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Abstract Background Benzodiazepines are frequently prescribed drugs; however, their prolonged use can lead to tolerance, dependence, and other adverse effects. Despite these risks, long-term use remains common, presenting a public health concern. This study aims to explore the beliefs and opinions held by the public regarding benzodiazepines, as understanding these perspectives may provide insights into their usage patterns. Methods We collected public tweets published in English between January 1, 2019, and October 31, 2020, that mentioned benzodiazepines. The content of each tweet and the characteristics of the users were analyzed using a mixed-method approach, including manual analysis and semi-supervised machine learning. Results Over half of the Twitter users highlighted the efficacy of benzodiazepines, with minimal discussion of their side effects. The most active participants in these conversations were patients and their families, with health professionals and institutions being notably absent. Additionally, the drugs most frequently mentioned corresponded with those most commonly prescribed by healthcare professionals. Conclusions Social media platforms offer valuable insights into users’ experiences and opinions regarding medications. Notably, the sentiment towards benzodiazepines is predominantly positive, with users viewing them as effective while rarely mentioning side effects. This analysis underscores the need to educate physicians, patients, and their families about the potential risks associated with benzodiazepine use and to promote clinical guidelines that support the proper management of these medications. Clinical trial number Not applicable.

Sex-related differences in psychopharmacology present unique challenges in both clinical and research settings. Recognition of sex differences in psychopharmacological treatment has increased in recent years, but a significant research gap regarding variations between men and women still exists. Biological factors, including hormonal fluctuations, genetic factors, and brain structure differences, contribute significantly to differential drug responses. Moreover, social determinants can influence the differential burden of psychiatric disorders between the sexes and may impact treatment plans. Incorporating sex as a key variable in personalized treatment programs and plans holds the potential to optimize efficacy and minimize adverse effects in psychopharmacology. Sex-related challenges in psychopharmacology necessitate a nuanced approach to treatment. Further research is needed to fully understand these differences and to develop guidelines for personalized medication management. By addressing these challenges, clinicians can improve treatment outcomes and enhance the quality of life of patients with psychiatric disorders.

Lisa Burback,1,2 Christine Forner,3 Olga Karolina Winkler,1 Huda F Al-Shamali,1 Yahya Ayoub,1 Jacquelyn Paquet,1 Myah Verghese4 1Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada; 2Neuroscience and Mental Health Institute (NMHI), University of Alberta, Edmonton, Alberta, Canada; 3Associated Counseling, Calgary, Alberta, Canada; 4Department of Neuroscience, University of Alberta, Edmonton, Alberta, CanadaCorrespondence: Lisa Burback, Department of Psychiatry, University of Alberta, 4-142A Katz Group Centre for Research, 11315 - 87 Ave NW, Edmonton, AB, T6G 2H5, Canada, Tel +1 780 342 5635, Fax +1 780 342 5230, Email burback@ualberta.caPurpose: Dissociation is a necessary part of our threat response system, common to all animal species, normally temporarily activated under conditions of extreme or inescapable threat. Pathological dissociation, however, continues to occur after the initial threat has passed, in response to reminders or inaccessibility of safety and security. Present across the spectrum of psychiatric diagnoses, recurrent dissociative symptoms are linked to severe trauma exposure, insecure attachment, treatment non-response, and maladaptive coping behaviors such as substance use, suicidality, and self-harm. However, empirical studies testing treatments specific to dissociative processes remain scarce. This narrative review summarizes existing studies and provides theoretical, neurobiological, and evolutionary perspectives on dissociative processes and treatments for pathological dissociation.Methods: A systematic search of five databases (MEDLINE, EMBASE, APA PsycINFO, CINAHL plus, Scopus) was conducted on April 13, 2023. Peer-reviewed clinical studies with adult participants, assessing intervention effects on dissociative symptoms, were included. Results were thematically analyzed and summarized.Results: Sixty-nine studies were identified, mainly focused on posttraumatic stress disorder, trauma-exposed populations, and borderline personality disorder. Psychotherapy was studied in 72.5% of studies; other interventions included medications and neurostimulation. The majority reported positive outcomes, despite the heterogeneous spectrum of interventions. However, treatment of dissociative symptoms was the primary objective in only a minority.&#x00A0Conclusion: Pathological dissociation is a complex phenomenon involving brain and body systems designed for perceiving and responding to severe threats, requiring an individualized approach. A literature is emerging regarding potentially evidence-based treatments to help those impacted by recurrent dissociative symptoms. When contextualized within a neurobiological and evolutionary perspective, these treatments can be understood as facilitating an internal and/or relational sense of safety, resulting in symptom reduction. Further studies are needed to explore effective treatments for dissociative symptoms.Keywords: derealization, depersonalization, posttraumatic stress disorder, psychotherapy, psychopharmacology, transcranial magnetic stimulation

Abstract Background Lisdexamfetamine dimesylate (LDX) has demonstrated safety and efficacy for treatment of Binge Eating Disorder (BED). However, to date, trials have not included participants with co-occurring psychiatric disorders. This study explores how LDX affects eating disorder psychopathology, symptoms of common psychiatric comorbidities of BED (ADHD, depression, anxiety), and psychological quality of life, in people with moderate to severe BED. Methods These are secondary analyses of an open-label LDX trial conducted in 41 adults (18–40 years) over eight-weeks. Participants received LDX titrated to 50 or 70 mg. Clinical assessments and self-report questionnaires were conducted at baseline and 8-week follow-up. Results Eating disorder psychopathology and psychological quality of life improved after 8-weeks of LDX. No significant group-level changes in depression, anxiety or ADHD severity scores were observed. However, the majority within the small subsets with elevated depression and ADHD symptoms experienced reduced depressive and inattentive symptom severity, respectively. Conclusions We provide proof-of-concept evidence that LDX may provide broader psychological benefits to individuals with BED, beyond reducing their BE frequency. Effects of LDX on anxiety should be monitored closely by clinicians. Early indications suggest that LDX may be effectively used in people with BED, with and without co-occurring psychiatric conditions, however tolerability may be lower in highly complex cases. Trial registration: Australian and New Zealand Clinical Trials Registry (anzctr.org.au) #ACTRN12618000623291.

BackgroundThe United States Food and Drug Administration (FDA) maintains a black-box warning for antidepressants warning of an increased risk of suicidality in children and young adults that is based on proprietary clinical trial data from study sponsors that were submitted for regulatory approval. This article aimed to assess whether the black-box warning for antidepressants is still valid today using recent drug safety data.MethodsPost-marketing adverse drug event data were obtained from the US FDA’s Adverse Event Reporting System (FAERS) for the years 2017 through 2023. Logistic regression analysis was conducted using the case versus non-case methodology and adjusted for gender, age group, drug role (primary drug, secondary drug, interacting drug, and concomitant drug), initial FDA reporting year, reporter country, and a drug*gene*age group interaction.ResultsIn the multivariate analysis, compared to fluoxetine and patients aged 25 to 64 years, children [adjusted reporting odds ratio (aROR) = 7.38, 95% CI, 6.02–9.05] and young adults (aROR = 3.49, 95% CI, 2.65–4.59) were associated with an increased risk of reporting suicidality, but not for the elderly (aROR = 0.76, 95% CI, 0.53–1.09). Relative to fluoxetine, esketamine was associated with the highest rate of reporting suicidality in children (aROR = 3.20, 95% CI, 2.25–4.54); however, esketamine was associated with a lower risk of reporting suicidality in young adults (aROR = 0.59, 95% CI, 0.41–0.84), but not significantly in the elderly (aROR = 0.77, 95% CI, 0.48–1.23). For country-specific findings, relative to the USA, the Slovak Republic, India, and Canada had the lowest risk of reporting suicidality. For the overall study population, desvenlafaxine (aROR = 0.61, 95% CI, 0.46–0.81) and vilazodone (aROR = 0.56, 95% CI, 0.32–0.99) were the only two antidepressants associated with a reduced risk of reporting suicidality.ConclusionThis study shows that with recent antidepressant drug safety data, the US FDA’s black-box warning for prescribing antidepressants to children and young adults is valid today in the USA. However, relative to the USA, 15 countries had a significantly lower risk of reporting suicidality, while 16 countries had a higher risk of reporting suicidality from 38 antidepressants and lithium.

