, placebo-controlled studies. In addition to improving classical emotional symptoms of MDD, duloxetine has in particular beneficial effects on somatic symptoms of depression including pain. The superiority of duloxetine was shown over placebo, while comparison studies with other antidepressants showed only partial superiority. Randomized clinical trials in GAD also provide evidence for beneficial effects compared with placebo and improvement in quality of life, wellbeing and general health. Moreover, duloxetine is effective and well tolerated in the treatment of diabetic peripheral neuropathic pain and stress urinary incontinence. First results indicate that duloxetine might also be effective in the treatment of children with depression and pain. Overall, duloxetine is an interesting novel treatment option in the management of major depression and has shown efficacy in a broad range of diseases. It therefore may provide additional benefit to current therapeutic options in the treatment of psychiatric, internal, as well as urological disorders such as spinal dysfunctions. Due to duloxetine's properties, a wide range of use will be encountered in the mid-to-long term.

Eser D, Baghai TC, Möller HJ. · Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Nussbaumstrasse, Munich, Germany. · Int Clin Psychopharmacol. · Pubmed #17917562 No free full text.

Abstract: Depressive disorders are of the highest socioeconomic and health-economic importance, as they are the psychiatric disorders that most frequently cause psychosocial disability. Despite the progress that has been made, currently available pharmacotherapies for depression still have a limited antidepressant efficacy with a delayed onset of several weeks, and still cause side effects; these unmet needs represent important reasons to continue to search for novel treatment options. A disorganization of circadian rhythms has been suggested to play an important role in the pathophysiology of major depression, and complaints regarding disturbed sleep are frequent in depressed patients. As endogenous melatonin secretion underlies the regulation of circadian rhythms, compounds with activity at melatonergic receptors have been proposed as potential novel therapeutics. Agomelatine (S-20098), a compound with agonistic properties at MT1 and MT2 receptors and antagonistic properties at the 5-HT2C receptor, has been shown preclinically to exhibit robust antidepressant effects in several experimental paradigms. Clinical trials, including phase III studies, have now demonstrated the superior efficacy of agomelatine in comparison with placebo, and a similar efficacy in comparison with active comparators, for the treatment of major depression. Agomelatine was even effective in severely depressed patients. In all studies published so far, agomelatine was found to be safe and its overall tolerability profile was superior to that of selective serotonin reuptake inhibitors and selective serotonin and noradrenaline reuptake inhibitors.

Rupprecht R, Eser D, Zwanzger P, Möller HJ. · Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany. · World J Biol Psychiatry. · Pubmed #17071543 No free full text.

Abstract: Anxiety disorders are highly prevalent and disabling disorders which are commonly treated with pharmacotherapy and/or psychotherapy. While benzodiazepines are of great value for the treatment of acute anxiety states, their long-term use is hampered by their well-known side effect profile. Meanwhile, antidepressants represent first line treatment options for anxiety disorders. However, their slow onset of action is a disadvantage for their use in these disorders. Therefore, there is need for novel anxiolytics with a rapid onset of action and a favourable side effect profile. Currently, there is a renaissance of gamma-aminobutyric acid type A (GABAA) receptors as targets for the development of novel anxiolytic drugs. While compounds structurally related to GABA, e.g., pregabalin, have already entered large scale clinical development, GABA transporter inhibitors, subtype specific benzodiazepines and GABAA receptor modulating neuroactive steroids are promising new candidates. However, their clinical efficacy has still to be shown in clinical trials.

Möller HJ. · Department of Psychiatry, Psychiatrische Universitatsklinik, Munich, Germany. · J Clin Psychiatry. · Pubmed #12562115 No free full text.

Abstract: Historically, the clinical term for mixed depression and anxiety was anxious depression. With the publication of DSM-III-R, 2 categories were established for the purpose of classifying disorders that involve both anxiety and depression, and that classification system is currently used in DSM-IV as well. These more specific diagnostic criteria have given us a much better understanding of the anxiety spectrum, but have created a need for a better understanding of the place of benzodiazepines in clearly defined indications on the anxiety spectrum. In spite of warnings about side effects, misuse, and dependence, benzodiazepines are frequently prescribed as adjunctive therapy to antidepressants for comorbid anxiety and depression. This article presents data on the prevalence, course, and outcome of comorbid anxiety and depression. It also compares efficacy data from trials of benzodiazepines used alone and in combination with antidepressants for the treatment of anxiety disorders comorbid with depression.

