Effects Of Mood Stabilizers Research Articles

Efficacy and Safety of Lithium for Suicide and Suicide-Related Behaviors in Youth: A Review of the Literature.

This systematic review evaluates the anti-suicidal properties of Lithium in children and adolescents with Bipolar Disorder (BD), addressing gaps in evidence regarding its efficacy and safety in reducing suicidality and self-harming behaviors. A comprehensive literature search was conducted across PubMed, Web of Science, and Scopus up to February 2024. Eligible studies were those focusing on patients aged 25 years or younger, examining Lithium therapy and its impact on suicidal ideation and behaviors. The review included randomized controlled trials, longitudinal prospective and retrospective studies, and cross-sectional studies, while excluding expert opinions and case reports. Evidence generally supports the efficacy of Lithium in reducing suicidal ideation and self-harming behaviors in youth with BD, though results are mixed. Randomized controlled trials demonstrated its effectiveness in mitigating suicidal thoughts during acute manic episodes, with effects persisting post-treatment. Longitudinal studies suggested that Lithium might offer superior outcomes compared to other mood stabilizers, although its specific impact on suicidality remains inconclusive. Cross-sectional studies and retrospective analyses reveal associations between Lithium use and reduced self-harming behaviors, but causality remains uncertain. While mood-stabilizing effects of Lithium offer potential benefits for reducing suicidality in youth, evidence on its direct impact on emotional dysregulation (ED) and long-term efficacy is limited. Variability in individual responses and adherence issues underscore the need for further research. Future studies should include larger, diverse samples, focus on ED symptoms, and explore Lithium mechanisms in suicidality prevention. Lithium remains a promising treatment for mood stabilization and reduction in suicidality in youth with BD.

Lamotrigine: A Safe and Effective Mood Stabilizer for Bipolar Disorder in Reproductive-Age Adults.

Lamotrigine belongs to the group of antiepileptic drugs and mood stabilizers, and its action is based on the selective blocking of voltage-deficient sodium channels. The effect of this mechanism is the stabilization of the presynaptic part of the neuronal membrane and subsequent inhibition of the secretion of the neurotransmitters glutamate and aspartate into the postsynaptic part of the neuron. Lamotrigine has been approved by the Food and Drug Administration for the maintenance treatment of adults with bipolar disorder since 1994. In the field of psychiatry, this medicine is also used off-label in the treatment of acute bipolar depression. Studies show promising effects of the use of lamotrigine in bipolar disorder type II with rapid phase change. Bipolar disorder is a common psychiatric problem that most often affects young adults. Lamotrigine is most effective in bipolar disorder in preventing depressive episodes, which dominate the clinical picture of this disease. The latest research focuses on extending its action, to include manic episodes. Lamotrigine, through an unexplained mechanism, can affect the immune system, causing Stevens-Johnson syndrome, hemophagocytic lymphohistiocytosis, and drug reaction with eosinophilia and systemic symptoms syndrome. These are rare, life-threatening adverse effects that require urgent intervention in the form of drug discontinuation and immunosuppressive treatment. Strict contraindications to the use of lamotrigine include sensitivity reactions accompanied by systemic symptoms. Phenotype testing enables screening of patients predisposed to serious hypersensitivity reactions. The aim of the article is to review the indications, contraindications, and adverse effects of lamotrigine in the treatment of bipolar disorder and depression.

Lithium and the risk of fractures in patients with bipolar disorder: A population-based cohort study

Lithium is considered to be the most effective mood stabilizer for bipolar disorder. Evolving evidence suggested lithium can also regulate bone metabolism which may reduce the risk of fractures. While there are concerns about fractures for antipsychotics and mood stabilizing antiepileptics, very little is known about the overall risk of fractures associated with specific treatments. This study aimed to compare the risk of fractures in patients with bipolar disorder prescribed lithium, antipsychotics or mood stabilizing antiepileptics (valproate, lamotrigine, carbamazepine).Among 40,697 patients with bipolar disorder from 1993 to 2019 identified from a primary care electronic health record database in the UK, 13,385 were new users of mood stabilizing agents (lithium:2339; non-lithium: 11,046). Lithium was associated with a lower risk of fractures compared with non-lithium treatments (HR 0.66, 95 % CI 0.44–0.98). The results were similar when comparing lithium with prolactin raising and sparing antipsychotics, and individual antiepileptics. Lithium use may lower fracture risk, a benefit that is particularly relevant for patients with serious mental illness who are more prone to falls due to their behaviors. Our findings could help inform better treatment decisions for bipolar disorder, and lithium's potential to prevent fractures should be considered for patients at high risk of fractures.

