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Stopping antidepressants can cause withdrawal (discontinuation) symptoms, the return of the original illness, and rebound. The latter means that the disease will return stronger, faster, or with greater likelihood than if it had not been treated with medication. The Psychiatry Working Group of the Drug Commission of the German Medical Association (AkdÄ) presents the scientific findings and provides practical recommendations for action. Withdrawal symptoms are multiform; unspecific physical symptoms are predominant. Distinguishing them from the recurrence of depressive symptoms can be difficult. Most of them are mild and self-limiting. There is insufficient evidence on the extent and frequency of rebound depression. The rebound risk implies that when establishing the medication, the short-term benefit must be weighed against the possible long-term risk of chronic depression or the possible need for long-term medication. Patients should be informed about the risk of withdrawal both as early as the joint decision-making process about treatment initiation and regularly during the course of treatment. Withdrawal should take place gradually, except in emergency situations, whereby small steps should be taken, especially in the low-dose range. [ABSTRACT FROM AUTHOR]

Background: German S3 guidelines are subject to the highest methodological standards. This includes that they are only valid for a certain time period. Following the first edition in 2012 the first update of the S3 guidelines on bipolar disorder has now been published (2019). Objective: What has changed in the field of pharmacological recommendations comparing the first edition with the update in 2019? Material and methods: Comparison of the 1st edition from 2012 with the update from 2019 of the S3 guidelines for the diagnostics and treatment of bipolar disorders. Results: The three principle treatment targets of acute treatment of bipolar depression, acute treatment of mania and phase prophylaxis (maintenance treatment) can be distinguished. For acute treatment of bipolar depression, for the first time a medication has received a level A recommendation: quetiapine. For the acute treatment of mania, several drugs are still recommended with the same level of recommendation (B). Asenapine has been added as the tenth substance. Lithium is still the only drug with a level A recommendation for maintenance and prophylactic treatment and is also the only drug approved for this indication without restrictions. A new recommendation is that in the absence of contraindications, phase prophylaxis with a serum level of at least 0.6 mmol/l should be carried out. With a B recommendation, quetiapine has been added to the drugs for phase prophylactic treatment. Conclusion: The S3 guidelines make recommendations at the highest scientific level. In view of these findings, lithium is clearly underutilized for maintenance therapy. In the absence of clear contraindications (advanced renal insufficiency), every patient with bipolar disease should be given the chance of lithium prophylaxis for an adequately long period. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and tolerability of baclofen vs. placebo for long‐term treatment of alcohol use disorder. Method: Systematic review and meta‐analysis following methods of the Cochrane Collaboration Handbook (PROSPERO registration: CRD42017073663). Primary outcome was the random‐effects summary estimate of all standardized mean differences (SMDs), as calculated from the primary outcomes of each study. Results: Fourteen double‐blind RCTs (1522 patients) were included. Heterogeneity was substantial for most analyses (I2 about 75%). Baclofen showed a small, but not statistically significant superiority over placebo: SMD = 0.22 ([95% CI: −0.03; 0.47], P = 0.09). This result was supported by a leave‐one‐out‐analysis, and Orwin's fail‐safe N, by predefined secondary analyses (on abstinence rates and amount of drinking), and by a post hoc‐analysis of high‐dose studies (>80 mg/day). An analysis of low risk of bias studies (SMD = 0.10 [−0.20; 0.41], P = 0.51, I2 = 43.3%) found no effect. Exclusion of four studies focusing on patients with comorbidity yielded a small positive effect. Drop‐out rates were similar. Conclusion: Our results question baclofen's utility in the long‐term treatment of alcohol use disorder at both normal and high doses. While the confidence intervals indicate that marginally harmful or moderately beneficial effects of baclofen remain a possibility, the most likely effect size is slightly above placebo effects. [ABSTRACT FROM AUTHOR]