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.

Möller HJ. · Psychiatric Hospital, Ludwig-Maximilians University, Munich, Germany. · J Clin Psychopharmacol. · Pubmed #10587278 No free full text.

Abstract: Benzodiazepines have been used to treat a wide variety of disorders, including generalized anxiety disorder, panic disorder, sleep disorders, somatopsychic disorders, and depression. Concerns regarding physiologic dependence, withdrawal, and abuse potential with benzodiazepines prompted the development of strict guidelines for the use of these agents. Studies have shown that the risk of physiologic dependence increases with factors such as the dose of the benzodiazepine used and the duration of treatment. Restrictions involving benzodiazepines have led to the substitution of alternative medicines that may have decreased efficacy and greater safety concerns. There is a need for a more balanced assessment of the benefits and risks associated with benzodiazepine use to ensure that patients who would truly benefit from these agents are not denied appropriate treatment.

Boerner RJ, Möller HJ. · Department of Psychiatry, Ludwig Maximilian University, Munich, Germany. · Pharmacopsychiatry. · Pubmed #10505481 No free full text.

Abstract: Patients suffering from anxiety and depression are often seen in clinical practice. In accordance with the diagnostic criteria of DSM-III/IV and ICD-10, respectively, there may be various combinations of symptoms and degrees of severity. The symptoms of these patients may range from subthreshold anxiety or depression to a combination of anxiety and depressive disorders. Besides giving an extensive survey of diagnostic problems and the epidemiological incidence of such combinations, pharmacotherapeutic approaches are critically reviewed. Metaanalyses have shown that various serotonin reuptake inhibitors (SSRI) are equivalent, if not superior, to tricyclic antidepressants (TCA) in their anti-anxiety effectiveness. Hence, SSRI may be considered a therapy of choice, not least on account of very few adverse effects and good tolerance. More recent antidepressants are under scrutiny for their anti-anxiety efficacy. Citalopram, venlafaxine and, because of its established sedative action, nefazodone seem to be particularly suited to fill a possible therapeutic gap and to provide agitated patients with an alternative to TCA.

Volz HP, Murck H, Kasper S, Möller HJ. · Psychiatric Department, University of Jena, Philosophenweg 3, 07740 Jena, Germany. · Psychopharmacology (Berl). · Pubmed #12424553 No free full text.

Abstract: RATIONALE AND OBJECTIVE: Preliminary data have shown that St John's wort might possess some specific efficacy in patients with somatoform complaints. Therefore, the efficacy of the Hypericum extract LI 160 in patients with somatoform disorders should be studied in a double-blind placebo-controlled fashion. METHODS: This was a multicentre, randomised, placebo controlled, 6-week trial comparing the efficacy of LI 160 (600 mg/day) and placebo in 151 out-patients suffering from somatization disorder (ICD-10: F45.0), undifferentiated somatoform disorder (F45.1), or somatoform autonomic dysfunctions (F45.3). The primary outcome measure was the decrease of the Hamilton Anxiety Scale, subfactor somatic anxiety (HAMA-SOM), during the trial period. RESULTS: LI 160 was superior effective concerning the primary outcome criterion HAMA-SOM [decrease from 15.39 (SD 2.68) to 6.64 (4.32) in the Hypericum group and from 15.55 (2.94) to 11.97 (5.58) in the placebo group (statistically significant difference, P=0.001)]. This was corroborated by the result of a statistically significant superior efficacy in the outcome criteria additionally used such as Clinical Global Impression, HAMA-total score, HAMA, subscore psychic anxiety, Hamilton Depression Scale, Self-Report Symptom Inventory 90 items - revised (SCL-90-R), and SCL-90-R, subscore somatic anxiety. The efficacy of LI 160 was preserved after splitting the population in those with and those without mild depressive symptoms [corrected]. Tolerability of LI 160 was excellent. CONCLUSION: The data from this trial show excellent efficacy and tolerability for LI 160 in somatoform disorders. The efficacy is independent of an existing depressive mood. This is the first study showing the efficacy of a drug in patients with somatisation disorder independent of depressive symptomatology.