Vortioxetine treatment for neuropathic pain in major depressive disorder: a three-month prospective study.

Several studies revealed the therapeutic potential of vortioxetine (Vo) for pain. In this context, we aimed to evaluate the efficacy of Vo as a safe and tolerable novel pharmacologic agent in treating neuropathic pain (NP) in patients with major depressive disorder (MDD). The population of this cross-sectional prospective study consisted of all consecutive patients who were newly diagnosed with MDD by a neurology doctor at a psychiatric clinic and had NP for at least 6 months. All patients included in the sample were started on Vo treatment at 10 mg/day. They were assessed with Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Self-Reported Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), Douleur Neuropathique 4 Questions (DN4), Montreal Cognitive Assessment (MoCA), and Neuropathic Pain Impact on Quality of Life (NePIQoL) at the beginning of treatment and during the follow visits conducted at the end of the first, second and third months of the treatment. During these follow-up visits, patients were also queried about any side effects of Vo. The mean age of 50 patients included in the sample, 76% of whom were female, was 45.8 ± 11.2 years. There was a significant reduction in patients' NP complaints based on DN4 and S-LANNS, the subscales of NePIQoL, and significant improvement in MoCA. There was a significant reduction in patients' NP complaints based on DN4 and S-LANNS scores and a significant improvement in scores of the subscales of NePIQoL and MoCA. The study's findings indicate that Vo, with its multiple mechanisms of action, can effectively treat NP independently of its mood-stabilizing effect. Future indication studies for Vo are needed to establish Vo's efficacy in treating NP.

Effect of creatine supplementation on cognitive function and mood

Background: Creatine, a naturally occurring compound plays a crucial role in cellular energy metabolism, particularly in tissues with high energy demands like muscles and the brain. Beyond its well-established role in physical performance enhancement, recent research has revealed its potential benefits for cognitive functions and mood regulation. This review paper aims to comprehensively analyze the existing literature on creatine supplementation's effects on cognitive functions and mood. State of Knowledge: Findings suggest that creatine supplementation enhances memory, attention, and executive functions, especially under conditions of stress or sleep deprivation. Moreover, it exhibits mood-stabilizing effects, potentially offering relief for symptoms of depression and fatigue. Creatine's ability to augment brain energy metabolism, alongside its neuroprotective properties, underlies its cognitive and mood-enhancing effects. While generally safe, caution is advised, particularly in populations with kidney diseases or those using medications affecting kidney function. Summary: Creatine emerges as a promising adjunct therapy for enhancing cognitive functions and promoting emotional well-being beyond its traditional role in physical performance.The review underscores the need for further research to elucidate the precise mechanisms of creatine's effects and explore its synergistic potential with other cognitive-enhancing supplements.

An Retrospective Study of Commonly Prescribed Antiepileptic Drugs and it’s Interaction with Other Drugs which are Already in use Respect to Other Disease

