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Background: QT prolongation is a potential serious adverse drug reaction, and assessing the risk of QT-prolonging drugs is routinely included in psychotropic medication reviews. However, the actual clinical benefits of such assessments are unknown. We investigate whether QT prolongation (QTc value > 480 ms) manifests in psychiatric inpatients at risk of QT prolongation as identified by assessing drug regimens. Secondly, we test the predictive value of well-known risk factors for QT prolongation. Results: The median patient age was 49 years (IQR 34–64) for patients treated with a median of nine drugs (IQR 6–12) and a median QT-prolonging drug sum of three daily defined dosages (IQR 1.88–4.76). We extracted 290 ECGs for patients where pharmacist-led-medication reviews (PMRs) identified an increased risk of QT prolongation and 190 ECGs for patients with no such risk, identifying 33 cases of verified QT prolongation equally distributed between groups. Unadjusted regression analysis revealed that advanced age (OR 3.27 CI 95% 1.60–6.84) and cardiovascular comorbidity (OR 3.53 CI 95% 1.71–7.29) were associated with manifest QT prolongation, while the QT-prolonging drug load was not. Methods: We reviewed electronic health records (EHRs) of 799 psychiatric inpatients exposed to PMRs made from 1 September 2016 to 31 December 2018 in Region Zealand Denmark. Conclusions: Patients at risk of QT prolongation as identified by drug reviews rarely manifests with actual QT prolongation. Non-pharmacological risk factors seem to be better predictors for identifying patients with QT prolongation. [ABSTRACT FROM AUTHOR]

Introduction: Seasonality in depressive and bipolar disorders, are recognized in the ICD-10/11 and DSM-5 diagnostic systems. The existence of a seasonal pattern of hospital diagnosis of major depression, bipolar disorder and prescription of antidepressant medications has not been evaluated in the Danish population. Methods: We retrieved date and year for all first-time hospital contacts with depression or bipolar disorder between 1999 and 2019, registered in the Danish National Patient Registry. Depression was defined using the ICD-10 F32-F33 codes, and for bipolar disorder the F30 or F31 codes. Date and year of all first-time purchases of antidepressant medications with ATC codes (N06A) between 1999 and 2021 were retrieved from the Danish National Prescription Registry, containing information on all prescribed drugs dispensed at pharmacies since 1995. Data on sunlight hours from 2012 to 2021 were retrieved from the Danish Metrological Institute. Results: Incidences of hospital diagnoses as well as purchases of medication varied with month and season. The monthly variations were larger for antidepressant medication and smallest for bipolar disorder. The multiple linear regression analysis showed that number of first-time diagnoses of depression or bipolar disorder did not correlate with season. For antidepressant medication the number of first-time prescriptions was significantly lower in summer compared to the winter season. Conclusion: This study found a seasonal variation of first-time prescriptions of antidepressant medication. We did not find a seasonal variation in first-time hospital diagnoses. Further research looking into depression severity, polarity of bipolar illness episodes, lag-time for sunlight exposure, and specific parts of the yearly photoperiods should be conducted. [ABSTRACT FROM AUTHOR]

Abstract 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.

There is a significant variability in the prevalence of psychotropic medication use among young autistic persons worldwide and this is under-studied in Australia. Apart from risperidone, approved by the Therapeutic Goods Administration to manage challenging behaviour, the appropriateness of other psychotropic medications prescribed to young autistic persons warrants scrutiny. This retrospective study aims to gain initial insight into the magnitude, types and indications of psychotropic medication use in autistic children and adolescents in Western Australia. We analysed de-identified data from 239 autistic children and adolescents (⩽21 years) who participated in the Western Australian Autism Biological Registry between 2011 and 2015 and who completed a questionnaire regarding medication use. One-quarter (n = 66, 28%) of young autistic people reported using a total of 137 medications. Most (n = 46, 70%) of those medicated were under 12 years of age; half (n = 33) were 6–12 years and a fifth (n = 13) were under 6 years. The most used medications were stimulants (n = 35, 53.0%), followed by antidepressants (n = 24, 36.4%), antiepileptics (n = 21, 31.8%), sedatives (n = 15, 22.7%) and antipsychotics (n = 14, 21.2%). These medications were mainly to manage attention deficit hyperactivity disorder, challenging behaviours, seizures, insomnia, undefined anxiety, depression and mood instability. While most autistic young people in the Western Australian Autism Biological Registry did not report using psychotropic medication, over a quarter were prescribed medications, primarily stimulants, to manage symptoms of attention deficit hyperactivity disorder. Various medications, including risperidone, were used to help manage challenging behaviours. Medication use should be studied more comprehensively in a larger cohort of autistic persons to confirm our current preliminary observations. Further, future studies should monitor the effectiveness and safety outcomes of such medications due to a limited understanding of their effectiveness in managing the atypical presentation of co-occurring disorders in young autistic persons. Prescriptions and use of medications to treat mental health conditions in young autistic populations are inconsistent worldwide. This makes it hard to compare findings from international studies to the Australian autistic population, where there are limited relevant studies. Apart from risperidone, there are no other medications specified for direct use in autistic persons. This study aims to gain initial broad understanding of the use of medications, commonly prescribed for mental health conditions, specifically by autistics under the age of 21 years. We analysed data that were previously collected as part of the Western Australian Autism Biological Registry between 2011 and 2015 which amounted to 239 surveys completed on young persons with diagnosed autism. The questionnaires included information on co-occurring conditions, current or previous use of medications and reasons for use of the medications. Only one-quarter of the participants in this study reported using at least one mental health–related medication in their lifetime. The most reported medications were stimulants, antidepressants and antiepileptics. The reasons for using medication included managing attention deficit hyperactivity disorder, challenging behaviours, seizures, sleep difficulties and symptoms of anxiety and depression. The number of individuals reporting medication use in this study was lower compared to other developed countries. Nevertheless, these medications should be monitored due to limited understanding of their use to manage co-occurring symptoms in young autistic persons. The findings highlight the importance of ongoing research to better understand mental health–related medications and inform best practice. [ABSTRACT FROM AUTHOR]

