Mood Stabilizers Research Articles

Impact of chronic lithium treatment on brain oxidative stress and anxiety-like behaviors in rats: Dose-dependent effects.

Lithium (Li) is a mood-stabilizing drug. Although one of the potential mechanisms underlying the neuroprotective effects of lithium is related to its antioxidative effect, its mechanisms of action are not fully understood. Herein we aimed to investigate the impact of varied dosages of long-term lithium therapy on oxidative stress parameters in the brains of healthy rats, and on anxiety-like behaviors, and whether any changes in behavior can be attributed to modifications in oxidative stress levels within the brain. Thirty-two adult Wistar albino male rats were randomly assigned to four treatment groups. While the control (C) group was fed with a standard diet, low Li (1.4 g/kg/diet), moderate Li (1.8 g/kg/diet), and high Li (2.2 g/kg/diet) groups were fed with lithium bicarbonate (Li2CO3) for 30 days. Malondialdehyde increased, while superoxide dismutase and catalase levels decreased in the brains of the high Li group animals. In addition, anxiety-like behaviors of animals increased in the high Li group considering fewer entries to and less time spent in the open arms of the elevated plus maze test. Our findings underscore the potential adverse effects of prolonged lithium treatment, especially at doses approaching the upper therapeutic range. The induction of toxicity, manifested through heightened oxidative stress, appears to be a key mechanism contributing to the observed increase in anxiety-like behaviors. Consequently, caution is warranted when considering extended lithium therapy at higher doses, emphasizing the need for further research to delineate the precise mechanisms underlying these effects and to inform safer therapeutic practices.

Exploring mood disorders and treatment options using human stem cells.

Despite their global prevalence, the mechanisms for mood disorders like bipolar disorder and major depressive disorder remain largely misunderstood. Mood stabilizers and antidepressants, although useful and effective for some, do not have a high responsiveness rate across those with these conditions. One reason for low responsiveness to these drugs is patient heterogeneity, meaning there is diversity in patient characteristics relating to genetics, etiology, and environment affecting treatment. In the past two decades, novel induced pluripotent stem cell (iPSC) research and technology have enabled the use of human-derived brain cells as a new model to study human disease that can help account for patient variance. Human iPSC technology is an emerging tool to better understand the molecular mechanisms of these disorders as well as a platform to test novel treatments and existing pharmaceuticals. This literature review describes the use of iPSC technology to model bipolar and major depressive disorder, common medications used to treat these disorders, and novel patient-derived alternative treatment methods for non-responders stemming from past publications, as well as presenting new data derived from these models.

Beyond the Clinic Walls: Fostering Well-Being in a Client with Schizoaffective Disorder (SAD) Through Home Care and Clozapine Therapy - A Case Report

Schizoaffective disorder SAD is a chronic severe and disabling illness associated with concurrent presentation of symptoms of schizophrenia and affective disorders. The mainstay of treatment is a combination of antipsychotic medications and depending on the subtype of schizoaffective disorder either mood stabilizers or antidepressants are given. Clozapine is a second-generation antipsychotic used in the treatment of SAD. Clozapine-induced agranulocytosis has the highest risk of occurrence during the first few months of treatment. Other common side effects are sialorrhea constipation dehydration and hyperglycaemia. Adequately managing side effects can improve adherence and quality of life. Physical health should be monitored at each clinical review particularly in the first few months of treatment to reduce the occurrence of serious sometimes fatal adverse reactions. Many clients find clozapine to help with their psychosis but they often need to balance the positive effect of psychosis with some of the side effects that clozapine can cause.

Associations Between COVID-19, Delirium, and 1-Year Mortality: Exploring Influences on Delirium Incidence in COVID-19 Patients.