Antiepileptic drugs (AED) are increasingly used in the treatment of some non-epileptic neurological diseases and psychiatric diseases. Most of the available data on the use of these agents in clinical conditions other than epilepsy are from case series, uncontrolled studies, or small randomized clinical trials, and their apparent efficacy requires confirmation in well-designed large phase III trials. Interactions between antiepileptic drugs or between antiepileptic drugs and other drugs can be pharmacokinetic or pharmacodynamic. Pharmacokinetic interactions include changes in absorption, distribution ,or eliminate , while pharmacodynamic interactions include synergism and antagonism at the site ,of action. Most clinically significant antiepileptic drug interactions are due to induction or inhibition of drug metabolism. Carbamazepine, phenytoin, phenobarbital and primidone are strong inducers of cytochrome P450 and glucuronide enzymes (as well as P-glycoprotein) and may reduce the effectiveness of concomitantly administered drugs such as oral anticoagulants, calcium antagonists, antimicrobial steroids. Mechanism Oxcarbazepine, eslicarbazepine acetate, felbamate, rufinamide, topiramate (at doses ≥ 200 mg/day) and perampanel (at doses ≥ 8 mg/day) have weaker inducing properties and less tendency to produce interactions mediated by enzyme induction. In contrast to enzyme induction, enzyme inhibition results in decreased metabolic clearance of the affected drug, which can increase serum concentrations leading to toxic effects. Examples of important interactions mediated by enzyme inhibition include valproic-induced increases in serum concentrations of phenobarbital and lamotrigine. There are also interactions where other drugs induce or inhibit the metabolism of antiepileptic drugs. Examples include an increase in serum carbamazepine concentration due to erythromycin and a decrease in serum lamotrigine concentration due to estrogen-containing contraceptives. Pharmacodynamic interactions between antiepileptic drugs may also be clinically important. These interactions can have potentially beneficial effects, such as the combined therapeutic synergy of valproic acid and lamotrigine, or adverse effects, such as the mutual potentiation of neurotoxicity in patients treated with a combination of sodium channel blocking antiepileptic drugs. AEDs are also used to treat psychiatric conditions, particularly bipolar disorder. To date, the AEDs most commonly used to treat this disorder have been carbamazepine and valproic acid, which have shown manic efficacy and likely long-term mood-stabilizing effects in many bipolar patients, including those who are lithium-intolerant. . The availability of new generation AEDs has expanded treatment options for bipolar disorder. Lamotrigine, oxcarbazepine, gabapentin, and topiramate appear to show promise in the treatment of bipolar disorder, both as monotherapy and in combination with traditional mood stabilizers. In addition, newer AEDs appear to have a more favorable tolerability and drug interaction profile than older compounds, thus improving compliance

Acute neural effects of the mood stabiliser lamotrigine on emotional processing in healthy volunteers: a randomised control trial.

Lamotrigine is an effective mood stabiliser, largely used for the management and prevention of depression in bipolar disorder. The neuropsychological mechanisms by which lamotrigine acts to relieve symptoms as well as its neural effects on emotional processing remain unclear. The primary objective of this current study was to investigate the impact of an acute dose of lamotrigine on the neural response to a well-characterised fMRI task probing implicit emotional processing relevant to negative bias. 31 healthy participants were administered either a single dose of lamotrigine (300 mg, n = 14) or placebo (n = 17) in a randomized, double-blind design. Inside the 3 T MRI scanner, participants completed a covert emotional faces gender discrimination task. Brain activations showing significant group differences were identified using voxel-wise general linear model (GLM) nonparametric permutation testing, with threshold free cluster enhancement (TFCE) and a family wise error (FWE)-corrected cluster significance threshold of p < 0.05. Participants receiving lamotrigine were more accurate at identifying the gender of fearful (but not happy or angry) faces. A network of regions associated with emotional processing, including amygdala, insula, and the anterior cingulate cortex (ACC), was significantly less activated in the lamotrigine group compared to the placebo group across emotional facial expressions. A single dose of lamotrigine reduced activation in limbic areas in response to faces with both positive and negative expressions, suggesting a valence-independent effect. However, at a behavioural level lamotrigine appeared to reduce the distracting effect of fear on face discrimination. Such effects may be relevant to the mood stabilisation effects of lamotrigine.

Human brain 7Li-MRI following low-dose lithium dietary supplementation in healthy participants

