Depression: Pfennig A

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).

Sasse J, Pilhatsch M, Forsthoff A, Grunze H, Neutze J, Pfennig A, Schmitz B, Schwenkhagen A, Bauer M. · Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Carl Gustav Carus, Technische Universität, Fetscherstrasse 74, 01307, Dresden, Deutschland. · Nervenarzt. · Pubmed #19229511 No free full text.

Abstract: This manuscript summarizes specific issues in the disease course and pharmacological treatment of women with bipolar disorders. Gender differences relevant to the female biology manifest in symptoms, outcome, and course. The preponderance of depressive symptoms is typical, and the risk of rapid cycling is estimated to be eight times higher for women than for men. Comorbid anxiety and eating disorders occur more frequently in female patients. In planning treatment it is important to take fertility, contraception, and pregnancy into consideration and adjust the pharmacotherapy to harmonize with the patient's current phase of life. Little is known about potential sexual dysfunctions of bipolar women. Further research should include clinical and observational studies focusing on gender-specific differences in symptomatology, treatment, and long-term outcome of bipolar disorders.

Pfennig A, Littmann E, Bauer M. · Department of Psychiatry and Psychotherapy, Charité - University Medicine Berlin, Campus Mitte, Berlin, Germany. · J Neuropsychiatry Clin Neurosci. · Pubmed #18070839 links to  free full text

Abstract: In a substantial percentage of patients, mood disorders are accompanied by persistent neurocognitive impairment. Elderly patients with dementia often suffer from depression. Neurocognitive tests and imaging are increasingly used to complement diagnostics. Tests assessing memory, attention, executive functions, and visuospatial abilities might help to distinguish mood disorder patients who can be expected to develop dementia from those who will not. This review presents a summary of knowledge on neurocognitive profiles differentiating impairment in mood disorders and dementia. Ideas on pathophysiological causation and progression are translated into recommendations for patient management.

Bschor T, Lewitzka U, Pfennig A, Bauer M. · Abteilung für Psychiatrie und Psychotherapie, Jüdisches Krankenhaus Berlin, Heinz-Galinski-Strasse 1, 13347 Berlin. · Nervenarzt. · Pubmed #17458527 No free full text.

Abstract: Twenty-five years ago the research group of the Canadian psychiatrist de Montigny reported treating antidepressant-refractory depressive patients successfully by adding lithium to their antidepressant. The report, published in 1981 as an open-label uncontrolled observation of only eight patients, falls short of today's methodological standards, but the treatment method, subsequently known as lithium augmentation, nonetheless was to change profoundly the pharmacological strategies for depressive disorders. The story of its development is remarkable, starting with a strictly theoretical idea conceived by Montigny and his colleagues after animal experiments in the 1970s had revealed that pretreatment with an antidepressant over several weeks led to sensitization of central nervous serotonin receptors. The team postulated that the proserotonergic characteristics of lithium, which had been systematically used as a psychotropic drug since 1949, could thus be used specifically to stimulate these receptors. Lithium augmentation demonstrated its effectiveness in the 1980s and 1990s, first in open-label and later in randomized and placebo-controlled studies. In the late 1990s studies aimed at optimizing its clinical application indicated that lithium augmentation must be administered for at least 2 weeks, with lithium serum levels within the range established for prophylactic treatment and assuming patient response, and that the combination of lithium and antidepressant must be continued as a maintenance therapy for 6 to 12 months. Research has yet to clarify how lithium augmentation actually works. Current results show that in addition to the idea postulated by Montigny, lithium could also have an activating effect on the cortisol axis. Thanks to the sound body of evidence which has accrued in the meantime, lithium augmentation is recommended in most guidelines and treatment algorithms as a main strategy for patients who do not respond to antidepressant monotherapy.