This study investigated the relationship between coronavirus disease 2019 (COVID-19), delirium, and 1-year mortality. Factors associated with delirium in COVID-19 patients were identified, along with the influence of psychotropic medications on delirium. The study used the South Korean National Health Insurance Service database. Adult COVID-19 patients diagnosed between October 2020 and December 2021 were included, with a propensity score-matched control group. Time-dependent Cox regression assessed associations among COVID-19, delirium, and mortality. Logistic regression analyzed the impact of psychotropic medications on delirium incidence. The study included 832,602 individuals, with 416,301 COVID-19 patients. COVID-19 (hazard ratio [HR], 3.03; 95% confidence interval [CI], 2.92-3.13) and delirium (HR, 2.33; 95% CI, 2.06-2.63) were independent risk factors for 1-year mortality. Comorbidities, insurance type, and residence were also related to mortality. Among COVID-19 patients, antipsychotic use was associated with lower delirium incidence (odds ratio [OR], 0.38; 95% CI, 0.30-0.47), while mood stabilizers (OR, 1.77; 95% CI, 1.40-2.21) and benzodiazepines (OR, 8.62; 95% CI, 7.46-9.97) were linked to higher delirium incidence. COVID-19 and delirium are risk factors for 1-year mortality. Some factors associated with delirium in COVID-19 patients are modifiable and can be targeted in preventive and therapeutic interventions.

Monoclonal antibody precision therapy targeting inflammation for bipolar disorder: a narrative review.

Bipolar disorder (BD) is a severe mental disorder with various hypotheses regarding its pathogenesis. This article provides a summary of numerous studies on the variations in inflammatory cytokine levels in patients with BD and the effects of treatment with antipsychotics, mood stabilizers, and antidepressants on these levels. In addition, patients with autoimmune diseases who use anti-inflammatory monoclonal antibodies experience symptoms, such as depression, anxiety, and insomnia. These pieces of evidence suggest a potential association between immune inflammation and BD and offer new possibilities for therapy. Building upon this relationship, the authors propose an innovative approach for treating BD through individualized and precise therapy using anti-inflammatory monoclonal antibody drugs. To support this proposal, the authors compile information on pharmacological effects and relevant studies, including trials of various anti-inflammatory therapeutic monoclonal antibody drugs (e.g. infliximab, tocilizumab, and canakinumab) for the potential treatment of BD and its associated side effects in psychiatry. The authors categorize these anti-inflammatory monoclonal antibody drugs into levels I-IV through a comprehensive analysis of their advantages and disadvantages. Their potential is examined, and the need for further exploration of their pharmaceutical effects is established.

Adverse Drug Reactions in the Bipolar Disorder Patients Treated With Mood Stabilizers

Abstract Background: Bipolar disorder is a chronic illness requiring long-term use of mood stabilizers such as lithium and sodium valproate. The adverse drug reactions (ADRs) of these medicines can severely affect the quality of life of the patients. A comparative study of ADR profile of lithium and valproate in terms of prevalence, severity, and causality has not been done in the rural population of India. Methodology: A cross-sectional, observational study was done in the psychiatry outpatient department of a tertiary health care center. The bipolar disorder patients on lithium carbonate or divalproate monotherapy were chosen for documentation of ADRs after informed consent. The Naranjo causality algorithm and Modified Hartwig and Siegel scale for severity assessment were applied to all participants. The data obtained were statistically analyzed using Epi Info open-source software. Results: The study participants having mean age of 33.83 ± 12.02 years comprised nearly equal number of males and females. Tremors (19.4%), polyuria (11.5%), and polydipsia (11.2%) were the most common ADRs due to lithium, whereas nausea (12.6%), anorexia (10.6%), and sedation (9.1%) were more commonly seen in patients on valproate. Most of the ADRs had a mild severity and were categorized as possible in the Naranjo causality algorithm. Conclusion: Although ADRs are common in bipolar disorder patients treated with lithium or valproate, they are often mild and well tolerated by the patients.

Psychotropic Medications Promote Time-Dependent Reduction of Suicidal Ideation in Mood Disorder: A Prospective Cohort Study.

Despite a plethora of research on the topic, there is still no solid evidence that pharmacological treatment actually reduces the risk of suicide in patients with mental illness. In this study, we aimed to assess the effect of psychotropic medications on suicidal ideation in patients with major depressive disorder (MDD) and bipolar disorder (BPD) in two age groups: less than 25 years and 25 years and older. We analyzed 312 patients with mood disorders with current suicidal thoughts or recent suicide attempts. We followed the participants from baseline for 6 months and assessed changes in suicidal ideation with Columbia-Suicide Severity Rating Scale (C-SSRS). The effect of psychotropic drug administration on suicidal ideation over time was analyzed using a linear mixed model. In patients aged 25 years and older with mood disorders, suicidal ideation was more severe when using psychotropic drugs than when not using them. However, suicidal ideation decreased rapidly over time. The time-dependent reduction in suicidal ideation was accelerated when using antidepressants and sedatives/hypnotics in adult MDD, and when using mood stabilizers in adult BPD. However, this effect was not observed in participants aged less than 25 years. Adequate psychotropic medication may reduce suicidal ideation in patients with mood disorders aged 25 years and older. Additional research on psychotropic drugs is needed to effectively reduce the risk of suicide among children and adolescents with mood disorders.

