Sleep alterations as a function of 88 health indicators.

BACKGROUND: Alterations in sleep have been described in multiple health conditions and as a function of several medication effects. However, evidence generally stems from small univariate studies. Here, we apply a large-sample, data-driven approach to investigate patterns between in sleep macrostructure, quantitative sleep EEG, and health. METHODS: We use data from the MrOS Sleep Study, containing polysomnography and health data from a large sample (N = 3086) of elderly American men to establish associations between sleep macrostructure, the spectral composition of the electroencephalogram, 38 medical disorders, 2 health behaviors, and the use of 48 medications. RESULTS: Of sleep macrostructure variables, increased REM latency and reduced REM duration were the most common findings across health indicators, along with increased sleep latency and reduced sleep efficiency. We found that the majority of health indicators were not associated with objective EEG power spectral density (PSD) alterations. Associations with the rest were highly stereotypical, with two principal components accounting for 85-95% of the PSD-health association. PC1 consists of a decrease of slow and an increase of fast PSD components, mainly in NREM. This pattern was most strongly associated with depression/SSRI medication use and age-related disorders. PC2 consists of changes in mid-frequency activity. Increased mid-frequency activity was associated with benzodiazepine use, while decreases were associated with cardiovascular problems and associated medications, in line with a recently proposed hypothesis of immune-mediated circadian demodulation in these disorders. Specific increases in sleep spindle frequency activity were associated with taking benzodiazepines and zolpidem. Sensitivity analyses supported the presence of both disorder and medication effects. CONCLUSIONS: Sleep alterations are present in various health conditions.

Challenges in defining treatment-resistant mania in adults: A systematic review.

OBJECTIVES: To review the definitions of treatment-resistant mania (TRM) in the literature and propose criteria for an operationalized definition. METHODS: A systematic search of five databases (MEDLINE, EMBASE, PsychInfo, Cochrane Central, and CINAHL) and data extraction of eligible articles. RESULTS: In total, 47 articles addressing the concept of TRM were included, comprising 16 case reports, 11 case series, 3 randomized clinical trials, 8 open-label clinical trials, 1 experimental study, 7 narrative reviews, and 1 systematic review. While reviews discussed several challenges in defining TRM, definitions varied substantially based on different criteria for severity of mania, duration of mania, and use of specific therapeutic agents with minimal dosages and duration of treatment. Only a handful of the reviewed articles operationalized these criteria. CONCLUSION: While the concept of TRM has been discussed in the literature for over three decades, we could not find an agreed-upon operationalized definition based on specific criteria. We propose and discuss a possible definition that could be used by clinicians to guide their practice and by researchers to assess the prevalence of TRM and develop and test interventions targeting TRM.

Off-label psychopharmacological interventions for autism spectrum disorders: strategic pathways for clinicians.

The prevalence of autism spectrum disorder (ASD) continues to see a trend upward with a noticeable increase to 1 in 36 children less than 8 years of age in the recent MMWR. There are many factors linked to the substantially increased burden of seeking mental health services, and clinically these individuals are likely to present for impairments associated with co-occurring conditions. The advances in cutting-edge research and the understanding of co-occurring conditions in addition to psychosocial interventions have provided a window of opportunity for psychopharmacological interventions given the limited availability of therapeutics for core symptomatology. The off-label psychopharmacological treatments for these co-occurring conditions are central to clinical practice. However, the scattered evidence remains an impediment for practitioners to systematically utilize these options. The review collates the crucial scientific literature to provide stepwise treatment alternatives for individuals with ASD; with an aim to lead practitioners in making informed and shared decisions. There are many questions about the safety and tolerability of off-label medications; however, it is considered the best practice to utilize the available empirical data in providing psychoeducation for patients, families, and caregivers. The review also covers experimental medications and theoretical underpinnings to enhance further experimental studies. In summary, amidst the growing clinical needs for individuals with ASD and the lack of approved clinical treatments, the review addresses these gaps with a practical guide to appraise the risk and benefits of off-label medications.

Ethical considerations for psychedelic-assisted therapy in military clinical settings.

