Temporal trends in medication and service use patterns for mental health issues among men with prostate cancer.

OBJECTIVE: Prostate cancer can significantly impact mental wellbeing, creating uncertainty and morbidity. This study described patterns of psychotropic medication and mental health service use, as a proxy measure for mental health problems, 5 years before and 5 years after prostate cancer diagnosis. METHODS: Population-based registry data were linked with Pharmaceutical Benefits Scheme and Medicare Benefits Schedule data for all prostate cancer patients diagnosed in South Australia between 2012 and 2020 (n = 13,693). We estimated the proportion and rates of psychotropic medication and mental health service use before and after diagnosis. Multivariable adjusted interrupted time series analyses (ITSA) were conducted to uncover temporal patterns. RESULTS: Fifteen percent of men commenced psychotropic medications and 6.4% sought out mental health services for the first time after diagnosis. Psychotropic medication use rose from 34.5% 5 years before to 40.3% 5 years after diagnosis, including an increase in use of antidepressants (from 20.7% to 26.0%) and anxiolytics (from 11.3% to 12.8%). Mental health service use increased from 10.2% to 12.1%, with the increase mostly being general practice mental health visits (from 7.8% to 10.6%). Multivariable ITSA indicated a significant rise in medication and service utilisation immediately before and in the first 2 years following prostate cancer diagnosis. CONCLUSION: There is a clear increase in psychotropic medication use and mental health service use around the time of prostate cancer diagnosis. Mental health outcomes of men with prostate cancer may be improved with early mental health screening, particularly during the diagnosis process, to enable early intervention.

Antidepressant drug use after intensive care: a nationwide cohort study.

Modern intensive care has improved survival rates, but emerging evidence suggests a high prevalence of post-intensive care unit (ICU) health problems, including post-traumatic stress disorder, depression and anxiety. These symptoms may have a detrimental effect on quality of life and increase mortality. The primary objective of this study is to examine the extent of initiation of antidepressant medication among ICU survivors and identify the factors associated with its usage. The secondary objective is to investigate whether the use of these medications is linked to an increased mortality. The nationwide study cohort included 125,130 ICU survivors admitted between 2010 and 2017. Within the first 3 months after ICU discharge, 7% of patients initiated antidepressant medication, by 1 year 15.5% had started medication. We found no tendency to a decrease during the 2-year follow-up period. Factors associated with antidepressant use included middle age, female sex, psychiatric and somatic comorbid conditions, substance dependence, higher illness severity, and longer ICU stay. Antidepressant users had a higher mortality rate, and deaths due to external causes and suicide were more frequent in this group. This study emphasizes the importance of detecting and addressing depression in ICU survivors to improve their quality of life and reduce mortality rates.

Depressive Disorders in Children and Adolescents: Evaluation and Management.

Depressive disorders among children and adolescents impact the practice of many providers, in many specialties. These disorders contribute to illness and disability throughout the world, and they are a significant risk factor for suicide. Depression in these age groups can differ from those in adults, and early recognition along with proper treatment can lead to improved outcomes. It is important for clinicians to differentiate depression from other possible diagnoses such as anxiety disorders, attention deficit hyperactivity disorder (ADHD), and other mood disorders. Once the diagnosis of depression is established, the severity should be assessed to determine the most appropriate level of treatment. Outpatient treatment often starts with therapy, and if medications are indicated, the use of selectiveserotonin reuptake inhibitors (SSRIs) tend to be first-line.

Antidepressant Medication Use During Lactation: A Review for Providers.

This article presents a summary of information found within the existing medical literature on the pharmacological treatment options for maternal depression during lactation and the concurrent effects on the breastfeeding infant. Existing data on safety and efficacy varies by treatment modality. Medications used to treat depression are all secreted in breast milk to some extent; however, most antidepressants are considered relatively safe to use during breastfeeding. The selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine are present in low levels and are considered preferred agents. Safety data for other antidepressants varies, however. monoamine oxidase inhibitors (MAOIs) should generally be avoided. Available references and resources can help providers optimize treatment of maternal depression while mitigating risk to the infant. Optimizing treatment of maternal depression is a complicated undertaking, which should be made in conjunction with the provider through shared decision making with the patient. Specific properties of any proposed medication, such as the relative infant dose and side effect profile, should always be taken into account during the decision-making process.

