Depression: Möller HJ

Bauer M, Bschor T, Pfennig A, Whybrow PC, Angst J, Versiani M, Möller HJ, Anonymous00106. · University Hospital Carl Gustav Carus, Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany. · World J Biol Psychiatry. · Pubmed #17455102 No free full text.

Abstract: These practical guidelines for the biological treatment of unipolar depressive disorders in primary care settings were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). They embody the results of a systematic review of all available clinical and scientific evidence pertaining to the treatment of unipolar depressive disorders and offer practical recommendations for general practitioners encountering patients with these conditions. The guidelines cover disease definition, classification, epidemiology and course of unipolar depressive disorders, and the principles of management in the acute, continuation and maintenance phase. They deal primarily with biological treatment (including antidepressants, other psychopharmacological and hormonal medications, electroconvulsive therapy, light therapy).

Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Möller HJ, Anonymous00259. · Department of Psychiatry and Psychotherapy, University of Saarland, Homburg/Saar, Germany. · World J Biol Psychiatry. · Pubmed #16173147 No free full text.

Abstract: These guide lines for the biological treatment of schizophrenia were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBO). The goal during the development of these guidelines was to review systematically all available evidence pertaining to the treatment of schizophrenia, and to reach a consensus on a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating people with schizophrenia. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for schizophrenia, as well as from meta-analyses, reviews and randomised clinical trials on the efficacy of pharmacological and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into four levels of evidence (A-D). This first part of the guidelines covers disease definition, classification, epidemiology and course of schizophrenia, as well as the management of the acute phase treatment. These guidelines are primarily concerned with the biological treatment (including antipsychotic medication, other pharmacological treatment options, electroconvulsive therapy, adjunctive and novel therapeutic strategies) of adults suffering from schizophrenia.

Bauer M, Whybrow PC, Angst J, Versiani M, Möller HJ, Anonymous00267. · University of California Los Angeles (UCLA), Neuropsychiatric Institute & Hospital, Department of Psychiatry and Biobehavioral Sciences, Los Angeles, CA, USA. · World J Biol Psychiatry. · Pubmed #12479080 No free full text.

Abstract: These practice guidelines for the biological treatment of unipolar depressive disorders were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal for developing these guidelines was to systematically review all available evidence pertaining to the treatment of the complete spectrum of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating patients with these conditions. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for depressive disorders, as well as from meta-analyses and reviews on the efficacy of antidepressant medications and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and was then categorized into four levels of evidence (A-D). The first part of these WFSBP guidelines on unipolar depressive disorders covered the acute and continuation treatment of major depressive disorder (Bauer et al 2002). This second part of the guidelines covers the management of the maintenance-phase treatment of major depressive disorder, as well as the treatment of chronic and subthreshold depressive disorders (dysthymic disorder, double depression, minor depressive disorder and recurrent brief depression). These guidelines are primarily concerned with the biological treatment (including antidepressants, lithium, other psychopharmacological and hormonal medications, and electroconvulsive therapy) of young adults and also, albeit to a lesser extent, children, adolescents and older adults.

Grunze H, Kasper S, Goodwin G, Bowden C, Baldwin D, Licht R, Vieta E, Möller HJ, Anonymous00265. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · World J Biol Psychiatry. · Pubmed #12478876 No free full text.

Abstract: These practice guidelines for the biological, mainly pharmacological treatment of bipolar depression were developed by an international task force of the World Federation of Societies of Biological Psychiatry (WFSBP). Their purpose is to supply a systematic overview of all scientific evidence pertaining to the treatment of bipolar depression. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, and from recent proceedings of key conferences and various national and international treatment guidelines. Their scientific rigor was categorised into four levels of evidence (A-D). As these guidelines are intended for clinical use, the scientific evidence was not only graded, but also commented on by the experts of the task force to ensure practicability.

Möller HJ. · Klinik und Poliklinik für Psychiatrie und Psychotherapie, Klinikum der Universität München. · MMW Fortschr Med. · Pubmed #19504826 No free full text.