BackgroundLithium is an effective mood stabiliser, but its mechanism of action is incompletely defined. Even at very low doses, lithium may have neuroprotective effects, but it is not clear if these relate to brain lithium concentration in vivo. We have developed magnetic resonance imaging (7Li-MRI) methods to detect lithium in the brain following supplementation at a very low dose. MethodsLithium orotate supplements were taken by nine healthy adult male subjects (5 mg daily) for up to 28 days, providing 2–7 % of the lithium content of a typical therapeutic lithium carbonate dose. One-dimensional 7Li-images were acquired on a 3.0 T MRI scanner. All subjects were scanned on day 14 or 28; seven were scanned on both, one at baseline and one after 7-days washout. Results7Li-MR signal amplitude was broadly stable between days 14 and 28. Two subjects had notably higher 7Li-signal intensities (approximately 2–4×) compared to other study participants. LimitationsLithium adherence was self-reported by all participants without formal validation. The coarse spatial resolution necessary for detection of low concentrations of 7Li exhibits imperfect spatial separation of signal from adjacent pixels. Conclusions7Li-MRI performed using a clinical 3T scanner demonstrated detection of lithium in the brain at very low concentration, in the range of approximately 10–60 mM. The methods are suited to studies assessing low dose lithium administration in psychiatric and neurodegenerative disorders, and permit the comparison of different lithium salt preparations at a time of emerging interest in the field.

Akt and AMPK activators rescue hyperexcitability in neurons from patients with bipolar disorder

Bipolar disorder (BD) is a multifactorial psychiatric illness affecting ∼1% of the global adult population. Lithium (Li), is the most effective mood stabilizer for BD but works only for a subset of patients and its mechanism of action remains largely elusive. In the present study, we used iPSC-derived neurons from patients with BD who are responsive (LR) or not (LNR) to lithium. Combined electrophysiology, calcium imaging, biochemistry, transcriptomics, and phosphoproteomics were employed to provide mechanistic insights into neuronal hyperactivity in BD, investigate Li's mode of action, and identify alternative treatment strategies. We show a selective rescue of the neuronal hyperactivity phenotype by Li in LR neurons, correlated with changes to Na+ conductance. Whole transcriptome sequencing in BD neurons revealed altered gene expression pathways related to glutamate transmission, alterations in cell signalling and ion transport/channel activity. We found altered Akt signalling as a potential therapeutic effect of Li in LR neurons from patients with BD, and that Akt activation mimics Li effect in LR neurons. Furthermore, the increased neural network activity observed in both LR & LNR neurons from patients with BD were reversed by AMP-activated protein kinase (AMPK) activation. These results suggest potential for new treatment strategies in BD, such as Akt activators in LR cases, and the use of AMPK activators for LNR patients with BD. Supported by funding from ERA PerMed, Bell Brain Canada Mental Research Program and Brain & Behavior Research Foundation.

Effects of Mood Stabilizers on Sleep and Circadian Rhythms: A Systematic Review

Effects of Mood Stabilizers on Sleep and Circadian Rhythms: A Systematic Review

Lithium-Induced Disruption of Intracellular Ca2+ Balance in the Collecting Duct Intercalated Cells Contributes to Metabolic Acidosis in Mice

INTRODUCTION. Lithium (Li+) is an effective mood stabilizer that continues to be widely used in modern psychiatric practice. One of the most common adverse effects of Li+ therapy is nephrogenic diabetes insipidus manifesting in reduced urinary concentrating ability due to impaired vasopressin (AVP) signaling in the collecting duct principal cells. While distal tubular acidosis has also been reported in patients receiving Li+, molecular determinants underlying the pathophysiological effects of Li+ on the collecting duct intercalated cells and renal acid-base transport remain to be fully elucidated. Activation of Gq-coupled vasopressin 1a receptors (V1aR) in A-intercalated cells reportedly induces intracellular Ca2+ ([Ca2+]i) mobilization and stimulates luminal H+ secretion, resulting in urine acidification. OBJECTIVE. The objective of this study was to test if Li+ impaired V1aR-induced [Ca2+]i response in the intercalated cells of murine collecting ducts. HYPOTHESIS. We hypothesized that Li+ markedly impaired V1aR-dependent [Ca2+]i signaling in A-intercalated cells causing the reduction of luminal proton secretion in the collecting duct. METHODS. We combined immunofluorescent imaging in freshly isolated collecting duct segments with metabolic cage studies in C57BL/6NJ (Jackson Labotatory) mice receiving a regular Teklad 2918 chow (control) or a Teklad 2918-based diet containing 0.3% lithium carbonate (Li+-treated) to evaluate how Li+ affects V1aR-mediated [Ca2+]i signal, H+ transport by intercalated cells, as well as urinary pH and ammonia excretion. RESULTS. We found that AVP elicited a transient [Ca2+]i response in the aquaporin-2 (AQP2) negative cells from collecting duct segments isolated from control mice. The response was mediated by Ca2+ release from the endoplasmic reticulum (ER), as it was inhibited by pretreatment of collecting duct segments with thapsigargin, a SERCA pump inhibitor. The amplitude of the AVP-induced calcium transient was 4 times lower in the AQP2-negative cells isolated from Li+-treated mice. Li+ intake remarkably facilitated store-operated calcium entry (SOCE) in the collecting duct cells, indicating chronic ER depletion and stress. At the systemic level Li+-treated mice exhibited urine alkalinization (by 0.8 pH units) and a 6-fold elevation in urinary ammonium excretion, when compared to controls. CONCLUSIONS. Intracellular Ca2+ signaling in the intercalated cells is an essential determinant of acid-base handling in the collecting duct. Our findings reveal that Li+ markedly alters [Ca2+]i signaling in the intercalated cells, causing urine alkalinization and elevated ammonium excretion, likely, to compensate for ensuing metabolic acidosis. NIDDK R01DK125464. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Therapeutic Dose of Lithium Triggers Anti-inflammatory Mechanisms in The Kidneys of Treated Mice