Möller HJ, Volz HP, Reimann IW, Stoll KD. · Psychiatrische Klinik der Ludwig-Maximilians-Universität, Munich, Germany. · J Clin Psychopharmacol. · Pubmed #11199949 No free full text.

Abstract: Opipramol, a drug widely prescribed in Germany, is a tricyclic compound with no reuptake-inhibiting properties. However, it has pronounced D2-, 5-HT2-, and H1-blocking potential and high affinity to sigma receptors (sigma-1 and sigma-2). In early controlled trials, anxiolytic effects were revealed. However, those studies were performed before the concept of generalized anxiety disorder (GAD) was established. Because of the interesting receptor-binding profile and promising results of the early clinical trials, the authors performed a state-of-the-art placebo-controlled trial using alprazolam as an active control. Three hundred seven outpatients with GAD were included. After a 7-day single-blind placebo washout, patients were randomly assigned to receive either opipramol (final dose, 200 mg/day), alprazolam (2 mg/day), or placebo and were treated for 28 days. The efficacy of both active compounds was higher than the effects with placebo treatment. There were statistically significant differences (p < 0.05, according to the analysis of covariance) in the main outcome criterion (baseline-adjusted final means of an intent-to-treat analysis of the total scores on the Hamilton Rating Scale for Anxiety) and in secondary efficacy parameters, with global improvement of 47% for placebo and significantly more for opipramol (63%) and alprazolam (64%). Regarding safety and tolerability, no substantial differences in the number of adverse events observed between treatment groups were obvious. Sedation seemed more pronounced with alprazolam treatment than with opipramol or placebo. In this trial, it was demonstrated for the first time that opipramol, a strong but nonselective sigma site ligand, possesses anxiolytic efficacy superior to placebo in the treatment of GAD.

Volz HP, Möller HJ, Reimann I, Stoll KD. · Psychiatric Department, Friedrich-Schiller-Universität Jena, Philosophenweg 3, D-07740, Jena, Germany. · Eur Neuropsychopharmacol. · Pubmed #10793324 No free full text.

Abstract: Although somatoform disorders are highly prevalent, so far there is no established pharmacological treatment. Opipramol is a psychopharmacon widely prescribed in Germany. Early trials with opipramol showed the drug's effectiveness in anxiety states coupled with somatic complaints. Therefore, the efficacy of opipramol in somatoform disorders was evaluated using adequate clinical trial methods. A multicentre, randomized, 6-week, placebo-controlled clinical trial was performed in a total of 200 patients suffering from somatoform disorders according to ICD-10. In the main outcome criterion, the somatic subscore of the Hamilton Anxiety Scale, and in nearly all other outcome criteria opipramol (200 mg/day) was statistically more effective than placebo. A similar number of adverse events was noted in both groups. The results of this first-placebo-controlled study in somatoform disorders suggest efficacy of opipramol in this indication but need replication.

van den Oord EJ, Kuo PH, Hartmann AM, Webb BT, Möller HJ, Hettema JM, Giegling I, Bukszár J, Rujescu D. · Center for Biomarker Research and Personalized Medicine, Medical College of Virginia, Virginia Commonwealth University, PO Box 980533, Richmond, VA 23298-0533, USA. · Arch Gen Psychiatry. · Pubmed #18762592 No free full text.