Meldonium, a promising pharmacological agent initially developed for cardiovascular indications, has sparked considerable interest in recent years due to its potential performance-enhancing effects. This review manuscript delves into the multifaceted roles of meldonium, examining its pharmacological mechanisms, therapeutic applications, and controversial implications in medicine. Beyond its cardiovascular applications, emerging research has shed light on meldonium’s neuroprotective properties and its potential for mitigating various psychiatric conditions. Moreover, recent investigations have explored meldonium’s potential in treating neurodegenerative disorders, alcohol use disorder, and even enhancing cognitive function. However, meldonium’s journey extends beyond the realm of medicine, as its use among athletes has stirred debates surrounding performance enhancement and fair competition. The substance’s inclusion in the World Anti-Doping Agency’s (WADA) prohibited list has intensified scrutiny and raised ethical considerations regarding its use in sports. This manuscript aims to provide a comprehensive resource for researchers, clinicians, and enthusiasts alike, fostering a deeper understanding of meldonium’s complex biological interactions and its potential contributions to psychiatry.

Abstract In children and adolescents, autism spectrum disorders (ASD) and obsessive–compulsive disorders (OCD) may share similar features, such as deficits in social communication, repetitive behaviours and presence of obsession and compulsion. Studies have shown that children with OCD may exhibit the presence of ASD traits. Up to date research shows that selective serotonin reuptake inhibitors are commonly used to treat OCD, while treatment options for ASD are limited. A literature search was performed using the PubMed database and retrieving relevant papers up to December 2022. This review includes 9 case reports and 8 randomized controlled trials. The main psychopharmacological drugs used include antidepressants and antipsychotics. This review shows that the management of OCD behaviours in individuals with ASD and related conditions is of complex nature and pharmacological interventions may not be an effective method in managing this group of patients. Hence, more comprehensive research and deeper knowledge is important in optimizing pharmacological management for patients with OCD behaviours with underlying ASD.

Daniel Guinart,1– 3 Andrea Fagiolini,4 Paolo Fusar-Poli,5– 8 Giulia Maria Giordano,9 Stefan Leucht,10 Carmen Moreno,11– 13 Christoph U Correll3,14– 16 1Institut de Salut Mental, Parc de Salut Mar, Barcelona, Spain; 2Hospital Del Mar Research Institute, CIBERSAM, Barcelona, Spain; 3Department of Psychiatry, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; 4Department of Molecular Medicine, University of Siena School of Medicine, Siena, Italy; 5Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; 6Department of Psychosis Studies, King’s College London, London, UK; 7Outreach and Support in South-London (OASIS) Service, South London and Maudsley (Slam) NHS Foundation Trust, London, UK; 8Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich, Munich, Germany; 9Department of Psychiatry, University of Campania “Luigi Vanvitelli”, Naples, Italy; 10Technical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy, Munich, Germany; 11Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (LISGM), Madrid, Spain; 12Centro de Investigación Biomedica en Red (CIBERSAM), ISCIII, Madrid, Spain; 13School of Medicine, Universidad Complutense, Madrid, Spain; 14Department of Psychiatry, The Zucker Hillside Hospital, New York, NY, USA; 15Department of Child and Adolescent Psychiatry, Charité Universitatsmedizin, Berlin, Germany; 16German Center for Mental Health (DZPG), Partner Site, Berlin, GermanyCorrespondence: Christoph U Correll, Department of Psychiatry, The Zucker Hillside Hospital, 75-59 263rd Street Glen Oaks, New York, NY, 11004, USA, Email ccorrell@northwell.eduIntroduction: Schizophrenia is a severe mental illness that usually begins in late adolescence or early adulthood. Current pharmacological treatments, while acceptably effective for many patients, are rarely clinically tailored or individualized. The lack of sufficient etiopathological knowledge of the disease, together with overall comparable effect sizes for efficacy between available antipsychotics and the absence of clinically actionable biomarkers, has hindered the advance of individualized medicine in the treatment of schizophrenia. Nevertheless, some degree of stratification based on clinical markers could guide treatment choices and help clinicians move toward individualized psychiatry. To this end, a panel of experts met to formally discuss the current approach to individualized treatment in schizophrenia and to define how treatment individualization could help improve clinical outcomes.Methods: A task force of seven experts iteratively developed, evaluated, and refined questionnaire items, which were then evaluated using the Delphi method. Descriptive statistics were used to summarize and rank expert responses. Expert discussion, informed by the results of a scoping review on personalizing the pharmacologic treatment of adults and adolescents with schizophrenia, ultimately generated recommendations to guide individualized pharmacologic treatment in this population.Results: There was substantial agreement among the expert group members, resulting in the following recommendations: 1) individualization of treatment requires consideration of the patient’s diagnosis, clinical presentation, comorbidities, previous treatment response, drug tolerability, adherence patterns, and social factors; 2) patient preferences should be considered in a shared decision-making approach; 3) identified barriers to personalized care that need to be overcome include the lack of actionable biomarkers and mechanistic similarities between available treatments, but digital tools should be increasingly used to enhance individualized treatment.Conclusion: Individualized care can help provide effective, tailored treatments based on an individual’s clinical characteristics, disease trajectory, family and social environment, and goals and preferences.Keywords: psychosis, psychopharmacology, treatment, personalized, psychiatry

Bipolar disorder is a chronic illness that often onsets in early stages of life, and the first episode of bipolar disorder frequently occurs in adolescence. Pediatric bipolar disorder (PBD) has more severe symptoms and a poorer prognosis compared to bipolar disorder in adults. Due to limited data on the psychopharmacological treatment of PBD, children and adolescents have been treated primarily in consideration of the findings obtained from clinical studies performed in adults. The efficacy of the psychotropic agents seems to differ in children and adolescents compared to adults. The evidence-based psychopharmacological treatment modalities of PBD are of growing interest in children and adolescents. This review discusses current Food and Drug Administration approved medications for PBD and guidelines for PBD. The psychopharmacologic evidence and algorithms of PBD treatment relevant to different stages of bipolar disorder, including acute manic/mixed episodes, bipolar depression, and maintenance treatment are examined in this review article.

Abstract 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.