In clinical practice, there is a need for a more individualized selection of antidepressants and adequate dosage. The investigation of pharmacokinetically relevant genes is a promising approach to assist this selection. In the past 2 years, two commercially available tests have been subject of advertisement, a test from Stada, which analyses variants of the cytochrome P450 isoenzymes CYP2D6 and CYP2C19 and a test from HMNC Brain Health, which analyses variants of the ABCB1 gene. The costs for both kits are not covered by the statutory health insurance and it is therefore proposed that the patients are invoiced directly in the form of individual healthcare payment. The companies claim that by applying the tests antidepressant treatment failure can be avoided and that patients will respond faster to the antidepressant used. These claims are not based on appropriate clinical trials, which are either lacking or reveal conflicting results. Hence, the routine use of these tests is not recommended. In accordance with the German S3 Guideline for unipolar depression, therapeutic drug monitoring (TDM) of serum levels should be carried out in cases of non-response to an antidepressant with adequate dosage and duration. As a rule the costs for TDM are covered by the statutory health insurance. Cytochrome P450 genotyping is only indicated when the serum level is not within the expected range and other reasons to explain this discrepancy are excluded. Many laboratories provide these analyses and in individual cases the costs are reimbursed by the statutory health insurance. Further research should be carried out to investigate the importance of the ABCB1 gene for the treatment with antidepressants. [ABSTRACT FROM AUTHOR]

Lithium and with restrictions, carbamazepine, valproic acid, lamotrigine, olanzapine, aripiprazole and quetiapine, are approved in Germany for maintenance treatment of bipolar disorder. Lithium is the only drug that (I) proved to be effective for the prevention of depressive as well as manic episodes in state-of-the-art studies without an enriched design and that (II) is approved for the maintenance treatment of bipolar disorders without restrictions. It (III) is also the only drug which is recommended for maintenance treatment by the current German S3 guidelines on bipolar disorders with the highest degree of recommendation (A) and (IV) is the only drug with a well proven suicide preventive effect. Hence, lithium is the mood stabilizer of first choice. No patient should be deprived of lithium without a specific reason. Side effects and risks are manageable if both the physician and the patient are well informed. Detailed and practical information on a safe use of lithium can be found in the S3 guidelines on bipolar disorders. For patients who do not respond sufficiently to lithium, have contraindications or non-tolerable side effects, other mood stabilizers should be used. Restrictions in their respective approval as well as specific side effects and risks have to be taken into account. Because maintenance treatment is a long-term treatment, particular concern should be paid to drugs with the potential risk of a metabolic syndrome, particularly atypical antipsychotics. [ABSTRACT FROM AUTHOR]

Lithium is the only drug that obtained the highest level of recommendation for maintenance therapy in the recent German S3 guidelines on bipolar disorders. In addition it is the only drug with proven efficacy for the prevention of manic as well as depressive episodes in studies with a non-enriched design. Therefore, it is highly welcomed that The Lancet recently published a systematic review and meta-analysis on the risks and side effects of lithium. This is the most comprehensive review on this topic so far. The glomerular filtration rate and maximum urinary concentration ability are slightly reduced under lithium. More patients suffered from renal failure compared to controls; however, renal failure remains a very rare event. The review confirmed the well known suppressive effects of lithium on the thyroid. An increase of serum calcium could be observed relatively frequently, therefore, regular control of serum calcium under lithium therapy is recommended. A relevant increase in body weight is more frequent under lithium than under placebo but less frequent than under olanzapine. No statistically significant increase could be found for hair loss, skin disorders or major congenital abnormalities. Lithium treatment is a safe therapy when clinicians follow the established recommendations. Data indicate that a risk for renal failure exists especially in patients without regular monitoring or with too high lithium serum levels. A (subclinical) hypothyroidism is not an indication to stop administration of lithium but is an indication for l-thyroxin substitution therapy. In pregnancy the risks of continuing lithium should be balanced against the risks of stopping lithium together with the patient. [ABSTRACT FROM AUTHOR]