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Möller HJ. · No affiliation provided · Nervenarzt. · Pubmed #19387602 No free full text.

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Möller HJ. · No affiliation provided · World J Biol Psychiatry. · Pubmed #15543512 No free full text.

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Damm J, Eser D, Schüle C, Möller HJ, Rupprecht R, Baghai TC. · Klinik für Psychiatrie und Psychotherapie, Ludwig-Maximilians-Universität, Nussbaumstrasse 7, 80336, München. · Nervenarzt. · Pubmed #19396418 No free full text.

Abstract: Core symptoms of depression are a combination of psychological and somatic symptoms, often associated with psychomotor and cognitive disturbances. The diagnostic classifications of depression include the concepts of melancholic, endogenous, or severe depression. All subgroups describe severely depressed patients suffering from most of the core symptoms of depression. In addition these patients exhibit the clinical characteristics of a recurrent unipolar or bipolar course, lower placebo response rates, or higher response rates to ECT, to antidepressant treatments with dually or mixed modes of action, or to lithium augmentation. Higher rates of HPA axis hyperactivity and specific EEG patterns may also occur in this patient group. This suggests a broad overlap of patient subgroups within the diagnostic classification of depression. Because the positive diagnosis of the core symptoms of depression may include clinical consequences, it would be useful to integrate all these concepts into the upcoming new versions of the diagnostic systems DSM-V and ICD-11.

Montgomery SA, Möller HJ. · Imperial College School of Medicine, University of London, London bLudwig Maximilians University, Munich, UK. · Int Clin Psychopharmacol. · Pubmed #19357527 No free full text.

Abstract: The methods of assessing the clinical relevance of a significant difference between antidepressants and placebo are discussed. The commonly used criteria of treatment effect and responder rates, as well as the percentage difference in responders between antidepressant and placebo, are critically reviewed and applied to assess the clinical relevance of the significant advantages reported in double-blind, randomized, controlled studies of escitalopram compared with other antidepressants. A significant advantage for escitalopram has been reported in randomized, double-blind, short-term studies compared with citalopram, paroxetine and duloxetine. The reported significant differences are clinically relevant based on a treatment effect difference of at least 2 points on the Montgomery and Asberg Depression Rating Scale as well as a significant advantage in the protocolled responder or remission analysis. The mean unadjusted treatment effect advantage for escitalopram compared with the antidepressants studied is 2.42 points on the Montgomery and Asberg Depression Rating Scale in the short-term treatment. Excluding one study that did not report short-term responder rates, there were significantly more responders on escitalopram (74%) than comparators (63%). Both of these measures demonstrate a clinically relevant difference in favour of escitalopram.

Baghai TC, Volz HP, Möller HJ. · Klinik für Psychiatrie und Psychotherapie, Ludwig-Maximilians-Universität München, Nussbaumstrasse 7, 80336, München, Deutschland. · Internist (Berl). · Pubmed #19183920 No free full text.

Abstract: During the past decade a variety of promising new compounds launched onto the market not only enhancing serotonergic and noradrenergic neurotransmission, but also influencing the dopamine and the melatonergic receptor system. In spite of misleading discussions both in the specialized and in the lay press the clinical effectiveness of antidepressants still is indisputable. The main advantages of the newer drugs are the broadening of the spectrum treatments and a far better tolerability profile in comparison to older compounds. Predominantly depression of medium to high severity should be treated pharmacologically. Especially severe depression seems to respond better to dually acting antidepressants. In children effectiveness of Omega3-fatty acids has been shown, in adolescents SSRI treatment was efficacious. Older patients respond to all antidepressant mechanisms, but more selective substances should be preferred due to a better tolerability. The study of new treatment options is of major importance to provide better strategies for the clinical management of depression in the future, and is thus also of great socio-economic importance.

Möller HJ, Baldwin DS, Goodwin G, Kasper S, Okasha A, Stein DJ, Tandon R, Versiani M, Anonymous00012. · Department of Psychiatry, Ludwig-Maximilians-University München, Nussbaumstrasse 7, 80336 Munich, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #18668279 No free full text.