Abstract Background Cognitive impairment are among the core features of schizophrenia, experienced by up to 75% of patients. Available treatment options for schizophrenia including dopamine antagonists and traditional antipsychotic medications have not been shown to confer significant benefits on cognitive deficits. Contrary to the focus on management of positive symptoms in schizophrenia, cognitive abilities are main predictor of independent living skills, functional abilities, employment, engagement in relapse prevention, and patients' subjective sense of well‐being and quality of life. This review aims to provide a summary of recent literature on pharmacological options for the treatment of cognitive deficits in schizophrenia. Methods We conducted a literature search of studies from 2011 to 2021 across four electronic databases including PubMed, PsycInfo, MEDLINE, and Embase. Human studies using a pharmacological treatment for cognitive impairment in schizophrenia were included. Results Fifty‐eight eligible publications, representing 11 pharmacological classes, were included in this review. Major limitations involved small sample size, methodological limitations as well as heterogeneity of participants and outcome measures. Conclusions Overall evidence remains inconclusive for any pharmacological classes studied for the treatment of cognitive deficits in schizophrenia. Methodological limitations in a majority of the studies rendered their findings preliminary. We further discuss possible explanations for these findings that could guide future research.

Practice variability may represent an opportunity to improve care by identifying the differences in outcomes associated with differences in practice. To characterize differences in depression treatment outcomes among individual providers in outpatient psychiatry practices and primary care practices, we examined a longitudinal cohort derived from outpatient electronic health records from two academic medical centers and six community hospitals in Eastern Massachusetts. This cohort included antidepressant-treated individuals with an ICD-9/10 diagnosis of major depressive disorder, and deidentified health care providers treating at least 10 such patients per year between 2008 and 2022. We examined the association between individual provider prescribing characteristics and proportions of treated patients who do not follow up after initial antidepressant prescription or who achieve a stable ongoing prescription. In binomial regression models, among 104 psychiatrists, greater heterogeneity in antidepressant prescribing and lesser proportion of serotonin reuptake inhibitors (SSRIs)1 prescribed were associated with greater rates of achieving stability (for heterogeneity, adjusted odds ratio AOR, 1.55 [95 % CI, 1.22 – 2.06]; for proportion of SSRIs, AOR, 0.01 [95 % CI, 0.00–0.59]). Among 369 primary care physicians, greater volume of depression encounters per year, but not prescribing heterogeneity, was associated with greater rates of achieving stability (for encounters, AOR, 2.15 [95 % CI, 1.61 – 2.89]; for heterogeneity, AOR, 0.99 [95 % CI, 0.85 – 1.15]). Primary care and psychiatry predictors are not the same and therefore suggest potentially distinct strategies to improve clinical outcomes in each setting. Trial Registration: N/A

Background There is limited evidence to support use of fixed dose combination (FDC) drugs in the treatment of psychiatric disorders. This study aimed to examine the sales and regulatory status of psychotropic FDCs in India, in the context of two government regulatory initiatives.Methods Official documents were searched to establish an account of the initiatives and measures targeting psychotropic FDCs. This was integrated with private market data (2008 to 2020). Descriptive statistics were used to examine changes in FDC numbers/formulations and sales volumes in standard units (SU) over time.Results Psychotropic FDC sales volumes (percentage market share) increased from 0.8 billion SU (18.4%) in 2008 to 1.4 billion SU (20.1%) in 2020. The numbers (formulations) of FDCs also increased, from 28 (101) in 2008 to 33 (143) in 2020. Unapproved FDCs accounted for 69.3% of psychotropic FDC sales in 2008, decreasing slightly to 60.3% in 2020. Of 21 psychotropic FDCs considered under the regulatory initiatives, three went on to be banned, and two of these remained on the market in 2020.Conclusions Unapproved FDCs continue to account for most psychotropic FDC sales, potentially putting the public at risk because their safety and efficacy have not been evaluated.

The introduction of a new psychopharmaceutical medication instead of the previous one always poses a certain challenge. In the case of antipsychotics (AP), these problems are considerably more complicated and are mainly caused by the question of dose equivalents, but also by the pharmacokinetic properties of the drug. In the case of partial dopamine D2 agonists, an additional issue is the possibility of deterioration when switching from the previous D2 antagonists to these drugs. Cross-titration is therefore generally recommended. Finally, due to the capsule form, it is not possible to increase the dose of cariprazine by less than 1.5 mg during titration. In this paper, we have presented our proposal to replace the most commonly used second-generation APs with the third-generation AP cariprazine. We have taken into account the dose equivalents, the pharmacological forms of the drugs and their pharmacokinetic and pharmacodynamic properties.

Background: Studies attempting to distinguish suicide attempters from ideators have found that impulsivity is consistently associated with attempts across the spectrum of suicidal behavior from self-harm to lethal suicidal behavior. Impulsivity is readily assessed using complementary clinical and laboratory measures, making it a viable target for pharmacological strategies to prevent suicide risk. Lithium reduces suicidal behavior across diagnoses, and has been implicated in the reduction of impulsivity triggered by stress mediated phosphatidylinositol turnover. We used a placebo controlled cross-over design to study the effects of repeated lithium dosing on risk factors predisposing to suicidal behavior. Methods: 15 patients with a recent (past year) medically severe suicide attempt (MSSA) (37.5% male, 40.13 ± 13.66 years) received lithium carbonate and matching pill placebo separately in a randomized double-blind crossover design administered six weeks apart. To test the effect of lithium on measures of impulsivity and arousal, participants completed the Immediate Memory Task (IMT), Internal State Scale (ISS), and the Time Perception Task (TPT). We conducted separate analyses for each variable using repeated measures analysis of covariance. Results: Lithium dosing was associated with increased IMT response latency (p = .017, pη2 = 0.23), and decision bias (p = .048, pη2 = 0.21). Lithium did not significantly alter time perception or activation. Conclusions: Our results suggest that lithium may reduce risk in MSSA survivors by increasing the response latency and increasing conservative response bias during decision-making. Future studies should conduct long-term follow-ups with adjunct behavioral therapy with lithium on factors contributing to suicidal behavior.

Key Clinical Message Elective amputation as a treatment for Body Integrity Identity Disorder (BIID) or Body Integrity Dysphoria (BID) where noninvasive treatments prove ineffective and the patient's distress is substantial, may permit long‐term remission of symptoms at follow‐up. Abstract We present the one‐year follow‐up post‐surgery of an ambidextrous male who sought elective amputation of his left hand's fourth and fifth fingers after an unsuccessful trial of psychotherapy and pharmacotherapy for Body Integrity Dysphoria. He had no psychiatric comorbidities. At one‐year follow‐up, his dysphoria was still in remission. He exhibited full adaptation in his social and occupational life, demonstrating increased ease in hand use compared to pre‐amputation. He reported sleeping well, happiness, good health and continued acceptance by friends and family. This one‐year post‐surgery follow‐up, at 22 years old, underscores the efficacy of amputation as a curative treatment, high patient satisfaction, and the quality of life gained through the procedure.

Although antipsychotics that act via monoaminergic neurotransmitter modulation have considerable therapeutic effect, they cannot completely relieve clinical symptoms in patients suffering from psychiatric disorders. This may be attributed to the limited range of neurotransmitters that are regulated by psychotropic drugs. Recent findings indicate the need for investigation of psychotropic medications that target less-studied neurotransmitters. Among these candidate neurotransmitters, lactate is developing from being a waste metabolite to a glial-neuronal signaling molecule in recent years. Previous studies have suggested that cerebral lactate levels change considerably in numerous psychiatric illnesses; animal experiments have also shown that the supply of exogenous lactate exerts an antidepressant effect. In this review, we have described how medications targeting newer neurotransmitters offer promise in psychiatric diseases; we have also summarized the advances in the use of lactate (and its corresponding signaling pathways) as a signaling molecule. In addition, we have described the alterations in brain lactate levels in depression, anxiety, bipolar disorder, and schizophrenia and have indicated the challenges that need to be overcome before brain lactate can be used as a therapeutic target in psychopharmacology.