Abstract: Background: Recent reports indicate that the prevalence of bipolar disorder (BD) in patients with an acute major depressive episode might be higher than previously thought. We aimed to study systematically all patients who sought therapy for major depressive episode (MDE) within the BRIDGE study in Germany, reporting on an increased number (increased from 2 in the international BRIDGE report to 5) of different diagnostic algorithms. Methods: A total of 252 patients with acute MDE (DSM-IV confirmed) were examined for the existence of BD (a) according to DSM-IV criteria, (b) according to modified DSM-IV criteria (without the exclusion criterion of ‘mania not induced by substances/antidepressants’), (c) according to a Bipolarity Specifier Algorithm which expands the DSM-IV criteria, (d) according to HCL-32R (Hypomania-Checklist-32R), and (e) according to a criteria-free physician''s diagnosis. Results: The five different diagnostic approaches yielded immensely variable prevalences for BD: (a) 11.6; (b) 24.8%; (c) 40.6%; (d) 58.7; e) 18.4% with only partial overlap between diagnoses according to the physician''s diagnosis or HCL-32R with diagnoses according to the three DSM-based algorithms. Conclusions: The diagnosis of BD in patients with MDE depends strongly on the method and criteria employed. The considerable difference between criteria-free physician''s diagnosis and the remaining algorithms indicate the usefulness of criteria lists within the everyday clinical setting. Limitations: Diagnoses based on DSM were only made with checklists. The diagnoses of (hypo-) manic episodes in the patient history were not systematically verifiable by indirect anamnesis. [Copyright &y& Elsevier]

Bipolar disorders are severe psychiatric disorders with extensive individual and health economic consequences. Starting in 2007 the first German evidence and consensus based guideline for diagnostics and treatment of bipolar disorders was developed which holds the potential of increasing confidence of therapists, patients and relatives in the decision-making process and improving healthcare service experiences of patients and relatives. Apart from recommendations for diagnostics and treatment the guidelines provide those for trialogue action, knowledge transfer and self-help and for strategies for healthcare provision of this complex disorder. In the present article the methodology and essential recommendations are outlined and complemented in specific topics by corresponding articles in this special issue. Due to restrictions of the length of this presentation there is the need to refer to the comprehensive version of the guidelines at several points also regarding a detailed discussion of the limitations. [ABSTRACT FROM AUTHOR]

Bschor T, Baethge C. No evidence for switching the antidepressant: systematic review and meta-analysis of RCTs of a common therapeutic strategy. Objective: Switching antidepressants is a common strategy for managing treatment-resistant depressed patients. However, no systematic reviews have been conducted to date. Method: We systematically searched MEDLINE/EMBASE/Cochrane Central Register of Controlled Trials and additional sources. We included double-blind studies of patients with depressive symptomatology who were not responding to initial antidepressant monotherapy and were subsequently randomized to another antidepressant or to continue the same antidepressant. Results were pooled for meta-analysis of response + remission rates using a fixed-effects model. Results: A total of three studies were included. Switching to another antidepressant was not superior to continuing the initial antidepressant in any of these studies. Our meta-analysis showed no significant advantages to either strategy and no significant heterogeneity of results [OR for response rates: 0.85 (95% CI: 0.55–1.30) favoring continuing]. Conclusion: There is a discrepancy between the published evidence and the frequent decision to switch antidepressants, indicating an urgent need for more controlled studies. Pending such studies we recommend that physicians rely on more thoroughly evaluated strategies. [ABSTRACT FROM AUTHOR]

