Mood Stabilizers Research Articles

New-onset seizures misdiagnosed as psychogenic non-epileptic seizures: a case of paraneoplastic limbic encephalitis with primary testicular cancer

BackgroundBehavioral psychiatric symptoms can be the only warning signs of more serious conditions such as paraneoplastic limbic encephalitis. Differentiating between primary psychiatric disorders and paraneoplastic neurological syndromes is crucial as they require distinct treatment approaches. In this case report, we provide an overview of paraneoplastic encephalitis and introduce a unique case that showcases a misdiagnosis of psychogenic non-epileptic seizures (PNES) in a male as the primary symptom of paraneoplastic encephalitis due to pure seminoma. This case highlights the underlying pathophysiology of antibody-mediated paraneoplastic encephalitis and its significance.Case presentationA 31-year-old male with no known past medical history presented due to recurrent seizures. There was no prior history of epilepsy or exposure to seizure-triggering agents. Imaging and electroencephalogram findings during his initial hospitalizations pointed to a potential diagnosis of PNES. The patient continued to experience seizures following discharge, leading to repeat hospitalizations. During the fourth hospitalization, the patient received mood-stabilizing anti-seizure medications and benzodiazepines, but he deteriorated and required intubation. It was during this time that the patient was transferred to our facility. Magnetic resonance imaging of the brain revealed multifocal areas of hyperintensity and restricted diffusion with avid enhancement. Immunotherapy was initiated with improvement of non-epileptic spells and encephalopathy. Outpatient workup uncovered malignant pure seminoma with metastases to the retroperitoneum. The authors theorize that paraneoplastic neurological disorders stemming from testicular cancer led to the neurological symptoms seen in this case.ConclusionThis report highlights a rare occurrence of paraneoplastic limbic encephalitis associated with pure testicular seminoma, clinically manifested as PNES. The diagnostic challenge posed by variability of presenting symptoms in paraneoplastic encephalitis emphasizes the importance of accurate differentiation from conditions such as autoimmune encephalitis. Current diagnostic approaches for paraneoplastic and autoimmune etiologies involve detection of known antibodies, as well as brain imaging. Notable antibodies associated with psychogenic non-epileptic seizures symptoms include anti-GAD-65, anti-Ma2, KLH11-antibodies, anti-Hu, and NMDA receptor antibodies. Recognizing paraneoplastic limbic encephalitis symptoms is challenging and often leads to misdiagnosis or overlooking of malignancies highlighting the need for awareness, comprehensive evaluation and timely treatment. Through this comprehensive case analysis, we enhance the understanding of underlying mechanisms, associated symptoms, and treatment options.

Bone Health in Mood Disorders: A Narrative Review about Clinical and Biological Connections

Evidence about bone health in people affected by psychiatric disorders is limited. This narrative review aims to highlight what is known, up to the present time, about clinical connections between bone health and psychiatric disorders, particularly depressive disorders (DD) and bipolar disorders (BD), in terms of common biological pathways. Besides inflammation, we focused on two molecules of growing interest: neuropeptide Y (NPY) and the neuro-hormone melatonin. Also, the role of psychoactive drugs on bone tissue was explored. For the preparation of this narrative review, the scientific literature of the most recent 7 years from PubMed, Springer Nature, Science Direct (Elsevier), Wiley Online, ResearchGate, and Google Scholar databases was analyzed. Reviewed evidence reveals that people diagnosed with BD or DD have an increased risk of both fractures and osteoporosis; NPY reduces bone loss induced by longer periods of depression and “buffers” psychological stress effects on bone health. MLT shows beneficial effects in osteoporosis and bone healing. Lithium, a mood stabilizer, shows potential bone-protective activity, while antipsychotic and antidepressant treatments may increase the risk of bone tissue damage, though further investigation is needed.

Usage Patterns of Traditional Chinese Medicine for Patients with Bipolar Disorder: A Population-Based Study in Taiwan.