Abstract Background The COVID-19 pandemic has impacted many aspects of everyday life, including the (mental) healthcare system. An increase in depression and anxiety symptoms has been reported worldwide, and is particularly pronounced in females and young people. We aimed to evaluate changes in prescription rates for psychopharmacological medication, which is often used to treat depression and anxiety. Method Based on data from the Austrian public health insurance institutions, we conducted an interrupted time series analysis of antidepressants and antipsychotics, comparing prescription rate developments before and throughout the COVID-19 pandemic (2013 to 2021), with a special focus on adolescents (10–19 years) in comparison to the general population. Data were based on all public prescriptions in the outpatient sector nationwide. Age- and sex-stratified time-series models were fitted to the pre-COVID period (first quarter (Q1) of 2013 to second quarter (Q2) of 2020). These were used to generate forecasts for the period from the third quarter (Q3) of 2020 to the fourth quarter (Q4) of 2021, which were subsequently compared to observed developments in order to assess significant deviations from the forecasted development paths. Results For the majority of the evaluated period, we found a significant excess of antidepressant prescriptions among both male and female adolescents (10–14 and 15–19 years) compared to the forecasted development path, while the general population was mostly within 97.5% confidence intervals of the forecasts. Regarding antipsychotics, the interrupted time series analysis revealed a significant excess in the group of female adolescents in almost all quarters, which was especially pronounced in the 15–19 age group. Prescription rates of antipsychotics in the general population only showed a significant excess in two quarters. Conclusion Increased rates of adolescents receiving psychopharmacological treatment echo the epidemiological trends of an increase in depression and anxiety symptoms reported in the literature. This increase is especially pronounced in female adolescents.

Key Clinical Message In select cases of body integrity identity disorder or body integrity dysphoria where noninvasive treatments prove ineffective and the patient's distress is substantial, elective amputation may serve as a viable and highly satisfying intervention, aligning the individual's physical self with their perceived identity. Abstract This case report presents an illustration of body integrity identity disorder (BIID), wherein a 20 years old ambidextrous male experiencing profound distress over his left hand's fourth and fifth fingers sought elective amputation after noninvasive treatments proved unsuccessful. Despite ethical concerns and limited literature on BIID, the decision to proceed with elective surgery was based on the patient's sustained desire, potential risks of self‐harm, and the distinct presentation involving two fingers rather than a complete limb. Following amputation, the patient experienced immediate relief, with nightmares ceasing, emotional distress subsiding, and improved functionality. This case highlights the potential efficacy and patient satisfaction associated with elective amputation in specific BIID presentations, shedding light on the unique challenges faced by affected individuals and emphasizing the importance of understanding, support, and inclusive healthcare practices.

IntroductionThe standard approach to treatment in psychiatry is known as “treatment as usual” (TAU), in which the same types of treatment are administered to a group of patients. TAU often requires numerous dose adjustments and medication changes due to ineffectiveness and/or the occurrence of adverse drug reactions (ADRs). This process is not only time-consuming but also costly. Antipsychotic medications are commonly used to treat various psychiatric disorders such as schizophrenia and mood disorders. Some of the inter-individual differences in efficacy and ADRs observed in psychopharmacotherapy can be explained by genetic variability in the pharmacokinetics and pharmacodynamics of antipsychotics. A better understanding of (in)efficacy and possible ADRs can be achieved by pharmacogenetic analysis of genes involved in the metabolism of antipsychotics. Most psychotropic drugs are metabolized by genetically variable CYP2D6, CYP1A2, CYP3A4, and CYP2C19 enzymes. To demonstrate the utility of pharmacogenetic testing for tailoring antipsychotic treatment, in this paper, we present the case of a patient in whom a pharmacogenetic approach remarkably altered an otherwise intolerant or ineffective conventional TAU with antipsychotics.MethodsIn this case report, we present a 60-year-old patient with psychotic symptoms who suffered from severe extrapyramidal symptoms and a malignant neuroleptic syndrome during treatment with risperidone, fluphenazine, aripiprazole, brexpiprazole, and olanzapine. Therefore, we performed a pharmacogenetic analysis by genotyping common functional variants in genes involved in the pharmacokinetic pathways of prescribed antipsychotics, namely, CYP2D6, CYP3A4, CYP3A5, CYP1A2, ABCB1, and ABCG2. Treatment recommendations for drug–gene pairs were made according to available evidence-based pharmacogenetic recommendations from the Dutch Pharmacogenetics Working Group (DPWG) or Clinical Pharmacogenetics Implementation Consortium (CPIC).ResultsPharmacogenetic testing revealed a specific metabolic profile and pharmacokinetic phenotype of the patient, which in retrospect provided possible explanations for the observed ADRs. Based on the pharmacogenetic results, the choice of an effective and safe medication proved to be much easier. The psychotic symptoms disappeared after treatment, while the negative symptoms persisted to a lesser extent.ConclusionWith the case presented, we have shown that taking into account the pharmacogenetic characteristics of the patient can explain the response to antipsychotic treatment and associated side effects. In addition, pharmacogenetic testing enabled an informed choice of the most appropriate drug and optimal dose adjustment. This approach makes it possible to avoid or minimize potentially serious dose-related ADRs and treatment ineffectiveness. However, due to the complexity of psychopathology and the polypharmacy used in this field, it is of great importance to conduct further pharmacokinetic and pharmacogenetic studies to better assess gene–drug and gene–gene–drug interactions.

Abstract Background The present study analysed data on children and adolescents with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) who were referred to the ADHD reference centre of Scientific Institute IRCCS E. Medea (Brindisi, Italy) for ADHD pharmacotherapy initiation and monitoring overtime. The main aim of the study was to examine differences in pharmacological treatment status (i.e., treatment continuation vs discontinuation) between patients. Methods Seventy-seven children and adolescents (mean age at pharmacotherapy initiation = 9.5, standard deviation = 2.6) with ADHD received drugs treatment for ADHD at the reference center between January, 2013 and May, 2022. Demographic and clinical data were obtained from the Italian Registry for ADHD and medical records. Child Behavior Checklist (CBCL) available data were used. Results Pharmacological treatment status was examined for patients (n = 63) with at least 12 months of follow-up after the first pharmacological treatment for ADHD. After starting pharmacotherapy treatment, 77.8% (n = 49) patients were still on treatment whereas 22.2% (n = 14) discontinued it. No between group difference were observed in demographic and clinical data except for the intelligence quotient/intellectual disability and rule-breaking behavior (n = 40). Conclusions This study stressed the need of periodical assessments, monitoring difficulties with treatment and/or reasons for poor treatment compliance to provide individualized care.