Bschor T, Ising M, Bauer M, Lewitzka U, Skerstupeit M, Müller-Oerlinghausen B, Baethge C. Time experience and time judgment in major depression, mania and healthy subjects. A controlled study of 93 subjects. Acta Psychiatr Scand 2004: 109: 222–229. © Blackwell Munksgaard 2004. Studies on the time sense of depressed patients have revealed inconsistent results. Manic patients have been almost neglected. Patients with a major depressive episode ( n = 32), or a manic episode ( n = 30) (both Diagnostic and Statistical Manual of Mental Disorders-IV, Mini-International Neuropsychiatric Interview-confirmed), and 31 healthy controls were included. The subjective time experience was assessed by a visual analog scale (VAS), the objectively measurable time judgment abilities by the Chronotest, a computer program developed for this study, consisting of time estimation and time production tasks. Controls reported a balanced, manic patients an enhanced, and depressive patients a slowed experience of time flow in the VAS ( P < 0.001). In the time judgment tasks, however, both depressed and manic patients showed time overestimation for the longer time spans ( P < 0.008). This largest study on time sense in manic patients confirmed results of a divergent alteration of time experience in depressive and in manic patients but revealed an uniform time overestimation by both patient groups in time judgment tasks. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Lithium augmentation is an established strategy in the treatment of refractory depression, but little is known about predictors of response and its mode of action. There is increasing evidence that low thyroid function indices within the normal range are associated with a poorer treatment response to antidepressants, but previous studies on the hypothalamic-pituitary-thyroid (HPT) system during lithium augmentation provide inconclusive results and have methodological limitations. This study aimed at exploring the role of thyroid function in lithium augmentation and used a prospective design that included a homogeneous sample of inpatients with unipolar major depressive disorder. METHODS: In 24 euthyroid patients with a major depressive episode who had not responded to antidepressant monotherapy of at least 4 weeks, we measured serum thyroid-stimulating hormone (TSH), total triiodothyronine (T3) and total thyroxine (T4) before (baseline) and during lithium augmentation therapy (follow-up). The time point of the endocrinological follow-up depended on the status of response, which was assessed weekly with the Hamilton Depression Rating Scale, 17-item version (HDRS17). Responders were reassessed immediately after response was determined, and non-responders after 4 weeks of lithium augmentation. RESULTS: There was a statistically significant change in thyroid system activity during lithium augmentation, with an increase of TSH levels and a decrease of peripheral T3 and T4 levels. However, there were no differences in any of the HPT hormones between responders and non-responders at baseline or at follow-up. CONCLUSIONS: The decrease of thyroid system activity during lithium treatment reflects the well-established 'antithyroid' properties of lithium. However, it appears that thyroid status does not predict response to lithium augmentation in euthyroid patients before treatment. [ABSTRACT FROM AUTHOR]

Background: [(I)] Profound alterations of the hypothalamic-pituitary-adrenocortical (HPA) axis regulation were repeatedly shown in depressed patients. The most sensitive challenge test of the HPA axis, the combined dexamethasone/CRH test (DEX/CRH test), shows an overstimulation of ACTH and cortisol in depressed patients. Under tricyclic antidepressant treatment, a normalization of the HPA axis overdrive was found to precede the clinical improvement. [(II)] Lithium is a well established drug for the treatment of affective disorders. Yet, its exact mode of action and its effects on the HPA axis are still unknown. Design and methods: Three 4-week studies with each 30 acutely depressed patients (unipolar, SCID I confirmed) were conducted. In study 1, patients refractory to a treatment trial with an antidepressant of at least four weeks were treated with lithium augmentation. In study 2 and 3, drug free patients were treated with lithium monotherapy or citalopram monotherapy respectively. Weekly HAM-D ratings were performed. In each study, the DEX/CRH test was conducted right before and four weeks after initiation of the pharmacotherapy. Results: All three pharmacological strategies showed good antidepressive efficacy. Both lithium monotherapy and lithium augmentation led to a (for most parameters significant) increase in the HPA axis activity. In contrast, citalopram monotherapy resulted in a decrease of the hormone response to the DEX/CRH test. [ABSTRACT FROM AUTHOR]

Treatment of bipolar depression requires complex treatment decisions in daily routine care. The best evidence for pharmacological treatment is given for quetiapine and with limitations also in off-label use for lamotrigine, especially in combination with lithium, carbamazepine and olanzapine. Effectiveness and recommendation of antidepressants in treatment of bipolar depression remain controversial because of insufficient data. Initially, in depressive episodes a phase prophylactic treatment should be initiated or (if already existing) optimized and more severe episodes should be treated with the substances described before. In case of non-response, the combination of lithium and lamotrigine or antidepressants in combination with lithium, antiepileptics or atypical antipsychotics may be necessary. If depressive episodes occur in the course of pharmacological treatment with prophylactic agents, combination therapies of different substances, even with antidepressants, are necessary. In case of treatment-resistant depressive episodes, complex treatment strategies (e.g. combination therapies and MAO inhibitors) should be considered. [ABSTRACT FROM AUTHOR]