The Effect of Neuropsychiatric Drugs on the Oxidation-Reduction Balance in Therapy.

The effectiveness of available neuropsychiatric drugs in the era of an increasing number of patients is not sufficient, and the complexity of neuropsychiatric disease entities that are difficult to diagnose and therapeutically is increasing. Also, discoveries about the pathophysiology of neuropsychiatric diseases are promising, including those initiating a new round of innovations in the role of oxidative stress in the etiology of neuropsychiatric diseases. Oxidative stress is highly related to mental disorders, in the treatment of which the most frequently used are first- and second-generation antipsychotics, mood stabilizers, and antidepressants. Literature reports on the effect of neuropsychiatric drugs on oxidative stress are divergent. They are starting with those proving their protective effect and ending with those confirming disturbances in the oxidation-reduction balance. The presented publication reviews the state of knowledge on the role of oxidative stress in the most frequently used therapies for neuropsychiatric diseases using first- and second-generation antipsychotic drugs, i.e., haloperidol, clozapine, risperidone, olanzapine, quetiapine, or aripiprazole, mood stabilizers: lithium, carbamazepine, valproic acid, oxcarbazepine, and antidepressants: citalopram, sertraline, and venlafaxine, along with a brief pharmacological characteristic, preclinical and clinical studies effects.

Antioxidant and Anti-Inflammatory Profiles of Two Mexican Heteropterys Species and Their Relevance for the Treatment of Mental Diseases: H. brachiata (L.) DC. and H. cotinifolia A. Juss. (Malpighiaceae).

Depression and anxiety are recognized as the most common mental diseases worldwide. New approaches have considered different therapeutic targets, such as oxidative stress and the inflammation process, due to their close association with the establishment and progression of mental diseases. In the present study, we evaluated the antioxidant and anti-inflammatory activities of the methanolic extracts of the plant species Heteropterys brachiata and Heteropterys cotinifolia and their main compounds, chlorogenic acid and rutin, as potential complementary therapeutic tools for the treatment of anxiety and depression, since the antidepressant and anxiolytic activities of these methanolic extracts have been shown previously. Additionally, we also evaluated their inhibitory activity on the enzyme acetylcholinesterase (AChE). Our results revealed that both species exhibited potent antioxidant activity (>90%) through the TBARS assay, while by means of the DPPH assay, only H. cotinifolia exerted potent antioxidant activity (>90%); additionally, low metal chelating activity (<40%) was detected for all samples tested in the ferrozine assay. The methanolic extracts of H. brachiata and H. cotinifolia exhibited significant anti-inflammatory activities in the TPA-induced ear edema, while only H. cotinifolia exerted significant anti-inflammatory activities in the MPO assay (>45%) and also exhibited a higher percentage of inhibition on AChE of even twice (>80%) as high as the control in concentrations of 100 and 1000 µg/mL. Thus, the potent antioxidant and inflammatory properties and the inhibition of AChE may be involved in the antidepressant activities of the species H. cotinifolia, which would be positioned as a candidate for study in drug development as an alternative in the treatment of depression.

Study on the antidepressant activity of (2R,6R; 2S,6S)-Hydroxynorketamine (HNK) and its derivatives.