Abstract: In the past few years several papers have reported critically on the risk of suicidal thoughts and behaviour associated with antidepressants, primarily SSRIs. The risk-benefit ratio of antidepressant (AD) treatment has been questioned especially in children and adolescents. The critical publications led to warnings being issued by regulatory authorities such as the FDA, MHRA and EMEA and stimulated new research activity in this field. However, potential harmful effects of antidepressants on suicidality are difficult to investigate in empirical studies because these have several methodological limitations. Randomised controlled trials (RCTs) are the most reliable way to test the hypothesis that AD have such side effects. In addition to meta-analyses of RCTs, complementary research methods should be applied to obtain the most comprehensive information. We undertook a comprehensive review of publications related to the topics ADs, suicide, suicidality, suicidal behaviour and aggression. Based on this comprehensive review we conclude that ADs, including SSRIs, carry a small risk of inducing suicidal thoughts and suicide attempts, in age groups below 25 years, the risk reducing further at the age of about 30-40 years. This risk has to be balanced against the well-known beneficial effects of ADs on depressive and other symptoms (anxiety, panic, obsessive-compulsive symptoms), including suicidality and suicidal behaviour. According to the principles of good clinical practice, decision making should consider carefully the beneficial effects of AD treatment as well as potentially harmful effects and attempt to keep the potential risks of AD treatment to a minimum. It is the major problem facing efforts to identify the possible 'suicidal effects' of antidepressants.

Frodl T, Möller HJ, Meisenzahl E. · Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany. · Acta Psychiatr Scand. · Pubmed #18644006 No free full text.

Abstract: OBJECTIVE: Stress-related changes in the hippocampus are influenced by genetic factors. To enhance our understanding of both the interaction between the brain, behaviour and genetics and of biological mechanisms in mood disorders neuroimaging genetics provide a good opportunity. METHOD: A MEDLINE search was conducted to identify articles on neuroimaging genetics in major depression (MD). RESULTS: Hippocampal volumes were found to be associated with polymorphisms in the promotor region of the serotonin transporter (5-HTTLPR) in patients with MD. Met-allele carriers of the BDNF (val66met) polymorphism had smaller hippocampal volumes in both patients and healthy controls when compared with homozygous val-allele carriers. Polymorphisms of the serotonin transporter (5-HTTLPR) and 5-HT1a receptor are associated with increased amygdala activation investigated with functional MRI in patients with MD. CONCLUSION: Genetic variants seem to modulate the effects of stress on hippocampal volumes as well as amygdala activity as well as the development of the brain.

Baghai TC, Möller HJ. · Dept of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Germany. · Dialogues Clin Neurosci. · Pubmed #18472488 No free full text.

Abstract: In spite of recent developments in the pharmacotherapy of depressive disorders, the delay until clinical improvement can be achieved, and the considerable rate of nonresponse and nonremission, are major problems which remain unresolved. Electroconvulsive therapy (ECT) is a nonpharmacologic biological treatment which has been proven to be a highly effective treatment option, predominantly for depression, but also for schizophrenia and other indications. Though there is a lack of controlled investigations on long-term treatments, ECT can also be used for relapse prevention during maintenance therapies. The safety and tolerability of electroconvulsive treatment have been enhanced by the use of modified stimulation techniques and by progress in modern anesthesia. Thus, today a safe treatment can also be offered to patients with higher somatic risks. ECT still represents an important option, especially in the therapy of treatment-resistant psychiatric disorders after medication treatment failures. Earlier consideration of ECT may reduce the rate of chronic and difficult-to-treat psychiatric disorders.

Möller HJ. · Department of Psychiatry, Ludwig-Maxmillians University, Munich, Germany. · World J Biol Psychiatry. · Pubmed #18428079 No free full text.

