No abstract

The meta-analysis was able to detect some trends in the data analyzed, but did not show any drug having a uniform positive cognitive profile.

Background Lithium has been used clinically for 70 years, mainly to treat bipolar disorder. Competing treatments and exaggerated impressions about complexity and risks of lithium treatment have led to its declining use in some countries, encouraging this update about its safe clinical use. We conducted a nonsystematic review of recent research reports and developed consensus among international experts on the use of lithium to treat major mood disorders, aiming for a simple but authoritative guide for patients and prescribers. Main text We summarized recommendations concerning safe clinical use of lithium salts to treat major mood disorders, including indications, dosing, clinical monitoring, adverse effects and use in specific circumstances including during pregnancy and for the elderly. Conclusions Lithium continues as the standard and most extensively evaluated treatment for bipolar disorder, especially for long-term prophylaxis.

IMPORTANCE Antipsychotics are used increasingly in youth for nonpsychotic and off-label indications, but cardiometabolic adverse effects and (especially) type 2 diabetes mellitus (T2DM) risk have raised additional concern. OBJECTIVE To assess T2DM risk associated with antipsychotic treatment in youth. DATA SOURCES Systematic literature search of PubMed and PsycINFO without language restrictions from database inception until May 4, 2015. Data analyses were performed in July 2015, and additional analyses were added in November 2015. STUDY SELECTION Longitudinal studies reporting on T2DM incidence in youth 2 to 24 years old exposed to antipsychotics for at least 3 months. DATA EXTRACTION AND SYNTHESIS Two independent investigators extracted study-level data for a random-effects meta-analysis and meta-regression of T2DM risk. MAIN OUTCOMES AND MEASURES The coprimary outcomes were study-defined T2DM, expressed as cumulative T2DM risk or as T2DM incidence rate per patient-years. Secondary outcomes included the comparison of the coprimary outcomes in antipsychotic-treated youth with psychiatric controls not receiving antipsychotics or with healthy controls RESULTS Thirteen studies were included in the meta-analysis, including 185 105 youth exposed to antipsychotics and 310 438 patient-years. The mean (SD) age of patients was 14.1 (2.1) years, and 59.5% were male. The mean (SD) follow-up was 1.7 (2.3) years. Among them, 7 studies included psychiatric controls (1 342 121 patients and 2 071 135 patient-years), and 8 studies included healthy controls (298 803 patients and 463 084 patient-years). Antipsychotic-exposed youth had a cumulative T2DM risk of 5.72 (95% CI, 3.45-9.48; P < .001) per 1000 patients. The incidence rate was 3.09 (95% CI, 2.35-3.82; P < .001) cases per 1000 patient-years. Compared with healthy controls, cumulative T2DM risk (odds ratio [OR], 2.58; 95% CI, 1.56-4.24; P < .0001) and incidence rate ratio (IRR) (IRR, 3.02; 95% CI, 1.71-5.35; P < .0001) were significantly greater in antipsychotic-exposed youth. Similarly, compared with psychiatric controls, antipsychotic-exposed youth had significantly higher cumulative T2DM risk (OR, 2.09; 95% CI, 1.50-52.90; P < .0001) and IRR (IRR, 1.79; 95% CI, 1.31-2.44; P < .0001). In multivariable meta-regression analyses of 10 studies, greater cumulative T2DM risk was associated with longer follow-up (P < .001), olanzapine prescription (P < .001), and male sex (P = .002) (r 2 = 1.00, P < .001). Greater T2DM incidence was associated with second-generation antipsychotic prescription (P Յ .050) and less autism spectrum disorder diagnosis (P = .048) (r 2 = 0.21, P = .044). CONCLUSIONS AND RELEVANCE Although T2DM seems rare in antipsychotic-exposed youth, cumulative risk and exposure-adjusted incidences and IRRs were significantly higher than in healthy controls and psychiatric controls. Olanzapine treatment and antipsychotic exposure time were the main modifiable risk factors for T2DM development in antipsychotic-exposed youth. Antipsychotics should be used judiciously an...