Psychedelic treatments, particularly 3,4-methylenedioxymethamphetamine (MDMA)-assisted and psilocybin-assisted therapies, have recently seen renewed interest in their clinical potential to treat various mental health conditions. Clinical trials for both MDMA-assisted and psilocybin-assisted therapies have shown to be highly efficacious for post-traumatic stress disorder and major depression. Recent research trials for psychedelic-assisted therapies (PAT) have demonstrated that although they are resource-intensive, their effects are rapid-acting, durable and cost-effective. These results have generated enthusiasm among researchers seeking to investigate psychedelic therapies in active-duty service members of the US military, particularly those with treatment refractory mental health conditions. At the same time, psychedelics remain in early stages of clinical investigation, have not yet achieved regulatory approval for general clinical use and may confer unique psychological and neurobiological effects that could raise novel ethical considerations when treating active-duty service members. Should psychedelics achieve regulatory approval, military relevant considerations may include issues of access to these treatments, appropriate procedures for informed consent, confidentiality standards, and possible unanticipated mental health risks and other psychological sequelae. A service member's deployability, as well as their ability to return to full military duty following PAT, may also be of unique concern. The authors argue that MDMA-assisted therapy currently represents a promising treatment that should be more rapidly investigated as a clinical therapy for service members while still taking a measured approach that accounts for the many military-specific uncertainties that remain.

Examining daily stimulant medication use and sleep in adolescents with ADHD.

Research has been inconclusive as to whether stimulant treatment causes or exacerbates sleep problems in adolescents with ADHD. This study examined sleep differences in adolescents with ADHD as a function of stimulant use. Participants were adolescents with ADHD (N = 159, ages 12-14). Parents reported on receipt of stimulant treatment (n = 92, 57.86%; n = 47 amphetamines, n = 45 methylphenidate). Adolescents wore actigraphs and completed daily diaries assessing sleep and daily use of stimulants for 2 weeks. Sleep parameters included daily-reported bedtime, sleep onset latency (SOL), sleep duration, daytime sleepiness, and difficulty waking the following morning; and actigraphy-measured sleep onset time, total time in bed, and sleep efficiency. We estimated between- and within-individual associations between stimulant medication use and sleep indices with all stimulants, after removing adolescents using sleep aids and weekend days, and as a function of stimulant type. Adolescent sleep did not differ between those receiving and not receiving stimulant treatment. Within individuals using stimulants, we largely observed no significant differences between medicated and unmedicated days, though findings were most often significant for school days only. Small effects were found indicating longer SOL, later sleep onset time, and more daytime sleepiness related to medication use. In contrast, there were slight improvements to sleep duration and sleep efficiency related to methylphenidate use, though methylphenidate was also associated with later sleep onset time and more daytime sleepiness. Given the inconsistent and small effects, findings suggest that stimulant medication may impact sleep, but does not appear to be a primary contributor to sleep problems in adolescents with ADHD.

Exploring the Therapeutic Potential of Terpenoids for Depression and Anxiety.

This review focus on the terpenoids as potential therapeutic agents for depression and anxiety disorders, which naturally found in a variety of plants and exhibit a wide range of biological activities. Among the terpenoids discussed in this review are α-pinene, ß-caryophyllene, α-phellandrene, limonene, ß-linalool, 1, 8-cineole, ß-pinene, caryophyllene oxide, p-cymene, and eugenol. All of these compounds have been studied extensively regarding their pharmacological properties, such as neuroprotective effect, anti-inflammation, antibacterial, regulation of neurotransmitters and antioxidant effect. Preclinical evidence are reviewed to highlight their diverse mechanisms of action and therapeutic potential to support antidepressant and anxiolytic properties. Additionally, challenges and future directions are also discussed to emphasize therapeutic utility of terpenoids for mental health disorders. Overall, this review provides a promising role of terpenoids as novel therapeutic agents for depression and anxiety, with potential implications for the development of more effective and well-tolerated treatments in the field of psychopharmacology.

COVID-19 and mental health treatment in primary care: Impacts of a global pandemic on a psychopharmacological collaborative care management program.

OBJECTIVE: The COVID-19 pandemic has had a profound impact on individuals with mental health (MH) disorders and on the delivery of MH services. Studies examining treatment models which did not require substantial changes to the delivery of services during pandemic restrictions, such as collaborative care management (CoCM) programs are minimal. Therefore, a longitudinal retrospective cohort analysis was conducted to examine the impacts of the COVID-19 pandemic on a psychopharmacological CoCM program. METHOD: Data was collected on all U.S. Veterans enrolled in a CoCM program at a large VA during the first 10 months of the COVID-19 pandemic and compared to a one-year prior date matched control group. Treatment in the program pre-COVID vs. treatment during the pandemic was compared in relation to baseline symptomatology, improvements in MH symptoms, and program adherence. RESULTS: 462 Veterans were referred during the control dates, compared to 351 during the pandemic. Veterans enrolled during the first four months of each study arm, done to allow for a minimum of 6 months of follow up data, had no differences in baseline symptoms of depression or anxiety. Veterans receiving care during the pandemic had higher rates of program completion than pre-pandemic controls. COVID-era Veterans had higher rates of depression response than controls, and no differences were observed in depression remission, anxiety response, or anxiety remission. CONCLUSIONS: Psychopharmacological CoCM treatment models can successfully manage depression and anxiety with no observed decrease in the effectiveness of this intervention even during periods of unprecedented disruptions to the delivery of MH services.