Abstract: It is increasingly recognised that major depressive disorder can be a chronic condition with many patients experiencing recurrent episodes. Remission from a depressive episode implies the absence or near absence of depressive symptoms. However, for many patients the periods between depressive episodes are not symptom free. Residual symptoms are predictors of relapse or recurrence, and may be associated with residual psychosocial impairment. In clinical studies, remission is commonly defined using a cut-off score on a rating scale for depressive symptoms, such as a score of < or = 7 on the 17-item Hamilton scale. However, there is debate about which scales and cut-offs are optimal and full-length rating scales are not widely used in clinical practice. In spite of such issues, it seems clear that a therapy should aim at the most complete remission possible. Unfortunately, recent studies have highlighted that in clinical practice usually only a low rate of remission is achieved. Although long-term treatment with antidepressants can reduce the risk of relapse or recurrence only a minority of patients in clinical practice achieve this as treatment is often prematurely stopped due to long-term side effects such as sleep disturbance, sexual dysfunctioning and weight gain. Therefore, it represents an unmet need to come up with antidepressant drugs of greater efficacy and improved tolerability as such treatments could lead to more complete remission in more patients.

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.

Kasper S, Gastpar M, Müller WE, Volz HP, Dienel A, Kieser M, Möller HJ. · Department of Psychiatry und Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, 1090, Austria. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #18084790 No free full text.

Abstract: Based on the original data from two double-blind, randomized, placebo-controlled clinical trials and the acute phase of a long-term study that investigated the antidepressant efficacy of St. John's wort extract WS 5570, we present a re-analysis of a subset of patients suffering from an acute episode of mild depression according to DSM criteria. Out of a total of more than 1,200 patients included into these trials 217 had a pre-treatment total score < or =20 points on the 17-item Hamilton Rating Scale for Depression (HAMD) and were eligible for our re-analysis. They received 600, 900, or 1,200 mg/day WS 5570 or placebo for 6 weeks. In patients treated with WS 5570 the HAMD total score decreased by averages of 10.8 (600 mg/day), 9.6 (900 mg/day), and 10.7 (1,200 mg/day) points between the pre-treatment baseline value and the end of acute treatment, compared to 6.8 points in the placebo group (p < 0.01 for all pairwise comparisons of WS 5570 against placebo). This corresponded to average relative decreases by 49-57% for WS 5570 and by 36% for placebo. The rates of responders (i.e., patients with a HAMD total score decrease > or =50%) were 73%, 64%, 71%, and 37% for WS 5570 600 mg/day, 900 mg/day and 1,200 mg/day, and placebo, respectively. At the end of acute treatment 57% of the patients treated with WS 5570 600 mg/day, 33% in the 900 mg/day group and 62% in the 1,200 mg/day group, as well as 25% in the placebo group were in remission (HAMD total score < or =7 points). The analysis shows that St. John's wort extract WS 5570 has a meaningful beneficial effect during acute treatment of patients suffering from mild depression and leads to a substantial increase in the probability of remission.

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.

Montgomery SA, Baldwin DS, Blier P, Fineberg NA, Kasper S, Lader M, Lam RW, Lépine JP, Möller HJ, Nutt DJ, Rouillon F, Schatzberg AF, Thase ME. · Imperial College School of Medicine, University of London, UK. · Int Clin Psychopharmacol. · Pubmed #17917550 No free full text.

Abstract: A review of published evidence of superior efficacy of a particular antidepressant in major depressive disorder may assist clinicians in making considered treatment choices. To identify such candidates, an international group of experts met to assess published evidence (identified through searches in Medline and Embase databases and discussions with experts in the field) from randomized, controlled trials and meta-analyses comparing two antidepressants under conditions of fair comparison. Criteria were defined to judge the strength of evidence. Two pivotal studies in moderate-to-severe major depressive disorder that demonstrate superiority on the primary efficacy measure, or alternatively one pivotal study supported by consistent results from meta-analyses, was considered to constitute evidence for definite superiority. Three antidepressants met these criteria: clomipramine, venlafaxine, and escitalopram. Three antidepressants were found to have probable superiority: milnacipran, duloxetine, and mirtazapine. Only escitalopram was found to have definite superiority in the treatment of severe depression; probable superiority was identified for venlafaxine and possible superiority for milnacipran and clomipramine. This review of published data found evidence that only a very few antidepressants are shown to be more effective than others.