Patients with bipolar disorder (BD) receive traditional Chinese medicine (TCM) for clinical needs unmet with psychotropic medications. However, the clinical characteristics of practices and outcomes of TCM in BD are not fully understood. This cohort study investigated the clinical characteristics, principal diagnoses, TCM interventions, and TCM prescriptions in patients with BD. Data for a total of 12,113 patients with BD between 1996 and 2013 were withdrawn from Taiwan's longitudinal health insurance database 2000 (LHID 2000). The chi-square test was used for categorical variables, and the independent t-test was used for continuous variables. A p-value less than 0.05 indicated significance. One thousand three hundred nineteen patients who visited TCM clinics after the diagnosis of BD were in the TCM group, while those who never visited TCM were in the non-TCM group (n = 1053). Compared to the non-TCM group, patients in the TCM group had younger average age, a higher percentage of female individuals, more comorbidities of anxiety and alcohol use disorders, and higher mood stabilizer usage rates. The TCM group exhibited pain-related indications, including joint pain, myalgia, myositis, headache, and sleep disturbances. Corydalis yanhusuo and Shu-Jing-Huo-Xue-Tang were the most useful single herbs and herbal formulae. Physicians need to be aware of the use of TCM in patients with BD.

Comorbid Obsessive-Compulsive Disorder and Bipolar Disorder in the Pediatric Population — Clinical and Therapeutic Challenges

Comorbidity between obsessive-compulsive disorder and bipolar disorder has been a well-documented phenomenon in the adult population for several decades. However, scant evidence exists regarding this comorbidity in the juvenile population. The objective of this review is to investigate the impact of obsessive-compulsive disorder and bipolar disorder comorbidity on the clinical course and therapeutic approaches for each disorder individually, with a particular focus on children and adolescents. A scientific review was conducted on a careful analysis of the evidence available on the electronic databases: MEDLINE, Embase and Cochrane Library. In children, it has been observed that up to one-third of individuals diagnosed with either obsessive-compulsive disorder or bipolar disorder also experience a lifetime co-occurrence of the other disorder, a notably higher prevalence when compared to adults. The primary diagnosis typically manifests with an earlier onset in this population. When bipolar disorder is present, children and adolescents with obsessive-compulsive disorder tend to exhibit an episodic course, more hoarding or saving obsessions and compulsions, and a significantly higher number of comorbidities. In this age group, obsessive-compulsive disorder and bipolar disorder comorbidity is further linked to increased severity symptoms, greater impulsivity, reduced responsiveness to pharmacological treatment, elevated suicide risk, and a diminished likelihood of achieving remission rates for manic and depressive symptoms. Obsessive-compulsive symptoms during childhood and adolescence may indicate vulnerability to have bipolar disorder, suggesting partially shared etiopathogenetic mechanisms between these psychiatric entities. The use of antidepressants poses a risk of inducing a switch to mania or rapid cycling in bipolar patients. Additionally, atypical antipsychotics have been reported to trigger and worsen obsessive-compulsive symptoms. The complexity involved in deciding on a suitable treatment scheme for individuals with this comorbidity may contribute to an unfavorable clinical course. A noteworthy portion of comorbid patients may require a combination of multiple mood stabilizers for effective management.

New Advances in the Pharmacology and Toxicology of Lithium: A Neurobiologically Oriented Overview.

Over the last six decades, lithium has been considered the gold standard treatment for the long-term management of bipolar disorder due to its efficacy in preventing both manic and depressive episodes as well as suicidal behaviors. Nevertheless, despite numerous observed effects on various cellular pathways and biologic systems, the precise mechanism through which lithium stabilizes mood remains elusive. Furthermore, there is recent support for the therapeutic potential of lithium in other brain diseases. This review offers a comprehensive examination of contemporary understanding and predominant theories concerning the diverse mechanisms underlying lithium's effects. These findings are based on investigations utilizing cellular and animal models of neurodegenerative and psychiatric disorders. Recent studies have provided additional support for the significance of glycogen synthase kinase-3 (GSK3) inhibition as a crucial mechanism. Furthermore, research has shed more light on the interconnections between GSK3-mediated neuroprotective, antioxidant, and neuroplasticity processes. Moreover, recent advancements in animal and human models have provided valuable insights into how lithium-induced modifications at the homeostatic synaptic plasticity level may play a pivotal role in its clinical effectiveness. We focused on findings from translational studies suggesting that lithium may interface with microRNA expression. Finally, we are exploring the repurposing potential of lithium beyond bipolar disorder. These recent findings on the therapeutic mechanisms of lithium have provided important clues toward developing predictive models of response to lithium treatment and identifying new biologic targets. SIGNIFICANCE STATEMENT: Lithium is the drug of choice for the treatment of bipolar disorder, but its mechanism of action in stabilizing mood remains elusive. This review presents the latest evidence on lithium's various mechanisms of action. Recent evidence has strengthened glycogen synthase kinase-3 (GSK3) inhibition, changes at the level of homeostatic synaptic plasticity, and regulation of microRNA expression as key mechanisms, providing an intriguing perspective that may help bridge the mechanistic gap between molecular functions and its clinical efficacy as a mood stabilizer.

Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Concurrent Use of Crocin During Chemoradiation for Esophageal Squamous Cell Carcinoma

Crocin is the major active carotenoid of saffron (Crocus sativus L.). Its pluripotent effects have led to a growing body of literature investigating its antitumor properties as well as its diverse potentials for mood stabilization, normal tissue protection, and inflammation reduction; However, there is a gap in clinical trials testing this substance in cancer patients. In this randomized, double-blind, placebo-controlled clinical trial, patients with newly diagnosed esophageal squamous cell carcinoma were randomly assigned to either 30 mg/day of crocin or placebo, prescribed during the neoadjuvant chemo-radiotherapy. The primary endpoints were pathological response and toxicity, and secondary endpoints were depression and anxiety levels and survival analysis.

(127) Sexual Health Implications Associated with Psychotropic Medication Use Among Adolescents During the COVID-19 Pandemic

Abstract Introduction The use of psychotropic medications has a notable effect on sexual well-being. Prolonged use is closely linked to dyspareunia, reduced sexual desire, hypogonadism, and erectile dysfunction. We hypothesized that there was an increase in the prescription rates of psychotropic medications among adolescent patients during the COVID-19 pandemic due to the unprecedented stress experienced by isolated youth. Objective We examined the prescription rates of psychotropic medications and the simultaneous usage of PDE5 inhibitors in adolescent patients during the COVID-19 pandemic in order to compare usage of these medications prior to the pandemic. Methods To conduct our retrospective matched cohort study, we utilized data obtained from the TriNetX Research Network. The study focused on adolescent patients aged 10-19 presenting for outpatient evaluation, and were placed into two cohorts: 1) those evaluated before the COVID-19 pandemic, and 2) those evaluated during the pandemic. Patients with previous psychiatric diagnoses or prior use of psychotropic medications were excluded from the study. Our primary interest was to examine new prescription patterns within 90 days of the outpatient evaluation. To ensure balanced cohorts, propensity score matching was conducted using logistic regression, resulting in cohorts of equal size. Results A total of 1,612,283 adolescents pre-COVID-19 and 1,008,161 adolescents presenting during the COVID-19 pandemic for outpatient evaluations were identified. After propensity matching, a total of 1,005,408 adolescents were included in each cohort each with an average age of 14.7 ± 2.84 and 52% female and 48% male. Prescribing of antipsychotics and benzodiazepines were more frequent during the pandemic for adolescents (RR: 1.58, 95% CI 1.01-2.2). However, they were less likely to receive antidepressants (Risk Ratio (RR): 0.6, 95% Confidence Interval (CI) 0.57-0.63), anxiolytics (RR: 0.78, 95% CI 0.75-0.81), stimulants (RR: 0.26, 95% CI 0.25-0.27), as well as mood stabilizers (RR: 0.44, 95% CI 0.39-0.49). Erectile dysfunction requiring oral PDE5i in this cohort was more frequent during the pandemic for adolescents (RR: 1.53, 95% CI 1.05-2.01). Conclusions During the global COVID-19 pandemic, there was a notable rise in the prescription rates of antipsychotic and benzodiazepine medications compared to previous years. Interestingly, this increase aligned with a statistically significant rise in the prescription of PDE5 inhibitors (PDE5i) for treating erectile dysfunction. These findings indicate that clinicians need to be aware of the potential increased risk of medication-related sexual dysfunction among adolescents. Disclosure Yes, this is sponsored by industry/sponsor: NIH health grant RO1 DK130991 and Clinician Scientist Development Grant from the American Cancer Society. Clarification: Industry funding only - investigator initiated and executed study.

