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Key content: The perinatal period confers an elevated risk of both relapses and new onset of mental illness. Suboptimal treatment can have a profound impact on maternal mortality and morbidity, neonatal outcomes and longer term child development.Most psychotropic medication can be used safely in pregnancy, with some notable exceptions.While decisions on the use of psychotropic medications in pregnancy are often complex and should be multidisciplinary, it is imperative that obstetricians and gynaecologists familiarise themselves with current literature to provide evidence‐based counselling and care.Existing guidelines on the use of psychotropic medication are largely aimed at psychiatrists, and to date there has been a lack of concise, digestible information with a focus on core knowledge for obstetricians and gynaecologists.We summarise existing evidence on the use of antidepressants, antipsychotics, mood stabilisers and sedatives in the perinatal period. For each drug class we describe the teratogenicity, impact on pregnancy, breastfeeding and the newborn. Learning objectives: To be familiar with common psychotropic medication used in pregnancy and the postpartum period.To understand key evidence on the safety profile of psychiatric medication in the perinatal period and apply this to individualised counselling. [ABSTRACT FROM AUTHOR]

Intro: Valproic acid (VPA) is a commonly prescribed mood stabilizer, available in both oral (OS) and intravenous (IV) formulations. However, few studies have compared their safety and efficacy. This retrospective study aimed to investigate the safety and efficacy of and IV‐VPA in patients with Bipolar Disorder. Methods: Fifty patients with Bipolar Disorder experiencing a manic or depressive episode, with concomitant symptoms of opposite polarity, admitted to our inpatient unit and treated with IV‐VPA were included in a retrospective, single‐centre, non‐randomized, open‐label, parallel‐group comparative study. Fifty patients experiencing a manic or depressive episode, with concomitant symptoms of opposite polarity, treated with oral‐VPA and selected among those who were admitted to the inpatient unit prior to the introduction of IV‐VPA in our clinical practice, were included as the control group (matched based on age, gender and clinical scales score at baseline). The Clinical Global Impression (CGI), Young Mania Rating Scale (YMRS), Montgomery‐Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM‐A) scores were recorded at baseline, after 3 days of treatment and discharge from the inpatient unit. Patients were asked to respond on the basis of the symptoms present on the day the scale was administered. Response rate and the presence of adverse effects were also recorded. Results: Both patients treated with oral and IV‐VPA demonstrated significant improvements in all psychometric scales (p < 0.001). However, the IV group exhibited superior efficacy, with significantly lower scores on the CGI, YMRS, MADRS and HAM‐A scales on Day 3 and at discharge from the inpatient unit. The IV‐VPA treatment showed higher response rates on all psychometric scales, and no adverse effects were reported in either group. Conclusion: This retrospective study supports the use of IV‐VPA as a more efficacious treatment option for patients with Bipolar Disorder, particularly in acute settings where rapid symptom improvement is crucial. Both oral and IV‐VPA were found to be safe and well‐tolerated. [ABSTRACT FROM AUTHOR]

We have postulated that common changes in gene expression after treatment with different therapeutic classes of psychotropic drugs contribute to their common therapeutic mechanisms of action. To test this hypothesis, we measured levels of cortical coding and non-coding RNA using GeneChip® Rat Exon 1.0 ST Array after treatment with vehicle (chow only), chow containing 1.8 g lithium carbonate/kg (n = 10) or chow containing 12 g sodium valproate/kg (n = 10) for 28 days. Differences in levels of RNA were identified using JMP Genomics 13 and the Panther Gene Ontology Classification System was used to identify potential consequences of RNA. Compared to vehicle treatment, levels of cortical RNA for 543 and 583 coding and non-coding RNAs were different after treatment with valproate and lithium, respectively. Moreover, levels of 323 coding and non-coding RNAs were altered in a highly correlated way by treatment with valproate and lithium, changes that would impact on cholinergic, glutamatergic, serotonergic and dopaminergic neurotransmission as well as on voltage gated ion channels. Our study suggests that treating with mood stabilisers cause many common changes in levels of RNA which will impact on CNS function, particularly affecting post-synaptic muscarinic receptor functioning and the release of multiple neurotransmitters. [ABSTRACT FROM AUTHOR]

Oxidative stress is widely accepted to contribute to the pathogenesis of several psychiatric diseases. Many antipsychotic drugs and mood stabilizers act through restoration of the dysregulated oxidative homeostasis in the brain. However, the long-term effect of these drugs per se in terms of their potential to interfere with the oxidative status in the brain remains largely controversial. The present study aimed to investigate the sole effect of three commonly used psychoactive drugs, lithium, valproic acid, and olanzapine, on lipid and protein oxidation status in the prefrontal cortex of healthy rats. A total of 80 adult male albino Wistar rats were used, and groups were treated with saline (control), lithium, valproic acid, or olanzapine daily for 30 days. Following sacrification, right prefrontal cortexes were dissected and homogenized. Lipid peroxidation (LPO) and protein oxidation (AOPP) assays were performed by ELISA. LPO levels were significantly higher in lithium and valproic acid-treated rats by 45% and 40%, respectively. Olanzapine treatment caused a mild 26% increase in LPO levels, but the effect was non-significant. Lithium, valproic acid, and olanzapine treatments significantly increased AOPP levels by 58%, 54%, and 36.5%, respectively. There was a strong positive correlation between the lipid peroxidation and protein oxidation levels. Our results call attention to the need to consider the pro-oxidative capacity of antipsychotic drugs per se and their potential to disturb the oxidative homeostasis in the brain during long-term medication for psychiatric diseases. [ABSTRACT FROM AUTHOR]

Objective: Patients with bipolar disorder treated with lithium often require additional antipsychotics or anticonvulsants. However, the comparative effectiveness and safety of these agents as add-on to lithium has not been studied. Methods: This secondary analysis combined two similar 24-week trials on outpatients with bipolar disorder randomized to lithium (target serum level 0.4–0.6 mEq/L). Guideline-based adjunctive antipsychotics (Li+AP) and anticonvulsants (Li+AC) could be used if clinically indicated and was assessed at every study visit. Response was measured on the Clinical Global Impression scale and we performed adjusted mixed effects linear regression analyses. Analysis of variance tests compared metabolic measures including a binary diagnosis of metabolic syndrome before and after 24 weeks of treatment. Results: Among 379 outpatients (57% female, mean age 38 years, mean Clinical Global Impression 4.4), users of Li+AP (N = 50, primarily quetiapine and aripiprazole) improved to a similar degree (mean Clinical Global Impression improvement = 1.6, standard deviation = 1.5) as those using lithium-only (i.e. without adjunctive antipsychotics or anticonvulsants, N = 149, mean Clinical Global Impression improvement = 1.7, standard deviation = 1.4) (p = 0.59). Users of Li+AC (N = 107, primarily lamotrigine and valproate, mean Clinical Global Impression improvement = 1.2, standard deviation = 1.3) and users of Li+AP+AC (N = 73, mean Clinical Global Impression improvement = 1.1, standard deviation = 1.3) showed worse response compared to lithium-only users (all p < 0.01). When comparing Li+AP to Li+AC, users of Li+AP improved slightly better on general (p = 0.05) and manic symptoms (p = 0.01), but showed a worse development of glucose, triglycerides, and metabolic syndrome. Conclusion: Despite treatment-by-indication confounding, these findings are relevant for real-world treatment settings and emphasize the need for randomized trials on this clinically important topic. [ABSTRACT FROM AUTHOR]