Bipolar depression and its clinical presentation is a frequent but complex psychiatric disease. Despite the high prevalence and the clinical and economic relevance of bipolar depression, few treatments are proven to be highly and consistently effective. In practice, the treatment of bipolar depression typically includes complex treatment decision-making. The best evidence for a pharmacological treatment exists for quetiapine. Alternatives with limitations are lamotrigine (also in the combination with lithium), carbamazepine and olanzapine. The eff ectiveness and recommendation of antidepressants in the treatment of bipolar depression remains controversial. Initially, depressive episodes should been treated with one of the named substances with antidepressant properties. In non-responders, a combination of lithium and lamotrigine, or antidepressants in combination with either lithium, an antiepileptic drug or atypical antipsychotics, may be necessary. If a depressive episode occurs under ongoing moodstabilizing treatment, combination treatments of different substances, even with antidepressants, can be necessary. In the case of treatment-resistant depressive episodes, complex treatment strategies (combination therapies, MAO inhibitors) should be considered. This review describes the treatment recommendations of different guidelines for bipolar depression and emphasizes their differences. Furthermore, alternative pharmacological treatment strategies and complex treatment situations are discussed. [ABSTRACT FROM AUTHOR]

Objective: Recent meta‐analyses on dose–response relationships of SSRIs are largely based on indirect evidence. We analyzed RCTs directly comparing different SSRI doses. Method: Systematic literature search for RCTs. Two raters independently screened articles and extracted data. Across SSRIs, doses defined as low, medium, and high doses, based on drug manufacturers' product monographs, were analyzed in pairwise random‐effects meta‐analyses and in a sensitivity network meta‐analysis with regard to differences in antidepressive efficacy (primary outcome). We also analyzed all direct comparisons of different dosages of specific SSRIs. (Prospero CRD42018081031). Results: Out of 5333 articles screened, we included 33. Comparisons of dosage groups (low, medium, and high) resulted in only small and clinically non‐significant differences for SSRIs as a group, the strongest relating to medium vs low doses (SMD: −0.15 [95%‐CI: −0.28; −0.01) and not sustained in a sensitivity analysis. Among different doses of specific SSRIs, no statistically significant trend emerged for efficacy at higher doses, but 60 mg/day fluoxetine are statistically significantly inferior to 20 mg/day. Paroxetine results are inconclusive: 10 mg/day are inferior to higher doses, but 30 and 40 mg/day are inferior to 20 mg/day. Meaningful effects cannot be ruled out for certain drugs and dosages, often investigated in only one trial. Dropout rates increase with dose—particularly due to side effects. Network meta‐analyses supported our findings. Conclusions: There is no conclusive level I or level II evidence of a clinically meaningful dose–response relationship of SSRIs as a group or of single substances. High SSRI doses are not recommended as routine treatment. [ABSTRACT FROM AUTHOR]

Since the first publication of the guideline in 2012, which included critically reviewed evidence up to 2010, several hundred articles with new evidence were published and some topics of the clinical consensus needed to be reconsidered. Therefore, it was urgently necessary to revise the guideline to bring them up to date. In this article important revisions and updates are presented and the chances and limitations of the development of the guidelines and their implementation are discussed. [ABSTRACT FROM AUTHOR]