Analysis of risk factors for hospital-acquired pneumonia in schizophrenia.

Hospital-acquired pneumonia is one of the most important causes of recurrent illness, disease progression, and even death during hospitalization. Patients with schizophrenia have the special characteristics of their disease, and at the same time, the occurrence of hospital-acquired pneumonia is more common among patients with schizophrenia due to the prolonged stay in closed wards, accompanied by various factors such as age, gender, and nutritional status. The PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature Database (CBM) databases were searched with a timeframe of build to February 2024 to collect studies on factors influencing hospital-acquired pneumonia in patients with schizophrenia. Two researchers independently screened the literature, extracted data, and analyzed them. A total of 5 papers including 85246 patients were included in the literature, which suggested that benzodiazepines (especially the use of clozapine), combination of antipsychotics, mood stabilizers, modified electroconvulsive therapy (MECT), duration of hospitalization, underlying diseases, hyperglycemia, and salivation/dysphagia were important risk factors for hospital-acquired pneumonia in schizophrenia patients, and that advanced age, smoking and alcohol drinking Older age, smoking and drinking habits, malnutrition, and underlying diseases are also risk factors for hospital-acquired pneumonia. Patients with schizophrenia are at a higher risk of developing hospital-acquired pneumonia, so identifying the risk factors associated with hospital-acquired pneumonia and evaluating them comprehensively and promptly during hospitalization facilitates the development of early interventions, which are essential for improving the prognosis of patients with schizophrenia.

Farmakološki tretman terapo-rezistentne depresije - ka preporukama zasnovanim na dokazima

Depression, a major global public health concern and leading cause of disability, necessitates effective management. This paper, as part of the development of comprehensive guidelines for the treatment of depressive disorder in Serbia, delves into the pharmacological treatment of treatment-resistant depression (TRD), focusing on augmentative and switching strategies, aiming to address the lack of response to standard treatments. The focus is on the efficacy and tolerability of various pharmacological agents, aimed at facilitating informed clinical decisions. In TRD, augmentation strategies involving atypical antipsychotics, NMDA antagonists, mood stabilizers, and other compounds are examined. Finally, the importance of an individualized approach in deciding between augmentation and switching strategies is emphasized. This narrative review aims to inform treatment guidelines and encourages a collaborative approach, which considers individual patient factors, to improve the quality of care for individuals with treatment-resistant depression.

Molecular mechanisms and therapeutic potential of lithium in Alzheimer's disease: repurposing an old class of drugs.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss. Despite advances in understanding the pathophysiological mechanisms of AD, effective treatments remain scarce. Lithium salts, recognized as mood stabilizers in bipolar disorder, have been extensively studied for their neuroprotective effects. Several studies indicate that lithium may be a disease-modifying agent in the treatment of AD. Lithium's neuroprotective properties in AD by acting on multiple neuropathological targets, such as reducing amyloid deposition and tau phosphorylation, enhancing autophagy, neurogenesis, and synaptic plasticity, regulating cholinergic and glucose metabolism, inhibiting neuroinflammation, oxidative stress, and apoptosis, while preserving mitochondrial function. Clinical trials have demonstrated that lithium therapy can improve cognitive function in patients with AD. In particular, meta-analyses have shown that lithium may be a more effective and safer treatment than the recently FDA-approved aducanumab for improving cognitive function in patients with AD. The affordability and therapeutic efficacy of lithium have prompted a reassessment of its use. However, the use of lithium may lead to potential side effects and safety issues, which may limit its clinical application. Currently, several new lithium formulations are undergoing clinical trials to improve safety and efficacy. This review focuses on lithium's mechanism of action in treating AD, highlighting the latest advances in preclinical studies and clinical trials. It also explores the side effects of lithium therapy and coping strategies, offering a potential therapeutic strategy for patients with AD.

Characterization of Psychiatric Inpatients: The Role of Gender Differences in Clinical and Pharmacological Patterns.