Abstract Background Impulsivity is a transdiagnostic feature linked to severe clinical expression and a potential target for psychopharmacological strategies. Biological underpinnings are largely unknown, but involvement of immune dysregulation has been indicated, and the effects of psychopharmacological agents vary. We investigated if impulsivity was associated with circulating immune marker levels and with a range of psychopharmacological treatment regimens in severe mental disorders. Methods Impulsivity was assessed in a sample (N = 657) of patients with schizophrenia or schizophreniform disorder (SCZ) (N = 116) or bipolar disorder (BD) (N = 159) and healthy participants (N = 382) using the Barratt Impulsiveness Scale (BIS-11) questionnaire. Plasma levels of systemic immune markers (RANTES, IL-1RA, IL-18, IL-18BP, sTNFR-1) were measured by enzyme immunoassays. Patients underwent thorough clinical assessment, including evaluation of psychotropic medication. Associations were assessed using linear regressions. Results Impulsivity was positively associated with SCZ (p

BackgroundEvidence has increased in recent years regarding the potential for ketamine to serve as a novel treatment option for a range of conditions, particularly depression (unipolar and bipolar). However, research regarding ketamine as a potential therapeutic for Autism Spectrum Disorder (ASD) is lacking, despite high overlap with bipolar depression and theoretical foundations for its use.Case presentationA 29-year-old man with bipolar disorder and Autism Spectrum Disorder, type 2 diabetes, presented with mood swings and suicidal thoughts, and anger outbursts occurring daily. The patient was referred by a psychiatrist due to irritability and outbursts during the previous 5 months. These outbursts were unable to be controlled by the medications prescribed, included yelling and screaming, and the patient was unable to speak with the psychiatrist. The patient underwent ketamine assisted psychotherapy with 6 initial IV infusions of ketamine over a 1 month period followed by 2 booster IV ketamine infusions. Following ketamine treatment, dramatic reductions in outbursts were observed as well as reductions in anxiety, suicidality, and depression scores.ConclusionThis case study adds to the scant literature regarding ketamine treatment for individuals with bipolar disorder and ASD. We did not find ASD to be a contraindication for IV ketamine and ketamine assisted psychotherapy. Reductions in anger outbursts, anxiety, suicidality, and depression suggest ketamine treatment might be tailored to individuals with bipolar disorder and ASD, and additional systematized research is warranted. Although potential mechanisms of action are not clear, these data add to the discussion regarding clinical practice considerations and the potential for ketamine to improve quality of life and associated metrics.

Abstract Background Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians’ treatment choices for post-traumatic stress disorder (PTSD). Methods The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148). Results About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct “profiles” of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines. Conclusions Clinicians’ decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.

Introduction: The history of psychiatry encompasses the evolving concepts about the relationship between body and mind and also of the definition of normality, which depend on the knowledge and customs of different times and places. For a better understanding of this journey, this study privileged the presentation of the influential figures on the construction of psychiatric nosology and classifications mainly unfolded on a descriptive or causal basis, from psychics or somatics driving, since the western renaissance. Because of the length of this historical path, this study is divided into two parts. This paper, the first in a two-part series, is a preamble to the development of the new nosography and psychopharmacology of the 21st century, merit of the second paper in this series. Method: Narrative review based on secondary sources. Results: Part One includes a review of prior studies concluding that the psychiatric nosography construction has many stations and it passes through the 18th century more structured morbid classifications based on taxonomies of the natural sciences. Psychiatric classifications navigate the course between different psychiatric theories, often marked by inherent prejudices, alongside advances achieved in neuroscience and its intricate connections with the physiology of emotions, cognition and behaviors, shedding light on their deviations or disorders. This evolution goes in parallel with that of the macro and microanatomy, physiology, chemistry, pharmacology, genetics, internal medicine, mainly neurology, apace with evaluation techniques that also reach the Blood-oxygen-level-dependent imaging (BOLD) fMRI (functional magnetic resonance imaging) that indirectly study the action of neurotransmitters and neuronal signalling. The biologic approach stands in contrast to the psychodynamic theory, particularly dominant until roughly the mid-20th century. Conclusion: The study of psychiatric nosohistoriography helps to understand the conceptual evolution of mental illnesses and the most recent importance of psychopharmacology for this.

Introduction: The history of psychiatry encompasses the evolving concepts about the relationship between body and mind and also of the definiton of normality, which depend on the knowledge and customs of different times and places. For a better understanding of this journey, this study privileged the presentation of the main influential figures on the construction of psychiatric nosology and classifications mainly unfolded on a descriptive or causal basis, from psychics or somatics driving, since the Western Renaissance. This article, the second in a two-part series, mainly discusses the importance of psychopharmacology for a better understanding of mental disorders and their classifications. Part one is a preamble to the historical development of the new nosography and psychopharmacology. Method: Narrative review based on secondary sources. Results: The current article illustrates how the understanding of the pathophysiological mechanisms underlying mental illness improves, mainly employing the psychopharmacology that may lead to the reclassification of certain mental disorders. This natural reductionism view of the sciences must be in cooperation with an integrative understanding of the human being, as is customary in the humanities. Conclusion: The study of psychiatric nosohistoriography helps to understand the conceptual evolution of mental illnesses and the most recent importance of psychopharmacology for this.

AbstractBackground Although the costs of bipolar disorder (BD) treatments are associated with local and universal factors, data from non-Western countries remain limited. The associations between clinical features and costs of outpatient pharmacotherapy have not been well characterize. To estimate the costs of outpatient BD treatments and their associations with clinical features in a Japanese population, we investigated with special reference to the costs of medicines constituted the bulk of the total healthcare expense and were steadily increasing.Methods The Multicenter Treatment Survey for Bipolar Disorder (MUSUBI) retrospectively evaluated 3130 patients with BD who visited 176 Japanese psychiatric outpatient clinics in 2016. Clinical features and drug prescriptions were recorded, and the total daily costs of psychotropic drug treatment were calculated. The annual medical costs related to outpatient BD treatments in Japan were estimated based on the corresponding demographics. The associations between daily medical costs and patients’ clinical features were analyzed using multiple regression analysis.Results The daily costs of psychotropic drugs ranged from zero to JPY3245 (mean, JPY349 equivalent to USD32.5) and were exponentially distributed. The annual costs for outpatients BD treatments were approximately 51.9 billion Japanese yens (519 million US dollars). Subsequent multiple regression analysis revealed that social adjustment, depressive symptoms, age, rapid cycling, psychotic symptoms, and comorbid mental disorders correlated strongly with the daily cost of psychotropic drugs.Conclusion The estimated annual costs for outpatient BD treatment in Japan were equivalent to those in OECD countries (except for the US) and higher than those in some Asian countries. The cost of psychotropic treatments was associated with individual characteristics and psychopathological conditions.Key MessagesPsychotropic treatment for an outpatient with bipolar disorder has a daily cost approximately JPY350.The annual outpatient treatment cost for bipolar disorder in Japan was estimated to 51.9 billion Japanese yen in 2016.Individual characteristics and psychopathological conditions affected the cost of drug treatment.

Dopamine is thought to play a crucial role in cost-benefit decision making, but so far there is no consensus on the precise role of dopamine in decision making. Here, we review the literature on dopaminergic manipulations of cost-benefit decision making in humans and evaluate how well different theoretical accounts explain the existing body of evidence. Reduced D2 stimulation tends to increase the willingness to bear delay and risk costs (i.e., wait for later rewards, take riskier options), while increased D1 and D2 receptor stimulation increases willingness to bear effort costs. We argue that the empirical findings can best be explained by combining the strengths of two theoretical accounts: in cost-benefit decision making, dopamine may play a dual role both in promoting the pursuit of psychologically close options (e.g., sooner and safer rewards) and in computing which costs are acceptable for a reward at stake. Moreover, we identify several limiting factors in the study designs of previous investigations that prevented a fuller understanding of dopamine’s role in value-based choice. Together, the proposed theoretical framework and the methodological suggestions for future studies may bring us closer to a unifying account of dopamine in healthy and impaired cost-benefit decision making.