Hintergrund: Obwohl eine große Zahl von Studien die generelle Wirksamkeit psychotherapeutischer Behandlungen depressiver Störungen zeigt, variiert die Wirksamkeit in Abhängigkeit von therapeuten- und patientenseitigen Einflussfaktoren sowie der Art des depressiven Störungsbildes.Ziel der Arbeit: Ziel ist die zusammenfassende Darstellung des aktuellen Wissens zu psychotherapeutischen Behandlungen bei Patienten mit chronischen bzw. therapieresistenten depressiven Störungen und bei Patienten mit psychischen oder somatischen Komorbiditäten.Material und Methoden: Im Rahmen der 2015 durchgeführten Revision der aktuell gültigen S3- bzw. Nationalen VersorgungsLeitlinie (NVL) Unipolare Depression erfolgte eine systematische Evidenzrecherche zu Psychotherapie bei spezifischen Patientengruppen. Diese Ergebnisse in Verbindung mit einem systematischen Rechercheupdate werden dargestellt.Ergebnisse: Für die spezifischen Patientengruppen der chronisch depressiven bzw. therapieresistenten Patienten sowie mit komorbiden psychischen oder somatischen Erkrankungen liegen Hinweise für die Wirksamkeit von Psychotherapie im Hinblick auf die Reduktion depressiver Symptome vor. Insbesondere für depressive Patienten mit psychischen Komorbiditäten ist die Evidenzlage allerdings noch nicht ausreichend.Diskussion: Basierend auf der aktuellen Evidenz und/oder auf klinischem Expertenkonsens empfiehlt die NVL eine alleinige Psychotherapie oder eine Kombination mit Antidepressiva bei den meisten der genannten Patientengruppen. Es bestehen Kenntnislücken, die deutlich machen, dass weitere wissenschaftliche Bemühungen notwendig sind, um die Behandlung spezifischer depressiver Patientengruppen weiter zu verbessern. [ABSTRACT FROM AUTHOR]

Hintergrund: Depressive Störungen beeinträchtigen wie kaum eine andere Erkrankung in zentraler Weise das Wohlbefinden und das Selbstwertgefühl von Patienten. Neben der Pharmakotherapie gehört die Psychotherapie zu den primären Behandlungsstrategien bei depressiven Störungen.Ziel der Arbeit: Ziel ist die Darstellung des aktuellen Wissens zu psychotherapeutischen Behandlungen bei depressiven Störungen.Material und Methoden: Im Rahmen der 2015 durchgeführten Revision der aktuell gültigen S3- bzw. Nationalen VersorgungsLeitlinie (NVL) Unipolare Depression erfolgte eine systematische Evidenzrecherche. Die Ergebnisse zu verschiedenen psychotherapeutischen Verfahren in Verbindung mit einem systematischen Rechercheupdate werden in komprimierter Form dargestellt.Ergebnisse: Die kognitive Verhaltenstherapie (KVT) ist das am häufigsten untersuchte Psychotherapieverfahren, ihre Wirksamkeit ist durch zahlreiche Studien belegt. Wirksamkeitsnachweise zur Behandlung depressiver Störungen liegen auch für die tiefenpsychologisch fundierte Psychotherapie und die interpersonelle Therapie (IPT) vor, gefolgt von der systemischen Therapie und der Gesprächspsychotherapie (GPT); die Evidenz ist aber weniger robust.Diskussion: Die Wirksamkeit psychotherapeutischer Behandlungen alleine oder in Kombination mit pharmakologischen Behandlungen kann als sehr gut gesichert betrachtet werden. Psychotherapie stellt einen zentralen Bestandteil der Behandlung depressiver Störungen dar. [ABSTRACT FROM AUTHOR]

Objective Adverse events of psychotherapy have often been neglected in research. In this study, potential adverse events of group psychotherapies in a psychiatric hospital were systematically assessed, explored for predictors and linked to treatment outcome. Method A naturalistic trial was conducted in 180 in-patients attending different group psychotherapies. Adverse events were assessed using three different measures: (i) weekly reporting of unwanted treatment reactions, (ii) mood changes in response to every single group session and (iii) premature group termination. Results Different measures of adverse events were weakly associated. Deterioration of mood state and/or unwanted treatment reactions were experienced by 60-65% of all patients. Reports of unwanted treatment reactions decreased over time and were negatively associated with symptom improvement. However, mood state deterioration was constant and unrelated to treatment outcome. The rate of premature group termination was 34%. Significant predictors of adverse events included patient characteristics as well as disadvantageous group conditions. Conclusions For the majority of patients, group psychotherapy in the in-patient setting is associated with adverse events. Changes over time and a strong correlation with general symptom severity must be considered in the assessment and interpretation of adverse events. Predictors should be considered as potential risk factors in future research. [ABSTRACT FROM AUTHOR]