Severe mental disorders that require hospitalization are disabling conditions that contribute to the burden of mental diseases. They pose increased clinical challenges and highlight the need to thoroughly explore variables emerging from daily clinical practice. In this study, we assessed to what extent gender differences may characterize a large population of psychiatric inpatients. We conducted a cross-sectional study in 2 Italian teaching medical centers, which included 2358 patients who were consecutively admitted to the psychiatric emergency units. We explored and characterized gender differences for variables such as prevalence of psychiatric diagnosis, presence of suicidal ideation, suicide attempts, age at onset of psychiatric illness, presence of substance or alcohol abuse, length of stay, number of hospitalizations, presence of involuntary admission, type of discharge from the hospital, and pharmacological treatment at discharge. Female patients were primarily diagnosed with bipolar disorder or personality disorders. Female patients had a significantly higher prevalence of lifetime suicide attempts (23.1% vs. 16.5%, P<0.001) and a longer length of hospitalization (11.43±10.73d vs. 10.52±10.37d, t=-2.099, gl=2356, P=0.036) compared with male patients. Male patients had more involuntary admissions (25.1% vs. 19.7%, χ2=9.616, gl=1, P=0.002), more use of illicit substances (34.1% vs. 20.9%, χ2=51.084, gl=1, P<0.001), and higher rates of alcohol abuse (21.3% vs. 14.7%, χ2=17.182, gl=1, P<0.001) compared with female patients. Finally, antidepressants and lithium were prescribed more frequently to the female patients, whereas other mood stabilizers were more often prescribed to the male patients. Our real-world results highlighted gender differences among patients with severe mental disorders admitted to psychiatric units, and suggest further investigations that may help in understanding trajectories accompanying disabling clinical conditions.

Pattern of adult psychiatric emergencies at a tertiary care center before and after the onset of the COVID-19 pandemic.

A gap exists in published data on psychiatric emergencies presenting to Indian centers over the entire pandemic. We assessed 2,048 consecutive adult psychiatric emergencies for the period April 2019-September 2021 to compare 18 months following the onset of the pandemic, with the pre pandemic year as the control. Mean age was 33.8 ± 13.6 years, with 55% females. The proportion with ICD-10 schizophrenia and related psychotic disorders (18.9% vs 15.3%; P = 0.031), mood disorders (21.8% vs 18.1%; P = 0.038), and personality disorders (3.8% vs 2%; P = 0.018) showed a significant increase during a pandemic, while those with no diagnosable illness reduced (28.6% vs 34.3%; P = 0.006). Suicidality was the reason for referral in 43%, comparable to pre pandemic year. Those with stay ≥24 hours increased (14% vs 11%; P = 0.034). Benzodiazepines remained the commonly prescribed medication, but a notable rise was seen in mood stabilizer prescriptions.

The real-world use of mood stabilisers as an augmentation strategy in Psychosis: a mirror design

The real-world use of mood stabilisers as an augmentation strategy in Psychosis: a mirror design

Daily Variation in Sleep Duration, Affect and Emotions in Croatian Youth: An Ambulatory Assessment

Introduction: Sleep habits are related to mood stability and mental health, and adolescence may be an appropriate time to address disturbed sleep patterns because it is a critical period for the onset of psychological problems. Aims: This study had two aims, namely: to explore associations between objectively measured sleep duration and positive and negative affect, as well as specific positive and negative emotions at the within-person and between-person levels in Croatian adolescents. Methods: In the present eight-day study, 102 Croatian adolescents with an average age of 15 years reported how they felt once a day, while sleep duration was objectively measured by collecting data from an accelerometer on participants’ smartphones. Results: Multilevel analyses showed that adolescents express more positive affect (Est. = 0.10, p &lt; .050) and feel less distracted (Est. = -0.12, p &lt; .050) and happier (Est. = 0.11, p &lt; .050) on days when they sleep longer, with a multiverse analysis suggesting that these results are moderately robust. In addition, they express higher levels of negative affect, stress and distraction on school days, and boys seem to experience more positive and fewer negative emotions. Conclusions: A better understanding of daily variations in sleep duration, sleep quality, and affect would promote the development of individualized, particularly smartphone-based, sleep interventions. Such interventions could be a valuable tool for preventing mental health problems in adolescence.