OBJECTIVE: This study mainly explores (2R,6R; 2S,6S)-HNK and its compounds whether there are antidepressant effects. METHODS: Four HNK compounds were obtained from 2-(Chlorophenyl) Cyclopentylmethanone. Forced swimming test, locomotor sensitization test, and conditioned location preference test were used to screen the antidepressant activity of the synthesized target compounds. RESULTS: In the case of 10 mg HNK treatment, compared with saline, the immobile time of mice in the HNK group, I5 group and I6 group at 1 h and 7 days had statistical significance. In the case of 10 mg HNK treatment, compared with saline, the immobile time of compound C and D groups in the glass cylinder area was significantly different. In the locomotor sensitization test, the movement distance of compound C and D groups on day 15 and day 7 mice increased significantly compared with the first day. In the conditioned place preference experiment, compound C and compound D induced conditioned place preference in mice compared with the Veh group. CONCLUSION: The results of the forced swimming test, locomotor sensitization test, and conditioned location preference test showed that compounds C and D may have certain anti-depressant activity. However, HNK exerts a rapid and significant antidepressant effect within 1 week, but the duration is short.

Prolonged increase in psychotropic drug use among young women following the COVID-19 pandemic: a French nationwide retrospective study.

BACKGROUND: The COVID-19 pandemic has had a significant impact on mental health, with evidence suggesting an enduring mental health crisis. Studies worldwide observed increased usage of antidepressants, anxiolytics, and hypnotics during the pandemic, notably among young people and women. However, few studies tracked consumption post-2021. Our study aimed to fill this gap by investigating whether the surge in the number psychotropic drug consumers in France persisted 2 years after the first lockdown, particularly focusing on age and gender differences. METHODS: We conducted a national retrospective observational study based on the French national insurance database. We retrieved all prescriptions of anxiolytics, hypnotics, and antidepressants dispensed in pharmacies in France for the period 2015-2022. We performed interrupted time series analyses based on Poisson models for five age classes (12-18; 19-25; 26-50; 51-75; 76 and more) to assess the trend before lockdown, the gap induced and the change in trend after. RESULTS: In the overall population, the number of consumers remained constant for antidepressants while it decreased for anxiolytics and hypnotics. Despite this global trend, a long-term increase was observed in the 12-18 and 19-25 groups for the three drug classes. Moreover, for these age classes, the increases were more pronounced for women than men, except for hypnotics where the trends were similar. CONCLUSIONS: The number of people using antidepressants continues to increase more than 2 years after the first lockdown, showing a prolonged effect on mental health. This effect is particularly striking among adolescents and young adults confirming the devastating long-term impact of the pandemic on their mental health.

Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, placebo-controlled and delayed-start, neuroimaging trial in depression.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin's acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression. METHODS: Fifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures. DISCUSSION: This study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin's antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.

New and emerging treatments for major depressive disorder.

Major depressive disorder (MDD) affects a substantial portion of the population; however, much is still unknown about the pathophysiology of this disorder. Treatment resistance highlights the heterogeneous nature of MDD and the need for treatments to target more than monoamine neurotransmission. This review summarizes research into the new and emerging targets of MDD. These include drugs such as psychedelics, antibiotics, opioid modulators, neuropeptides, and onabotulinumtoxin. Neuromodulatory treatments such as light based therapies and neuromodulation involving either magnetic or electrical stimulation are also discussed. Almost all interventions, pharmacological and neuromodulation, were trialed as adjunctive treatments to an antidepressant. Most research has been conducted on psychedelics, with trials suggesting rapid antidepressant and anti-suicidal effects. Trial findings, tolerability, study design limitations and quality of research have been considered throughout this review. There remains challenges in forming recommendations with the current research at present. With there being considerable interest into the research of new and emerging treatments-in particular, psychedelics-there may be scope in the future to form more robust recommendations.

Immune-Targeted Therapies for Depression: Current Evidence for Antidepressant Effects of Monoclonal Antibodies.