Catatonia is a complex neuropsychiatric syndrome, occurring in the context of different psychiatric and neurodevelopmental disorders, in neurological and medical disorders, and after substance abuse or withdrawal. The relationship between Autism Spectrum Disorder (ASD), Schizophrenia Spectrum Disorders (SSDs) and catatonia has been previously discussed, with the three disorders interpreted as different manifestations of the same underlying brain disorder (the "Iron Triangle"). We discuss in this paper the diagnostic, clinical and therapeutic implications of this complex relationship in an adolescent with ASD, who presented an acute psychotic onset with catatonia, associated with mixed mood symptoms. Second-generation antipsychotics were used to manage psychotic, behavioral and affective symptoms, with worsening of the catatonic symptoms. In this clinical condition, antipsychotics may be useful at the lowest dosages, with increases only in the acute phases, especially when benzodiazepines are ineffective. Mood stabilizers with higher GABAergic effects (such as Valproate and Gabapentin) and Lithium salts may be more useful and well tolerated, given the frequent association of depressive and manic symptoms with mixed features. [ABSTRACT FROM AUTHOR]

A retrospective cohort study with a 10‐year follow‐up has found that lithium treatment does not result in increased risk of physical disorders compared with lamotrigine and valproate. The study examined results for groups of patients using the medications for bipolar disorder and for other illnesses. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of adjunctive therapy are unclear in bipolar depression. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of second-generation antipsychotic, lamotrigine, lithium, or valproate therapy used in adjunction with lamotrigine, lithium, or valproate monotherapy in bipolar depression. A literature search of major electronic databases was conducted in February 2021, and all articles published until then were eligible. Two researchers independently screened relevant publications, extracted data, and evaluated methodological quality according to the Cochrane criteria. Results: Five studies met the inclusion criteria. The meta-analysis revealed significant differences in the following outcomes: (i) remission rates from depressive episodes (risk ratio [RR]: 1.23, 95% confidence interval [CI] 1.01–1.50, p = 0.04), (ii) improvement in depressive symptoms (standardized mean difference [SMD]: 0.21, 95% CI 0.09–0.34, p = 0.001), (iii) improvement in quality of life (SMD: 0.22, 95% CI 0.06–0.37, p = 0.005), and (iv) rate of adverse events during the study period (RR: 1.12, 95% CI 1.03–1.22, p = 0.008). There was no significant difference between adjunctive therapy and monotherapy in the emergence of suicide-related behaviors, dropout rate during the study period, or rate of manic switching. Conclusions: Our results suggest that adjunctive second-generation antipsychotics, lamotrigine, lithium, or valproate increase both the benefits and risks in patients with bipolar depression, although there is no significant difference in severe adverse events. Adjunctive therapy should be provided through shared decision-making while considering the patients' condition in clinical settings. [ABSTRACT FROM AUTHOR]

Introduction: Lithium nephropathy can occur in long-term lithium-treated bipolar disorder patients. Key risk factors include duration of lithium exposure, cumulative dose, acute intoxication episodes, advanced age, and comorbidities such as hypertension, diabetes mellitus, hyperparathyroidism, and hyperuricemia, along with concurrent use of antipsychotics. The clinical presentation is gradual, with mild proteinuria, often accompanied by arginine vasopressin resistance. Histological studies show a correlation between interstitial fibrosis and cumulative lithium duration. Approximately 15 to 25 per cent of exposed patients may experience a gradual decline in glomerular filtration rate. The outcome after lithium discontinuation varies. Objectives: This case study aims to analyze and document the clinical presentation, diagnosis, and management of lithium nephropathy in a patient with Bipolar Disorder. Methods: We gathered data on the medical history, lab results, and treatment approach for a patient with Bipolar Disorder. Results: The patient, a 50-year-old woman, had been under the care of Psychiatry since 2008 due to a diagnosis of Bipolar Disorder Type I. During this time, she had experienced depressive and manic episodes but had not presented significant symptom decompensation for the past 14 years, successfully managed with lithium at a current dose of 600 mg per day. However, on this occasion, the patient sought hospitalization due to recent behavioural disturbances, including restlessness, disinhibition, abrupt changes in behaviour, pressured speech, sleep problems, agitation, and aggression. The patient also reported an increased sense of polyuria and polydipsia. Evaluation in the emergency department revealed elevated lithium levels of 1.47 mmol/L and hypokalemia, that justified lithium withdrawal. After lithium levels decreased, an estimated glomerular filtration rate remained low. She was diagnosed with lithium nephropathy, an adverse effect of long-term lithium therapy. Treatment with lithium changed to sodium valproate. Treatment with asenapine started and sustained for two months. Over the following two years, the patient experienced four additional hospital admissions in Psychiatry due to manic episodes. Conclusions: Long-term lithium therapy can lead to lithium nephropathy with symptoms such as polyuria, polydipsia, and acute kidney failure. Consistent monitoring of patients receiving lithium is crucial to detect potential adverse effects.This case highlights the challenges in managing bipolar patients, as discontinuing lithium exacerbated symptoms despite switching to sodium valproate for nephropathy prevention. Long-term lithium treatment, while effective for bipolar disorder, poses significant renal risks. We emphasize continuous renal function monitoring and assessing the risk-benefit of lithium treatment while actively researching lithium nephropathy and its impact on glomerular function. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Objective: In a nation-wide population-based longitudinal register linkage study for the first time 1) to investigate long-term response to lithium in patients with bipolar disorder with and without comorbid epilepsy, and 2) within patients with bipolar disorder and comorbid epilepsy to compare differences in responses between lithium, valproate and lamotrigine.Methods: We used Danish nation-wide population-based longitudinal register linkage to identify 154 patients with bipolar disorder and comorbid epilepsy and 8381 patients with bipolar disorder without comorbid epilepsy during a study period from 1995 to 2017. Response was defined as continuous monotherapy with lithium, valproate or lamotrigine without switch to or add-on of an antipsychotic drug or an antidepressant or hospitalization during an up to ten-year follow-up period. We calculated standardized absolute risks and differences thereof with respect to age, gender, socioeconomic status and comorbidity with other physical disorders than epilepsy.Results: Response to lithium was decreased in patients with bipolar disorder with versus without comorbid epilepsy during the ten-year follow-up period and the difference remained after standardization for comorbidity with other physical disorders than epilepsy. Within patients with bipolar disorder and comorbid epilepsy, response to lithium was decreased compared with responses to valproate and lamotrigine.Conclusions: The findings suggest that valproate and lamotrigine should be given priority in patients with comorbid bipolar disorder and epilepsy. The study highlights the need for closely clinical monitoring and psychological support for patients with bipolar disorder and comorbid epilepsy and emphasize the need for further long-term studies of effect of interventions. [ABSTRACT FROM AUTHOR]