Hauser M, Pfennig A, Ozgürdal S, Heinz A, Bauer M, Juckel G. · Early Recognition Center of Beginning Psychoses, Department of Psychiatry, Charité, Campus Mitte, Berlin, Germany. · Eur Psychiatry. · Pubmed #17142013 No free full text.

Abstract: Bipolar disorders are frequently not diagnosed until long after their onset, leaving patients with no or correspondingly inadequate treatment. The course of the disorder is all the more severe and the negative repercussions for those affected all the greater. Concerted research effort is therefore going into learning how to recognize bipolar disorders at an early stage. Drawing on current research results, this paper presents considerations for an integrative Early Symptom Scale with which persons at risk can be identified and timely intervention initiated. This will require prospective studies to determine the predictive power of the risk factors integrated into the scale.

Bauer M, Pfennig A. · Charité-University Medicine Berlin, Campus Charité Mitte (CCM), Department of Psychiatry and Psychotherapy, Berlin, Germany. · Epilepsia. · Pubmed #15968806 No free full text.

Abstract: Bipolar, or manic-depressive, disorders are frequent and severe mental illnesses associated with considerable morbidity and mortality. Epilepsy and bipolar disorder could probably share some aspects of pathophysiology because manic as well as depressive symptoms are seen in patients with seizures, and a number of antiepileptic drugs are effectively used in the acute and prophylactic treatment of bipolar disorder. Epidemiologic research suggests a dimensional composition of bipolar illness at the population level. Apart from the DSM-IV diagnostic features of bipolar I (mania and depression) and bipolar II (hypomania and depression), the concept of bipolar spectrum disorders comprises a range of bipolar conditions with less obvious manifestations with estimated lifetime prevalence rates ranging from 2.8 to 6.5%. Expanding the definition of bipolar II disorders shows that half of the patients currently diagnosed with a unipolar depressive episode could suffer from unrecognized bipolar II disorder, and about the same number of mild depressive patients could be minor bipolars. Research efforts to refine the diagnostic criteria of bipolar disorder aim at an earlier and complete recognition of the disease to provide appropriate pharmacological and nonpharmacological treatment early in the course of the illness to anticipate individual suffering, suicidal behavior, and increased socioeconomic costs for society. This article also discusses risk factors, comorbid conditions, course of illness, as well as the individual and socioeconomic impact of bipolar disorders. CONCLUSIONS: The findings suggest reconceptualizing bipolar illnesses as highly recurrent, malignant disorders that occur far more frequently than previously thought. Interdisciplinary knowledge transfer could help to increase our understanding of the pathophysiology of these disorders as well as provide grounds for better recognition and treatment of patients with manic and/or depressive symptoms.

Bauer M, Pfennig A, Linden M, Smolka MN, Neu P, Adli M. · Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany. · J Clin Psychopharmacol. · Pubmed #19593170 No free full text.

Abstract: OBJECTIVE: Medication algorithms have been proposed as effective means to offer optimal treatment and improved outcome for patients with severe mental illness. This single-center prospective study compared the efficacy and effects on treatment prescriptions of an algorithm-guided treatment regimen with treatment as usual (TAU) in depressed inpatients. METHODS: Depressed inpatient participants were randomized to an algorithm-guided standardized stepwise drug treatment regimen (SSTR, n = 74) or TAU (n = 74). The SSTR regimen included sleep deprivation, antidepressant monotherapy, lithium augmentation, monoamine oxidase inhibitor therapy, or electroconvulsive therapy guided by scores on the clinician-rated Bech-Rafaelsen Melancholia Scale. The primary outcome was time to remission (defined as a Bech-Rafaelsen Melancholia Scale score of < or =7). Secondary outcomes were remission rates, number of changes in treatment strategies (types), and the number of different prescribed medications over the treatment period. RESULTS: Patients receiving SSTR had a significantly shorter time to remission (7.0 +/- 0.9 weeks vs 12.3 +/- 1.8 weeks for TAU). Compared with that in remitters in SSTR, the number of strategy changes was significantly higher in TAU remitters (3.0 +/- 2.7 and 1.0 +/- 1.5) and had more psychotropic medications (fix agents: 3.0 +/- 1.5 and 1.9 +/- 1.1; optional agents: 1.5 +/- 1.0 and 0.9 +/- 0.7). Although more patients dropped out of the SSTR group (33 of SSTR, 12 of TAU), the probability of remission tended to be higher in SSTR. CONCLUSIONS: Algorithm-guided treatment produces better outcomes and less frequent medication changes than TAU. A systematic, stepwise, measurement-based approach to the treatment of depressed inpatients is warranted.