Objective: To review the literature from the last twenty years on pharmacological treatments for post-traumatic stress disorder to clarify questions about the efficacy and tolerability of pharmacotherapy and the superiority of one specific agent over another for creating a treatment guideline based on levels of evidence. Methods: Randomized clinical trials and systematic reviews were searched in Medline-PubMed, PsycINFO, Web of Science, Scielo, and Lilacs. The screening of the criteria established by the Transparent Reporting of Systematic Reviews and Meta-Analyses was used, followed by the analysis of risk of bias of the Critical Appraisal Skills Programme. Lastly, the level of evidence and grade of recommendation was acquired, following the Oxford Center for Evidence-based Medicine 2009 Levels of Evidence. Results: The search retrieved double-blind, randomized and placebo-controlled clinical trials. Comparative clinical trials between different drugs were also evaluated and systematic reviews on drug efficacy and meta-analyses. A total of 1.458 studies were found; 58 of these studies were pre-selected and the final sample was composed of 20 studies. Conclusions: Of the 17 drugs included, the following is the order of recommendation based on the levels of evidence established in this study - 1st sertraline; 2nd venlafaxine and paroxetine; 3rd atypical antipsychotics.

The intricate neural pathways involved in obsessive-compulsive disorder (OCD) affect areas of our brain that control executive functioning, organization, and planning. OCD is a chronic condition that can be debilitating, afflicting millions of people worldwide. The lifetime prevalence of OCD in the US is 2.3%. OCD is predominantly characterized by obsessions consisting of intrusive and unwanted thoughts, often with impulses that are strongly associated with anxiety. Compulsions with OCD encompass repetitive behaviors or mental acts to satisfy their afflicted obsessions or impulses. While these factors can be unique to each individual, it has been widely established that the etiology of OCD is complex as it relates to neuronal pathways, psychopharmacology, and brain chemistry involved and warrants further exploration.

It is known that inflammation worsen the course of schizophrenia and induce high clozapine serum levels. However, no study evaluated this change in function of clozapine daily dose in schizophrenia. We assessed the correlation between inflammation and severity symptoms in patients with schizophrenia that take and do not take clozapine. We also assessed the correlation between clozapine daily dose and inflammatory markers to patients who take this drug. Patients were recruited from Schizophrenia Ambulatory and Psychosocial Care Center of Clinical Hospital of Porto Alegre and from an association of relatives of patients with schizophrenia. Exam results, and other important clinical exam were assessed in patients record or patients were asked to show their exam in the case of outpatients. We included 104 patients, 90 clozapine users and 14 non-clozapine users. We calculate the systemic inflammatory markers [neutrophil-lymphocyte ratio (NLR), systemic immune inflammation index (SII), and the psychopathology severity by the Brief Psychiatric Rating Scaled anchored (BPRS-a)]. These variables were compared between clozapine users and non-clozapine users. It was used mean/median test according to data distributing, with study factor (SII, MLR, and PLR), the clinical outcome: severity of symptomatology (BPRS score), and clozapine daily dose as adjustment factor. Clozapine users exhibited a significantly higher neutrophil count (mean ± SD: 5.03 ± 2.07) compared to non-clozapine users (mean ± SD: 3.48 ± 1.27; p = 0.031). After controlling for comorbidity, other parameters also showed significant differences. These findings are consistent with previous studies that have demonstrated an inflammatory response following the administration of clozapine.

Introduction. Behavioral methods on laboratory animals are recognized as the main approach in studying the activity of potential psychotropic drugs and allow us to evaluate the main effects of new compounds, increase the possibility of predicting a successful outcome of future clinical trials.Text. This review article analyzes the main modern behavioral models in rodents that are widely used for screening and studying the pharmacological activity of potential psychotropic drugs. The advantages and disadvantages of each test are highlighted and complexes of behavioral methods are demonstrated that most conclusively confirm the reproducibility of the results obtained in clinical trials. The description and evaluation of behavioral methods that characterize the state of anxiety, which are used to screen for new compounds with anxiolytic activity (tests «Open field», «Dark-light chamber», «Elevated plus maze», «Sequence of rays»). The range of tests used to study cognitive functions and memory processes is widely presented (various mazes – T-shaped, U-shaped, radial maze, Barnes maze, E-maze; water mazes – Morris, T-maze) with a description of a comparative analysis and necessary conditions that ensure the reliability of information. An important direction in the field of behavioral pharmacology is the modeling of violations of social behavior and the study of approaches for its correction – the main methods necessary for the study of social behavior are presented in the review by the tests «Three-chamber social test», «Open field» extended test, etc.Conclusion. Behavioral pharmacology dictates the need for close interaction between preclinical and clinical stages of research in the framework of the development of translational medicine and the development of approaches that provide evidence for the reproducibility of the results obtained in clinical trials. It is also necessary to improve existing and develop new behavioral models of mental disorders and to search for new ways to study the mechanisms of formation of behavioral disorders.

Whereas MDD is characterized in part by changes in mood, other symptoms can also cause significant impairment, including sexual dysfunction, cognitive impairment, and fatigue. Newer antidepressants are explored with the goal of more optimally treating these non–mood-related symptoms of MDD. The 3 oral antidepressants that have been FDA-approved most recently include vortioxetine, vilazodone, and levomilnacipran. Unique features of these antidepressants are explored through 3 patient cases.

Abstract Ortho-eugenol is a synthetic derivative from eugenol, the major compound of clove essential oil, which has demonstrated antidepressant and antinociceptive effects in pioneering studies. Additionally, its effects appear to be dependent on the noradrenergic and dopaminergic systems. Depression and anxiety disorders are known to share a great overlap in their pathophysiology, and many drugs are effective in the treatment of both diseases. Furthermore, high levels of anxiety are related to working memory deficits and increased oxidative stress. Thus, in this study we investigated the effects of acute treatment of ortho-eugenol, at 50, 75 and 100 mg/kg, on anxiety, working memory and oxidative stress in male Swiss mice. Our results show that the 100 mg/kg dose increased the number of head-dips and reduced the latency in the hole-board test. The 50 mg/kg dose reduced malondialdehyde levels in the prefrontal cortex and the number of Y-maze entries compared to the MK-801-induced hyperlocomotion group. All doses reduced nitrite levels in the hippocampus. It was also possible to assess a statistical correlation between the reduction of oxidative stress and hyperlocomotion after the administration of ortho-eugenol. However, acute treatment was not able to prevent working memory deficits. Therefore, the present study shows that ortho-eugenol has an anxiolytic and antioxidant effect, and was able to prevent substance-induced hyperlocomotion. Our results contribute to the elucidation of the pharmacological profile of ortho-eugenol, as well as to direct further studies that seek to investigate its possible clinical applications.

A transition in viewing mental disorders from conditions defined as a set of unique characteristics to one of the quantitative variations on a collection of dimensions allows overlap between disorders. The overlap can be utilized to extend to treatment approaches. Here, we consider the overlap between attention-deficit/hyperactivity disorder and substance use disorder to probe the suitability to use methylphenidate as a treatment for substance use disorder. Both disorders are characterized by maladaptive goal-directed behavior, impaired cognitive control, hyperactive phasic dopaminergic neurotransmission in the striatum, prefrontal hypoactivation, and reduced frontal cortex gray matter volume/density. In addition, methylphenidate has been shown to improve cognitive control and normalize associated brain activation in substance use disorder patients and clinical trials have found methylphenidate to improve clinical outcomes. Despite the theoretical basis and promising, but preliminary, outcomes, many questions remain unanswered. Most prominent is whether all patients who are addicted to different substances may equally profit from methylphenidate treatment.