Antipsychotics, when used to treat neuropsychological symptoms associated with dementia, are associated with low effectiveness but a high risk of side effects. Some of these unwanted effects are severe and include an increased rate of cerebrovascular events and increased mortality. Although neuropsychiatric symptoms are frequently associated with dementia, it appears that antipsychotics are often used without clear indications and for too long time periods. Antipsychotics should be used only when all non-pharmacological strategies have failed. A clear definition of the treatment target in advance and a continuous monitoring of the therapy are mandatory. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this prospective study was to investigate the influence of lithium serum levels on subclinical psychopathological features during the euthymic interval in patients with an affective disorder. Methods: The study included 54 patients with a recurrent affective disorder undergoing a continuous prophylactic lithium treatment (31 unipolar, 23 bipolar). The observation period lasted for 2 years and included 332 visits. Visits consisted of a detailed interview, a continuous measurement of lithium levels and the collection of validated scales including HAMD, YMRS, CGI, VAMS and the SCL-90R. Several correlations between lithium serum levels and different psychopathological features during the euthymic interval were calculated on an individual patient basis and on a group basis to reveal generally occurring correlations. Results: No generally occurring significant correlations between lithium serum levels and specific psychopathological features were found. Only on a single patient level, 32 significant correlations between lithium level and specific psychopathological features were found, partly indicating a negative and partly indicating a positive influence of higher lithium levels on psychopathological symptoms. Nevertheless, in the group analyses no significant correlations were found. Discussion: Higher lithium levels were not associated with an improved psychopathological status, but they were not associated with a worse status (due to a higher burden of side effects) either. According to the literature there is currently no strong evidence to treat patients with a higher lithium level. It is recommended to start with a lower level and to continue with individual adjustments in accordance to prophylactic efficacy and tolerability. [ABSTRACT FROM AUTHOR]

Unipolar depressive disorders are among the most frequent reasons for utilizing the health care system. Although efficacious treatments are available and further advances have recently been made there is still a need for improving diagnostic and therapeutic procedures. Alignment of treatment on evidence-based treatment guidelines establishes an essential mainstay. The new S3 and National Health Care guidelines on unipolar depression, the compilation of which was coordinated by the German Society of Psychiatry, Psychotherapy and Neurology (DGPPN) and which were approved by 29 scientific and professional associations, is the ambitious effort to present state of the art evidence and clinical consensus for the treatment of depression. For pharmacotherapy of depression differentiated recommendations can be given, also separate from and in addition to psychotherapy. [ABSTRACT FROM AUTHOR]

Abstract: This prospective, longitudinal study compared the frequency and pattern of mood changes between outpatients receiving usual care for bipolar disorder who were either taking or not taking antidepressants. One hundred and eighty-two patients with bipolar disorder self-reported mood and psychiatric medications for 4 months using a computerized system (ChronoRecord) and returned 22,626 days of data. One hundred and four patients took antidepressants, 78 did not. Of the antidepressants taken, 95% were selective serotonin or norepinephrine reuptake inhibitors, or second-generation antidepressants. Of the patients taking an antidepressant, 91.3% were concurrently taking a mood stabilizer. The use of antidepressants did not influence the daily rate of switching from depression to mania or the rate of rapid cycling, independent of diagnosis of bipolar I or II. The primary difference in mood pattern was the time spent normal or depressed. Patients taking antidepressants frequently remained in a subsyndromal depression. In this naturalistic study using self-reported data, patients with bipolar disorder who were taking antidepressants—overwhelmingly not tricyclics and with a concurrent mood stabilizer—did not experience an increase in the rate of switches to mania or rapid cycling compared to those not taking antidepressants. Antidepressants had little impact on the mood patterns of bipolar patients taking mood stabilizers. [Copyright &y& Elsevier]