Objectives: Sexual satisfaction is an important aspect of quality of life. Chronic pain, depression and anxiety, and relational problems correspond with higher risk for sexual difficulties. Less is known about how risk factors for sexual dysfunction and other problems--such as medical conditions, pain severity, and medication side effects--affect the sexual satisfaction of people with chronic pain. Using a biopsychosocial framework, this study explored factors related to sexual satisfaction among patients presenting for evaluation of chronic pain. Methods: Researchers used a hierarchical multiple regression analysis to model potential predictors of sexual satisfaction. Variables analyzed were demographic features, medical history, average pain severity, depressed mood, anxiety, and perceived significant other support. Data collection involved administration of retrospective questionnaires and chart review. The sample included male and female participants (N = 134) presenting for evaluation at a multidisciplinary pain rehabilitation clinic. Results: Medical history (i.e., medical conditions, surgical history, and medications) and clinical self-report variables (i.e., pain severity, depressed mood, anxiety, and perceived significant other support) were associated with sexual satisfaction. In this sample, antidepressant use and higher pain severity were unique predictors of lower sexual satisfaction. Married marital status and higher levels of perceived significant other support were predictive of greater sexual satisfaction. Discussion: Findings highlight the importance of understanding the unique impact of biopsychosocial variables on the sexual satisfaction of patients presenting for evaluation at a multidisciplinary pain rehabilitation clinic. Further exploration of protective factors that account for sexual satisfaction among individuals with chronic pain may help inform screening, referrals, and treatment. [ABSTRACT FROM AUTHOR]

Given the high rate of depression associated with narcolepsy or obstructive sleep apnea (OSA), this analysis compared effects of solriamfetol treatment of excessive daytime sleepiness (EDS) in participants with/without a history of depression (DHx+/DHx-). This secondary analysis included data from two randomized, controlled trials in which participants were randomized to 12 weeks placebo or solriamfetol 37.5 (OSA only), 75, 150, or 300 mg/day. Efficacy/safety (combined solriamfetol doses) was summarized for DHx+/DHx-subgroups. 27.5% (65/236) with narcolepsy and 23.4% (111/474) with OSA were DHx+. In narcolepsy (DHx+ and DHx-), 40-min Maintenance of Wakefulness Test (MWT40) mean sleep latency increased (5.4 and 7.0 min), Epworth Sleepiness Scale (ESS) score decreased (3.8 and 3.5 points), and percentage of participants improved on Patient Global Impression of Change (PGI-C) was higher (31.7% and 39.4%) relative to placebo. In OSA (DHx+ and DHx-), MWT40 mean sleep latency increased (7.7 and 10.7 min), ESS decreased (3.5 and 3.7 points), and percentage of participants improved on PGI-C was higher (41.1% and 29.4%) relative to placebo. Common treatment-emergent adverse events (headache, decreased appetite, nausea, anxiety) were similar in DHx+/DHx-. This study suggests that safety and efficacy of solriamfetol for treating EDS in narcolepsy and OSA are not affected by depression history. Moreover, the findings emphasize the high prevalence of depression in people with sleep disorders and suggest that increased awareness of this association may have clinical significance.

Background: QT prolongation is a potential serious adverse drug reaction, and assessing the risk of QT-prolonging drugs is routinely included in psychotropic medication reviews. However, the actual clinical benefits of such assessments are unknown. We investigate whether QT prolongation (QTc value > 480 ms) manifests in psychiatric inpatients at risk of QT prolongation as identified by assessing drug regimens. Secondly, we test the predictive value of well-known risk factors for QT prolongation. Results: The median patient age was 49 years (IQR 34–64) for patients treated with a median of nine drugs (IQR 6–12) and a median QT-prolonging drug sum of three daily defined dosages (IQR 1.88–4.76). We extracted 290 ECGs for patients where pharmacist-led-medication reviews (PMRs) identified an increased risk of QT prolongation and 190 ECGs for patients with no such risk, identifying 33 cases of verified QT prolongation equally distributed between groups. Unadjusted regression analysis revealed that advanced age (OR 3.27 CI 95% 1.60–6.84) and cardiovascular comorbidity (OR 3.53 CI 95% 1.71–7.29) were associated with manifest QT prolongation, while the QT-prolonging drug load was not. Methods: We reviewed electronic health records (EHRs) of 799 psychiatric inpatients exposed to PMRs made from 1 September 2016 to 31 December 2018 in Region Zealand Denmark. Conclusions: Patients at risk of QT prolongation as identified by drug reviews rarely manifests with actual QT prolongation. Non-pharmacological risk factors seem to be better predictors for identifying patients with QT prolongation.

