Lithium Treatment Over the Lifespan in Bipolar Disorders

Lithium has been the treatment of choice for patients with bipolar disorder (BD) for nearly 70 years. It is recommended by all relevant guidelines as a first-line treatment for maintenance therapy. In this review, we outline the current state of evidence for lithium in the treatment of BD over the lifespan. First, we summarize the evidence on efficacy in general, from relapse prevention to acute anti-manic treatment and its role in treating mood episodes with mixed features and bipolar depression. As patients are often treated for many years and different aspects have to be considered in different phases of life, we discuss the particularities of lithium in the treatment of paediatric BD, in older aged individuals and in pregnant women. Lastly, we discuss the evidence on lithium's proposed suicide-preventive effects, the dangers of rapid discontinuation and lithium's adverse effects, particularly with regard to long-term treatment

Subjective response to and tolerability of long-term supraphysiological doses of levothyroxine in refractory mood disorders

NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Affective Disorders. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Affective Disorders, [VOL 64, ISSUE 1, (2001)] DOI:10.1016/S0165-0327(00)00215-9

Antipsychotic Withdrawal Symptoms: A Systematic Review and Meta-Analysis

Objective Avoiding withdrawal symptoms following antipsychotic discontinuation is an important factor when planning a safe therapy. We performed a systematic review and meta-analysis concerning occurrence of withdrawal symptoms after discontinuation of antipsychotics. Data Sources We searched the databases CENTRAL, Pubmed, and EMBASE with no restriction to the beginning of the searched time period and until October 1, 2019 (PROSPERO registration no. CRD42019119148). Study Selection Of the 18,043 screened studies, controlled and cohort trials that assessed withdrawal symptoms after discontinuation of oral antipsychotics were included in the random-effects model. Studies that did not implement placebo substitution were excluded from analyses. The primary outcome was the proportion of individuals with withdrawal symptoms after antipsychotic discontinuation. We compared a control group with continued antipsychotic treatment in the assessment of odds ratio and number needed to harm (NNH). Data Extraction We followed guidelines by the Cochrane Collaboration, PRISMA, and MOOSE. Results Five studies with a total of 261 individuals were included. The primary outcome, proportion of individuals with withdrawal symptoms after antipsychotic discontinuation, was 0.53 (95% CI, 0.37–0.70; I2 = 82.98%, P < 0.01). An odds ratio of 7.97 (95% CI, 2.39–26.58; I2 = 82.7%, P = 0.003) and NNH of 3 was calculated for the occurrence of withdrawal symptoms after antipsychotic discontinuation. Conclusion Withdrawal symptoms appear to occur frequently after abrupt discontinuation of an oral antipsychotic. The lack of randomized controlled trials with low risk of bias on antipsychotic withdrawal symptoms highlights the need for further research

Low effective organizational strategies in visual memory performance of unmedicated alcoholics during early abstinence

Objective: Alcohol-dependent patients in early abstinence show an impairment of cognitive functions which can be seen in poor implementation of newly learned skills for avoiding relapse. Executive dysfunction may persist during abstinence in alcohol-dependent persons, thus mitigating long-term abstinence. This study assessed visual memory function and choice of organizational strategies in alcoholics, as these are major factors necessary to implement ongoing behavior changes which are required for maintaining abstinence

Controlled drinking-non-abstinent versus abstinent treatment goals in alcohol use disorder: a systematic review, meta-analysis and meta-regression.

BACKGROUND AND AIMS: The proportion of untreated patients with alcohol use disorder (AUD) exceeds that of any other mental health disorder, and treatment alternatives are needed. A widely discussed strategy is to depart from the abstinence paradigm as part of controlled drinking approaches. This first systematic review with meta-analysis aims to assess the efficacy of non-abstinent treatment strategies compared with abstinence-based strategies. METHODS: CENTRAL, PubMed, PsycINFO and Embase databases were searched until February 2019 for controlled (randomized and non-randomized) clinical trials (RCTs and non-RCTs) among adult AUD populations, including an intervention group aiming at controlled drinking and a control group aiming for abstinence. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane Collaboration guidelines, literature search, data collection and risk of bias assessment were carried out independently by two reviewers [International Prospective Register of Systematic Reviews (PROSPERO), registration no. CRD42019128716]. The primary outcome was the proportion of participants consuming alcohol at or below the recommended threshold. Secondary outcomes were social functioning, drinking reductions, abstinence rates and dropouts. Using random-effects models, RCTs and non-RCTs were analyzed separately. Sensitivity and subgroup analyses accounted for methodological rigor, inclusion of goal-specific treatment, length of follow-up and AUD severity. RESULTS: Twenty-two studies (including five RCTs) with 4204 patients were selected. There was no statistically significant difference between both treatment paradigms in RCTs [odds ratio (OR) = 1.32, 95% confidence interval (CI) = 0.51-3.39]. Non-randomized studies of free goal choice favored abstinence-orientation (OR = 0.60, 95% CI = 0.40-0.90), unless goal-specific treatment was provided (OR = 0.79, 95% CI = 0.40-1.56), or in studies of low risk of bias (OR = 0.73, 95% CI = 0.49-1.09) or with long follow-up (OR = 1.49, 95% CI = 0.78-2.85). Effect sizes were not clearly dependent upon AUD severity. Abstinence- and controlled drinking interventions did not clearly differ in their effect on social functioning and drinking reductions. CONCLUSIONS: Available evidence does not support abstinence as the only approach in the treatment of alcohol use disorder. Controlled drinking, particularly if supported by specific psychotherapy, appears to be a viable option where an abstinence-oriented approach is not applicable