Abstract: CONTEXT: Neuroticism is a trait that reflects a tendency toward negative mood states. It has long been linked to internalizing psychiatric conditions, such as anxiety and depression, and it accounts for much of the substantial comorbidity seen between these disorders. OBJECTIVE: To identify common genetic variants that affect neuroticism to better understand (the comorbidity between) a broad range of psychiatric disorders and to develop effective treatments. DESIGN, SETTING, AND PARTICIPANTS: More than 420,000 genetic markers were tested for their association with neuroticism in a genomewide association study (GWAS). The GWAS sample consisted of 1227 healthy individuals ascertained from a US national sampling frame and available from the National Institute of Mental Health genetics repository. The most promising markers were subsequently tested in a German replication sample comprising 1880 healthy individuals. MAIN OUTCOME MEASURES: A strict definition of replication (same marker, same direction of effects, and same measure) combined with a threshold we proposed previously for declaring significance in genetic studies that ensures a mean probability of producing false-positive findings of less than 10%. RESULTS: The most promising results in the GWAS and replication samples were single-nucleotide polymorphisms (SNPs) in the gene MAMDC1. These SNPs all tagged the same 2 haplotypes and had P values of 10(-5) to 10(-6) in the GWAS sample and of .006 to .02 in the replication sample. Furthermore, the replication involved the same SNPs and the same direction of effects. In a combined analysis of all data, several SNPs were significant according to the threshold that allows for 10% false-positive findings. CONCLUSIONS: The small effect sizes may limit the prognostic, diagnostic, and therapeutic use of SNP markers such as those in MAMDC1. However, the present study demonstrates the potential of a GWAS to discover potentially important pathogenic pathways for which clinically more powerful (bio)markers may eventually be developed.

Scherk H, Backens M, Zill P, Schneider-Axmann T, Wobrock T, Usher J, Reith W, Falkai P, Möller HJ, Bondy B, Gruber O. · Department of Psychiatry and Psychotherapy, Georg-August-University Goettingen, von-Siebold-Str. 5, 37075, Göttingen, Germany. · J Neural Transm. · Pubmed #18726138 No free full text.

Abstract: The SNAP-25 gene is an integral part of the vesicle docking and fusion machinery that controls neurotransmitter release. Several post mortem studies revealed a reduction of SNAP-25 protein in the hippocampus of patients with schizophrenia and bipolar disorder (BD). Thirty-eight patients with schizophrenia, BD or obsessive-compulsive disorder and 17 healthy controls participated in the study. Proton magnetic resonance spectroscopy in left hippocampus was performed in each individual. Three single nucleotide polymorphisms (SNP) of the SNAP-25 gene were genotyped. Individuals with the homozygous CC genotype of the DdeI SNP presented a significantly higher ratio of N-acetyl-aspartate (NAA)/choline-containing compounds (Cho) in the left hippocampus compared to the group of individuals with the homozygous TT genotype. The SNAP-25 genotype may modulate synaptic plasticity and neurogenesis in the left hippocampus, and altered NAA/Cho ratio may be an indicator for this genetic modulation of neuronal function in the hippocampus.

Curtis VA, Katsafouros K, Möller HJ, Medori R, Sacchetti E. · Institute of Psychiatry, Maudsley Hospital, London, UK. · J Psychopharmacol. · Pubmed #18308804 No free full text.

Abstract: The aim of this paper was to evaluate the efficacy of risperidone long-acting injectable (RLAI) for reducing negative symptoms of schizophrenia in patients with predominantly negative symptoms at baseline. A subanalysis was performed on data from the 6-month, open-label Switch to Risperidone Microspheres trial. Patients with Positive and Negative Syndrome Scale (PANSS) negative subscale score > or = 21, which was higher than their PANSS positive subscale score, were included in this subanalysis. Improvement in negative symptoms was measured by assessing change in the PANSS negative subscale and a negative factor score. Additional outcome variables included measures in general functioning, quality of life and patient satisfaction. A total of 842 patients were eligible for inclusion in this subanalysis. Six months of treatment was completed by 631 (74.9%) patients. Forty-three (5.1%) patients discontinued treatment due to an adverse event. Negative symptoms were significantly reduced by 6.1 +/- 6.3 points for the PANSS negative score and 6.1 +/- 6.4 points for the negative factor score (P < 0.0001 for both). Significant improvements were also noted for total PANSS and other PANSS subscale scores, general functioning, quality of life and patient satisfaction (P < 0.0001). The most common treatment-emergent adverse events (>5%) were: anxiety (6.8% of patients), exacerbation of disease (6.2%) and insomnia (5.7%). Overall, RLAI was well tolerated and associated with significant reductions in movement disorder severity. The treatment resulted in a significant improvement in negative symptom severity and was well tolerated in patients with predominantly negative symptoms, who switched from a stable antipsychotic regimen

Seemüller F, Riedel M, Wickelmaier F, Adli M, Mundt C, Marneros A, Laux G, Bender W, Heuser I, Zeiler J, Gaebel W, Jäger M, Möller HJ, Henkel V. · Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich, Nussbaumstrasse 7, 80336 Munich, Germany. · J Affect Disord. · Pubmed #18164767 No free full text.