Aspects of the Use of Lithium Particles in the Treatment of Bipolar Disorder

Bipolar Disorder (BD) is characterized by chronic and complex disturbances, featuring periods of depression and phases of mania or hypomania. Considering the studies already conducted, it is important to highlight the efficacy of lithium in individuals, especially in relapse prophylaxis, acute mani a phases, and suicide prevention. Thus, this article aims to address various aspects related to the intrinsic relationship between Bipolar Disorder and the use of lithium, specifically for the maintenance therapy of this condition; to explore the mechanism of action of lithium, demonstrating the benefits of this therapy so that professionals and students in the field can gain a clearer understanding of the subject and evaluate the effectiveness of continuous lithium particle use in treatment. This work is based on a literature review conducted on the Pubmed and Scielo databases from 2018 to 2023. The descriptors used were lithium, treatment, and bipolar disorder. In this context, the review of studies on lithium is essential for healthcare proof essionals and the families of individuals to understand the importance of this substance in maintaining mood stability in patients.

Patterns of ingestion of rats during chronic oral administration of lithium chloride

Chronic lithium administration to rodents is used to explore the potential neural mechanisms of mood stabilization, as well as to model the side effects of chronic lithium on multiple organ systems. Oral administration of lithium in the maintenance diet or drinking water is convenient, but lithium can acutely affect intake and it can mediate acquisition of conditioned taste aversions (CTA). We compared ad libitum food and fluid intake by male rats with LiCl or NaCl solutions as their sole source of fluid across 20 days, with a commonly used dosage of LiCl (24 mM: 1 g / L LiCl). To quantify the pattern of intake, rats were housed in cages equipped with lickometers to detect licks and infrared photobeams to detect food access with 6-s resolution. To determine if rats formed a CTA to LiCl, they were subsequently tested with access to NaCl. Rats showed an immediate avoidance of the LiCl solution, as seen on the first day of access by an increased latency to initiate drinking and a decreased size of drinking bouts. Rats showed a differential response to LiCl vs. NaCl after as few as 5 licks. Chronic consumption of LiCl solution led to significantly decreased food and fluid intake compared to baseline, with concomitant weight loss. The decreased intake was realized by marked changes in the pattern of drinking and feeding bouts: a decrease in per-lick volume and a decrease in licks per drinking bout, and an increase in feeding bout duration resulting in an overall decrease in eating rate. Conversely, chronic NaCl access led to an increase in drinking bout number and licks/bout. The avoidance of LiCl was likely a combination of toxic effects of ingested LiCl and rapid acquisition of a learned aversion to the taste of LiCl, as shown by an extinguishable generalized aversion to NaCl solution during subsequent NaCl test days. The marked effect of chronic oral LiCl on ingestion may impact the oral dosing of lithium as well as the rat's metabolic status.

Непсихотичні психічні розлади у пацієнтів з хронічними соматичними неінфекційними захворюваннями в умовах перманентного стресу: роль метаболічної терапії

bstract. The article discusses the current issues of comorbidity between mental disorders and chronic non-infectious somatic diseases, highlighting the importance of a multidisciplinary patient-centered approach in the treatment of these conditions. Additionally, in light of the negative impact of the Russian military aggression on the mental health of Ukrainians, this paper presents the positive experience of using the dietary supplement Cognitium® in a regimen of 1 ampule twice a day as an additional therapy for non-psychotic mental disorders in adult patients with chronic somatic diseases under conditions of chronic stress. The positive impact of Cognitium® was noted in the reduction of affective, cognitive and somatoform symptoms, specifically: decreasing in the level of anxiety and depression, mood stabilization, improvement of concentration and memorization of new information, increasing energy levels, restoration of sleep and appetite.

Valproic Acid in Pregnancy Revisited: Neurobehavioral, Biochemical and Molecular Changes Affecting the Embryo and Fetus in Humans and in Animals: A Narrative Review.

Valproic acid (VPA) is a very effective anticonvulsant and mood stabilizer with relatively few side effects. Being an epigenetic modulator, it undergoes clinical trials for the treatment of advanced prostatic and breast cancer. However, in pregnancy, it seems to be the most teratogenic antiepileptic drug. Among the proven effects are congenital malformations in about 10%. The more common congenital malformations are neural tube defects, cardiac anomalies, urogenital malformations including hypospadias, skeletal malformations and orofacial clefts. These effects are dose related; daily doses below 600 mg have a limited teratogenic potential. VPA, when added to other anti-seizure medications, increases the malformations rate. It induces malformations even when taken for indications other than epilepsy, adding to the data that epilepsy is not responsible for the teratogenic effects. VPA increases the rate of neurodevelopmental problems causing reduced cognitive abilities and language impairment. It also increases the prevalence of specific neurodevelopmental syndromes like autism (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). High doses of folic acid administered prior to and during pregnancy might alleviate some of the teratogenic effect of VPA and other AEDs. Several teratogenic mechanisms are proposed for VPA, but the most important mechanisms seem to be its effects on the metabolism of folate, SAMe and histones, thus affecting DNA methylation. VPA crosses the human placenta and was found at higher concentrations in fetal blood. Its concentrations in milk are low, therefore nursing is permitted. Animal studies generally recapitulate human data.