Evaluation of postoperative delirium in geriatric patients given acetaminophen with and without melatonin: A retrospective cohort study.

OBJECTIVE: Postoperative delirium has many consequences and should be prevented when possible. Non-opioid pain treatments have known delirium prevention benefits, while melatonin has promising prevention data in non-surgical populations. The incidence of postoperative delirium was retrospectively compared in patients prescribed acetaminophen with and without melatonin following orthopedic surgery. METHODS: Retrospective data was analyzed in adults ≥65-years-old who were hospitalized within one health system following an orthopedic procedure. Patients receiving at least acetaminophen 1000 mg/day with and without melatonin 1 mg/day for at least 48 hours perioperatively were included. Patients were excluded if they had prior delirium, an intensive care unit placement >24 hours, or other risk factors for developing delirium to reduce confounders. The primary outcome was delirium incidence or positive CAM-ICU score. Key secondary endpoints included hospital length of stay and 30-day hospital readmission. RESULTS: Two hundred patients were assessed, and 134 patients were included in the analysis (ie, 66 acetaminophen plus melatonin, 68 acetaminophen alone). There was a lower rate of delirium when comparing the combination vs acetaminophen alone (5% vs 25%; P = 0.001). There were no differences in 30-day readmission. Patients taking the combination had a longer length of stay than acetaminophen alone (5 vs 4 days; P = 0.04). CONCLUSION: Geriatric patients taking acetaminophen plus melatonin after orthopedic surgery had a significantly lower risk of delirium than patients receiving acetaminophen alone. Using combination melatonin and acetaminophen before orthopedic surgery is a promising delirium prevention strategy and should be considered in future prospective trials.

Impact of Psychiatric Pharmacist-Led Psychopharmacology Didactics for Psychiatry Residents.

OBJECTIVE: The purpose of this study is to explore the impact of board-certified psychiatric pharmacist (BCPP)-led psychopharmacology lectures to psychiatry residents and fellows. METHODS: Surveys were administered to psychiatry residents and geriatric psychiatry fellows at two teaching institutions between Fall 2021 and Spring 2023, including two distinct residency programs and one fellowship program. The survey consisted of three quantitative questions and one qualitative question soliciting open-ended constructive feedback. RESULTS: Of 39 participants (response rate: 80%), 100% strongly agreed that learning from a BCPP enhanced their learning of psychopharmacology concepts. Additionally, 100% strongly agreed they would recommend psychopharmacology lectures from a BCPP to other psychiatry residents and that concepts taught by the BCPP were applicable to their clinical practice. Qualitative feedback indicated valuing pharmacist input and stated preference to learn from medication-experts on psychopharmacology topics. CONCLUSIONS: Integrating BCPPs into psychiatry resident/fellow didactic training is well received by psychiatry residents and may simultaneously enhance education of psychopharmacologic concepts in addition to enrichment of interprofessional experiences by increased routine exposure to working directly with a clinical pharmacist. Program directors are encouraged to meet with BCPPs at their respective institutions to discuss opportunities for collaboration.

Cosmetic psychiatry: A concept in urgent need of consideration.

OBJECTIVE: To explore the concept of, ethics surrounding, and arguments for and against cosmetic psychiatry. CONCLUSIONS: Cosmetic psychiatry may be defined as the science and practice of interventions that subjectively enhance the mental states of healthy people. Cosmetic medicine (including surgery) is a professionally and socially accepted part of contemporary medical practice; cosmetic psychiatry is not. Like cosmetic medicine, there are significant risks associated with cosmetic psychiatry. There is an urgent need for a broader conversation about this emerging clinical reality.

Implementation and Evaluation of Educational Workshops to Increase Primary Care Provider and Medical Student Comfort in Psychiatric Care.