Möller HJ. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336, Munich, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #17143567 No free full text.

Abstract: The role of antidepressants in suicide prevention is a major public health question given the high prevalence of both depression and depression-related suicidality. Therefore all available means should be utilised to clarify the influence of antidepressants on suicidality, especially in view of the ongoing intensive debate about possible suicidality-inducing effects of antidepressants that may outweigh their traditionally hypothesised beneficial effects. This paper gives a systematic and comprehensive review of the empirical data which might indicate that antidepressants have negative effects on suicidality. First, principal methodological issues related to this research question are discussed. Thereafter, the results of controlled trials and epidemiological and cohort studies are presented. Altogether, there seems to be only a small amount of evidence from different research approaches that antidepressants, not only serotonin reuptake inhibitors (SSRIs), might induce, aggravate or increase the risk of suicidal ideation and suicide attempts. As to suicide, there are no hints in this direction. TCAs have a higher risk of fatal outcome in overdose compared to SSRIs, which, in case of mono-intoxication, carry almost no risk of lethal consequences. The ongoing discussion about suicidality-inducing effects should not prevent physicians from prescribing SSRIs and other antidepressants to their patients if they are clinically indicated. However, they should take into account potential risks and manage them by good clinical practice.

Baghai TC, Volz HP, Möller HJ. · Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany. · World J Biol Psychiatry. · Pubmed #17071541 No free full text.

Abstract: During the past 10 years our knowledge about the pharmacotherapy of depression has been consolidated, and a variety of very interesting new compounds launched onto the market. The pipeline of the pharmaceutical industry is still filled with an assortment of new developments and very promising new approaches towards the pharmacotherapy of depressive disorders. Future pharmacological treatments of depression will not only enhance serotonergic and noradrenergic neurotransmission: other systems, such as the melatonergic receptor system and the hypothalamus-pituitary-adrenal axis, are also the targets of newly developed and upcoming substances with putative antidepressant effects. The main advantages of the currently available newer pharmacotherapeutic options are the broadening of the spectrum of possible antidepressant treatments, which is of particular importance for the growing number of patients suffering from difficult-to-treat depression, and a far better tolerability profile in comparison to older compounds such as tricyclic antidepressants. Unresolved issues are the unacceptably high rate of non-responsiveness during antidepressant treatment, a latency of sometimes several weeks until clinical improvement and remission can be achieved, and a variety of possible side effects also present during treatment with modern compounds. This review mainly presents the development of antidepressant pharmacotherapies during the past 10 years, together with pharmacokinetic and pharmacodynamic information and a comparison of different pharmacological treatment principles evaluated in randomized controlled clinical trials. In addition, new pharmacological strategies that are not yet available on the market and strategies currently under development are reviewed in detail. The study of new treatment options is of major importance to provide better strategies for the clinical management of depression in the future, and is thus also of great socio-economic importance.

Möller HJ. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336, Munich, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #16783501 No free full text.

Abstract: The role of antidepressants in suicide prevention is a major public health question, given the high prevalence of both depression and depression-related suicidality. Therefore all means available should be utilised to clarify the influence of antidepressants on suicidality. This paper gives a comprehensive overview of the positive effects of antidepressants on suicidality. In the first section, principal methodological issues related to suicidology in general as well as to clinical and epidemiological studies that investigate the influence of antidepressants on suicidality are discussed. In the second section, the results of controlled clinical studies on the efficacy of antidepressants in suicidality are presented. The third section reports on the results of other types of studies, especially epidemiological studies. Altogether, there seems to be reasonable evidence from different research approaches that antidepressants are able to reduce suicidal ideation and also suicidal behaviour in depressive patients. While the evidence for the beneficial effect on suicidal ideation comes from randomised control group studies, some of which used a placebo arm, the evidence for the prophylactic effect on suicidal behaviour, especially suicide, was primarily obtained from well-designed epidemiological studies.

Bauer M, Möller HJ, Schneider E. · Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Schumannstrasse 20/21, D-10117 Berlin, Germany. · Expert Opin Pharmacother. · Pubmed #16503814 No free full text.