A novel capillary electrophoresis method was developed for the determination of new 4-aryl-pyrido[1,2-c]pyrimidine derivatives, potential antidepressant agents, in serum. The derivatives have conformationally restricted tryptamine moiety in pharmacophore portion and exhibit high affinity to molecular targets: 5-HT1A receptor and serotonin transporter protein. The separation process was conducted using an eCAP fused-silica capillary, detection wavelength 214 nm, 200 mM phosphate buffer adjusted to pH = 8.0, temperature 20 °C, voltage 5 kV. The proposed method was validated by determining its linearity in the concentration range of 200–1000 ng/mL. A satisfactory linearity was obtained for the method, with R2 from 0.9978 to 0.9999 for all five derivatives and a limit of quantification level from 287.1 to 310.1 ng/mL. The recoveries for all derivatives were in the range from 94.7 to 100%. The speed of obtaining the result of the analysis was only 3 min. The developed method allows to determine all five derivatives both in water solutions and serum. [ABSTRACT FROM AUTHOR]

ObjectivesSexual satisfaction is an important aspect of quality of life. Chronic pain, depression and anxiety, and relational problems correspond with higher risk for sexual difficulties. Less is known about how risk factors for sexual dysfunction and other problems—such as medical conditions, pain severity, and medication side effects—affect the sexual satisfaction of people with chronic pain. Using a biopsychosocial framework, this study explored factors related to sexual satisfaction among patients presenting for evaluation of chronic pain.MethodsResearchers used a hierarchical multiple regression analysis to model potential predictors of sexual satisfaction. Variables analyzed were demographic features, medical history, average pain severity, depressed mood, anxiety, and perceived significant other support. Data collection involved administration of retrospective questionnaires and chart review. The sample included male and female participants (N = 134) presenting for evaluation at a multidisciplinary pain rehabilitation clinic.ResultsMedical history (i.e., medical conditions, surgical history, and medications) and clinical self-report variables (i.e., pain severity, depressed mood, anxiety, and perceived significant other support) were associated with sexual satisfaction. In this sample, antidepressant use and higher pain severity were unique predictors of lower sexual satisfaction. Married marital status and higher levels of perceived significant other support were predictive of greater sexual satisfaction.DiscussionFindings highlight the importance of understanding the unique impact of biopsychosocial variables on the sexual satisfaction of patients presenting for evaluation at a multidisciplinary pain rehabilitation clinic. Further exploration of protective factors that account for sexual satisfaction among individuals with chronic pain may help inform screening, referrals, and treatment.

Abstract Background Esketamine (ESK) nasal spray, taken with oral antidepressant therapy, is approved for the treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior. In pooled analyses of two pivotal phase 3 studies, ASPIRE I and II, remission rates were consistently higher among patients with MDD with active suicidality who were treated with ESK + standard of care (SOC) versus placebo (PBO) + SOC at all time points in the double-blind and most time points in the follow-up phases. The current analysis of the ASPIRE data sets assessed the effect of ESK + SOC versus PBO + SOC on additional remission-related endpoints: time to achieving remission and consistent remission, proportion of patients in remission and consistent remission, and days in remission. Methods Post hoc analysis of pooled data from ASPIRE I and II (N = 451). Remission and consistent remission were defined as Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤ 12 at any given visit or two consecutive visits, respectively. Combined endpoints utilizing Clinical Global Impression-Severity of Suicidality-revised version [CGI-SS-r] ≤ 1 (i.e., not suicidal/questionably suicidal) along with the remission and consistent remission definitions (i.e., MADRS total score ≤ 12) were also examined. Results The median times to remission and consistent remission of MDD were significantly shorter in ESK + SOC versus PBO + SOC (15 versus 23 [p = 0.005] and 23 versus 50 days [p = 0.007], respectively) and a greater proportion of patients in ESK + SOC achieved remission and consistent remission by Day 25 (65.2% versus 55.5% and 54.2% versus 39.8%, respectively). Similar results were obtained using the combined endpoint for both remission definitions. The median percent of days in remission during the double-blind treatment phase was significantly greater in ESK + SOC (27.1% or 5 days) versus PBO + SOC (8.3% or 2 days; p = 0.006), and the significant difference was maintained during follow-up. Conclusion Treatment with ESK + SOC versus PBO + SOC resulted in significantly shorter time to remission, greater proportion of patients in remission, and greater percent of days in remission using increasingly rigorous definitions of remission. These findings underscore the clinical benefits of ESK for adults with MDD with suicidality. Trial registration ClinicalTrials.gov registry NCT03039192 (registered February 1, 2017) and NCT03097133 (registered March 31, 2017).