Background: We primarily aimed to explore the associations between duration of untreated illness (DUI), treatment response, and functioning in a cohort of patients with bipolar disorder (BD).Methods: 261 participants with BD were recruited. DUI was defined as months from the first affective episode to the start of a mood-stabilizer. The functioning assessment short test (FAST) scores and treatment response scores for lithium, valproate, or lamotrigine according to the Alda Scale Total Score (TS) were compared between patients with short (<24 months) or long DUI. Differences in FAST scores among good (GR; TS≥7), poor (PR; TS=2-6), or non-responders (NR; TS<2) to each mood-stabilizer were analyzed. Linear regression was computed using the FAST global score as the dependent variable.Results: DUI and FAST scores showed no statistically significant correlation. Patients with a longer DUI showed poorer response to lithium (Z=-3.196; p<0.001), but not to valproate or lamotrigine. Response to lithium (β=-1.814; p<0.001), number of hospitalizations (β=0.237; p<0.001), and illness duration (β=0.160; p=0.028) were associated with FAST total scores. GR to lithium was associated with better global functioning compared to PR or NR [H=27.631; p<0.001].Limitations: The retrospective design could expose our data to a recall bias. Also, only few patients were on valproate or lamotrigine treatment.Conclusions: Poor functioning in BD could be the result of multiple affective relapses, rather than a direct effect of DUI. A timely diagnosis with subsequent effective prophylactic treatment, such as lithium, may prevent poor functional outcomes in real-world patients with BD. [ABSTRACT FROM AUTHOR]

Background: In vitro studies have demonstrated that lithium has antiviral properties, but evidence from human studies is scarce. Lithium is used as a mood stabilizer to treat patients with bipolar disorder. Here, the aim was to investigate the association between lithium use and the risk of respiratory infections in patients with bipolar disorder. To rule out the possibility that a potential association could be due to lithium's effect on psychiatric symptoms, we also studied the effect of valproate, which is an alternative to lithium used to prevent mood episodes in bipolar disorder. Method: We followed 51,509 individuals diagnosed with bipolar disorder in the Swedish Patient register 2005–2013. We applied a within-individual design using stratified Cox regression to estimate the hazard ratios (HRs) of respiratory infections during treated periods compared with untreated periods. Results: During follow-up, 5,760 respiratory infections were documented in the Swedish Patient Register. The incidence rate was 28% lower during lithium treatment (HR 0.73, 95% CI 0.61–0.86) and 35% higher during valproate treatment (HR 1.35, 95% CI 1.06–1.73) compared with periods off treatment. Conclusions: This study provides real-world evidence that lithium is associated with decreased risk for respiratory infections and suggests that the repurposing potential of lithium for potential antiviral or antibacterial effects is worthy of investigation. [ABSTRACT FROM AUTHOR]

In this study we describe the management of postnatal women with a bipolar disorder diagnosis who were prescribed either lithium or sodium valproate. There was a 38.2% (13 out of 34) relapse rate in patients discharged on lithium, compared to 46.7% (14 out of 30) relapse in patients discharged with valproate. Only 20 women (29.9%) continued to breastfeed at discharge. There were 32 (47.8%) who ceased breastfeeding during their MBU admission and 23 (34.3%) of whom ceased due to initiation of lithium therapy. [ABSTRACT FROM AUTHOR]

Few methodologically sound trials of pharmacotherapy for cannabis use disorder have been conducted, and the evidence that does exist appears to suggest that several drug classes are ineffective, a systematic review of 26 trials has concluded. The possibility that cannabinoids could relieve symptoms of withdrawal in individuals with cannabis use disorder merits further exploration, researchers stated. Results of the review were published online March 3 in the Annals of Internal Medicine. [ABSTRACT FROM AUTHOR]

Objective: Lithium and valproate are commonly used either in monotherapy or in combination with atypical antipsychotics in maintenance treatment of bipolar I disorder; however, their comparative efficacy is not well understood. This study aimed to compare the efficacy of valproate and lithium on mood stability either in monotherapy or in combination with atypical antipsychotics. Methods: We performed a post hoc analysis using data from a 52-week randomized double-blind, placebo-controlled trial, that recruited 159 patients with recently remitted mania during treatment with lithium or valproate and adjunctive atypical antipsychotic therapy. Patients were randomized to discontinue adjunctive atypical antipsychotic at 0, 24 or 52 weeks. Results: No significant differences in efficacy were observed between valproate and lithium (hazard ratio: 0.99; 95% confidence interval: [0.66, 1.48]) in time to any mood event. Valproate with 24 weeks of atypical antipsychotic was significantly superior to valproate monotherapy in preventing any mood relapse (hazard ratio: 0.46; 95% confidence interval: [0.22, 0.97]) while lithium with 24 weeks of atypical antipsychotic was superior to lithium monotherapy in preventing mania (hazard ratio: 0.27; 95% confidence interval: [0.09, 0.85]) but not depression. Conclusion: Overall, this study did not find significant differences in efficacy between the two mood-stabilizing agents when used as monotherapy or in combination with atypical antipsychotics. However, study design and small sample size might have precluded from detecting an effect if true difference in efficacy existed. Further head-to-head investigations with stratified designs are needed to evaluate maintenance therapies. [ABSTRACT FROM AUTHOR]