Challenges in the Treatment of Psychotic Bipolar Depression.

Psychotic bipolar depression (PBD) is a prevalent yet understudied psychiatric illness, and there are no specific guidelines or Food and Drug Administration-approved medications for its treatment. Recent studies suggest that some antipsychotics and mood stabilizers may be effective in managing bipolar depression; however, their effectiveness for PBD remains unclear. Given the urgent need for more focused research for managing PBD, we conducted a literature review to summarize the existing literature on PBD. We conducted an electronic literature search from the 1960s to 2023, utilizing PubMed, MEDLINE, EMBASE, and Google, and selected studies based on their relevance to PBD. PBD is a complex disorder, with 50%-75% of patients with bipolar disorder exhibiting psychotic features. This likelihood increases among those with a history of psychotic mania. Treatment guidelines often recommend a combination of mood stabilizers, antipsychotics, or electroconvulsive therapy, but they do not specify a first-line treatment. PBD symptoms can be masked by mixed high mood and energy feelings, potentially delaying diagnosis and treatment while increasing suicide risk. Limited research has evaluated outcomes of various treatments for PBD, and despite the lack of evidence for superior efficacy, in clinical practice, antipsychotics are frequently prescribed. Notably, combining an antipsychotic with selective noradrenaline reuptake inhibitors or tricyclic antidepressants may be effective, but including a mood stabilizer is necessary. PBD poses a significant challenge in mental health due to its severity and the lack of consensus on optimal treatment approaches. There is a critical need for more dedicated clinical trials and research to answer key questions about the effective treatment of acute PBD, ideal follow-up care, traits of responders to different therapies, and decision models for subsequent treatments.

New Psychometric Strategies for the Evaluation of Affective, Cognitive, and Psychosocial Functioning in Unipolar versus Bipolar Depression: Impact of Drug Treatment.

Different studies have been conducted to understand how patients with unipolar and bipolar depression differ in terms of cognitive and affective symptoms as well as in psychosocial function. Furthermore, the impact of antidepressants, second-generation antipsychotics, and mood stabilizers on these dimensions needs to be characterized, as well as the best psychometric approach to measure changes after pharmacological treatment. This study aims to analyze the impact of psychotropic drugs on cognitive, affective, and psychosocial functioning in MDD and BD patients; to test the sensitivity of psychometric tools for measuring those changes; also, to understand how psychosocial abilities are associated with affective and cognitive dimensions in patients with MDD and BD. A total of 22 patients with MDD and 21 patients with BD in the depressive phase were recruited. Several psychometric tests were administered to assess affective, cognitive, and psychosocial symptoms before and after 12 weeks of drug treatment (T0 and T1) with different psychotropic drugs including second-generation antidepressants, second-generation antipsychotics and mood stabilizers (lamotrigine). MDD patients showed significant improvement in MoCA, Delayed Recall of Rey's 15 Words and HDRS, while a significant worsening was detected on Digit Span Backwards and on FAST scores. Instead, patients with BD showed significant improvements in the MoCA as the MDD patients, but only a trend of improvement (non-statistically significant) on the BDI-II. A positive correlation was detected in both groups between FAST and HDRS and BDI-II scores, especially in BD patients. Our results demonstrate that drug treatment with psychotropic drugs can improve cognitive and affective symptoms, but not all psychometric tools may be equally sensitive to detect those changes in MDD vs. BD patients. Moreover, we found that affective and cognitive dimensions can be considered as different psychopathological dimensions both in unipolar and bipolar depression.

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.

Schizoaffective Disorder in an Individual with Mowat-Wilson Syndrome (MWS)

Mowat-Wilson Syndrome (MWS) is an autosomal dominant genetic syndrome caused by mutations in the ZEB2 gene. It is characterized by distinctive facial appearance, intellectual disability (ID), epilepsy, Hirschsprung disease (HSCR), and other congenital anomalies. The psychiatric symptoms, associated with MWS have rarely been reported. The following report highlights a case of schizoaffective disorder in a 24-year-old male with MWS and the challenges he encountered over his treatment course. After considering numerous diagnoses including bipolar disorder and psychosis secondary to a general medical condition, the patient was diagnosed with schizoaffective disorder. Various trials consisting of atypical antipsychotics and mood stabilizers were unsuccessful in managing his symptoms. Eventually, the patient stabilized on a medication regimen consisting of clozapine 300 mg once daily, topiramate 75 mg twice per day, and lithium 1800 mg once daily. This case report documents co-occurrence of MWS and Schizoaffective disorder.