Background: This research was designed to investigate Algorithm Guided Treatment (AGT) and clinical traits for the prediction of antidepressant treatment outcomes in Chinese patients with major depressive disorder (MDD). Methods: This study included 581 patients who had reached treatment response and 406 patients remained non-responded observed after three months of treatment. Sociodemographic factors, clinical traits, and psychiatric rating scales for evaluating therapeutic responses between the two groups were compared. Logistic regression analysis was adopted to determine the risk factors of unresponsive to antidepressant (URA) in MDD. Kaplan-Meier survival analysis was utilized to compare the therapeutic response between AGT and treatment as usual (TAU). Results: Compared to the MDD responsive to antidepressant (RA) group, the URA group had significantly lower rates of the following clinical traits: married status, anxious distress, moderate to severe depressive symptoms, and higher rates of comorbidity (p-value < 0.05). Logistic Regression Analysis showed that eight clinical traits from psychiatric rating scales, such as anxious characteristics, were correlated positively with URA, while the other eight symptoms, such as autonomic symptoms, were negatively correlated. Time to symptomatic remission was longer in TAU without statistically significant (p-value = 0.11) by log-rank testing. Conclusions: The factors may affect the therapeutic responses and compliance of patients, increasing the non-response risk for antidepressants. Therapeutic responses might be improved by increasing the clarification and elucidation of different symptom clusters of patients. Benefits on treatment response to AGT were not found in our study, indicating a one-size-fits-all approach may not work.Trial Registration: We registered as a clinical trial at the International Clinical Trials Registry Platform (No. NCT01764867) and obtained ethical approval 2012-42 from SMHC.

Background: Esketamine (ESK) nasal spray, taken with oral antidepressant therapy, is approved for the treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior. In pooled analyses of two pivotal phase 3 studies, ASPIRE I and II, remission rates were consistently higher among patients with MDD with active suicidality who were treated with ESK + standard of care (SOC) versus placebo (PBO) + SOC at all time points in the double-blind and most time points in the follow-up phases. The current analysis of the ASPIRE data sets assessed the effect of ESK + SOC versus PBO + SOC on additional remission-related endpoints: time to achieving remission and consistent remission, proportion of patients in remission and consistent remission, and days in remission. Methods: Post hoc analysis of pooled data from ASPIRE I and II (N = 451). Remission and consistent remission were defined as Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤ 12 at any given visit or two consecutive visits, respectively. Combined endpoints utilizing Clinical Global Impression-Severity of Suicidality-revised version [CGI-SS-r] ≤ 1 (i.e., not suicidal/questionably suicidal) along with the remission and consistent remission definitions (i.e., MADRS total score ≤ 12) were also examined. Results: The median times to remission and consistent remission of MDD were significantly shorter in ESK + SOC versus PBO + SOC (15 versus 23 [p = 0.005] and 23 versus 50 days [p = 0.007], respectively) and a greater proportion of patients in ESK + SOC achieved remission and consistent remission by Day 25 (65.2% versus 55.5% and 54.2% versus 39.8%, respectively). Similar results were obtained using the combined endpoint for both remission definitions. The median percent of days in remission during the double-blind treatment phase was significantly greater in ESK + SOC (27.1% or 5 days) versus PBO + SOC (8.3% or 2 days; p = 0.006), and the significant difference was maintained during follow-up. Conclusion: Treatment with ESK + SOC versus PBO + SOC resulted in significantly shorter time to remission, greater proportion of patients in remission, and greater percent of days in remission using increasingly rigorous definitions of remission. These findings underscore the clinical benefits of ESK for adults with MDD with suicidality. Trial registration: ClinicalTrials.gov registry NCT03039192 (registered February 1, 2017) and NCT03097133 (registered March 31, 2017). [ABSTRACT FROM AUTHOR]

Background/Aims Stigma related with antidepressants is prevalent in patients with functional dyspepsia. It affects medication compliance and efficacy. Herbal medicine acquired a deep-rooted cultural identity in relieving dyspeptic symptoms in Asians. The research was designed to compare the effectiveness of Zhizhu Kuanzhong capsules (ZZKZ) versus doxepin hydrochloride (doxepin) on alleviating stigma and medication nonadherence among patients with refractory FD (rFD). Methods Patients with rFD from February 2021 to February 2022 were randomly allocated to receive either doxepin (n = 56) or ZZKZ (n = 57) combined with omeprazole for 4 weeks. Medication possession ratio (MPR), the disease- and medication-associated stigma were analyzed. The scales were utilized to assess dyspeptic symptoms (Leeds Dyspepsia Questionnaire) and psychological conditions (Generalized Anxiety Disorder Questionnaire and Patient Health Questionnaire). Results The MPR values for ZZKZ were significantly higher than those for doxepin (P < 0.001). The stigma scores decreased in ZZKZ group while increased in doxepin group compared to baseline after treatment. The proportion of patients showing ZZKZ-associated stigma was significantly lower than doxepin-associated stigma (P < 0.001). The MPR values were negatively correlated with posttreatment stigma scores in both groups (P < 0.001). Dyspeptic symptoms and psychological condition were improved in both groups after treatment, with no significant difference on post-treatment Leeds Dyspepsia Questionnaire, Generalized Anxiety Disorder Questionnaire, or Patient Health Questionnaire scores between 2 groups. Conclusion ZZKZ is superior to doxepin in alleviating stigma and medication non-adherence, with comparable efficacy in improving dyspeptic symptoms and psychological condition of patients with rFD. [ABSTRACT FROM AUTHOR]