Binder EB, Künzel HE, Nickel T, Kern N, Pfennig A, Majer M, Uhr M, Ising M, Holsboer F. · Max-Planck Institute of Psychiatry, Kraepelinstrasse 2-10, D80804 Munich, Germany. · Psychoneuroendocrinology. · Pubmed #18829172 No free full text.

Abstract: A concatenation of data implicates a hyperactivity of the hypothalamus pituitary adrenal (HPA)-axis in the pathogenesis of depression and its normalization as a necessary predecessor of clinical response to antidepressant drugs. In addition, regulation of the HPA-axis has been shown to be dependent on sex hormones. We therefore investigated gender differences in HPA-axis regulation in depression and its normalization during remission of clinical symptoms. We used the combined dexamethasone suppression/CRH stimulation (Dex-CRH) test to evaluate the degree of HPA-axis dysregulation in 194 in-patients with unipolar depression from the Munich Antidepressant Response Signature (MARS) study at both admission and discharge. The Hamilton Depression (HAM-D) Rating Scale was used to monitor clinical response to antidepressant treatment. For both genders, we observed a normalization of HPA-axis dysregulation in remitters but not in non-remitters, both after 5 weeks of treatment and at discharge. The pattern of HPA-axis normalization with remission of depressive symptoms, however, showed gender-specific differences. In male patients, remission after 5 weeks of in-patient treatment was associated with a significantly higher cortisol response in the Dex-CRH test at admission. In female patients, 5-week remitters and non-remitters had a comparable cortisol response at admission. Cortisol response at admission was not correlated with gonadal steroid levels at this time point and the results were similar for pre-menopausal women vs. post-menopausal women. Gender-associated biological characteristics, likely independent of circulating gonadal steroids, thus seem to influence HPA-axis regulation in depression. In male patients, a single measure of HPA-axis dysregulation at admission may serve as a predictor of response to antidepressant treatment in addition to the previously reported repeated measure of the Dex-CRH test.

Bauer M, Wilson T, Neuhaus K, Sasse J, Pfennig A, Lewitzka U, Grof P, Glenn T, Rasgon N, Bschor T, Whybrow PC. · Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany. · Psychiatry Res. · Pubmed #18423616 No free full text.

Abstract: With the widespread recognition of the value of active patient participation in their care, ChronoRecord software was developed to automate daily self-reporting by patients with bipolar disorder. A prior study demonstrated concurrent validity between self-ratings on ChronoRecord and clinician ratings on the Hamilton Depression Rating Scale (HAMD), but validity with the Young Mania Rating Scale (YMRS) could not be shown due to a lack of data when the outpatients were manic (Bauer et al., Bipolar Disorders 6, 67-74, 2004). This study expanded upon the prior validation study to include inpatients with mania. Self-reported mood ratings on ChronoRecord and clinician ratings on the YMRS were obtained on the same day from 27 inpatients (57 ratings); these data were also combined with the ratings from the 80 outpatients (total 107 patients, 340 ratings). Using Pearson correlation, the self-reported ratings on ChronoRecord were significantly correlated with the YMRS. The accuracy of ChronoRecord to discriminate hypomania and mania was high, as described by the area under the receiver operating characteristic curve. Post-hoc analysis of the level of agreement between ChronoRecord and YMRS ratings was excellent or good in all cases using the kappa statistic. These data demonstrate concurrent validity between ChronoRecord and YMRS.