Lithium (Li+) is an effective mood stabilizer in people with schizoaffective disorders with more than 2 million prescriptions per year. Accumulation of Li+ in blood can cause neprotoxicity, manifesting in nephrogenic diabetes insipidus, renal tubular acidosis and tubulointerstitial nephropathy. Damage to renal cells often leads to a local immune response, playing a pivotal role in the ensuing renal injury and subsequent recovery. While both pro- and anti-inflammatory actions of Li+ were reported in various tissues, our understanding of the immunomodulatory effects of Li+ in the kidney is fragmentary. Here, we studied how immune mechanisms contribute to the development of Li+-induced adverse effects in the kidneys of C57BL/6 mice receiving a 0.3% lithium carbonate diet for 28 days. Given the insidious development of Li+-induced renal injury, we hypothesize that nephrotoxic effects of Li+ are alleviated by its anti-inflammatory action. We used fluorescence-activated cell sorting, qPCR, immunoblotting and proteome profiler arrays to assess the pyroptotic inflammatory cascade, characterize the infiltrating immune cells and cytokine markers in the renal tissue isolated from Li+-treated and control mice. We found that both biomarkers of tubular damage, kidney injury marker, KIM-1, and neutrophil gelatinase-associated lipocalin, NGAL, are elevated in the renal tissue of Li+-treated mice. This correlated with a moderate but significant increase in renal fibrosis in mice on Li+ diet. Expression of most genes associated with pyroptotic inflammatory cascade, including NLRP3, Casp-1, IL-1b, was not different in the renal tissue isolated from control and Li+-treated mice. Higher mRNA levels of apoptosis-associated speck-like protein (ASC), in the renal tissue of Li+-treated mice could be attributed to its a pro-apoptotic, rather than inflammasome forming, function. This is in line with elevated levels of CD93 marker in the kidneys of mice on Li+ diet, reflecting increased clearance of apoptotic cells. In general, Li+-treated mice had markedly higher levels of anti-inflammatory cytokine markers in the renal tissue, most notably, IL-10 and adiponectin, and lower abundance of pro-inflammatory markers, such as CD26, CLCX16, PCSK9 and osteopontin. Higher abundance of proinflammatory IL-6 in the kidneys of Li+-treated mice made a notable exception. However, this cytokine can also be released by tubular epithelial cells under insult and induce polarization of anti-inflammatory M2 macrophages. Mice on Li+-diet had higher levels of macrophages (F4.80+ cells) in the renal tissue. Future studies will determine their polarization phenotype. Overall, our results suggest that Li+-induced toxic insult to the tubular epithelial cells is paralleled by the anti-inflammatory immune response localized to the renal tissue. NIDDK 1R01DK125464. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Practice recommendations to manage Alzheimer’s disease based on the targeted behavioral and psychological symptoms