Background and Objective: Olanzapine is an atypical antipsychotic indicated for the treatment of schizophrenia and, either as monotherapy or as an adjunct to lithium or valproate, for bipolar I disorder. Multiple daily doses of olanzapine do not affect the pharmacokinetics of lithium or valproate; therefore, concomitant olanzapine administration does not require dosage adjustment of lithium or valproate. ALKS 3831, a combination of olanzapine and the opioid receptor antagonist samidorphan (OLZ/SAM), is currently under development to provide the established antipsychotic efficacy of olanzapine while mitigating olanzapine-induced weight gain. Olanzapine is recognized as one of the most efficacious antipsychotics; however, the benefits of olanzapine are offset by its propensity to cause significant weight gain, which may lead to long-term metabolic sequelae. This study evaluated the effects of multiple daily doses of OLZ/SAM on the pharmacokinetics of lithium or valproate in healthy subjects. Methods: This was an open-label, single-sequence, two-cohort study (ALKS3831-B101) conducted at a single center in the USA. Thirty-four healthy adult subjects were assigned (1:1) to receive lithium carbonate 300-mg tablets (cohort 1) or divalproex sodium 500-mg tablets (cohort 2), once every 12 h on days 1–7. Once-daily oral doses of OLZ/SAM (olanzapine 10 mg/samidorphan 10 mg) bilayer tablets were administered on days 8–18. Subjects resumed every 12-h doses of lithium or valproate concomitantly with the once-daily oral doses of OLZ/SAM on days 12–18. Plasma concentrations of lithium and valproic acid (valproate) were quantified in blood samples collected prior to and up to 12 h after lithium or valproate dose administration on days 7 and 18. Pharmacokinetic parameters of lithium and valproate, including maximum plasma concentration and area under the plasma concentration–time curve over a 12-h dosing interval, were calculated. The ratio of geometric means of maximum plasma concentration and area under the plasma concentration–time curve over a 12-h dosing interval in the presence and absence of OLZ/SAM, and its two-sided 90% confidence intervals, were derived from a mixed-effects model. Adverse events were monitored throughout the study. Results: The 90% confidence intervals for the ratios of geometric means, in the presence vs. absence of OLZ/SAM, were within the equivalence interval of 80–125% for both maximum plasma concentration and area under the plasma concentration–time curve over a 12-h dosing interval of lithium and of valproate. The safety profiles of lithium or valproate co-administered with OLZ/SAM were consistent with what has been previously reported for lithium or valproate. The safety profile of OLZ/SAM was consistent with that observed in previous clinical studies with OLZ/SAM. Conclusions: Consistent with previously reported findings on olanzapine, administration of multiple doses of OLZ/SAM did not have a clinically significant effect on the pharmacokinetics of lithium or valproate. Co-administration of OLZ/SAM and lithium or valproate was generally well tolerated; the safety profile of OLZ/SAM was consistent with that observed in previous clinical studies. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the effects of treatment with lithium (Li) and valproate (VPA) on behaviors and brain BDNF, NGF, NT-3, NT-4 and GDNF levels in mice submitted to paradoxical sleep deprivation (PSD), which induces an animal model of mania. Male C57BL/6J mice received an intraperitoneal (i.p.) injection of saline solution (NaCl 0.09%, 1 ml/kg), Li (47.3 mg/kg, 1 ml/kg) or VPA (200 mg/kg, 1 ml/kg) once a day for seven days. Animals were randomly distributed into six groups (n = 10 per group): (1) Control + Sal; (2) Control + Li; (3) Control + VPA; (4) PSD + Sal; (5) PSD + Li; or (6) PSD + VPA. Animals were submitted to 36 h of PSD, and then, they were submitted to the open field test. The frontal cortex and hippocampus were dissected from the brain. The manic-like behaviors in the mice were analyzed. Treatment with Li and VPA reversed the behavioral alterations induced by PSD. PSD decreased BDNF, NGF, and GDNF levels in the frontal cortex and hippocampus of mice. The administration of Li and VPA protected the brain against the damage induced by PSD. However, PSD and the administration of Li and VPA did not affect the levels of NT-3 and NT-4 in either brain structure evaluated. In conclusion, the PSD protocol induced manic-like behavior in rats and induced alterations in neurotrophic factor levels. It seems that neurotrophic factors and sleep are essential targets to treat BD. • PSD decreased BDNF, NGF and GDNF levels in the frontal cortex and hippocampus of mice. • Li and VPA protected the brain against the damage induced by PSD. • PSD can mimic the neurotrophic alterations observed in BD. [ABSTRACT FROM AUTHOR]

Lurasidone is used for treatment of bipolar depression in adults and adolescents. Lurasidone-associated manic switch has been reported in adults but not yet in adolescents. We report a case of lurasidone-induced manic switch in a male adolescent treated for bipolar I depression. Five days after adding lurasidone to his regimen (sodium valproate and olanzapine), our patient became manic with psychotic features. After discontinuation of lurasidone, he was stabilised with electroconvulsive therapy, and the medication was switched to a lithium-quetiapine combination. This case highlights the potential risk of lurasidone-induced manic switch in adolescents with bipolar depression. [ABSTRACT FROM AUTHOR]

Objectives: Substance use disorders (SUDs), including those for alcohol, stimulants, tobacco, opioids and cannabis, in patients with bipolar disorder are a major clinical and public health problem, and are present in the majority of these patients. Nonetheless, the development of effective pharmacological treatments for co‐occurring SUDs in bipolar illness have not been well‐developed and may be an important practical reason for the reduced effectiveness of these medications in community practice. Methods: We conducted a systematic review of the literature (PubMed, Medline, Google Scholar), and identified N = 29 clinical studies, which evaluated both mental health and SUD outcomes in patients with co‐occurring bipolar disorders and SUDs. Results: Our findings suggest the potential of valproate sodium and lamotrigine as preferred pharmacological agents for the treatment of co‐occurring psychiatric and substance use outcomes in these patients. However, many of the reviewed studies are of open‐label designs and of modest sample sizes. Conclusions: Thus, given the gaps in our knowledge, recommendations for treatment of this common and important co‐morbidity are preliminary. Accordingly, the conduct of larger, randomized controlled trials for this co‐morbidity is clearly needed. [ABSTRACT FROM AUTHOR]

Background: To treat patients with bipolar disorders (BPD) during the acute phase, the standard procedure is to administer lithium or sodium valproate. To further optimize treatment, acetylcholinesterase inhibitors such as donepezil and galantamine have gained increased interest, though with conflicting results. In the present randomized, double-blind, placebo-controlled clinical trial, we investigated whether, and to what extent, adjuvant rivastigmine might improve symptoms of mania in patients with BPD during the acute manic phase. Methods: A total of 70 patients with BPD in an acute state of mania (mean age 33.8 years; 24% females) took part in this study. After a thorough clinical interview, standard treatment consisted of 20mg/kg/day of sodium valproate; next, patients were randomly assigned either to the adjuvant rivastigmine or to the placebo condition. The study duration was 24 days. The dose of rivastigmine was 1.5 mg for the first 7 days and 3 mg from day 8 to day 24. Experts blind to the patients' study condition rated patients' mania scores, symptom severity, and symptom improvements at baseline (except symptom improvements) and 4, 8, 12, and 24 days after the beginning of this study. Results: Symptoms of mania improved over time, but more so in the adjuvant rivastigmine compared to the placebo condition. Greater improvements were observed from day 8 on. Conclusions: The pattern of results from the present randomized, placebo-controlled, double-blind study suggests that adjuvant rivastigmine, a cholinesterase inhibitor, improved symptoms of mania among a larger sample of inpatients with BPD and in the acute manic state. However, the improvements were modest, and the results should be replicated and above all balanced against side effects. [ABSTRACT FROM AUTHOR]