Specific phobia is frequently unrecognized or untreated unless it causes significant impairment. In this report, we documented a rare case of a pregnant patient who had a specific fear related to vaginal penetration. Due to abnormal fetal cardiac development in the second trimester, the patient was admitted for termination of pregnancy. The patient’s persistent request for surgical termination via cesarean delivery prompted the obstetrician to seek psychiatric consultation for tokophobia, a labor- and childbirth-related phobia. The consulting psychiatrist discovered that the patient had developed a significant fear of vaginal penetration during adolescence. Throughout the extended period of this specific phobia, the patient established a range of avoidance strategies. Had it not been for the unforeseen need for abortion, her phobia may not have been identified. Psychoeducation on specific phobias, exposure therapy, muscle relaxation techniques, and the administration of anxiolytics were implemented. The pregnancy was terminated through a vaginal labor induction procedure 2 days later. Collaboration across disciplines is necessary to support a thorough assessment of obstetric patients who express hesitancy toward vaginal delivery.

BackgroundAmong antipsychotics, sialorrhea is most associated with clozapine, and when it occurs, it is uncomfortable, socially stigmatizing, and can contribute to medication non-adherence. Risperidone has a generally negligible muscarinic activity compared to clozapine, and yet, multiple reports of severe sialorrhea associated with risperidone have been reported.Case presentationThis case report describes risperidone-induced sialorrhea that was unintentionally masked by simultaneous clonidine administration that was intended to treat hypertension. Interestingly, sialorrhea was present but mild when clonidine was present; however, when risperidone was further titrated and clonidine removed, a significant worsening of sialorrhea developed. Sialorrhea did not respond to treatment with anticholinergic medication.ConclusionThe pathophysiology of antipsychotic-induced sialorrhea is complex and varies between antipsychotics. Risperidone-induced sialorrhea is suspected of having prominent adrenergic pathophysiology that is likely composed of highly viscoelastic saliva (high protein content), differing from the more commonly encountered clozapine-induced sialorrhea. Risperidone-induced sialorrhea is reported as more likely to respond to dose reduction and treatment with α2-adrenergic receptor agonists or β-adrenergic receptor antagonists and less likely to respond to anticholinergic (antimuscarinic) medications.

IntroductionThe ultimate goal in major depressive disorder (MDD) treatment is recovery. A proportion of MDD patients with formal remission experience persistent difficulties, which impair their daily functioning. Residual insomnia is one of the most common residual symptoms. Patients with residual insomnia experience relapse significantly earlier and have a poor prognosis. Little is known about possible ways of treatment and what subtype of insomnia is mostly reported.MethodsA systematic literature review was carried out in PubMed and Web of Science to synthesize the current status of knowledge about effective treatment methods and insomnia subtypes in residual insomnia in MDD.ResultsA few non-pharmacological treatment methods e.g., Cognitive Behavioral Therapy for Insomnia (CBT-I), Mindfulness-Based Cognitive Therapy (MBCT), behavioral activation (BA) and pharmacological methods (gabapentin, clonazepam) have proven to mitigate residual insomnia. Cognitive Behavioral Therapy for Depression (CBT-D) ameliorates insomnia complaints to a limited extent. Mid-nocturnal insomnia is the most common residual insomnia subtype in MDD patients.ConclusionResidual insomnia is a very common complaint and most often appears as mid-nocturnal insomnia. Scarce data points out the benefits from pharmacotherapy, psychotherapy, and BA. More research is needed.

Eating disorders (EDs) are serious mental health conditions characterised by impaired eating behaviours and nutrition as well as disturbed body image, entailing considerable mortality and morbidity. Psychopharmacological medication is an important component in the treatment of EDs. In this review, we performed a historic analysis of pharmacotherapeutic research in EDs based on the scientific studies included in the recently published World Federation of Societies for Biological Psychiatry (WFSBP) guidelines for ED treatment. This analysis focuses on early approaches and trends in the methods of clinical pharmacological research in EDs, for example, the sample sizes of randomised controlled trials (RCTs). We found the development of psychopharmacological treatments for EDs followed advancements in psychiatric pharmacotherapy. However, the application of RCTs to the study of pharmacotherapy for EDs may be an impediment as limited participant numbers and inadequate research funding impede generalisability and statistical power. Moreover, current medication usage often deviates from guideline recommendations. In conclusion, the RCT model may not effectively capture the complexities of ED treatment, and funding limitations hinder research activity. Novel genetically/biologically based treatments are warranted. A more comprehensive understanding of EDs and individualised approaches should guide research and drug development for improved treatment outcomes.

(1) Background Pharmacological treatment for psychiatric disorders has shown to only be effective in about one-third of patients, as it is associated with frequent treatment failure, often because of side effects, and a long process of trial-and-error pharmacotherapy until an effective and tolerable treatment is found. This notion emphasizes the urgency for a personalized medicine approach in psychiatry. (2) Methods This prospective patient- and rater-blinded, randomized, controlled study will investigate the effect of dose-adjustment of antidepressants escitalopram and sertraline or antipsychotics risperidone and aripiprazole according to the latest state-of-the-art international dosing recommendations for CYP2C19 and CYP2D6 metabolizer status in patients with mood, anxiety, and psychotic disorders. A total sample of N = 2500 will be recruited at nine sites in seven countries (expected drop-out rate of 30%). Patients will be randomized to a pharmacogenetic group or a dosing-as-usual group and treated over a 24-week period with four study visits. The primary outcome is personal recovery using the Recovery Assessment Scale as assessed by the patient (RAS-DS), with secondary outcomes including clinical effects (response or symptomatic remission), side effects, general well-being, digital phenotyping, and psychosocial functioning. (3) Conclusions This is, to our knowledge, the first international, multi-center, non-industry-sponsored randomized controlled trial (RCT) that may provide insights into the effectiveness and utility of implementing pharmacogenetic-guided treatment of psychiatric disorders, and as such, results will be incorporated in already available dosing guidelines.

Abstract Background While medicalization and pharmaceuticalization trends of feelings of anxiety and depression have been described in great detail, an empirical examination of these trends is to date lacking. The current study fills this gap in the literature by mapping the use of psychotropic medicines for feelings of anxiety and depression between 2004 and 2013 in Belgium, as well as by examining whether a social gradient might act as a mediator. Methods We analyzed data from three repeated cross-sectional waves (2004, 2008, and 2013) of the Belgian National Health Interview Survey (HIS). Multinomial logistic regression was applied to estimate odds in psychotropic drugs use over the observed period. Results Using an ideal-typical distinction between traditional anxiety drugs (psycholeptics) and depression drugs (psychoanaleptics), we found that treatment methods for feelings of anxiety and depression were converging. Persons having feelings of anxiety consumed less psycholeptic drugs, in favor of psychoanaleptic drugs throughout the observed period. Moreover, these results were partially mediated by educational level. Persons with higher education were less likely to consume psychotropic drugs than those with lower education, suggesting a trend of demedicalization for feelings of anxiety and depression. Limitations Our study observes a limited period, makes use of an ideal typical distinction between psycholeptic and psychoanaleptic drugs, and measurements may be biased by response-bias due to psychotropic drugs use. Conclusion Our study shows that psycholeptics increasingly give way to psychoanaleptics in the treatment of both anxiety and depression, despite several scientists calling their effectiveness for both disorders into question.