IntroductionBehavioral and psychological symptoms (BPS) of Alzheimer’s disease, known as neuropsychiatric symptoms, involve a range of symptoms that include agitation, psychosis (hallucinations, delusions), affective symptoms (depression and anxiety), apathy, and sleep disturbances. These behavioral and psychological symptoms harm the patients’ daily lives and significantly burden their families. Managing BPS of Alzheimer’s disease requires a targeted approach focused on each symptom to achieve a better therapeutic response.ObjectivesProviding practice pharmacological recommendations targeted to each of the behavioral and psychological symptoms of Alzheimer’s disease.MethodsA literature review was conducted using Medline via PubMed, Embase, PsycINFO, and Cochrane databases until September 2023.ResultsThere is a consensus in the literature that non-pharmacological approaches should be recommended as the first-line treatment for most behavioral and psychological symptoms of Alzheimer’s.Second-generation antipsychotics (risperidone and olanzapine, with improved efficacy; aripiprazole and quetiapine, with better tolerance) are recommended for severe agitation states with a risk of self or hetero-aggression, as well as for persistent psychotic symptoms in Alzheimer’s disease. The benefit-risk balance of these agents must be assessed, with close monitoring of heart arrhythmias, metabolic risk, orthostatic hypotension, and extrapyramidal symptoms. The recommendations suggest tapering antipsychotics within the first three months of their prescription. Selective serotonin reuptake inhibitors (SSRIs) such as Escitalopram, Citalopram, and Sertraline can be considered a therapeutic option for persistent affective symptoms (depression and anxiety) with significant functional impairment or suicidal risk, severe apathy, or constant agitation. Minimum effective doses are recommended for Escitalopram and Citalopram due to the risk of QT interval prolongation. There is limited evidence regarding the effectiveness of benzodiazepines, mood stabilizers, cholinesterase inhibitors, and memantine for various behavioral and psychological symptoms; the benefit-risk ratio and therapeutic response do not support the prescription of these agents. Melatonin and Mirtazapine have limited benefits for sleep disturbances, while benzodiazepines, antihistamines, and antipsychotics should be avoided.ConclusionsThe pharmacological approach should target a thorough clinical assessment of the psychopathological dimensions of behavioral and psychological symptoms of Alzheimer’s disease. The prescription should be based on evaluating the benefit-risk balance and adherence to literature recommendations for patient safety.Disclosure of InterestNone Declared

Lithium-induced Discontinuation Refractoriness: A Report of Two Cases

Introduction: Lithium is an effective mood stabilizer. In patients with bipolar disorder using long-term lithium, discontinuation of lithium can lead to severe clinical outcomes such as lithium-induced discontinuation refractoriness. We present two clinical cases of lithium- induced discontinuation refractoriness. Case Presentation: We present two female patients with a good long-term response to lithium. Both patients did not have a mood episode for many years and had residual symptoms. The first patient discontinued lithium voluntarily, while the second patient discontinued lithium treatment due to impaired thyroid function. Lithium was added to the treatment of both patients, but lithium-induced discontinuation refractoriness developed. Conclusion: It should be kept in mind that it may develop refractoriness to lithium when deciding to discontinue lithium treatment, especially in patients with a good long-term response to lithium.

Cerebellar-cortical connectivity in bipolar disorder: Exploring the regulatory action of modafinil

Bipolar and related disorders (BD) are characterized by frequent deregulation and changes in mood and energy states. The neurobiological mechanisms underlying these changes remain unknown. The cerebellum has recently demonstrated its role in emotional and behavioral regulation in psychiatric illnesses and may be an essential structure for mood regulation and clinical stabilization in bipolar disorder. Modafinil has demonstrated efficacy in improving and controlling symptoms of bipolar depression through its control of symptoms such as fatigue, drowsiness, and regulation of wakefulness levels. However, since this drug also showed effects on mood improvement and treated BD patients do not have an increased risk of manic episodes, it appears to have mood-stabilizing effects whose neurobiological mechanisms are not yet established. In this regard, recent research has demonstrated the modulating effect of modafinil on the connectivity of the cerebellum and cortex. This article explores the interaction between this effect and its possible interference in maintaining euthymia in bipolar disorder.

Impact of psychotropic medications on cognition among older adults: a systematic review.