Background: Although clozapine is the most effective medication for treatment refractory schizophrenia, only 40% of people will meet response criteria. We therefore undertook a systematic review and meta-analysis of global literature on clozapine augmentation strategies. Methods: We systematically reviewed PubMed, PsycInfo, Embase, Cochrane Database, Chinese Biomedical Literature Service System and China Knowledge Resource Integrated Database for randomised control trials of augmentation strategies for clozapine resistant schizophrenia. We undertook pairwise meta-analyses of within-class interventions and, where possible, frequentist mixed treatment comparisons to differentiate treatment effectiveness. Results: We identified 46 studies of 25 interventions. On pairwise meta-analyses, the most effective augmentation agents for total psychosis symptoms were aripiprazole (standardised mean difference: 0.48; 95% confidence interval: -0.89 to -0.07) fluoxetine (standardised mean difference: 0.73; 95% confidence interval: -0.97 to -0.50) and, sodium valproate (standardised mean difference: 2.36 95% confidence interval: -3.96 to -0.75). Memantine was effective for negative symptoms (standardised mean difference: -0.56 95% confidence interval: -0.93 to -0.20). However, many of these results included poor-quality studies. Single studies of certain antipsychotics (penfluridol), antidepressants (paroxetine, duloxetine), lithium and Ginkgo biloba showed potential, while electroconvulsive therapy was highly promising. Mixed treatment comparisons were only possible for antipsychotics, and these gave similar results to the pairwise metaanalyses. Conclusions: On the basis of the limited data available, the best evidence is for the use of aripiprazole, fluoxetine and sodium valproate as augmentation agents for total psychosis symptoms and memantine for negative symptoms. However, these conclusions are tempered by generally short follow-up periods and poor study quality. [ABSTRACT FROM AUTHOR]

It is important to differentiate between the various disorders that feature mood instability because this has significant implications for management. In this article, the authors discuss the differential diagnosis of bipolar disorder and other types of mood instability and the current recommended treatment options. [ABSTRACT FROM AUTHOR]

Background: Clinicians treating a patient with bipolar disorder who is pregnant or breastfeeding may seek advice from bipolar management guidelines that provide recommendations for perinatal treatment. We examine the consistency of such recommendations across several evidence-based guidelines.Methods: A literature search in the National Guideline Clearinghouse, the Cochrane Database of Systematic Reviews, PsycInfo and PubMed was undertaken using the search terms "bipolar disorder" and "guidelines," which generated 11 sets of evidence-based guidelines published by professional organizations during the 2005-2015 period. Information relevant to management during the perinatal period was reviewed by two independent reviewers, with key themes qualitatively analysed.Results: There was a moderate level of agreement across guidelines regarding the potential teratogenic effects of lithium, sodium valproate and carbamazepine, with most highlighting caution in using these medications during the perinatal period. There was less agreement regarding the safety risks associated with lamotrigine, antipsychotics, and antidepressants, and little agreement regarding the risks and recommendations of medications during breastfeeding.Limitations: Some differences in recommendations are likely due to varying publication dates, with recent guidelines having more up-to-date evidence available to use when formulating recommendations. Further, due to ethical issues surrounding pregnancy and infant research, the evidence used to formulate perinatal recommendations is largely based on retrospective reports and/or case studies. It is therefore unrealistic to expect such recommendations to be entirely consistent and based on rigorous evidence.Conclusions: While there was some consistency across guidelines on key recommendations, there were also substantial inconsistencies, with the latter risking compromising clinical management. [ABSTRACT FROM AUTHOR]

Introduction: The evidence base regarding characteristics of older adults with bipolar disorder (BD) remains limited. The NIH-funded multicenter study Acute Pharmacotherapy of Late-Life Mania (GERI-BD) assessed various clinical domains before and during mood stabilizer treatment in older adults participating in a 9-week, double-blind randomized controlled trial. We describe the rationale for selecting these instruments.Methods: Domains and instruments were selected on the basis of the study design and the participants. The investigators' experience in clinical trials involving young adults with BD or older adults with major depressive disorder, along with open studies of older adults with BD, contributed to the selection process.Results: We identified domains and selected instruments that could be used to assess the participants given their diagnostic, treatment history, and medical and mood state characteristics. They were also intended to measure tolerability and efficacy and permit examination of potential moderating and mediating factors.Conclusions: Decisions regarding the assessment domains to be included in the clinical trial highlight the challenges facing researchers studying drug treatments for older adults with BD, or more generally, mood disorders. We suggest that the domains and instruments selected by GERI-BD investigators constitute a "toolbox" that can be customized for other investigators. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: Many patients with bipolar disorder are reaching old age, but whether they are receiving evidence-based psychotropic treatment remains unclear. Our objective was to describe current psychotropic prescribing patterns in a large Canadian late-life bipolar sample.Methods: Population-based cross-sectional study of 1443 bipolar disorder patients aged ≥ 66, discharged from a psychiatric hospitalization in Ontario, Canada from 1 April 2006 to 31 March 2012. We described psychotropic medication prescribing within 30 days post-discharge.Results: Prescription of ≥2 psychotropic medications was highly prevalent (81.5%). The most common medications were atypical antipsychotics (75.3%), benzodiazepines/zopiclone (42.3%), and antidepressants (38.5%), with less frequent use of valproate (35.4%) and lithium (23.4%). Only 1.4% of patients were on lithium monotherapy, while 4.4% and 15.7% of patients were on antidepressant or atypical antipsychotic monotherapy; 8.9% of all patients were using ≥2 atypical antipsychotics.Conclusions: In clinical practice, older adults hospitalized with bipolar disorder are often prescribed multiple psychotropic medications upon discharge. In many instances, practices did not reflect bipolar treatment guidelines and may be putting patients at risk for poor physical health and psychiatric outcomes. One such example is the very infrequent use of lithium monotherapy. Future research should examine whether health system-wide protocolized late-life bipolar treatment may optimize prescribing to improve effectiveness and safety. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: Clinicians treating older patients with bipolar disorder with mood stabilizers need evidence from age-specific randomized controlled trials. The authors describe findings from a first such study of late-life mania.Method: The authors compared the tolerability and efficacy of lithium carbonate and divalproex in 224 inpatients and outpatients age 60 or older with bipolar I disorder who presented with a manic, hypomanic, or mixed episode. Participants were randomly assigned, under double-blind conditions, to treatment with lithium (target serum concentration, 0.80-0.99 mEq/L) or divalproex (target serum valproate concentration, 80-99 μg/mL) for 9 weeks. Participants with an inadequate response after 3 weeks received open adjunctive risperidone. The authors hypothesized that divalproex would be better tolerated and more efficacious than lithium. Tolerability was assessed based on a measure of sedation and on the proportions of participants achieving target concentrations. Efficacy was assessed with the Young Mania Rating Scale (YMRS).Results: Attrition rates were similar for lithium and divalproex (14% and 18% at week 3 and 51% and 44% at week 9, respectively). The groups did not differ significantly in sedation. Participants in the lithium group tended to experience more tremor. Similar proportions of participants in the lithium and divalproex groups achieved target concentrations (57% and 56%, respectively). A longitudinal mixed model of improvement (change from baseline in YMRS score) favored lithium (change in score, 3.90; 97.5% CI=1.71, 6.09). Nine-week response rates did not differ significantly between the lithium and divalproex groups (79% and 73%, respectively). The need for adjunctive risperidone was low and similar between groups (17% and 14%, respectively).Conclusions: Both lithium and divalproex were adequately tolerated and efficacious; lithium was associated with a greater reduction in mania scores over 9 weeks. [ABSTRACT FROM AUTHOR]