OBJECTIVE: Mental health treatment is often initiated in primary care settings, but many primary care providers (PCPs), residents, and medical students report discomfort in managing psychiatric conditions. This study evaluated the effect of an educational workshop that featured an evidence-based psychopharmacology clinical decision support tool (CDST) on trainee confidence and willingness to treat psychiatric conditions. METHODS: Participants completed pre- and post-workshop surveys. Nine months after the workshop, a subset of trainees participated in a focus group. RESULTS: Of the participants, 62.5% of the obstetrics-gynecology (OB-GYN) resident physicians (10/16) and 100% of the medical students (18/18) completed both pre- and post-surveys. Following the workshop, OB-GYN resident physicians reported significantly improved confidence in treating psychiatric disorders (p < 0.001), sense of having psychiatric support tools (p < 0.001), and knowledge of treating psychiatric disorders (p = 0.021). Medical students reported significantly improved confidence in treating psychiatric disorders (p < 0.001), willingness to devise treatment plans for psychiatric disorders (p = 0.024), sense of having psychiatric support tools (p < 0.001), knowledge of treating psychiatric disorders (p < 0.001), and comfort in presenting a psychiatric treatment plan to an attending (p = 0.003). Most focus group participants (93.75%; 15/16) reported that they continued to use the CDST, and it increased their confidence in formulating psychiatric treatment plans. CONCLUSIONS: These findings suggest that educational workshops that introduce high-quality psychopharmacology CDSTs may be an effective method for improving provider comfort in treating psychiatric disorders.

Trends in the nonmedical misuse of benzodiazepines and Z-hypnotics among school-aged adolescents (2016-2021): gender differences and related factors.

BACKGROUND: The misuse of psychotropic medication has increased during the past decade, especially among adolescents. The aim of our study was to describe the prevalence and patterns of the nonmedical use of benzodiazepines (BDZ) and Z-hypnotics among school-aged adolescents through the lens of sex. In addition, we sought to analyze the temporal evolution of the nonmedical use of these drugs during the period 2016-2021. METHODS: The temporal evolution of the nonmedical use of these drugs was analyzed based on survey data collected in 2016, 2018 and 2021, which includes the first years of the COVID-19 pandemic. To assess the possible effect of the COVID-19 pandemic, the year at survey was conducted was introduced as a categorical variable. We used data from the Spanish State Survey on Drug Use in Secondary Education, which covers drug use among students aged 14-18 years. Using multivariate logistic regression models, we estimated the independent effect of different variables (sociodemographic data, use of other psychoactive substances, risk perception and availability) on the nonmedical use of BDZ and Z-hypnotics. RESULTS: In total, survey data from 95,700 adolescents were included in our analysis. The nonmedical use of BDZ and Z-hypnotics increased among adolescents during the study period. The adjusted odds ratio (AOR) from 2016 to 2018 was 1.11 (95% CI 0.94-1.31) and from 2018 to 2021 the AOR was 1.26 (95% CI 1.08-1.46), using 2016 and 2018, respectively, as reference years. The nonmedical use of BDZ and Z-hypnotics was more likely in adolescent girls than boys (AOR = 2.11). The nonmedical use of prescription opioids (AOR = 3.44), novel psychoactive substances and other illicit psychoactive drugs (AOR = 4.10) were risk factors for the nonmedical use of BDZ and Z-hypnotics in both sexes. Use of cannabis (AOR = 1.38) was a predictor of nonmedical use in female adolescents only. CONCLUSIONS: This study shows that the trend of the nonmedical use of BDZ and Z-hypnotics among school-aged adolescents in Spain increased between 2016 and 2021. Among adolescents aged 14 to 18, the probability of nonmedical use of these psychoactive substances was twice as high for female adolescents as for male adolescents.

Cheerfulness in the history of psychiatry.

In 1762, Louis-Antoine Marquis de Caraccioli (1719-1803), a prolific writer of the eighteenth century, dedicated a book to a psychological theme that medicine has forgotten: 'gaité' in French, which we will translate as 'cheerfulness'. At the beginning of the nineteenth century, this work inspired two doctoral theses in medicine, one defended in Montpellier, the other in Paris. In their texts, Louis Monferran (1785-?) and Vincent Rémi Giganon (1794-1857) explored the therapeutic benefits of the medical prescription of cheerfulness. In addition to lifestyle recommendations, they focused on the psychotropic substances available to them: alcohol, coca, hemp and opiates. In an original and novel way, Giganon introduced and recommended 'le gaz oxydule d'azote inspiré', or inhaled nitrous oxide gas.