The aim of this systematic review is to examine the cognitive impact of psychotropic medications including benzodiazepines, antidepressants, mood stabilizers, antipsychotics, or a combination of these drugs on older adults. Systematic review. We searched Medline, PsycINFO, and Embase through the Ovid platform, CINAHL through EBSCO, and Web of Science. Randomized control trials (RCTs) and cohort studies that used a validated scale to measure cognition with a follow-up period of at least six months were included. The primary outcome of interest was cognitive change associated with psychotropic medication use. A total of 7551 articles were identified from the primary electronic literature search across the five databases after eliminating duplicates. Based on full-text analysis, 27 articles (two RCTs, 25 cohorts) met the inclusion criteria. Of these, nine each examined the impact of benzodiazepines and antidepressants, five examined psychotropic combinations, three on antipsychotic drugs, and one on the effects of mood stabilizers. This is the first systematic review to examine the cognitive impact of multiple psychotropic drug classes in older adults over an extended follow-up period (six months or more) using robust sample sizes, drug-free control groups, and validated cognitive instruments. We found evidence to indicate cognitive decline with the cumulative use of benzodiazepines and the use of antidepressants, especially those with anticholinergic properties among older adults without cognitive impairment at baseline. Further, the use of antipsychotics and psychotropic combinations is also associated with cognitive decline in older adults.

Role of DAG Signaling Pathway in Bipolar Disorder

Lithium is an effective mood stabilizer in 70-80 percent of bipolar disorder patients. It has been observed that the membrane potential is hyperpolarized in bipolar patients and lithium treatment depolarizes it. Hokin and his colleagues found that the lithium increases accumulation of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) in brain cortex slices in species ranging from mouse to monkey. DAG and IP3 activate the DAG signaling pathway depolarizing the membrane potential. The DAG signaling pathway regulates the calcium activated potassium (CAK) channels. The CAK channels in turn control the membrane potentials and excitabilities of neurons. The clinical observations that the membrane potential is hyperpolarized (lower) in bipolar disorder patients and lithium depolarizes (increases) are explained using the action of DAG signaling pathway. Lithium increases the concentration of DAG thereby increasing the activity of DAG signaling pathway which controls the potassium flow through the CAK channel. If this result is established through further independent corroboration it would greatly enhance our understanding of the mechanisms of bipolar disorder. Knowledge of this signaling pathway elucidates how lithium treats bipolar disorder. Additionally, the mechanism of induced switching associated with certain antidepressants given to patients who are bipolar can also be explained by this pathway. Further analysis of this pathway would lead to the discovery of new drugs for this disease.

Mental Health Symptoms in Oral Contraceptive Users During Short-Term Hormone Withdrawal

Hormonal contraception has been linked to mood symptoms and the ability to recognize emotions after short periods of treatment, whereas the mental health of users of long-term hormonal contraceptives has had limited investigation. To evaluate whether short-term hormonal withdrawal, which users of combined oral contraceptives (COCs) undergo once a month (pill pause), was associated with altered mood and emotional recognition in long-term users of COCs. This case-control study included a community sample of individuals assigned female sex at birth who identified as women and used COC for 6 months or longer. The control group included women with natural menstrual cycles who otherwise fulfilled the same inclusion criteria. The study was conducted between April 2021 and June 2022 in Salzburg, Austria. COC users and women with natural menstrual cycles were tested twice within a month, once during their active pill phase or luteal phase and once during their pill pause or menses. Negative affect, anxiety, and mental health problems were assessed during each session. The percentage increase in mental health symptoms was calculated during the pill pause compared with that during the active intake phase in COC users. How this change compared with mood fluctuations along the menstrual cycle in women with natural menstrual cycles was assessed. A total of 181 women aged 18 to 35 years (mean [SD] age, 22.7 [3.5] years) were included in the analysis (61 women with androgenic COC use, 59 with antiandrogenic COC use, 60 women with a menstrual cycle not taking COCs). COC users showed a 12.67% increase in negative affect (95% CI, 6.94%-18.39%), 7.42% increase in anxiety (95% CI, 3.43%-11.40%), and 23.61% increase in mental health symptoms (95% CI, 16.49%-30.73%; P < .001) during the pill pause compared with the active intake phase. The effect size of this change did not differ depending on progestin type (negative affect: F1,117 = 0.30, P = .59; state anxiety: F1,117 = 2.15, P = .15; mental health: F1,117 = .16, P = .69) or ethinylestradiol dose (negative affect: F1,57 = .99, P = .32; state anxiety: F1,57 = 2.30, P = .13; mental health: F1,57 = .14, P = .71) was comparable with mood changes along the menstrual cycle in women with natural cycles (negative affect: F2,175 = 0.13, P = .87; state anxiety: F2,175 = 0.14, P = .32; mental health: F2,175 = 0.65, P = .52). Mood worsening during the pill pause was more pronounced in women with higher baseline depression scores (negative affect increase of 17.95% [95% CI, 7.80%-28.10%] in COC users with higher trait depression [BDI >8]). Emotion recognition performance did not differ between active pill phase and pill pause. In this case-control study of long-term COC users, withdrawal from contraceptive steroids during the pill pause was associated with adverse mental health symptoms similar to those experienced by women during menses with withdrawal from endogenous steroids. These results question the use of the pill pause from a mental health perspective. Long-term COC users may benefit more from the mood-stabilizing effects of COCs in cases of continuous intake.