Lithium (Li) and valproate (VPA) are used in the treatment of bipolar disorder (BD), with narrow therapeutic window requiring periodic control of serum levels. This prevents intoxication, lack of efficacy due to low serum concentrations, and allows monitoring adherence. We aimed at evaluating the bioequivalence of salivary and blood levels of LI or VPA in a sample of adult BD patients. Secondarily, lithium bioequivalence was evaluated across different patients’ lifespans. BD patients treated with either Li or VPA underwent contemporary standard serum and salivary measurements. Blood levels of both drugs were taken according to standard procedures. Li salivary levels were performed by an adapted potentiometric method on the AVL9180 electrolyte analyzer. VPA salivary levels were taken with an immune-assay method with turbidimetric inhibition. A total of 50 patients (38 on Li, 12 on VPA) were enrolled. Blood-saliva bioequivalence for VPA was not found due to a high variability in salivary measures. Li measures resulted in a high correlation ( r =0.767, p <0.001), showing no partial correlation with age ( r =0.147, p =0.380). Li salivary test is a reliable method of measuring Li availability and is equivalent to serum levels. Potential advantages of Li salivary testing are its non-invasive nature and the possibility of doing the test during the usual appointment with the psychiatrist. [ABSTRACT FROM AUTHOR]

Background The management of depressive and mixed symptoms in children and adolescents with bipolar disorder (BD) remains a matter of debate. The goal of this review is, thus, to systematically examine the impact of atypical antipsychotics (AAPs) and mood stabilisers in the treatment of bipolar depression and/or mixed states. Methods A literature search was conducted for studies assessing the efficacy of pharmacological treatments for bipolar disorder type I, type II and not otherwise specified with a recent depressive, mixed or manic episode (with depressive symptoms) following DSM-IV criteria in children and adolescents as either acute or maintenance treatment. The databases searched were PubMed/Medline, Google Scholar and Tripdatabase, as well as ClinicalTrials.gov. The search was limited to clinical trials, systematic reviews, meta-analyses and open-label trials published in the English language between the years 2000 and 2015. Sixty clinical studies were found assessing the efficacy of mood stabilisers and AAPs in paediatric BD. Fifteen studies were not included in the primary analysis because they did not assess depressive symptomology/include scores on rating scales of depressive symptoms (Online Supplementary Material). Results There is sufficient evidence for a Grade A recommendation of the use of olanzapine plus fluoxetine at reducing depressive symptoms in bipolar depression and of quetiapine at high doses for depressive symptoms occurring during mixed episodes. Importantly, even though monotherapy with aripiprazole, risperidone, valproate and lithium was effective at controlling mania, these drugs were not effective at reducing depressive symptoms (level A evidence for nonrecommendation). Conclusions These results mostly overlap with the approved treatments for bipolar depression in adults. [ABSTRACT FROM AUTHOR]

Objective: Conclusions regarding lithium's antisuicidal effect for bipolar disorder have been limited due to nonrepresentative subjects and potential confounding factors, including varying severity of illness. Findings regarding the effect of valproate, the most common alternative to lithium, are inconsistent for suicidal behavior. This study investigated the associations of these two drugs with the risk of suicide-related events, and possible differences between drugs, by using within-individual designs in a register-based longitudinal cohort.Method: Through linkage of multiple Swedish national registers, 51,535 individuals with bipolar disorder were followed from 2005 to 2013 for treatment with lithium and valproate. Stratified Cox regression was used to estimate the hazard ratios of suicide-related events during treated periods compared with untreated periods. For significant associations between medication and suicide-related events, the population attributable fraction was estimated to assess the public health impact for patients with bipolar disorder.Results: During follow-up, 10,648 suicide-related events occurred. The incidence rate was significantly decreased by 14% during lithium treatment (hazard ratio 0.86, 95% confidence interval [CI] 0.78-0.95) but not during valproate treatment (hazard ratio 1.02, 95% CI 0.89-1.15). The difference in hazard ratios of suicide-related events between lithium and valproate was statistically significant. Estimates of the population attributable fraction suggested that 12% (95% CI 4%-20%) of suicide-related events could have been avoided if patients had taken lithium during the entire follow-up.Conclusions: The results suggest that lithium should be considered for patients with bipolar disorder with suspected suicidal intentions, although risk for suicide is only one of the considerations when providing clinical care. [ABSTRACT FROM AUTHOR]