Depression is one of the most common neuropsychiatric disorders and is associated with dysfunction of the neuroendocrine system and alterations in specific brain proteins. Boophone disticha (BD) is an indigenous psychoactive bulb that belongs to the Amaryllidacae family, which is widely used in Southern Africa to treat depression, with scientific evidence of potent antidepressant-like effects. The present study examined the antidepressant effects of BD and its mechanisms of action by measuring some behavioural parameters in the elevated plus maze, brain content of corticosterone, brain derived neurotropic factor (BDNF), and neuroblast differentiation in the hippocampus of Balb/c mice exposed to the five day repeated forced swim stress (5d-RFSS). Male Balb/c mice were subjected to the 5d-RFSS protocol to induce depressive-like behaviour (decreased swimming, increased floating, decreased open arm entry, decreased time spent in the open arms and decreased head dips in the elevated plus maze test) and treated with distilled water, fluoxetine and BD. BD treatment (10 mg/kg/p.o for 3 weeks) significantly attenuated the 5d-RFSS-induced behavioural abnormalities and the elevated serum corticosterone levels observed in stressed mice. Additionally, 5d-RFSS exposure significantly decreased the number of neuroblasts in the hippocampus and BDNF levels in the brain of Balb/c mice, while fluoxetine and BD treatment attenuated these changes. The antidepressant effects of BD were comparable to those of fluoxetine, but unlike fluoxetine, BD did not show any anxiogenic effects, suggesting better pharmacological functions. In conclusion, our study shows that BD exerted antidepressant-like effects in 5d-RFSS mice, mediated in part by normalizing brain corticosterone and BDNF levels. [ABSTRACT FROM AUTHOR]

Background: Serotonergic antidepressants may predispose to bleeding, but little is known of the risk for traumatic intracranial bleeding. Methods: This was a prospective case-control study of 218 patients with mild traumatic brain injuries (TBI) who were treated at a Finnish tertiary trauma hospital. Injury-related information and clinical findings were prospectively collected in the emergency department. Detailed pre-injury health history was collected from electronic medical records. Information on the use of serotonergic antidepressants was attained from the Finnish national prescription registry. All head CT scans were reviewed by a neuroradiologist based on the Common Data Elements. Cases were patients with traumatic intracranial hemorrhage on head CT. Controls were patients from the same cohort, but without traumatic intracranial lesions on CT. The proportion with traumatic intracranial bleeding for patients on serotonergic antidepressant medication was compared to the proportion for patients not on serotonergic medication. Results: The study cohort consisted of 24 cases with traumatic intracranial bleeding and 194 injured controls. The median age of the sample was 70 years (interquartile range = 50-83). One fifth (21.6%) of all the patients were taking a serotonergic antidepressant. Of the patients on an antidepressant, 10.6% (5/47) had an acute hemorrhagic lesion compared to 11.1% (19/171) of those who were not on an antidepressant (p = 0.927). In the regression analysis, traumatic intracranial hemorrhage was not associated with antidepressant use. Conclusion: Serotonergic antidepressant use was not associated with an increased risk of traumatic intracranial hemorrhage after a mild TBI. The patients in this relatively small cohort were mostly middle-aged and older adults. These factors limit the generalizability of the results in younger patients with mild TBI. [ABSTRACT FROM AUTHOR]

BackgroundSerotonergic antidepressants may predispose to bleeding, but little is known of the risk for traumatic intracranial bleeding.MethodsThis was a prospective case-control study of 218 patients with mild traumatic brain injuries (TBI) who were treated at a Finnish tertiary trauma hospital. Injury-related information and clinical findings were prospectively collected in the emergency department. Detailed pre-injury health history was collected from electronic medical records. Information on the use of serotonergic antidepressants was attained from the Finnish national prescription registry. All head CT scans were reviewed by a neuroradiologist based on the Common Data Elements. Cases were patients with traumatic intracranial hemorrhage on head CT. Controls were patients from the same cohort, but without traumatic intracranial lesions on CT. The proportion with traumatic intracranial bleeding for patients on serotonergic antidepressant medication was compared to the proportion for patients not on serotonergic medication.ResultsThe study cohort consisted of 24 cases with traumatic intracranial bleeding and 194 injured controls. The median age of the sample was 70 years (interquartile range = 50–83). One fifth (21.6%) of all the patients were taking a serotonergic antidepressant. Of the patients on an antidepressant, 10.6% (5/47) had an acute hemorrhagic lesion compared to 11.1% (19/171) of those who were not on an antidepressant (p = 0.927). In the regression analysis, traumatic intracranial hemorrhage was not associated with antidepressant use.ConclusionSerotonergic antidepressant use was not associated with an increased risk of traumatic intracranial hemorrhage after a mild TBI. The patients in this relatively small cohort were mostly middle-aged and older adults. These factors limit the generalizability of the results in younger patients with mild TBI.