Factors Associated With Physical Restraints in a Psychiatric Unit in Japan: a Retrospective Study.

To identify factors associated with the use and duration of physical restraint (PR) in a psychiatric unit in Japan. Medical records of 1308 patients admitted first time to the psychiatric emergency unit of Showa University Northern Yokohama Hospital between 1 January 2014 and 31 December 2021 were retrospectively reviewed. Data collected included patient age, sex, outpatient treatment, living arrangements, disability pension status, diagnosis (based on ICD-10), and psychotropic medication use at admission (chlorpromazine equivalent dose, imipramine equivalent dose, diazepam equivalent dose, and number of mood stabilisers administered). Logistic regression analysis and multiple regression analysis were used to identify factors associated with the use and duration of PR, respectively. Of 1308 patients, 399 (30.5%) were subjected to PR and 909 (69.5%) were not. Among the 399 patients subjected to PR, 54 were excluded from the multiple regression analysis for duration of PR as they remained subject to PR on the day of discharge. The remaining 345 patients were subject to PR for a median of 10 days. PR utilisation was associated with male sex (odds ratio [OR] = 1.420), treatment at our hospital (OR = 0.260), treatment at other hospitals (OR = 0.645), F3 diagnosis (depression) [OR = 0.290], F4-9 diagnosis (OR = 0.309), and imipramine equivalent dose at admission (unit OR = 0.994). The log-transformed duration of PR was independently associated with the age group of 50 to 69 years (β = 0.248), the age group of ≥70 years (β = 0.274), receiving a disability pension (β = 0.153), an F1 diagnosis (β = -0.187), an F4-9 diagnosis (β = -0.182), chlorpromazine equivalent dose at admission (β = 0.0004), and number of mood stabilisers administered at admission (β = -0.270). Identifying factors associated with the use and duration of PR may lead to reduction in the use and duration of PR.

The relationship between familial-genetic risk and pharmacological treatment in a Swedish national sample of patients with major depression, bipolar disorder, and schizophrenia.

Using Swedish registers, we examine whether the prescription of and the response to antidepressants (AD), mood stabilizers (MS), and antipsychotics (AP) in the treatment of, respectively, major depression (MD), bipolar disorder (BD), and schizophrenia (SZ), are influenced by familial-genetic risk. We examined individuals born in Sweden 1960-1995 with a first diagnosis of MD (n = 257,177), BD (n = 23,032), and SZ (n = 4248) from 2006 to 2018. Drug classes and Defined Daily Dose (DDD) were obtained from the Pharmacy register using the Anatomical Therapeutic Chemical system. We utilized the Familial Genetic Risk Scores (FGRS) calculated from morbidity risks in first- through fifth degree relatives. Treatment with antidepressants (AD) in MD, mood-stabilizers (MS) in BD, and antipsychotics (AP) in SZ were associated with significantly higher disorder-specific familial-genetic risks. Using dosage trajectory analysis of AD, MS, and AP treatment for MD, BD, and SZ, respectively, familial-genetic risk was positively associated with higher and/or increasing drug dosages over time. For MD and BD, examining cases started on the most common pharmacologic treatment class (SSRIs for MD and "other anti-epileptics" for BD), familial-genetic risks were significantly lower in those who did not versus did later receive treatment from other AD and MS classes, respectively. Higher familial-genetic risk for BD predicted switching AD medication in cases of MD. Among pharmacologically treated cases of BD, familial-genetic risk was significantly higher for those treated with lithium. In a large population-based patient cohort, we found evidence of a wide-spread association between higher familial-genetic risk and i) increased likelihood of receiving pharmacologic treatment but 2) responding more poorly to it-as indicated by a switching of medications -- and/or requiring higher doses. Further investigations into the clinical utility of genetic risk scores in the clinical managements of MD, BD, and SZ are warranted.