Abstract: Antidepressants that inhibit the re-uptake of serotonin and noradrenaline might offer a chance to reduce the multiple symptoms of depression, as both serotonin and noradrenaline seem to be responsible for the emotional and physical symptoms of depression. The potential superiority of a dual mechanism of action has already been demonstrated in a number of clinical trials. Duloxetine, a novel dual acting, selective serotonin and noradrenaline-re-uptake inhibitor, has demonstrated high remission rates and good efficacy on physical symptoms, especially painful physical symptoms of depression. The results from studies in diabetic neuropathic pain provide further evidence of the effect of duloxetine on pain, independent of its effect on depression. Therefore, duloxetine provides an alternative to current therapeutic options in the treatment of the different symptoms of depression.

Baghai TC, Möller HJ, Rupprecht R. · Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University of Munich, Nussbaumstrasse 7, D-80336 Munich, Germany. · Curr Pharm Des. · Pubmed #16472142 No free full text.

Abstract: In spite of recent progress in the pharmacotherapy of depression major issues are still unresolved. These include the non-response rate of approximately 30% to conventional antidepressant pharmacotherapy, side effects of available antidepressants and the latency of several weeks until clinical improvement. The only non-pharmacological biological treatment options available so far which exert more rapid antidepressant efficacy are electroconvulsive therapy and, as an augmentation strategy, sleep deprivation. Current pharmacological treatments aim to enhance serotonergic and/or noradrenergic neurotransmission. In spite of emerging knowledge, the crucial mechanisms underlying both non-pharmacological treatments, which are responsible for antidepressant efficacy, are not yet clear so far. In the meantime several new pharmacological principles are under investigation with regard to their putative antidepressant potency. These include 5-HT1A receptor agonists, tachykinin receptor antagonists and various interventions within the hypothalamic-pituitary-adrenal system. While there is evidence for antidepressant properties of these new treatments in animal studies, in case series, in open studies and to some degree also in placebo controlled studies, no definite proof for the antidepressant efficacy of these new pharmacological strategies according to the requirements for evaluation of antidepressant drugs has been furnished so far. In contrast, for the established non-pharmacological treatment strategies including bright light therapy the clinical efficacy has been proven at least in subgroups of depression, but more knowledge of the main mechanisms underlying their antidepressant efficacy is still necessary. In addition new non-pharmacological treatments like repetitive transcranial magnetic stimulation, magnetic seizure therapy and Vagus nerve stimulation are currently under development. Nevertheless, a follow-up of both the new pharmacological strategies and non-pharmacological treatment options is of major importance to provide even better strategies for the clinical management of depression, which also is of great socio-economic impact.

Möller HJ. · Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany. · World J Biol Psychiatry. · Pubmed #16272080 No free full text.

Abstract: Depressive symptoms are a common feature of schizophrenic disorders, a fact that has become increasingly apparent over the last two decades. Apparently the introduction of standardized rating scales in cross-sectional and longitudinal investigations played an important role in the recognition of the relevance of depressive symptoms. They can be interpreted as being cosyndromal or comorbid, depending on the conceptual perspective applied. This is not simply a difference in terminology but is of great aetiopathogenetic relevance. Of particular clinical relevance is the observation that schizophrenic patients with concomitant depressive symptoms have a greater risk of suicidality or an unfavourable disease course. For this reason it is important that sufficient attention is paid to the diagnosis and treatment of depressive symptoms occurring during schizophrenic psychoses. Besides treatment with antidepressants, modern neuroleptics are of great importance in this context as they are more efficacious than classical neuroleptics in treating depressive symptoms.

Möller HJ, Grunze H, Broich K. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #16078087 No free full text.

Abstract: This conceptual review summarises the results of relevant studies on antidepressants, mood stabilisers such as lithium and anticonvulsants, and second generation antipsychotics in the indication of bipolar depression. Based on methodological and clinical considerations, the position of antidepressants and the possible alternatives in this indication are reviewed very carefully. In addition the regulatory requirements for licensing a drug for the indication "short-term treatment of bipolar depression" are described.