Given the high rate of depression associated with narcolepsy or obstructive sleep apnea (OSA), this analysis compared effects of solriamfetol treatment of excessive daytime sleepiness (EDS) in participants with/without a history of depression (DHx+/DHx-). This secondary analysis included data from two randomized, controlled trials in which participants were randomized to 12 weeks placebo or solriamfetol 37.5 (OSA only), 75, 150, or 300 mg/day. Efficacy/safety (combined solriamfetol doses) was summarized for DHx+/DHx-subgroups. 27.5% (65/236) with narcolepsy and 23.4% (111/474) with OSA were DHx+. In narcolepsy (DHx+ and DHx-), 40-min Maintenance of Wakefulness Test (MWT40) mean sleep latency increased (5.4 and 7.0 min), Epworth Sleepiness Scale (ESS) score decreased (3.8 and 3.5 points), and percentage of participants improved on Patient Global Impression of Change (PGI-C) was higher (31.7% and 39.4%) relative to placebo. In OSA (DHx+ and DHx-), MWT40 mean sleep latency increased (7.7 and 10.7 min), ESS decreased (3.5 and 3.7 points), and percentage of participants improved on PGI-C was higher (41.1% and 29.4%) relative to placebo. Common treatment-emergent adverse events (headache, decreased appetite, nausea, anxiety) were similar in DHx+/DHx-. This study suggests that safety and efficacy of solriamfetol for treating EDS in narcolepsy and OSA are not affected by depression history. Moreover, the findings emphasize the high prevalence of depression in people with sleep disorders and suggest that increased awareness of this association may have clinical significance. [Display omitted] • Solriamfetol treatment outcomes were analyzed according to depression history. • Depression history was prevalent in people with narcolepsy/obstructive sleep apnea. • Solriamfetol improved excessive daytime sleepiness regardless of depression history. • Concomitant antidepressant use did not affect response to solriamfetol. • Safety/tolerability was similar regardless of depression history/antidepressant use. [ABSTRACT FROM AUTHOR]

The occurrence of heavy menstrual bleeding (HMB) induced by pharmacological agents has been reported in young adult women. This study aimed to investigate a possible association between the occurrence rates of HMB and different treatment methods such as antidepressant agents alone and in combination with other pharmacological agents. The examined cohort included young women (age 18-35 years, n = 1,949) with bipolar disorder (BP) or major depressive disorder (MDD). Menstruation history for 24 months was recorded and evaluated according to pictorial blood loss assessment charts of HMB.Multivariate analyses were conducted to determine odds ratios (ORs) and 95% confidence intervals. The examined antidepressant agents had varying ORs for patients with BP vs. those with MDD. For example, the ORs of venlafaxine-induced HMB were 5.27 and 4.58 for patients with BP and MDD, respectively; duloxetine-induced HMB, 4.72 and 3.98; mirtazapine-induced HMB, 3.26 and 2.39; fluvoxamine-induced HMB, 3.11 and 2.08; fluoxetine-induced HMB, 2.45 and 1.13; citalopram-induced HMB, 2.03 and 1.25; escitalopram-induced HMB, 1.85 and 1.99; agomelatine-induced HMB, 1.45 and 2.97; paroxetine-induced HMB, 1.19 and 1.75; sertraline-induced HMB, 0.88 and 1.13; reboxetine-induced HMB, 0.45 and 0.45; and bupropion-induced HMB, 0.33 and 0.37, in each case. However, when antidepressant agents were combined with valproate, the OR of HMB greatly increased, with distinct profiles observed for patients with BP vs. those with MDD. For example, the ORs of HMB induced by venlafaxine combined with valproate were 8.48 and 6.70 for patients with BP and MDD, respectively; for duloxetine, 5.40 and 4.40; mirtazapine, 5.67 and 3.73; fluvoxamine, 5.27 and 3.37; fluoxetine, 3.69 and 4.30; citalopram, 5.88 and 3.46; escitalopram, 6.00 and 7.55; agomelatine, 4.26 and 5.65; paroxetine, 5.24 and 3.25; sertraline, 4.97 and 5.11; reboxetine, 3.54 and 2.19; and bupropion, 4.85 and 3.46, in each case. In conclusion, some antidepressant agents exhibited potential risks of inducing HMB. Therefore, a combined prescription of antidepressant agents and valproate should be carefully considered for young women with HMB. [ABSTRACT FROM AUTHOR]

Abstract Background Traditionally tricyclic antidepressants (TCAs) have an important place in treatment of major depressive disorder (MDD). Today, often other antidepressant medications are considered as first step in the pharmacological treatment of MDD, mainly because they are associated with less adverse effects, whereby the position of TCAs appears unclear. In this study we aimed to examine the current practice of TCAs in treatment of unipolar MDD. Methods A mixed methods approach was applied. First, a selection of leading international and national guidelines was reviewed. Second, actual TCA prescription was examined by analyzing health records of 75 MDD patients treated with the TCAs nortriptyline, clomipramine or imipramine in different centers in the Netherlands. Third, promotors and barriers influencing the choice for TCAs and dosing strategies were explored using semi-structured interviews with 24 Dutch psychiatrists. Results Clinical practice guidelines were sometimes indirective and inconsistent with each other. Health records revealed that most patients (71%) attained therapeutic plasma concentrations within two months of TCA use. Patients who achieved therapeutic plasma concentrations reached them on average after 19.6 days (SD 10.9). Both health records and interviews indicated that therapeutic nortriptyline concentrations were attained faster compared to other TCAs. Various factors were identified influencing the choice for TCAs and dosing by psychiatrists. Conclusions Guideline recommendations and clinical practice regarding TCA prescription for MDD vary. To increase consistency in clinical practice we recommend development of an up-to-date guideline integrating selection and dosing of TCAs, including the roles of therapeutic drug monitoring and pharmacogenetics. Such a guideline is currently lacking and would contribute to optimal TCA treatment, whereby efficacy and tolerability may be increased.