Abstract: OBJECTIVE: The objective was (1) to assess the frequency of atypical depression (AD) in depressed inpatients; (2) to compare clinical features of patients with atypical and nonatypical depression (Non-AD) (3) to evaluate the meaning of single psychopathological symptoms with special respect to mood reactivity. METHOD: Diagnoses of 1073 inpatients were assessed according to DSM-IV using SCID (Structured Clinical Interview for the DSM-IV) and AMDP (Association for Methodology and Documentation). Diagnosis of atypical depression was defined according to criteria of the DSM-IV specifier for AD. All patients were rated using HAMD-21 (Hamilton Depression Scale). RESULTS: A high percentage of patients met criteria for AD (15.3%, 95% CI 13.0-17.9%). Women were more likely to suffer from AD (OR=1.54, p=0.037). There were no significant differences between AD and Non-AD patients regarding age, HAMD total baseline score, and diagnosis of any bipolar illness. In terms of psychopathology patients with AD were significantly more likely to suffer from somatic anxiety, somatic symptoms, guilt, genital symptoms, depersonalisation and suspiciousness as defined by HAMD-21 items. Interestingly, mood reactivity was not found to be significantly associated with the presence of two or more additional symptoms of AD. LIMITATIONS: Results were assessed by a post-hoc analysis, based on prospectively collected data. Compared to other inpatient samples with MDE, prevalence of bipolar disorder was rather low. CONCLUSION: (1) Frequency of AD may be underestimated, especially in inpatient samples. Further studies of inpatient samples are recommended. (2) Quality of distinct anxiety symptoms may be different in both groups, with AD patients being more likely to suffer from somatic symptoms and somatic anxiety. The presence of suspiciousness and even paranoid phenomena may not exclude a diagnosis of AD, but may be related to rejection sensitivity. (3) The mandatory presence of mood reactivity for the diagnosis of AD needs further consideration, regarding its validity for the concept.

Karch S, Jäger L, Karamatskos E, Graz C, Stammel A, Flatz W, Lutz J, Holtschmidt-Täschner B, Genius J, Leicht G, Pogarell O, Born C, Möller HJ, Hegerl U, Reiser M, Soyka M, Mulert C. · Department of Psychiatry, Ludwig-Maximilians-University of Munich, Nussbaumstrasse 7, D-80336 Munich, Germany. · J Psychiatr Res. · Pubmed #17826793 No free full text.

Abstract: Alcohol-dependence is often associated with comorbid psychiatric symptoms. However, the results concerning the influence of these symptoms on cognitive functioning in alcoholism are still inconsistent. The aim of this study was to determine performance monitoring in healthy volunteers and alcohol-dependent patients, and to assess the influence of trait anxiety on these processes. Sixteen healthy volunteers and 16 detoxified alcohol-dependent patients completed an auditory go/nogo paradigm. Functional magnetic resonance imaging, event-related potentials and behavioral data were acquired simultaneously. The patients were classified by median split based on level of self-rated trait anxiety (state-trait anxiety inventory; STAI). The results showed no significant differences regarding inhibition-associated electrophysiological and behavioral responses between alcohol-dependent patients with high-trait anxiety scores and alcohol-addicts with low-STAI scores. However, the functional MRI data revealed elevated activations during the response inhibition task especially in the middle frontal gyrus (BA 6/9), the superior frontal gyrus (BA 6/8/9) and the right inferior frontal gyrus, as well as temporo-parietal brain regions in patients with high-trait anxiety compared to non-anxious alcohol-addicts. Patients and healthy controls showed comparable results with regard to neural and behavioral responses. These results suggest that inhibitory control capacities of alcohol-dependent patients are not consistent: alcohol-addicts with high-trait anxiety ratings showed elevated neural responses compared to patients without any comorbid psychiatric symptoms. This may indicate that comorbid psychiatric symptoms need to be considered when assessing brain responses in alcohol-dependent patients.