Dopaminergic Modulation of Dynamic Emotion Perception.

Emotion recognition abilities are fundamental to our everyday social interaction. A large number of clinical populations show impairments in this domain, with emotion recognition atypicalities being particularly prevalent among disorders exhibiting a dopamine system disruption (e.g., Parkinson's disease). Although this suggests a role for dopamine in emotion recognition, studies employing dopamine manipulation in healthy volunteers have exhibited mixed neural findings and no behavioral modulation. Interestingly, while a dependence of dopaminergic drug effects on individual baseline dopamine function has been well established in other cognitive domains, the emotion recognition literature so far has failed to account for these possible interindividual differences. The present within-subjects study therefore tested the effects of the dopamine D2 antagonist haloperidol on emotion recognition from dynamic, whole-body stimuli while accounting for interindividual differences in baseline dopamine. A total of 33 healthy male and female adults rated emotional point-light walkers (PLWs) once after ingestion of 2.5 mg haloperidol and once after placebo. To evaluate potential mechanistic pathways of the dopaminergic modulation of emotion recognition, participants also performed motoric and counting-based indices of temporal processing. Confirming our hypotheses, effects of haloperidol on emotion recognition depended on baseline dopamine function, where individuals with low baseline dopamine showed enhanced, and those with high baseline dopamine decreased emotion recognition. Drug effects on emotion recognition were related to drug effects on movement-based and explicit timing mechanisms, indicating possible mediating effects of temporal processing. Results highlight the need for future studies to account for baseline dopamine and suggest putative mechanisms underlying the dopaminergic modulation of emotion recognition.SIGNIFICANCE STATEMENT A high prevalence of emotion recognition difficulties among clinical conditions where the dopamine system is affected suggests an involvement of dopamine in emotion recognition processes. However, previous psychopharmacological studies seeking to confirm this role in healthy volunteers thus far have failed to establish whether dopamine affects emotion recognition and lack mechanistic insights. The present study uncovered effects of dopamine on emotion recognition in healthy individuals by controlling for interindividual differences in baseline dopamine function and investigated potential mechanistic pathways via which dopamine may modulate emotion recognition. Our findings suggest that dopamine may influence emotion recognition via its effects on temporal processing, providing new directions for future research on typical and atypical emotion recognition.

Adverse Effects of α-2 Adrenergic Agonists and Stimulants in Preschool-age Attention-deficit/Hyperactivity Disorder: A Developmental-Behavioral Pediatrics Research Network Study.

OBJECTIVES: To characterize and compare the type and frequency of a range of common and uncommon adverse effects (AEs) associated with α-2 adrenergic agonist (A2A) and stimulant treatment of attention-deficit/hyperactivity disorder at preschool-age as well as to evaluate the impact of age on common AEs. STUDY DESIGN: This was a retrospective electronic medical record review of children <72 months of age (n = 497) evaluated at outpatient developmental-behavioral pediatric practices at 7 US academic medical centers within the Developmental-Behavioral Pediatrics Research Network. Data on AEs were abstracted for children who had treatment initiated by a developmental-behavioral pediatrician with an A2A or stimulant medication between January 2013 and July 2017; follow-up was complete by February 2019. RESULTS: A2A and stimulants had distinctive AE profiles. A2A compared with stimulants had a greater proportion with daytime sleepiness and headaches; stimulants had significantly greater proportions for most other AE, including moodiness/irritability, difficulty with sleep, appetite suppression, stomachaches, skin picking/repetitive behaviors, withdrawn behavior, and weight loss. Younger age was associated with disruptive behavior and difficulty with sleep. CONCLUSIONS: Stimulants had a greater rate of most AEs compared with A2A. AE profiles, together with efficacy, should inform clinical decision-making. Prospective randomized clinical trials are needed to fully compare efficacy and AE profiles of A2A and stimulants.

Longitudinal effect of clozapine-associated sedation on motivation in schizophrenia: naturalistic longitudinal study.

Negative symptoms of schizophrenia manifest as reduced motivation and pleasure (MAP) and impaired emotional expressivity (EXP). These can occur as primary phenomena, but have also been suggested to occur secondary to other clinical factors, including antipsychotic-induced sedation. However, this relationship has not been established formally. Here, we examined the effect of antipsychotic-induced sedation (assessed via the proxy of total daily sleep duration) on MAP and EXP in a cohort of 187 clozapine-treated patients with schizophrenia followed for over 2 years on average, using multilevel regression and mediation models. MAP, but not EXP, was adversely influenced by sedation, independently of the severity of psychosis or depression. Moreover, clozapine impaired MAP indirectly by worsening sedation, but after accounting for clozapine-induced sedation, clozapine improved MAP. Our results highlight the importance of addressing sedative side-effects of antipsychotics to improve clinical outcomes.