Vitamin E has various functions in humans, including antioxidant, anti-inflammatory, anti-cancer, and anti-atherogenic actions, as well as direct effects on enzymatic activities and modulation of gene transcription. In addition to these functions, vitamin E is also important for the central nervous system, and its role in the prevention and/or treatment of some neurological diseases has been suggested. In particular, the role of vitamin E in the modulation of major depressive disorder (MDD) is an issue that has emerged in recent studies. Many factors have been implicated in the pathophysiology of this disorder, including inflammation, oxidative, and nitrosative stress. This narrative review discusses the involvement of inflammation, oxidative, and nitrosative stress in the pathophysiology of MDD and presents clinical and preclinical studies that correlate vitamin E with this psychiatric disorder. We gathered evidence from clinical studies that demonstrated the relationship between low vitamin E status and MDD symptoms. Vitamin E has been reported to exert a beneficial influence on the oxidative and inflammatory status of individuals, factors that may account for the attenuation of depressive symptoms. Preclinical studies have reinforced the antidepressant-like response of vitamin E, and the mechanisms underlying its effect seem to be related to the modulation of oxidative stress and neuroinflammation. We suggest that vitamin E has potential to be used as an adjuvant for the management of MDD, but more studies are clearly needed to ascertain the efficacy of vitamin E for alleviating depressive symptoms. [ABSTRACT FROM AUTHOR]

Purpose To assess the concurrent validity of a single question on medication use for depression in a general population survey. Methods: Using data from 2015 to 2016 and 2017 to 2018 National Health and Nutrition Examination Survey, we compared responses to a single question on medication use for depression with responses to a detailed questionnaire confirmed by inspecting medication packages or pharmacy printouts. Results: There was a strong agreement (96.4%) between response to a single question about using medication for depression and responses to questions about using antidepressants or other psychiatric medications for depression on the detailed questionnaire. The single‐question assessment had excellent sensitivity (93.8%) and specificity (96.7%), positive predictive value (71.5%), and kappa (0.79). Psychometric properties were mostly consistent across population subgroups. Conclusions: Single‐question assessments of medication use for depression have acceptable concurrent validity against more detailed assessments and provide an efficient method for assessing medication treatment of depression in population health surveys. [ABSTRACT FROM AUTHOR]

Sertraline hydrochloride is a first-line antidepressant with potential antineoplastic properties because of its structural similarity with other drugs capable to inhibit the translation-controlled tumor protein (TCTP), a biomolecule involved in cell proliferation. Recent studies suggest it could be repositioned for cancer treatment. In this review, we systematically map the findings that repurpose sertraline as an antitumoral agent, including the mechanisms of action that support this hypotesis. From experimental in vivo and in vitro tumor models of thirteen different types of neoplasms, three mechanisms of action are proposed: apoptosis, autophagy, and drug synergism. The antidepressant is able to inhibit TCTP, modulate chemotherapeutical resistance and exhibit proper cytotoxicity, resulting in reduced cell counting (in vitro) and shrunken tumor masses (in vivo). A mathematical equation determined possible doses to be used in human beings, supporting that sertraline could be explored in clinical trials as a TCTP-inhibitor.

Forkhead box-O (FoxO) transcriptional factors perform essential functions in several physiological and biological processes. Recent studies have shown that FoxO is implicated in the pathophysiology of depression. Changes in the upstream mediators of FoxOs including brain-derived neurotrophic factor (BDNF) and protein kinase B have been associated with depressive disorder and the antidepressant agents are known to alter the phosphorylation of FoxOs. Moreover, FoxOs might be regulated by serotonin or noradrenaline signaling and the hypothalamic-pituitary-adrenal (HPA)-axis,both of them are associated with the development of the depressive disorder. FoxO also regulates neural morphology, synaptogenesis, and neurogenesis in the hippocampus, which accounts for the pathogenesis of the depressive disorder. The current article underlined the potential functions of FoxOs in the etiology of depressive disorder and formulate few essential proposals for further investigation. The review also proposes that FoxO and its signal pathway might establish possible therapeutic mediators for the management of depressive disorder. [ABSTRACT FROM AUTHOR]

Background: Serotonergic antidepressants may predispose to bleeding but the effect on traumatic intracranial bleeding is unknown. Methods: The rate of intracranial bleeding in patients with antidepressant medication was compared to patients not antidepressants in a cohort of patients with acute head injury. This association was examined by using a consecutive cohort of head trauma patients from a Finnish tertiary center emergency department (Tampere University Hospital, Tampere, Finland). All consecutive (2010–2012) adult patients (n = 2,890; median age = 58; male = 56%, CT-positive = 22%, antithrombotic medication users = 25%, antidepressant users = 10%) who underwent head CT due to head trauma in the emergency department were included. Results: Male gender, GCS <15, older age, and anticoagulation were associated with an increased risk for traumatic intracranial bleeding. There were 17.8% of patients not taking antidepressants and 18.3% of patients on an antidepressant who had traumatic intracranial bleeding (p = 0.830). Among patients who were taking antithrombotic medication, 16.6% of the patients not taking antidepressant medication, and 22.5% of the patients taking antidepressant medication, had bleeding (p = 0.239). In a regression analysis, traumatic intracranial hemorrhage was not associated with antidepressant use. Conclusions: Serotonergic antidepressant use was not associated with an increased risk of traumatic intracranial hemorrhage. [ABSTRACT FROM AUTHOR]