Karch S, Graz C, Jager L, Karamatskos E, Flatz AS, Lutz J, Holtschmidt-Taschner B, Genius J, Reiser GL, Möller HJ, Hegerl U, Soyka M, Mulert C. · Dept. of Psychiatry, Ludwig-Maximilians-University, Munich, Germany. · Clin EEG Neurosci. · Pubmed #17515174 No free full text.

Abstract: Anxiety disorders are highly prevalent in patients with alcohol use disorder. The purpose of the present study was to examine the neural correlates of behavioral inhibition in alcohol-dependent patients (ICD-10: F 10.2), and in healthy controls and to determine the influence of anxiety on these processes. Therefore, behavioral responses (reaction times; error rates) and event-related potentials of 16 patients with alcohol dependence syndrome and 16 age-and gender-matched healthy controls were recorded while the participants performed an auditory go/no-go task. The patient group was stratified according to their self-rated trait anxiety (STAI) with scores above and below median. We hypothesized that patients suffering from alcohol dependence would show reduced no-go P3 amplitudes involved in response inhibition compared to healthy subjects. In patients with alcoholism and high trait anxiety the decline of no-go P3 amplitudes was expected to be less distinct. The estimation of effect size based on the reaction times of patients with high and low anxiety ratings revealed a cohen's d of 0.61 indicating a small effect. High trait anxiety ratings were also associated with slightly enhanced no-go P3 amplitudes in central brain regions (Mean no-go P3 amplitude at Cz: 10.43 microV) compared to patients with low anxiety scores (Mean 8.98 microV). The effect size (cohen's d) revealed a small effect. Using the Mann-Whitney-U-test for independent samples of the comparison of high- and low-anxious patients, however, did not reveal any significant differences concerning no-go P3 amplitudes. Patients with alcohol use disorder and healthy controls did not differ significantly with regard to reaction time, error rate and no-go P3 amplitudes. This study suggests that no-go P3 amplitudes in patients with alcohol use disorder might be affected to some degree by habitual anxiety. The results emphasize the importance of monitoring trait anxiety in studies regarding cognitive functions in subjects with alcohol use disorder.

Mergl R, Seidscheck I, Allgaier AK, Möller HJ, Hegerl U, Henkel V. · Department of Psychiatry, Ludwig-Maximilians-University Munich, Munich, Germany. · Depress Anxiety. · Pubmed #16900465 No free full text.

Abstract: Recent studies emphasize the negative impact of comorbidity on the course of depression. If undiagnosed, depression and comorbidity contribute to high medical utilization. We aimed to assess (1) prevalences of depression alone and with comorbidity (anxiety/somatoform disorders) in primary care, (2) coexistence of anxiety/somatoform disorders in depressive patients, and (3) diagnostic validity of two screeners regarding depression with versus without comorbidity. We examined 394 primary care outpatients using the Composite International Diagnostic Interview (CIDI), the General Health Questionnaire (GHQ-12), and the Well-Being Index (WHO-5). We conducted configurational frequency analyses to identify nonrandom configurations of the disorders and receiver operating characteristic (ROC)-analyses to assess diagnostic validity of the screeners. Point prevalence of any depressive disorder was 22.8%; with at least one comorbid disorder, 15%; and with two comorbid conditions, 6.1%, which significantly exceeded expected percentage (0.9%, P< or =.0001). Depression without comorbidity occurred significantly less often than expected by chance (P< or =.0007). Comorbidity of depressive and anxiety or somatoform disorders was associated with a high odds ratio (6.25). The screeners were comparable regarding their diagnostic validity for depression with [GHQ-12: area under the curve (AUC)=0.86; WHO-5: AUC=0.88] and without comorbidity (GHQ-12: AUC=0.84; WHO-5: AUC=0.86). It can be concluded that comorbidity between depression and anxiety/somatoform disorders in primary care may occur much more frequently than expected. These results confirm assumptions that the current division between depression and anxiety might be debatable. Validity of screeners tested in our study was not affected by comorbid conditions (e.g., anxiety or somatoform disorders).

Zwanzger P, Eser D, Völkel N, Baghai TC, Möller HJ, Rupprecht R, Padberg F. · Department of Psychiatry, Ludwig-Maximilian-University of Munich, Munich, Germany. · Int J Neuropsychopharmacol. · Pubmed #16817979 No free full text.