Lithium carbonate revitalizes tumor-reactive CD8+ T cells by shunting lactic acid into mitochondria

The steady flow of lactic acid (LA) from tumor cells to the extracellular space via the monocarboxylate transporter symport system suppresses antitumor T cell immunity. However, LA is a natural energy metabolite that can be oxidized in the mitochondria and could potentially stimulate T cells. Here we show that the lactate-lowering mood stabilizer lithium carbonate (LC) can inhibit LA-mediated CD8+ T cell immunosuppression. Cytoplasmic LA increased the pumping of protons into lysosomes. LC interfered with vacuolar ATPase to block lysosomal acidification and rescue lysosomal diacylglycerol–PKCθ signaling to facilitate monocarboxylate transporter 1 localization to mitochondrial membranes, thus transporting LA into the mitochondria as an energy source for CD8+ T cells. These findings indicate that targeting LA metabolism using LC could support cancer immunotherapy.

Marked alteration of phosphoinositide signaling-associated molecules in postmortem prefrontal cortex with bipolar disorder.

The etiology of bipolar disorder (BD) remains unknown; however, lipid abnormalities in BD have received increasing attention in recent years. In this study, we examined the expression levels of enzyme proteins associated with the metabolic pathway of phosphoinositides (PIs) and their downstream effectors, protein kinase B (Akt1) and glycogen synthase kinase 3β (GSK3β), which have been assumed to be the targets of mood stabilizers such as lithium, in the postmortem brains of patients with BD. The protein expression levels of phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C), phosphatidylinositol 4-kinase alpha (PIK4CA), phosphatase and tensin homolog deleted from chromosome 10 (PTEN), Akt1, and GSK3β were measured using enzyme-linked immunosorbent assays and multiplex fluorescent bead-based immunoassays in the prefrontal cortex (PFC). Specifically, PTEN, Akt1, GSK3β, and PIP5K1C were measured in seven BD patients and 48 controls. Additionally, PIK4CA was analyzed in 10 cases and 34 controls. PTEN expression levels were markedly decreased in the PFCs of patients with BD, whereas those of Akt and GSK3β were prominently elevated. Moreover, patients medicated with lithium exhibited higher Akt1 expression levels and lower PTEN expression levels in comparison with the untreated group. Our results suggest that the expression levels of Akt1/GSK3β and its upstream regulator PTEN are considerably altered.

Pharmacoepidemiology and Clinical Correlates of Lithium Treatment for Bipolar Disorder in Asia.

As clinical practices with lithium salts for patients diagnosed with bipolar disorder (BD) are poorly documented in Asia, we studied the prevalence and clinical correlates of lithium use there to support international comparisons. We conducted a cross-sectional study of use and dosing of lithium salts for BD patients across 13 Asian sites and evaluated bivariate relationships of lithium treatment with clinical correlates followed by multivariate logistic regression modeling. In a total of 2139 BD participants (52.3% women) of mean age 42.4 years, lithium salts were prescribed in 27.3% of cases overall, varying among regions from 3.20% to 59.5%. Associated with lithium treatment were male sex, presence of euthymia or mild depression, and a history of seasonal mood change. Other mood stabilizers usually were given with lithium, often at relatively high doses. Lithium use was associated with newly emerging and dose-dependent risk of tremors as well as risk of hypothyroidism. We found no significant differences in rates of clinical remission or of suicidal behavior if treatment included lithium or not. Study findings clarify current prevalence, dosing, and clinical correlates of lithium treatment for BD in Asia. This information should support clinical decision-making regarding treatment of BD patients and international comparisons of therapeutic practices.

Measuring anxiety disorder in bipolar disorder using EVestG: broad impact of medication groups.