Background: Mania/hypomania is the cardinal feature of bipolar disorder. Recently, single administration of the dopamine transporter (DAT) inhibitor, GBR12909, was related to mania-like alterations. In the present study we aimed at testing behavioral and brain oxidant/neurotrophic alterations induced by the repeated administration of GBR12909 and its prevention/reversal by the mood stabilizing drugs, lithium (Li) and valproate (VAL) as well as by the neuroprotective drug, minocycline (Mino).Methods: Adult Swiss mice were submitted to 14 days protocols namely prevention and reversal. In the reversal protocol mice were given GBR12909 or saline and between days 8 and 14 received Li, VAL, Mino (25 or 50mg/kg) or saline. In the prevention treatment, mice were pretreated with Li, VAL, Mino or saline prior to GBR12909.Results: GBR12909 repeated administration induced hyperlocomotion and increased risk taking behavior that were prevented and reversed by the mood stabilizers and both doses of Mino. Li, VAL or Mino were more effective in the reversal of striatal GSH alterations induced by GBR12909. Regarding lipid peroxidation Mino was more effective in the prevention and reversal of lipid peroxidation in the hippocampus whereas Li and VAL prevented this alteration in the striatum and PFC. Li, VAL and Mino25 reversed the decrease in BDNF levels induced by GBR12909.Conclusion: GBR12909 repeated administration resembles manic phenotype. Similarly to classical mood-stabilizing agents, Mino prevented and reversed GBR12909 manic-like behavior in mice. Thus, our data provide preclinical support to the design of trials investigating Mino's possible antimanic effects. [ABSTRACT FROM AUTHOR]

Background: Data on real-world rehospitalization risks in patients using different drugs and combination therapies for relapse prevention after a manic episode is limited.Methods: We conducted a nationwide population based cohort study using data from Swedish national registers. Swedish residents aged 18-75 years who were hospitalized for a manic episode between July 1, 2006 and December 2, 2014 were included. Prescription fills of lithium, valproate, olanzapine, quetiapine and aripiprazole were recorded throughout the first four weeks after hospital discharge, after which the patients were followed for up to one year. General and treatment specific rehospitalization risks were determined and results were adjusted for clinical and sociodemographic factors.Results: The study included follow-up data from 6 502 hospitalizations for mania. Pharmacologic relapse prevention was used after 78% of these hospitalizations. Monotherapies and combination therapies were equally common. The average one-year rehospitalization risk for patients who did versus did not initiate prophylactic treatment was 39% and 46%, respectively. The lowest rehospitalization risks were seen in patients on combination therapy with olanzapine and valproate or olanzapine and lithium, experiencing one year rehospitalization risks of 32% and 34% (adjusted hazard ratios 0.76 (95% confidence interval [CI] 0.62-0.93) and 0.83 (95% CI 0.70-0.98), compared to lithium monotherapy).Limitations: Register data does not provide information on all clinical parameters affecting treatment choices.Conclusions: One-year rehospitalization rates after a manic episode are considerable also for patients who initiate prophylactic treatment. Combination therapies including olanzapine and a classic mood-stabilizer may be beneficial for reducing rehospitalization risks after a manic episode. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the effects of mood stabilizers, specifically lithium (Li) and valproate (VPA), on the PI3K/Akt signaling pathway in the brains of rats subjected to the ouabain (OUA)-induced animal model of mania. In addition, the effects of AR-A014418, a GSK-3β inhibitor, on manic-like behavior induced by OUA were evaluated. In the first experimental protocol Wistar rats received a single ICV injection of OUA or artificial cerebrospinal fluid (aCSF). From the day following ICV injection, the rats were treated for 6 days with intraperitoneal injections of saline, Li or VPA twice a day. In the second experimental protocol, rats received OUA, aCSF, OUA plus AR-A014418, or aCSF plus AR-A014418. On the 7th day after OUA injection, locomotor activity was measured using the open-field test. In addition, we analyzed the levels of p-PI3K, p -MAPK, p -Akt, and p -GSK-3β in the brain of rats by immunoblot. Li and VPA reversed OUA-related hyperactivity. OUA decreased p-PI3K, p-Akt and p-GSK-3β levels. Li and VPA improved these OUA-induced cellular dysfunctions; however, the effects of the mood stabilizers were dependent on the protein and brain region analyzed. In addition, AR-A014418 reversed the manic-like behavior induced by OUA. These findings suggest that the manic-like effects of ouabain are associated with the activation of GSK-3β, and that Li and VPA exert protective effects against OUA-induced inhibition of the GSK-3β pathway. [ABSTRACT FROM AUTHOR]

Background: Antidepressant response to a single subanesthetic dose infusion of the glutamatergic modulator ketamine is transient in most depressed patients; however, a minority continue to experience an extended response. This study examined depressive symptoms and potential clinical predictors of extended response to ketamine in subjects with mood disorders.Methods: Subjects were diagnosed with either major depressive disorder (MDD) or bipolar depression. All subjects were treatment-resistant and experiencing a major depressive episode of at least moderate severity. MDD subjects were unmedicated and those with bipolar depression were receiving therapeutic-dose lithium or valproate. All subjects received a single 0.5mg/kg ketamine infusion. Data were collected pre-infusion (baseline) and at days one, 14, and 28 post-infusion.Results: Twelve of 93 (12.9%) participants continued to meet response criteria (50% reduction in Montgomery-Asberg Depression Rating Scale (MADRS) score) at two weeks. All depressive symptoms assessed by the MADRS were improved at two weeks in ketamine responders except for sleep duration/depth. A positive family history of alcohol use disorder in a first-degree relative (FHP) and greater dissociation during the infusion were associated with better antidepressant response at two weeks. Improved measures of apparent sadness, reported sadness, inability to feel, and difficulty concentrating at day 1 correlated most strongly with antidepressant effects at two weeks.Limitations: Post-hoc design, small sample size, diagnostic heterogeneity.Conclusions: Static (FHP) and dynamic (improved depressive symptoms) factors may be clinically useful in predicting whether a patient will have an extended response to ketamine. [ABSTRACT FROM AUTHOR]

The article discusses the efficacy of LATUDA as a drug for the treatment of major depressive episodes associated with bipolar I disorder. It presents a 6-week monotherapy study and a 6-week adjunctive therapy study with lithium or valproate in adult patients with bipolar depression to determine its effectiveness. The need for the physician who elects to use LATUDA for extended periods to reevaluate the long-term usefulness of the drug for the individual patient is also explored.