Abstract: Low-frequency (LF) rTMS shows beneficial effects in patients with depression and anxiety disorders. To explore its anxiolytic properties we investigated the effects of rTMS on experimentally induced panic attacks. Eleven healthy subjects underwent 1 Hz rTMS or sham rTMS over the right dorsolateral prefrontal cortex in a randomized cross-over protocol. Panic induction with 50 mug CCK-4 was carried out immediately after rTMS. Response to CCK-4 was assessed using the Acute Panic Inventory and the Panic Symptom Scale and measurements of heart rate, plasma ACTH and cortisol. All subjects reported a marked panic response following CCK-4 administration after both real and sham rTMS. Moreover, injection of CCK-4 induced a marked increase in heart rate, cortisol and ACTH concentrations. However, ANOVA showed no significant differences in any of the measures between both conditions. In contrast to the effects of pretreatment with alprazolam on CCK-4-induced panic in healthy subjects LF rTMS does not affect CCK-4-induced panic and cortisol or ACTH release.

Pogarell O, Juckel G, Mavrogiorgou P, Mulert C, Folkerts M, Hauke W, Zaudig M, Möller HJ, Hegerl U. · Department of Psychiatry, Division of Clinical Neurophysiology, Ludwig-Maximilians-University of Munich, Germany. · Int J Psychophysiol. · Pubmed #16554100 No free full text.

Abstract: Neurophysiological studies in patients with obsessive-compulsive disorder (OCD) consistently revealed frontal alterations of cortical activity but otherwise showed inhomogeneous results, conceivably due to variable subgroups with diverse pathomechanisms involved. The aim of this study was to investigate quantitative electroencephalography (EEG) in patients with OCD as compared to healthy controls and to correlate neurophysiological data with clinical variables. EEGs were digitally recorded from 18 unmedicated patients (8 male, mean age 32.4+/-11.8 years, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) 15.3+/-7.9) and 18 matched healthy controls, and analysed quantitatively. The mean frequency of EEG background activity and absolute power in delta, theta, alpha and beta frequency bands were calculated. Mean frequency of background activity was significantly lower in patients as compared to controls (-1.44/s, p<0.01), predominantly for the frontal electrode positions. Power spectra revealed increased delta- and decreased alpha-/beta-power in the group of patients (p<0.05, patients vs. controls). Correlation analyses showed significant positive correlations of EEG-power with the Y-BOCS sub-scores "obsessions", and negative correlations with the sub-scores "compulsions" (Spearman's correlations, r(s)=+0.48 to +0.70, and -0.47 to -0.6, respectively, p<0.05). The data provide evidence of a dysfunction of frontal cortical activity in patients with OCD. The opposite correlations of neurophysiological data and clinical features, i.e. obsessions and compulsions, are suggestive of pathophysiological differences based on the presence of the respective cardinal symptoms of OCD.

Van den Oord EJ, Rujescu D, Robles JR, Giegling I, Birrell C, Bukszár J, Murrelle L, Möller HJ, Middleton L, Muglia P. · Virginia Institute for Psychiatric and Behavioral Genetics, Medical College of Virginia of Virginia Commonwealth University, P.O. Box 980126, Richmond VA 23298-0126, USA. · Schizophr Res. · Pubmed #16229988 No free full text.

Abstract: Considerable controversy exists concerning the positive and negative syndrome scale (PANSS), one of the most widely used instruments in schizophrenia research. In this article we revisited the factor structure and external validity of the PANSS in a sample of 500 participants with DSM IV diagnoses of schizophrenia. We found that a model with six latent factors provided a relatively good fit, considered adequate by two rules of thumb. Five factors corresponded closely to those typically derived in other studies: Negative, Positive, Excited/Activation, Anxious-Depressed/Dysphoric, and Disorganized/Autistic preoccupation. The sixth factor seemed to have face validity and was labeled Withdrawn. With the exception of Anxious-Depressed/Dysphoric, Cronbach's Alpha ranged from 0.70 to 0.85 suggesting an acceptable internal consistency. External validity was studied through correlations with socio-demographic variables, DSM IV (subtype) diagnoses, clinical characteristics, and drug use. The many significant correlations suggested that the six PANSS scales measure meaningful aspects of schizophrenia. Furthermore, the pattern of correlations varied, providing evidence that the scales assessed partly different aspects of the disease. Our analyses also suggested that some of the controversy about the PANSS can possibly be attributed to methodological factors where the substantial cross-loadings of some PANSS items may play an important role.