Anxiety disorder is present in approximately half of all bipolar disorder (BD) patients. There are neurologic bases for the comorbidity of balance (vestibular) disorders and anxiety. Our objective is to use electrovestibulography (EVestG), which is predominantly a measure of vestibular neural activity to not only quantitatively detect and measure comorbid anxiety disorder but also to quantitatively measure the impacts of anti-depressant, anti-psychotic, and mood stabilizer medication groups on anxiety measures in BD patients. In a population of 50 (24 with anxiety disorder) depressive phase BD patients, EVestG signals were measured. Participants were labeled depression-wise as anxious or non-anxious using standard questionnaires. Analyses were conducted on the whole dataset as well as on matched (age/gender/MADRS) and "modeled medication-free" subsets. Modulations of the low-frequency EVestG firing pattern data were measured. For BD, the main anxious minus non-anxious difference was the presence of an increase in spectral power proximal to 8-9 Hz, which was best attenuated by mood stabilizers. This is the first study to use an oto-acoustic physiological measure to quantify anxiety disorder in BD wherein it appears to manifest as a peak proximal to 8-9 Hz which we hypothesize as likely linked to hippocampal theta.

Psychotropic Medications and Dermatological Side Effects: An In-Depth Review

Psychotropic medications, commonly prescribed for psychiatric disorders, can have underappreciated dermatological side effects. This in-depth review explores the intricate relationship between psychotropic drugs and the skin, emphasizing the significance of recognizing and managing these side effects in clinical practice. It categorizes the dermatological side effects associated with different classes of psychotropic medications. These include antidepressants, antipsychotics, mood stabilizers, and anxiolytics. We delve into the spectrum of dermatological conditions, from mild issues like dry skin and acne to severe complications such as Stevens–Johnson syndrome and drug-induced lupus erythematosus. In conclusion, a comprehensive understanding of the dermatological side effects of psychotropic medications is essential for healthcare providers, enabling a holistic approach to patient care. This review is a valuable resource for clinicians, researchers, and educators, facilitating better-informed decision-making in the treatment of mental health disorders while prioritizing skin health and overall well-being.

Hypothalamic Subunit Volumes in Schizophrenia and Bipolar Spectrum Disorders.

The hypothalamus is central to many hormonal and autonomous nervous system pathways. Emerging evidence indicates that these pathways may be disrupted in schizophrenia and bipolar disorder. Yet, few studies have examined the volumes of hypothalamic subunits in these patient groups. We compared hypothalamic subunit volumes in individuals with psychotic disorders to healthy controls. We included 344 patients with schizophrenia spectrum disorders (SCZ), 340 patients with bipolar disorders (BPD), and 684 age- and-sex-matched healthy controls (CTR). Total hypothalamus and five hypothalamic subunit volumes were extracted from T1-weighted magnetic resonance imaging (MRI) using an automated Bayesian segmentation method. Regression models, corrected for age, age2, sex, and segmentation-based intracranial volume (sbTIV), were used to examine diagnostic group differences, interactions with sex, and associations with clinical symptoms, antipsychotic medication, antidepressants and mood stabilizers. SCZ had larger volumes in the left inferior tubular subunit and smaller right anterior-inferior, right anterior-superior, and right posterior hypothalamic subunits compared to CTR. BPD did not differ significantly from CTR for any hypothalamic subunit volume, however, there was a significant sex-by-diagnosis interaction. Analyses stratified by sex showed smaller right hypothalamus and right posterior subunit volumes in male patients, but not female patients, relative to same-sex controls. There was a significant association between BPD currently taking antipsychotic medication and the left inferior tubular subunits volumes. Our results show regional-specific alterations in hypothalamus subunit volumes in individuals with SCZ, with relevance to HPA-axis dysregulation, circadian rhythm disruption, and cognition impairment.

Medication Dosage Impact on Mortality in Old-Age Individuals with Schizophrenia: A National Cohort Study.