Modification of 40X13 steel at high-intensity nitrogen ion implantation

This paper presents the results of the formation of deep modified layers in 40X13 steel using a high-intensity repetitively pulsed nitrogen ion beam with a current density up to 0.25 A/cm2. An arc generator with a hot cathode provided the DC nitrogen plasma flow. A plasma immersion approach was used for high-frequency, short-pulse very intense nitrogen ion beam formation. A grid hemisphere with radii of 7.5 cm was immersed in the plasma. Negative bias pulses with an amplitude of 1.2 kV, a pulse duration of 4 µs, and a pulse repetition rate of 105 pulses per second were applied to the grid. The substrates were implanted at the temperature of 500 °C and various processing times ranging from 20 to 120 minutes with 1.2 keV nitrogen ions using a very-high current density up to 0.25 A/cm2 ion beams. The work explores the surface morphology, elemental composition, and mechanical properties of deep-layer modified 40X13 steel after low ion energy, very-high-intensity nitrogen ion beam implantation

Long-Term Outcome after Lithium Augmentation in Unipolar Depression: Focus on HPA System Activity

Background: Lithium augmentation is a first-line strategy for depressed patients resistant to antidepressive therapy, but little is known about patients’ subsequent long-term course or outcome predictors. We investigated long-term outcomes of unipolar depressed patients who had participated in a study on the effects of lithium augmentation on the hypothalamic-pituitary-adrenocortical system using the combined dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test. Methods: Twelve to 28 months (mean 18.6 ± 4.6 months) after lithium augmentation, 23 patients were assessed with a standardized interview, of which 18 patients had complete DEX/CRH test results. Relapse was diagnosed by DSM-IV criteria (Structured Clinical Interview for DSM-IV; SCID I). Results: Only 11 patients (48%) had a favorable follow-up, defined as absence of major depressive episodes during the observation period. Patients with a favorable and an unfavorable course did not differ in clinical or sociodemographic parameters, endocrinological results or continuation of lithium. However, fewer previous depressive episodes tended to correlate (p = 0.09) with a favorable course. Conclusion: Results from studies using the DEX/CRH test to predict relapse in depressed patients treated with antidepressants were not replicated for lithium augmentation. Our finding could reflect the elevation of DEX/CRH results by lithium, independent of clinical course. Limitations of the study are its small sample size, the heterogeneous clinical baseline conditions and the lack of lithium serum levels. The fact that lithium continuation did not predict the course might be related to the difference between the efficacy of lithium in controlled studies and its effectiveness in naturalistic settings.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany

Autoimmune encephalitis (AE) can rarely manifest as a predominantly psychiatric syndrome without overt neurological symptoms. This study’s aim was to characterize psychiatric patients with AE; therefore, anonymized data on patients with suspected AE with predominantly or isolated psychiatric syndromes were retrospectively collected. Patients with readily detectable neurological symptoms suggestive of AE (e.g., epileptic seizures) were excluded. Patients were classified as “probable psychiatric AE (pAE),” if well-characterized neuronal IgG autoantibodies were detected or “possible pAE” (e.g., with detection of nonclassical neuronal autoantibodies or compatible cerebrospinal fluid (CSF) changes). Of the 91 patients included, 21 (23%) fulfilled our criteria for probable (autoantibody-defined) pAE and 70 (77%) those for possible pAE. Among patients with probable pAE, 90% had anti-NMDA receptor (NMDA-R) autoantibodies. Overall, most patients suffered from paranoid-hallucinatory syndromes (53%). Patients with probable pAE suffered more often from disorientation (p < 0.001) and impaired memory (p = 0.001) than patients with possible pAE. Immunotherapies were performed in 69% of all cases, mostly with high-dose corticosteroids. Altogether, 93% of the patients with probable pAE and 80% of patients with possible pAE reportedly benefited from immunotherapies (p = 0.251). In summary, this explorative, cross-sectional evaluation confirms that autoantibody-associated AE syndromes can predominantly manifest as psychiatric syndromes, especially in anti-NMDA-R encephalitis. However, in three out of four patients, diagnosis of possible pAE was based on nonspecific findings (e.g., slight CSF pleocytosis), and well-characterized neuronal autoantibodies were absent. As such, the spectrum of psychiatric syndromes potentially responding to immunotherapies seems not to be limited to currently known autoantibody-associated AE. Further trials are needed