Optimization of Therapy in Patients with Epilepsy and Psychiatric Comorbidities: Key Points.

Psychiatric disorder comorbidity in patients with epilepsy (PWE) is very frequent with a mean percentage prevalence of up to 50% and even higher. Such a high frequency suggests that epilepsy and psychiatric disorders might share common pathological pathways. Various aspects contribute in making the matter very complex from a therapeutic point of view. Some antiseizure medications (ASMs), namely valproic acid, carbamazepine, and lamotrigine, have mood-stabilising effects and are routinely used for the treatment of bipolar disorder in patients who do not have epilepsy. Pregabalin and, to a lesser extent, gabapentin, exerts anxiolytic effects. However, several ASMs, in particular levetiracetam, topiramate, and perampanel, may contribute to psychiatric disorders, including depression, aggressive behaviour, and even psychosis. If these ASMs are prescribed, the patient should be monitored closely. A careful selection should be made also with psychotropic drugs. Although most of these can be safely used at therapeutic doses, bupropion, some tricyclic antidepressants, maprotiline, and clozapine may alter seizure threshold and facilitate epileptic seizures. Interactions between ASMs and psychotropic medication may make it difficult to predict individual response. Pharmacokinetic interactions can be assessed with drug monitoring and are consequently much better documented than pharmacodynamic interactions. Another aspect that needs a careful evaluation is patient adherence to treatment. Prevalence of non-adherence in PWE and psychiatric comorbidities is reported to reach values even higher than 70%. A careful evaluation of all these aspects contributes in optimizing therapy with a positive impact on seizure control, psychiatric wellbeing, and quality of life.

Does the comorbidity of borderline personality disorder affect the response to treatment in bipolar patients?

Bipolar disorder (BD) is a highly prevalent condition whose response to pharmacological treatment is associated with a number of factors including psychiatric comorbidity. Borderline personality disorder (BPD) shares clinical symptoms and biological vulnerability with BD and the two conditions are frequently comorbid, thus representing a clinical challenge. The purpose of the present review is to summarize the data related to treatment response in bipolar patients with comorbid BPD. According to systematic review process, a literature search was performed on the PubMed, Embase, PsycInfo, Isi Web of Knowledge, Medscape, and Cochrane Library databases. Peer-reviewed articles until December 2022 were eligible for inclusion. Comorbidity with BPD seems to be associated with a more difficult clinical stabilization in bipolar patients, often requiring poly-therapy or a longer duration of hospitalization. However, three studies, assessing the effectiveness of mood stabilizers in bipolar patients, did not demonstrate a prominent influence of BPD comorbidity in achieving clinical response. The most frequently administered pharmacological treatments in the selected studies include mood stabilizers and atypical antipsychotics. The presence of comorbid BPD in bipolar patients may hamper treatment effectiveness. Future studies, comparing different treatments and with larger samples, are needed to confirm the results critically summarized in the present review.