OBJECTIVE: Because the role of thyroid autoimmunity in the development of lithium-induced thyroid dysfunction remains controversial, we compared the prevalence of thyroid autoantibodies in patients with affective disorders receiving long-term lithium maintenance therapy with that of age- and sex-matched controls. METHODS: We conducted a cross-sectional study with 100 adult patients with major affective disorders diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, revised (DSM-III-R), who were undergoing lithium therapy for 6 months or more at a specialized lithium university clinic and 100 age- and sex-matched controls with no history of an axis I psychiatric disorder. Serum autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and TSH receptors (TRAb) were measured. RESULTS: TPOAb were found in 7 patients and 11 controls, and TgAb were found in 8 patients and 15 controls. TRAb were not found in either group. CONCLUSIONS: In this sample of patients with affective disorders, long-term lithium treatment did not increase the prevalence of thyroid autoimmunity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the effectiveness of lithium prophylaxis in unipolar major depressive disorder (MDD) and to identify predictors of outcome including comedication. METHODS: In this long-term naturalistic study, clinical data from 55 patients with MDD (DSM-III-R) were collected prospectively in an outpatient clinic specializing in the treatment of affective disorders. OUTCOME MEASURES: Change in hospital admission rate (number and duration) during prophylaxis compared with the period before prophylaxis, Morbidity-Index during prophylaxis and time to first recurrence after initiation of lithium treatment. RESULTS: During an average follow-up period of 6.7 years, a significant decline in the number of days spent in hospital (p<0.001; 52 d/yr less; 95; CI 31-73 d) and a low Morbidity-Index (mean 0.07) was observed. Only in 6 patients did medication have to be changed because of side-effects (n=4) or a lack of efficacy (n=2). None of the independent variables we analyzed proved to be important in predicting the outcome of lithium prophylaxis. Comedication was necessary in 21 patients. The overall outcome of their prophylactic treatment, however, did not differ from the group that did not receive comedication in the symptom-free intervals. CONCLUSIONS: The results of this study, with its long observation period and the inclusion of comedication as a confounding variable, indicate that lithium is a potent prophylactic agent for unipolar MDD in a naturalistic setting. In contrast to the findings of others, age was not associated with the outcome of prophylaxis, and latency did not predict outcome. Contrary to doubts that have been raised in recent years with regard to the effectiveness of lithium in everyday clinical practice, lithium appears to be a safe and potent alternative to antidepressants. [ABSTRACT FROM AUTHOR]

Background: To investigate the long-term effects of supraphysiological, TSH suppressive doses of levothyroxine (TSDL) on bone mineral density (BMD) in patients with affective disorders during an average treatment duration of 69 months.Methods: In 22 patients, BMD of the spine (lumbar vertebrae L1-4) and femur (femoral neck) was measured by dual energy X-ray absorptiometry (DXA). Forty (40) measurements from the prior study and 48 new follow-up measurements were included. BMD was expressed as Z-scores as a population standard reference. We used a linear mixed model to investigate the duration of TSDL as an explanatory factor for change in BMD compared to an age and gender matched reference population.Results: We found no significant differences in bone loss between the study and the reference population. The estimated non-significant decrease in Z-score compared to the reference population found was: a) lumbar spine (L1-4): -0.00069/month (p=0.9759) b) neck region of femur: -0.01405/month (p=0.4436). We did not find the factors age, thyroxine-dose or postmenopausal state as predictors for a decline in BMD.Limitations: Small sample size, no bone density assessment prior to treatment with TSDL, no patient control group with mood disorders who did not receive TSDL, variable bone density follow-up intervals.Conclusion: This study did not demonstrate evidence that long-term treatment of affectively ill patients with TSDL accelerates loss of BMD compared to an age- and gender-matched reference population. [ABSTRACT FROM AUTHOR]