Möller HJ, Bauer M, Fritze J, Haen E, Laux G, Müller WE, Rüther E. · Psychiatrische Klinik der Ludwig-Maximilians-Universität München. · MMW Fortschr Med. · Pubmed #15727113 No free full text.

Abstract: With the tricyclics, selective serotonin reuptake inhibitors (SSRIs) and other substances, we now have available a range of medications for the treatment of depression and other psychological disorders (e.g. anxiety, panic). Nevertheless, only some of the patients experience a remission of their depressive symptoms. The occurrence of side effects and the only modest level of effectiveness result in inadequate compliance on the part of the patient. With venlafaxine and duloxetine two representatives of the selective serotonin and noradrenaline reuptake inhibitor (SSNRI) class of antidepressants are now available. SSNRIs have a dual effect coupled with high selectivity. The present article the extent to which this particular action mechanism results in an improved clinical efficacy and tolerability profile of the SSNRIs, in particular in comparison with SSRIs.

Sato T, Bottlender R, Kleindienst N, Möller HJ. · Psychiatrische Klinik, Ludwig-Maximilians-Universität München, Nussbaumstrasse 7 80336 Munich, Germany. · J Affect Disord. · Pubmed #15708416 No free full text.

Abstract: BACKGROUND: Early authors described hypomanic symptoms as mixed features in depressive episode, but this syndrome has not been sufficiently explored in previous studies. METHODS: 958 consecutive depressed patients were assessed by using a standardized method in terms of 43 psychiatric symptoms at hospitalization. RESULTS: A principal component analysis, followed by varimax rotation, extracted six interpretable factors: typical vegetative symptoms, depressive retardation/loss of feeling, hypomanic syndrome, anxiety, psychosis, and depressive mood/hopelessness. The extracted factor structure was relatively stable among several patient groups. There was no evidence that the hypomanic factor was exaggerated by antidepressant pretreatments before hospitalization. Bipolar diagnoses were associated with higher scores on depressive retardation and hypomanic symptoms, and a lower score on anxiety. LIMITATIONS: Psychiatric syndromes and their interrelationships, found in the present study, may be strongly influenced by the rating instrument used. The sample of this study was depressed inpatients. The results should not be generalized for depressed outpatients or epidemiological depressed populations. CONCLUSIONS: Hypomanic symptoms, as characterized by the flight of ideas, racing thought, increased drive, excessive social contact, irritability, and aggression are a salient syndrome in acutely ill depressed patients, lending support to the factor validity of mixed depression. The symptoms may not be related to pretreatments with antidepressants, or comorbidity of substance abuse, suggesting that they reflect various natural phenomenological manifestations of depressive episodes. Anxiety is unlikely to play a major role in the core phenomenological features of mixed depression. Hypomanic symptoms during a depressive episode were more represented in bipolar disorders, which may serve for further clarifications of latent bipolarity in unipolar depression, and prediction of switch into maniform states under biological depression treatments.

Rupprecht R, Möller HJ. · Klinik für Psychiatrie und Psychotherapie, Ludwig-Maximilians-Universität München. · MMW Fortschr Med. · Pubmed #15536705 No free full text.

Abstract: Panic disorder is defined as, recurrent, unexpected panic attacks. Panic attack means a period of intensive fear or discomfort, accompanied by a range of physical or psychological symptoms. Subsequently, anticipatory anxiety and avoidance behavior often develop. Panic disorder may or may not be accompanied by agoraphobia. Panic disorder can be treated both by psychotherapeutic and pharmacological measures. An ideal approach is combination therapy in the sense of a multimodal concept; with regard to cognitive behavioral therapy in particular, its effectiveness in the treatment of panic disorder is well documented. For pharmacotherapy, antidepressive agents, in particular selective serotonin reuptake inhibitors, are the drugs of first choice. Benzodiazepines should be given for only a few weeks until the antipanic effect of the antidepressants kicks in. With appropriate treatment, the prognosis is favorable.