As the prevalence of old-age individuals with schizophrenia (OAS) increases in a society undergoing demographic aging, the exploration of medication choices becomes increasingly crucial. Due to the current scarcity of literature on OAS, this study seeks to examine how the utilization and cumulative dosages of psychotropic medications influence both overall and cause-specific mortality risks within this population. A national cohort of 6433 individuals diagnosed with OAS was followed up for 5 years. This study involved comparing the mortality rates associated with low, moderate, and high dosages of antipsychotics, antidepressants, mood stabilizers, and sedative/hypnotic drugs against the 'no exposure' category, based on individual dosages. Cox regression was employed for survival analyses to compare overall mortality and specific-cause mortality across various dosage groups. The exposure variable examined was the dosage of a specific psychotropic medication. Covariates were adjusted accordingly. The analysis revealed that patients on low/moderate antipsychotic doses had improved survival compared to non-exposed individuals. Moderate antipsychotic use corresponded to reduced cardiovascular disease mortality risk. Similarly, those exposed to antidepressants had enhanced survival in low and moderate doses. Sedative-hypnotic exposure was linked to decreased mortality risk in low doses. This study observed that low/moderate antipsychotic doses in older adults with schizophrenia were associated with decreased all-cause mortality, emphasizing the significance of precise medication selection and dosing. It underscores the need for vigilant polypharmacy management and tailored medication strategies in addressing the complexities of treating OAS.

Effectiveness of Quetiapine as a Mood Stabilizer: A Case Series

Effectiveness of Quetiapine as a Mood Stabilizer: A Case Series

Mortality risk and mood stabilizers in bipolar disorder: a propensity-score-weighted population-based cohort study in 2002-2018.

Accumulating studies have assessed mortality risk associated with mood-stabilizers, the mainstay treatment for bipolar disorder (BD). However, existing data were mostly restricted to suicide risk, focused on lithium and valproate and rarely adequately adjusted for potential confounders. This study aimed to assess comparative mortality risk with all, natural and unnatural causes between lithium, valproate and three frequently prescribed second-generation antipsychotics (SGA), with adjustment for important confounders. This population-based cohort study identified 8137 patients with first-diagnosed BD, who had exposed to lithium (n = 1028), valproate (n = 3580), olanzapine (n = 797), quetiapine (n = 1975) or risperidone (n = 757) between 2002 and 2018. Data were retrieved from territory-wide medical-record database of public healthcare services in Hong Kong. Propensity-score (PS)-weighting method was applied to optimize control for potential confounders including pre-existing chronic physical diseases, substance/alcohol use disorders and other psychotropic medications. PS-weighted Cox proportional-hazards regression was conducted to assess risk of all-, natural- and unnatural-cause mortality related to each mood-stabilizer, compared to lithium. Three sets of sensitivity analyses were conducted by restricting to patients with (i) length of cumulative exposure to specified mood-stabilizer ≥90 days and its medication possession ratio (MPR) ≥90%, (ii) MPR of specified mood-stabilizer ≥80% and MPR of other studied mood-stabilizers <20% and (iii) monotherapy. Incidence rates of all-cause mortality per 1000 person-years were 5.9 (95% confidence interval [CI]: 4.5-7.6), 8.4 (7.4-9.5), 11.1 (8.3-14.9), 7.4 (6.0-9.2) and 12.0 (9.3-15.6) for lithium-, valproate-, olanzapine-, quetiapine- and risperidone-treated groups, respectively. BD patients treated with olanzapine (PS-weighted hazard ratio = 2.07 [95% CI: 1.33-3.22]) and risperidone (1.66 [1.08-2.55]) had significantly higher all-cause mortality rate than lithium-treated group. Olanzapine was associated with increased risk of natural-cause mortality (3.04 [1.54-6.00]) and risperidone was related to elevated risk of unnatural-cause mortality (3.33 [1.62-6.86]), relative to lithium. The association between olanzapine and increased natural-cause mortality rate was consistently affirmed in sensitivity analyses. Relationship between risperidone and elevated unnatural-cause mortality became non-significant in sensitivity analyses restricted to low MPR in other mood-stabilizers and monotherapy. Valproate- and lithium-treated groups did not show significant differences in all-, natural- or unnatural-cause mortality risk. Our data showed that olanzapine and risperidone were associated with higher mortality risk than lithium, and further supported the clinical guidelines recommending lithium as the first-line mood-stabilizer for BD. Future research is required to further clarify comparative mortality risk associated with individual SGA agents to facilitate risk-benefit evaluation of alternative mood-stabilizers to minimize avoidable premature mortality in BD.