Aims To systematically review the existing trials on optimal serum levels for lithium for maintenance treatment of bipolar disorder and to develop clinical recommendations. Methods Systematic literature search. Discussion of major characteristics, limitations, methodological quality, and results of selected trials. Delphi survey consisting of clinical questions and corresponding statements. For statements endorsed by at least 80% of the members, consensus was considered as having been achieved. Results With strict inclusion criteria no studies could be selected, making it difficult to formulate evidence‐based recommendations. After loosening the inclusion criteria 7 trials were selected addressing our aims at least to some extent. Four of these studies suggest better efficacy being associated with lithium serum levels in a range above a lower threshold around 0.45/0.60 and up to 0.80/1.00 mmol/L. These findings support the outcome of the Delphi survey. Conclusions For adults with bipolar disorder there was consensus that the standard lithium serum level should be 0.60‐0.80 mmol/L with the option to reduce it to 0.40‐0.60 mmol/L in case of good response but poor tolerance or to increase it to 0.80‐1.00 mmol/L in case of insufficient response and good tolerance. For children and adolescents there was no consensus, but the majority of the members endorsed the same recommendation. For the elderly there was also no consensus, but the majority of the members endorsed a more conservative approach: usually 0.40‐0.60 mmol/L, with the option to go to maximally 0.70 or 0.80 mmol/L at ages 65‐79 years, and to maximally 0.70 mmol/L over age 80 years.

No abstract

Background: Since its introduction in modern medicine, naturalistic observations emerged about possible uses of lithium treatment for conditions different from recurring affective disorders, for which it is still a first-line treatment option. Some evidence about the antiviral properties of lithium began in the early 1970s, when some reports found a reduction of labial-herpetic recurrences. The present review aims to present most of the pre-clinical and clinical evidence about lithium's ability to inhibit DNA and RNA viruses, including Coronaviridae, as well as the possible pathways and mechanisms involved in such antiviral activity. Main body: Despite a broad number of in vitro studies, the rationale for the antiviral activity of lithium failed to translate into methodologically sound clinical studies demonstrating its antiviral efficacy. In addition, the tolerability of lithium as an antiviral agent should be addressed. In fact, treatment with lithium requires continuous monitoring of its serum levels in order to prevent acute toxicity and long-term side effects, most notably affecting the kidney and thyroid. Yet lithium reaches heterogeneous but bioequivalent concentrations in different tissues, and the anatomical compartment of the viral infection might underpin a different, lower need for tolerability concerns which need to be addressed. Conclusions: Lithium presents a clear antiviral activity demonstrated at preclinical level, but that remains to be confirmed in clinical settings. In addition, the pleiotropic mechanisms of action of lithium may provide an insight for its possible use as antiviral agent targeting specific pathways.

Background Patients with severe mental illness (SMI) have a reduced life expectancy of one to two decades as compared to the general population, with most years of life lost due to somatic diseases. Most previous studies on disorders constituting SMI, e.g. schizophrenia and bipolar disorder, have investigated the disorders separately and hence not compared the disorders in terms of mortality rates relative to the background population. Methods A register-based cohort study including the entire Danish population comparing mortality rates relative to the background population, controlling for age and sex, i.e. standardized mortality ratios (SMRs) in patients diagnosed with schizophrenia with those in patients diagnosed with bipolar disorder, during the study period from 1995 to 2014. Results The SMR of patients with SMI was significantly higher than one for each calendar year in the study period with an overall SMR of 4.58, 95% CI (4.48–4.69) in patients diagnosed with schizophrenia (n = 38,500) and of 2.57 (95% CI 2.49–2.65) in patients diagnosed with bipolar disorder (n = 23,092). When investigating time trends in SMR for schizophrenia and for bipolar disorder, respectively, an increase in SMR over time was shown with a mean increase of 0.03 per year for schizophrenia and 0.02 for bipolar disorder (p < 0.01 for both disorders). The ratio between SMR for schizophrenia and SMR for bipolar disorder for each calendar year over the study period was constant (p = 0.756). Conclusions Increasing SMRs over the last 20 years were found for both patients diagnosed with bipolar disorder and patients diagnosed with schizophrenia. Despite clear differences between the two disorders regarding SMRs, the increases in SMR over time were similar, which could suggest similar underlying factors influencing mortality rates in both disorders.