Risk of repeated suicide attempt after redeeming prescriptions for antidepressants: a register-based study in Denmark.

BACKGROUND: It remains unclear how SSRIs and other antidepressants are associated with the risk of repeated suicide attempts. We aimed to analyse the association between redeemed antidepressant prescriptions and the risk of repeated suicide attempts, hypothesising that antidepressant treatment is associated with increased risk of repeated suicide attempts. METHODS: The study was based on Danish register data and a validated cohort of 1842 suicide attempts. We used three Cox regression models (crude, adjusted and propensity score matched) to analyse the data; these models included both static and dynamic time-dependent factors. RESULTS: 1842 individuals attempted suicide in the study period, with a total of 210 repeated attempts. Individuals redeeming antidepressant prescriptions were more likely to repeat a suicide attempt. All crude models showed all antidepressants to be significant risk factors (HR around 1.39), whereas all adjusted models showed all antidepressants to be insignificant risk factors. CONCLUSION: We found no significant increased risk of repeated suicide attempts in individuals redeeming a prescription for any antidepressant (or only SSRIs) when considering the individuals' baseline risk of repetition. This study is based on validated suicide attempts, register data, and strong epidemiology designs, but it still has some limitations, and the results should be replicated and confirmed in other studies.

Are all antidepressants the same? The consumer has a point.

BACKGROUND: Although a large variety of antidepressants agents (AD) with different mechanisms of action are available, no significant differences in efficacy and safety have been shown. However, there have been few attempts to incorporate data on subjective experiences under different AD. METHOD: We conducted a qualitative and quantitative analysis of the posts from the website www.askapatient.com from different AD. We reviewed a random sample of 1000 posts. RESULT: After applying the inclusion and exclusion criteria, we included a final sample of 450 posts, 50 on each of the most used AD: sertraline, citalopram, paroxetine, escitalopram, fluoxetine, venlafaxine, duloxetine, mirtazapine, and bupropion. Bupropion, citalopram, and venlafaxine had the higher overall satisfaction ratings. Sertraline, paroxetine, and fluoxetine had high reports of emotional blunting, while bupropion very few. Overall satisfaction with AD treatment was inversely associated with the presence of the following side-effects: suicidality, irritability, emotional blunting, cognitive disturbances, and withdrawal symptoms. After adjusting for confounders, only emotional blunting was shown to be more frequently reported by users of serotonergic agents, as compared to non-serotoninergic agents. CONCLUSION: This research points out that the subjective experience of patients under treatment should be taken into consideration when selecting an AD as differences between agents were evident. In contrast to the more frequent treatment decisions, users might prefer receiving a non-serotoninergic agent over a serotonergic one due to their lower propensity to produce emotional blunting.

The emergence, implementation, and future growth of pharmacogenomics in psychiatry: a narrative review.

Psychotropic medication efficacy and tolerability are critical treatment issues faced by individuals with psychiatric disorders and their healthcare providers. For some people, it can take months to years of a trial-and-error process to identify a medication with the ideal efficacy and tolerability profile. Current strategies (e.g. clinical practice guidelines, treatment algorithms) for addressing this issue can be useful at the population level, but often fall short at the individual level. This is, in part, attributed to interindividual variation in genes that are involved in pharmacokinetic (i.e. absorption, distribution, metabolism, elimination) and pharmacodynamic (e.g. receptors, signaling pathways) processes that in large part, determine whether a medication will be efficacious or tolerable. A precision prescribing strategy know as pharmacogenomics (PGx) assesses these genomic variations, and uses it to inform selection and dosing of certain psychotropic medications. In this review, we describe the path that led to the emergence of PGx in psychiatry, the current evidence base and implementation status of PGx in the psychiatric clinic, and finally, the future growth potential of precision psychiatry via the convergence of the PGx-guided strategy with emerging technologies and approaches (i.e. pharmacoepigenomics, pharmacomicrobiomics, pharmacotranscriptomics, pharmacoproteomics, pharmacometabolomics) to personalize treatment of psychiatric disorders.

Is intravenous valproate more efficacious than oral valproate for inpatients with bipolar I disorder with a manic or depressive episode and concomitant symptoms of opposite polarity?

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