Importance: Increasing evidence suggests a potential role of immune-modulatory drugs for treatment-resistant depression. This scoping review explores the emerging evidence regarding the antidepressant effects of monoclonal antibodies (mAbs), a relatively newer class of immune therapeutics with favorable safety profile.Observations: PubMed was searched up to November 2023 for English publications addressing the antidepressant effects of mAbs, including meta-analyses, randomized controlled trials, open-label, single-arm studies, and case series. Several mAbs have shown potential antidepressant effects, but most studies in primary inflammatory disorders included patients with mild depression. Only infliximab and sirukumab were directly examined in individuals with primary depression. mAbs that do not require laboratory monitoring, such as ixekizumab and dupilumab, could hold potential promise if future studies establish their safety profile regarding suicide risk.Conclusions and Relevance: The use of several mAbs for the treatment of primary inflammatory disorders has been associated with improvement of comorbid depressive symptoms. Given their unique mechanisms of action, mAbs may offer a new hope for depressed patients who do not respond to currently available antidepressants. Further research addressing individuals with more severe depressive symptoms is essential. Direct examination of antidepressant effects of mAbs in people with primary depressive disorders is also crucial to refine their clinical use in the treatment of depression.

A Nationwide Target Trial Emulation Assessing the Risk of Antidepressant-Induced Mania Among Patients With Bipolar Depression.

OBJECTIVE: Antidepressants are commonly used to treat bipolar depression but may increase the risk of mania. The evidence from randomized controlled trials, however, is limited by short treatment durations, providing little evidence for the long-term risk of antidepressant-induced mania. The authors performed a target trial emulation to compare the risk of mania among individuals with bipolar depression treated or not treated with antidepressants over a 1-year period. METHODS: The authors emulated a target trial using observational data from nationwide Danish health registers. The study included 979 individuals with bipolar depression recently discharged from a psychiatric ward. Of these, 358 individuals received antidepressant treatment, and 621 did not. The occurrence of mania and bipolar depression over the following year was ascertained, and the intention-to-treat effect of antidepressants was analyzed by using Cox proportional hazards regression with adjustment for baseline covariates to emulate randomized open-label treatment allocation. RESULTS: The fully adjusted analyses revealed no statistically significant associations between treatment with an antidepressant and the risk of mania in the full sample (hazard rate ratio=1.08, 95% CI=0.72-1.61), in the subsample concomitantly treated with a mood-stabilizing agent (hazard rate ratio=1.16, 95% CI=0.63-2.13), and in the subsample not treated with a mood-stabilizing agent (hazard rate ratio=1.16, 95% CI=0.65-2.07). Secondary analyses revealed no statistically significant association between treatment with an antidepressant and bipolar depression recurrence. CONCLUSIONS: These findings suggest that the risk of antidepressant-induced mania is negligible and call for further studies to optimize treatment strategies for individuals with bipolar depression.

Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response from 13 clinical studies using genotype imputation: a meta-analysis.

Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from 13 studies of European and East Asian ancestry populations were collected. The antidepressant response was clinically assessed as remission and percentage improvement. Imputed genotype was used to translate genetic polymorphisms to metabolic phenotypes (poor, intermediate, normal, and rapid+ultrarapid) of CYP2C19 and CYP2D6. CYP2D6 structural variants cannot be imputed from genotype data, limiting the determination of metabolic phenotypes, and precluding testing for association with response. The association of CYP2C19 metabolic phenotypes with treatment response was examined using normal metabolizers as the reference. Among 5843 depression patients, a higher remission rate was found in CYP2C19 poor metabolizers compared to normal metabolizers at nominal significance but did not survive after multiple testing correction (OR = 1.46, 95% CI [1.03, 2.06], p = 0.033, heterogeneity I2 = 0%, subgroup difference p = 0.72). No metabolic phenotype was associated with percentage improvement from baseline. After stratifying by antidepressants primarily metabolized by CYP2C19, no association was found between metabolic phenotypes and antidepressant response. Metabolic phenotypes showed differences in frequency, but not effect, between European- and East Asian-ancestry studies. In conclusion, metabolic phenotypes imputed from genetic variants using genotype were not associated with antidepressant response. CYP2C19 poor metabolizers could potentially contribute to antidepressant efficacy with more evidence needed. Sequencing and targeted pharmacogenetic testing, alongside information on side effects, antidepressant dosage, depression measures, and diverse ancestry studies, would more fully capture the influence of metabolic phenotypes.