Epidemiological studies have shown that low doses of lithium in the environment can have beneficial effects on mental health. Autism spectrum disorder, a neurodevelopmental disorder in which patients exhibit abnormal behaviors, pharmacological interventions usually relied on a range of psychotropic medications. However, such medications often produce severe side effects or are ineffective in symptoms. Finding alternative ways to improve abnormal behaviors in individuals with autism are warranted, in which case lithium may be a relatively safe and effective medication. Lithium salt therapy is used to treat a variety of neuropsychiatric disorders and has neuroprotective effects. In this study, we investigated the effects of different doses of lithium on neurobehavioural disorders using the rat model of autism established by valproic acid (VPA) injection. Lithium was observed to have an ameliorative effect on the social cognitive, social memory and anxiety levels in the rat model of autism. Immunofluorescence staining showed that subchronic LiCl administration (1.0 mmol/kg) significantly reduced the number of Iba-1 positive cells in the CA1 region of the hippocampus in VPA group and brought it close to the levels of control group. Significantly lower levels of the pro-inflammatory marker IL-6 were observed in the hippocampus and serum after lithium treatment. In addition, the lithium treatment increased the levels of H3K9 acetylation in the hippocampus of VPA-exposed rats. The results showed a defensive effect of environment-related lithium exposure doses on neurobehavioural deficits in the rat valproic acid model of autism, suggesting that it may be a potential drug for the treatment of autism. • The effects of environment-related exposure doses of lithium on autistic-like behaviors were tested. • Lithium ameliorated the social cognitive, social memory and anxiety levels in the rat model of autism. • Lithium attenuated levels of proinflammatory cytokines of VPA-exposed rats. • Lithium may attenuate neuroinflammation by upregulating the acetylation level of H3K9. [ABSTRACT FROM AUTHOR]

Objectives: Cytokine level alterations suggest a role for the immune system in the pathophysiology of bipolar disorder (BD). Pharmacotherapy is an important confounding factor in clinical research on cytokine levels. In this systematic review we collate the evidence on blood cytokine levels in medication-free BD and the effects of single mood-stabilizing drugs on these levels.Methods: A systematic review was conducted according to the PRISMA statement. We searched the Pubmed and Embase databases for clinical studies reporting either on cytokine levels in medication-free BD or on the effects of single mood-stabilizing drugs on cytokine levels in BD.Results: Of the 564 articles screened, 17 were included. Fourteen articles report on medication-free patients with BD and indicate state-related cytokine alterations. Six articles discuss the effect of lithium. Whereas no data on short-term effects of lithium were found, ≥2 months lithium use in euthymic populations is associated with normal cytokine levels. Two studies report no effect of valproate and no studies were found on carbamazepine, lamotrigine or antipsychotics.Limitations: The available studies are characterized by a broad methodological heterogeneity and limited replication between studies.Conclusions: This systematic review suggests the presence of state-related cytokine level alterations in medication-free BD with most evidence pointing to a proinflammatory cytokine response in mania. Euthymia and long-term lithium use are associated with normal cytokine levels. To improve our understanding of the impact of mood-stabilizing drugs on cytokine levels, longitudinal studies with medication-free baseline, randomized controlled single-drug treatment protocols and close mood state monitoring are needed. [ABSTRACT FROM AUTHOR]

In this study, designed to evaluate the efficacy of lurasidone as adjunctive therapy with lithium or valproate, patients with bipolar I depression were randomized to 6 weeks of double-blind treatment with lurasidone (N = 180) or placebo (N = 176), added to background treatment with lithium or valproate. All patients were treated with lithium or valproate for a minimum of 4 weeks prior to screening. This was confirmed either by prospective treatment after study enrolment (run-in cohort), or retrospectively, with blood levels of lithium and valproate at screening (non-run-in cohort). Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness (CGI-BP-S), respectively. Treatment with lurasidone was associated with non-significant improvement at week 6 vs. placebo for the MADRS total score (−11.8 vs −10.4; P = 0.176), and the CGI-BP-S score (−1.36 vs −1.13; P = 0.095). Significant separation from placebo was observed from weeks 2–5 for the MADRS and weeks 3–5 for the CGI-BP-S. Improvement in the placebo-subtracted MADRS total score was notably larger at week 6 for the non-run-in cohort compared to the run-in cohort (LS mean difference in endpoint change scores, −4.6; P = 0.009). Adverse events most frequently reported for lurasidone were akathisia, somnolence, and extrapyramidal side effects. In conclusion, lurasidone adjunctive with lithium or valproate demonstrated significant improvement in depressive symptoms based on the MADRS from weeks 2–5 but not at the primary week 6 endpoint. [ABSTRACT FROM AUTHOR]

Background: The suicide rate is high among bipolar disorder (BD) patients. Previous studies have focused on the anti-suicidal effect of long-term treatment with mood stabilizers but less on the immediate preventive effects of interventions. The aim of the study was to evaluate the short-term and immediate anti-suicidal effects of mood stabilizers on recent-onset BD patients.Methods: The National Health Insurance Database (NHID) of Taiwan was used to perform a nationwide cohort observation study of suicide behaviors in bipolar disorder. All the recent-onset BD patients (ICD-9-CM code 296 except 296.2 and 296.3) diagnosed between 2000-2005 were collected (n=5091) and followed through 2009. The primary endpoint was the presence of a suicide code or the end of observation; exposure to mood stabilizers in the final month of observation was the independent variable.Results: The hazard ratios (HRs) of suicide-related events, completed suicide, and all-cause mortality were significantly lower for those treated with lithium, divalproex, or carbamazepine compared with no use in the last month (HRs of suicide-related events were 0.10, 0.14 and 0.10, respectively, and all-cause mortality HRs were 0.03; P<0.0001); there was no significant difference in HR between the mood stabilizers.Limitations: The NIHD does not provide information on the severity, mood status, or treatment adherence of BD patients. Neither substance-related disorder nor personality disorder were included in the analysis. We focused on the effect of the final prescription time period, not the long-term protective effect.Conclusions: The immediate recent use of any mood stabilizer significantly lowers the rate of death, suicide, or suicidal behavior in BD. [ABSTRACT FROM AUTHOR]

Background: Lithium is a first line treatment option in bipolar disorder, but several alternative treatments have been introduced in recent years, such as antiepileptic and atypical antipsychotic drugs. Little is known about how this has changed the prescription patterns. We investigated possible changes in the use of mood stabilizers and antidepressants in Sweden during 2007-2013.Methods: Data was collected from Swedish registers: the National Quality Assurance Register for bipolar disorder (BipoläR), the Prescribed Drug Register, and the Patient Register. Logistic regression models with drug use as outcomes were used to adjust for confounding factors such as sex, age, year of registration, and subtypes of bipolar disorder.Results: In both bipolar subtypes, lithium use decreased steadily during the study period, while the use of lamotrigine and quetiapine increased. The use of valproate decreased in bipolar II disorder and the use of olanzapine decreased among women. The use of antidepressant remained principally unchanged but increased somewhat in bipolar I disorder.Limitations: We only report data from 2007 as the coverage of BipoläR prior to 2007 was too low to allow for reliable analyses.Conclusion: Significant changes in the prescription of drugs in the treatment of bipolar disorder have occurred in recent years in Sweden. Further studies are needed to clarify whether these changes alter the outcome in bipolar disorder. [ABSTRACT FROM AUTHOR]