Bauer M, Glenn T, Grof P, Pfennig A, Rasgon NL, Marsh W, Munoz RA, Sagduyu K, Alda M, Quiroz D, Sasse J, Whybrow PC. · Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Germany. · J Affect Disord. · Pubmed #17224186 No free full text.

Abstract: OBJECTIVE: Patients with bipolar disorder often report depressive symptoms that do not meet the DSM-IV criteria for an episode. Using daily self-reported mood ratings, we studied how changing the length requirement to that typical of recurrent brief depression (2-4 days) would impact the number of depressed episodes. METHOD: 203 patients (135 bipolar I and 68 bipolar II by DSM-IV criteria) recorded mood daily using ChronoRecord software on a home computer (30,348 total days; mean 150 days). Episodes of depression and days of depression outside of episodes were determined. Symptom intensity (mild versus moderate or severe) was investigated within and outside of depressive episodes. RESULTS: Decreasing the minimum duration criterion for an episode of depression to 2 days increased the number of patients with a depressed episode two and a half times (52 to 131), and quadrupled both the number of depressed episodes per patient (0.62 to 2.88) and the number of depressed episodes for all patients (125 to 584). With a 2-day episode length, 34% of days of depression remained outside an episode. The ratio of days with severe symptoms within episodes remained consistent (about 25%) in spite of decreasing the episode length to 2 days. Considering only days with severe symptoms, about 25% remained outside of episodes even with a 2-day length. None of the results distinguished bipolar I from bipolar II disorder. LIMITATIONS: Self-reported data, computer access required, relatively short study length, no control group. CONCLUSION: Brief depressive episodes and single days of depression outside of episodes occur frequently in both bipolar I and bipolar II disorder. Moderate or severe symptoms occur during brief episodes at a ratio similar to that for episodes that meet the DSM-IV criteria.

Ising M, Horstmann S, Kloiber S, Lucae S, Binder EB, Kern N, Künzel HE, Pfennig A, Uhr M, Holsboer F. · Max Planck Institute of Psychiatry, Munich, Germany. · Biol Psychiatry. · Pubmed #17123470 No free full text.

Abstract: BACKGROUND: Exaggerated corticotropin (ACTH) and cortisol response to the combined dexamethasone (DEX)/corticotropin releasing hormone (CRH) test, indicating impaired regulation of the hypothalamus-pituitary-adrenocortical (HPA) system, is frequently observed in depression. In the present study, we examined whether change in HPA system function during the first weeks of hospitalization predicts response to antidepressant treatment in major depression and thus constitutes a potential biomarker. METHODS: We conducted the DEX/CRH test in 50 inpatients suffering from severe major depression, once after study inclusion and a second time 2 to 3 weeks later while under continuous antidepressant treatment. RESULTS: We found increased ACTH and cortisol responses to the first DEX/CRH test compared with healthy control subjects. In the second DEX/CRH test 2 to 3 weeks later, 36 of the 50 patients showed an attenuated cortisol response, while 14 patients did not display improvement or exhibited even aggravation of the altered HPA system function. Improved HPA system regulation in the second DEX/CRH test was associated with beneficial treatment response after 5 weeks and a higher remission rate at the end of hospitalization. CONCLUSIONS: The results suggest that change in HPA system regulation assessed with repeated DEX/CRH tests is a potential biomarker that may predict clinical outcome at follow-up. There is consensus that the drug development process could be improved, once reliable biomarkers become available that help to allow a judgement regarding the efficacy of a novel drug candidate. The combined DEX/CRH test seems to be a promising candidate for such a biomarker.

Pfennig A, Kunzel HE, Kern N, Ising M, Majer M, Fuchs B, Ernst G, Holsboer F, Binder EB. · Max-Planck Institute of Psychiatry, Munich, Germany. · Biol Psychiatry. · Pubmed #15705348 No free full text.