Managing abdominal cocoon syndrome complicated by intestinal necrosis and unexpected amelioration of depression after surgery: a case report.

BACKGROUND: Abdominal cocoon is a very uncommon yet dangerous cause of intestinal obstruction. CASE PRESENTATION: We present a case of a 62-year-old Asian male patient with a history of depression who exhibited an idiopathic abdominal cocoon complicated by necrosis. Upon laparotomy investigation, nearly the entire small intestine was enveloped in a thick membrane resembling a cocoon, and it was discovered that he lacked a greater omentum. The patient recovered well and was discharged on an oral diet on the 20th day following surgery. During the 3-month follow-up, the patient was asymptomatic, even gaining 10 kg in weight, and noted that his depression had improved. CONCLUSIONS: Small bowel obstruction presents with nonspecific symptoms, posing challenges in differential diagnosis. Contrast-enhanced computed tomography is recommended since it facilitates precise preoperative assessment, optimizing surgical planning and reducing postoperative complications. Remarkably, cessation of antidepressant medication post-surgery hints at a potential correlation between omental deficit, gut microbiota alterations, and depressive symptoms.

Therapeutic potential of cannabidiol in depression.

Major depressive disorder (MDD) is a widespread and debilitating condition affecting a significant portion of the global population. Traditional treatment for MDD has primarily involved drugs that increase brain monoamines by inhibiting their uptake or metabolism, which is the basis for the monoaminergic hypothesis of depression. However, these treatments are only partially effective, with many patients experiencing delayed responses, residual symptoms, or complete non-response, rendering the current view of the hypothesis as reductionist. Cannabidiol (CBD) has shown promising results in preclinical models and human studies. Its mechanism is not well-understood, but may involve monoamine and endocannabinoid signaling, control of neuroinflammation and enhanced neuroplasticity. This chapter will explore CBD's effects in preclinical and clinical studies, its molecular mechanisms, and its potential as a treatment for MDD.

A randomized controlled pilot study of daily intravenous ketamine over three days for treatment-resistant depression.

BACKGROUND: Studies have confirmed the rapid antidepressant action of ketamine in depressive episodes. Nevertheless, a standardized procedure for the delivery of ketamine infusion in individuals suffering from treatment-resistant depression, particularly in terms of infusion frequency and total dosage, remains undetermined. In addition, an efficacious ketamine regimen for persistent pain management involved a continuous 10-day infusion period with no notable adverse effects. Consequently, the primary objective of this study was to evaluate the antidepressant capacity of consecutive ketamine infusions spanning over three successive days, the duration of therapeutic response, and the overall safety profile of the treatment. METHODS: In this randomized controlled trial, participants aged 18-64 with treatment-resistant depression were randomized to receive either intravenous ketamine or midazolam (used as an active placebo) for 40 min daily over three consecutive days. Statistical analysis using repeated measures ANOVA was employed to assess the changes in the total score of the Montgomery-Åsberg Depression Rating Scale (MADRS) and the clinical global impression-Severity from the initial assessment to 10 and 31 days post-infusion. Additionally, the duration of response and remission was evaluated using Kaplan-Meier survival analysis. RESULTS: Out of 33 randomized participants, 20 underwent the treatment as planned. By day 10th, the ketamine group had a mean reduction in MADRS score of 12.55 (95% CI = 6.70-18.09), whereas the midazolam group had a decrease of 17.22 (95% CI = 11.09-23.36). This pattern continued to day 31, with ketamine showing a mean score decrease of 13.73 (95% CI = 7.54-19.91) and midazolam a fall of 12.44 (95% CI = 5.61-19.28). Both treatments were well tolerated, with dissociative symptoms in the ketamine group being temporary and ceasing by the end of each infusion. CONCLUSION: Intravenous ketamine given for three consecutive days did not show a notable antidepressant advantage when compared to the active placebo midazolam, highlighting the need for further research into effective treatments schedules for treatment-resistant depression. TRIAL REGISTRATION: NCT05026203, ClinicalTrials.gov, registered on 24/08/2021.