Post-traumatic stress disorder is a debilitating chronic illness that affects 6 out of 100 adults after a severe trauma. The alpha-adrenergic antagonist prazosin, which is prescribed off-label for flashbacks and nightmares due to trauma, is often continued indefinitely due to reports of symptoms returning upon discontinuation. There is no standard guidance for a trial of discontinuation of prazosin due to intolerance or side effects. In this case series, three patients are started on prazosin leading to remission of trauma-related symptoms, and symptoms continue to remit after treatment for an average of about 2 years followed by discontinuation of the medication. There are many similarities in these case reports which serve to provide guidance as to when a trial of prazosin discontinuation may be warranted.

Background: Hot flashes (HF) are a common symptom during the menopausal transition. It is therefore important to identify effective drugs that can alleviate HF. This study aimed to systematically review published clinical trials on the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in the treatment of HF in healthy menopausal women.Methods: In this systematic review, articles published during 2003-2019 in PubMed, MEDLINE, Web of Science, Scopus, Science Direct, PsycINFO, CINAHL, the Cochrane Central Register of Controlled Trials, and Google Scholar as well as Iranian databases such as SID, and Magiran were searched. The quality of the selected articles was assessed using the Jadad score calculation. Results: Thirty-six articles on randomized controlled trials were included in this study, out of which 27 articles had acceptable, and nine had weak methodological quality. Findings on SSRIs class of drugs indicated that escitalopram, paroxetine, and fluoxetine have higher efficacy and safety in the treatment of menopausal HF than other drugs. Studies on the effectiveness of sertraline, citalopram, and fluvoxamine are limited in number or show inconsistent results. Therefore, further high-quality studies are required to confirm their effectiveness in alleviating HF. Within the SNRIs class, venlafaxine and desvenlafaxine showed significant efficacy in the treatment of menopausal HF. However, studies on the effectiveness of duloxetine are also limited, which requires further research. Conclusion: Most studies have indicated the efficacy and safety of some antidepressants, such as SSRIs and SNRIs, in decreasing the frequency and severity of HF. These drugs are therefore recommended for the treatment of menopausal HF.

The effectiveness of the esketamine nasal spray (ESK-NS) for treatment-resistant depression (TRD) has been confirmed by real-world studies. Available evidence derived from clinician-rated assessments might differ from patients’ perceptions about the helpfulness of treatments. We aimed to verify the effect of ESK-NS from patients’ view in 25 TRD patients (56% males, 55.1 ± 10.9 years) treated with ESK-NS (mean dose: 78.4 ± 11.43 mg) for three months and evaluated at different time-points through clinician-rated and self-administered scales, assessing changes in depression, anhedonia, sleep, cognition, suicidality, and anxiety. We observed an overall early improvement that lasted over time (endpoint total score reduction in Montgomery-Åsberg Depression Rating Scale, p < 0.001, Beck Depression Inventory, p = 0.003). Patients reported a significant self-rated decrease in anhedonia at two months (Snaith–Hamilton Pleasure Scale, p = 0.04) and in suicide ideation at endpoint (BDI subitem 9, p = 0.039) vs. earlier improvements detected by clinicians (one-month reduction in MADRS subitem 8, p = 0.005, and subitem 10, p = 0.007). These findings confirm the effectiveness of a three-month treatment with ESK-NS in TRD patients, highlighting an overall overlapping response from patients’ and clinicians’ perspectives, although with some differential effects on specific symptoms at given time-points. Including patients’ viewpoints in routine assessments could inform clinical practice, ensuring a better characterization of clinical phenotypes to deliver personalized interventions.

Bipolar disorder (BD) is one of the most common mental disorders in the world with high mortality and a hard economic burden. Although suicide is the leading cause of death in BD, cardiovascular disease (CVD) also contributes significantly to this rate, the risk of which is seriously underestimated in BD. A sample assessment was made of current studies focusing on the link between BD and CVD. The search was carried out in the PubMed and eLIBRARY databases for the following keywords: bipolar disorder, psychopharmacology, cardiovascular disease, metabolic syndrome. The association between BD and vascular disease is large. The analysis of adjusted mortality estimates in patients with bipolar disorder showed a significant contribution of CVD. A detailed study of the mutual influence of bipolar disorder BD and CVD is difficult due to the earlier manifestation of BD in comparison with CVD. Most of the studies have focused on cardiovascular risk factors (CVRFs), which are more common in BD than in the general population. Metabolic syndrome (MS) plays a significant role among CVRFs. The reasons for the development of MS in patients with BD are currently not known for sure, however, the instigated factors are certainly a disturbance of the diet, decreased physical activity, pharmacological therapy, and the lack of early preventive and medical care. Patients with hyperuricemia had a higher risk of developing MS. Lifestyle correction and a reduction of CVFRs, as well as the rational use of certain cardiac drugs can improve the better prognosis of the disease and reduce mortality in patients with BD. The predisposition of patients with BD to CVD is undeniable. It is necessary to consider the high frequency of CVRFs in people with BD, and promptly recommend appropriate treatment and special rehabilitation programs for the prevention of CVD complications, considering the change in affective phases and the applied mood-stabilizing drugs.

Monoamine oxidases are mitochondrial enzymes that catalyze the oxidative deamination of biogenic amines (adrenaline, noradrenaline, serotonin, and dopamine), causing their inactivation and subsequently playing a fundamental role in the homeostasis of various neurotransmitters. As the regulation of these effects was deemed important in clinical practice, numerous modulators of these enzymes were tested for various clinical effects. The purpose of this paper is to present a few historical landmarks regarding monoaminoxidase inhibitors and their usefulness as psychopharmacological agents. We will be focusing on banisterine, iproniazid, selegiline, rasagiline, tranylcypromine, moclobemide, and their role in the history of psychopharmacology. An almost unknown fact is that harmine, an MAO-A alkaloid, was used as early as the latter half of the 1920s in Bucharest, to reduce catatonic symptoms in schizophrenia, thus ushering the dawn of psychopharmacology era which started with chlorpromazine in the 1950s.

Antipsychotics (APs), especially second-generation antipsychotics, are being increasingly used around the world. At the same time their off-label use has also increased worldwide, as well as in Finland. The aim of our study was to find out the off-label prescribing of APs in Finland among physicians in different healthcare units. The study was conducted as a questionnaire survey. Particular attention was paid to practices between psychiatrists and other physicians (mostly general practitioners and occupational health doctors). Similar studies have not been conducted on this topic in Finland before. Altogether 216 physicians answered the questionnaire. The most common indications for off-label prescription were insomnia and anxiety, and this was evident for both psychiatrists as well as other physicians. Quetiapine was the one most commonly prescribed off-label AP. Over one-third of psychiatrists (39%) and about one-third of other physicians (30%) did not give instructions on the length of the treatment. The metabolic values were reported to be followed by 44% of the psychiatrists and by 18% of other physicians. Nearly two-thirds of all respondents thought that off-label use had more benefits than harms. Compared to other physicians, psychiatrists prescribed APs for off-label use more frequently and for more varied psychiatric conditions. Off-label use of APs seems to be a clinical reality in Finland. There is need for further studies on efficacy and adverse effects of APs in off-label use, and also a need for clinical guidelines on monitoring the patients using APs off-label.