Abstract: BACKGROUND: One of the most demanding tasks in psychiatry is to protect patients from suicidal attempts. Preventive strategies could be improved by increasing our knowledge on the pathophysiologic disturbances underlying this behavior. More than 70-80% of suicides occur in the context of depressive disorders, in which dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is one of the most prominent neurobiological findings. So far data on the involvement of the HPA axis in the pathophysiology of suicidal behavior in depressed patients are controversial. METHODS: In this retrospective study, we administered the combined dexamethasone-suppression/CRH stimulation (Dex/CRH) test to 310 patients with a depressive syndrome characterized at admission for acute and past suicidal behavior within the first 10 days after hospitalization. RESULTS: Suicidal behavior in depressed patients, including past and recent suicide attempts as well as suicidal ideation, was associated with a lower adrenocorticotropin and cortisol response in the combined Dex/CRH test, with lowest hormone levels observed in patients with a recent suicide attempt. DISCUSSION: The findings suggest that suicidal behavior may alter HPA axis regulation in depressed patients. Large-scale prospective studies assessing neuroendocrine changes may help to develop predictors for an early identification of patients at risk for committing suicide.

Binder EB, Salyakina D, Lichtner P, Wochnik GM, Ising M, Pütz B, Papiol S, Seaman S, Lucae S, Kohli MA, Nickel T, Künzel HE, Fuchs B, Majer M, Pfennig A, Kern N, Brunner J, Modell S, Baghai T, Deiml T, Zill P, Bondy B, Rupprecht R, Messer T, Köhnlein O, Dabitz H, Brückl T, Müller N, Pfister H, Lieb R, Mueller JC, Lõhmussaar E, Strom TM, Bettecken T, Meitinger T, Uhr M, Rein T, Holsboer F, Muller-Myhsok B. · Max-Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany. · Nat Genet. · Pubmed #15565110 No free full text.

Abstract: The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant-dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.

Künzel HE, Binder EB, Nickel T, Ising M, Fuchs B, Majer M, Pfennig A, Ernst G, Kern N, Schmid DA, Uhr M, Holsboer F, Modell S. · Department of Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany. · Neuropsychopharmacology. · Pubmed #12931142 links to  free full text

Abstract: The most consistent biological findings in patients with depression are abnormalities in the hypothalamic-pituitary-adrenal (HPA)-axis, which can be measured using the combined dexamethasone-suppression/CRH-stimulation (Dex-CRH) test. The reactivity of the HPA-axis in this test, however, ranges over several orders of magnitude in depressed patients with comparable severity of symptoms. In this present study, we investigate which factors influence the magnitude of the response in the Dex-CRH test in 235 acutely depressed in-patients. We first examined the effects of common confounders shown to influence the HPA-axis, such as caffeine and nicotine consumption, acute stressors during the test, weight, gender, and age. Of all these variables, only female sex and nicotine consumption were positively correlated with the cortisol or ACTH response, respectively. As for the effects of psychopharmacological treatment, only the intake of carbamazepine and the fact of having relapsed under an established pharmacotherapy significantly increased the response in the Dex-CRH test, whereas the presence or absence of antidepressant treatment, the type of antidepressant treatment, or the number of ineffective antidepressant treatment trials during the index episode up to admission did not have any effect. We also found a positive correlation of the number of previous episodes, the overall HAM-D score and the severity of somatic/vegetative symptoms with the results in the Dex-CRH test. These results underline that in depressed patients this test is not majorly influenced by disease-unrelated factors. In addition, current antidepressant treatment does not appear to affect test outcome in the absence of clinical response. The influence of the number of previous episodes and relapse under pharmacotherapy suggests that HPA-axis reactivity may be altered by repetitive states of hypercortisolemia or continuous antidepressant treatment. Finally, more severe vegetative symptoms are associated with an enhanced HPA-axis activity.