Background: Traditionally tricyclic antidepressants (TCAs) have an important place in treatment of major depressive disorder (MDD). Today, often other antidepressant medications are considered as first step in the pharmacological treatment of MDD, mainly because they are associated with less adverse effects, whereby the position of TCAs appears unclear. In this study we aimed to examine the current practice of TCAs in treatment of unipolar MDD. Methods: A mixed methods approach was applied. First, a selection of leading international and national guidelines was reviewed. Second, actual TCA prescription was examined by analyzing health records of 75 MDD patients treated with the TCAs nortriptyline, clomipramine or imipramine in different centers in the Netherlands. Third, promotors and barriers influencing the choice for TCAs and dosing strategies were explored using semi-structured interviews with 24 Dutch psychiatrists. Results: Clinical practice guidelines were sometimes indirective and inconsistent with each other. Health records revealed that most patients (71%) attained therapeutic plasma concentrations within two months of TCA use. Patients who achieved therapeutic plasma concentrations reached them on average after 19.6 days (SD 10.9). Both health records and interviews indicated that therapeutic nortriptyline concentrations were attained faster compared to other TCAs. Various factors were identified influencing the choice for TCAs and dosing by psychiatrists. Conclusions: Guideline recommendations and clinical practice regarding TCA prescription for MDD vary. To increase consistency in clinical practice we recommend development of an up-to-date guideline integrating selection and dosing of TCAs, including the roles of therapeutic drug monitoring and pharmacogenetics. Such a guideline is currently lacking and would contribute to optimal TCA treatment, whereby efficacy and tolerability may be increased. [ABSTRACT FROM AUTHOR]

Background: Serotonergic antidepressants may predispose to bleeding but the effect on traumatic intracranial bleeding is unknown.Methods: The rate of intracranial bleeding in patients with antidepressant medication was compared to patients not antidepressants in a cohort of patients with acute head injury. This association was examined by using a consecutive cohort of head trauma patients from a Finnish tertiary center emergency department (Tampere University Hospital, Tampere, Finland). All consecutive (2010–2012) adult patients (n = 2,890; median age = 58; male = 56%, CT-positive = 22%, antithrombotic medication users = 25%, antidepressant users = 10%) who underwent head CT due to head trauma in the emergency department were included.Results: Male gender, GCS

Abstract Introduction Pre‐treatment blood oxygenation level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) has been used for the early identification of patients with major depressive disorder (MDD) who later respond or fail to respond to medication. However, BOLD responses early after treatment initiation may offer insight into early neural changes associated with later clinical response. The present study evaluated both pre‐treatment and early post‐treatment fMRI responses to an emotion processing task, to further our understanding of neural changes associated with a successful response to pharmacological intervention. Methods MDD patients who responded (n = 22) and failed to respond (n = 12) after 8 weeks of treatment with either citalopram or quetiapine extended release, and healthy controls (n = 18) underwent two fMRI scans, baseline (pre‐treatment), and early post‐treatment (one week after treatment commencement). Participants completed an emotional face matching task at both scans. Results Using threshold‐free cluster enhancement (TFCE) and non‐parametric permutation testing, fMRI activation maps showed that after one week of treatment, responders demonstrated increased activation in the left parietal lobule, precentral gyrus, and bilateral insula (all P

Introduction: Pre‐treatment blood oxygenation level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) has been used for the early identification of patients with major depressive disorder (MDD) who later respond or fail to respond to medication. However, BOLD responses early after treatment initiation may offer insight into early neural changes associated with later clinical response. The present study evaluated both pre‐treatment and early post‐treatment fMRI responses to an emotion processing task, to further our understanding of neural changes associated with a successful response to pharmacological intervention. Methods: MDD patients who responded (n = 22) and failed to respond (n = 12) after 8 weeks of treatment with either citalopram or quetiapine extended release, and healthy controls (n = 18) underwent two fMRI scans, baseline (pre‐treatment), and early post‐treatment (one week after treatment commencement). Participants completed an emotional face matching task at both scans. Results: Using threshold‐free cluster enhancement (TFCE) and non‐parametric permutation testing, fMRI activation maps showed that after one week of treatment, responders demonstrated increased activation in the left parietal lobule, precentral gyrus, and bilateral insula (all P < 0.05 threshold‐free cluster enhancement (TFCE) family‐wise error‐corrected) to negative facial expressions. Non‐responders showed some small increases in the precentral gyrus, while controls showed no differences between scans. Compared to non‐responders, responders showed some increased activation in the superior parietal lobule and middle temporal gyrus at the post‐treatment scan. There were no group differences between responders, non‐responders, and controls at baseline. Conclusions: One week after treatment commencement, BOLD signal changes in the parietal lobules, insula, and middle temporal gyrus were related to clinical response to pharmacological treatment. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the risk of first-time antidepressant prescriptions as a proxy for depression or anxiety and associated risk factors in patients with prostate cancer and their female partners. Methods: We followed all men (n = 25,126) and their female cohabiting partners (n = 8785) without a history of cancer or antidepressants from the Danish Diet, Cancer and Health cohort from 1997 to 2014 or 2010, respectively. We estimated the cumulative incidence of first-time antidepressant prescriptions in men with prostate cancer compared with cancer-free men and their respective female partners, using the Danish National Prescription Registry. Sociodemographic, lifestyle-related, and clinical risk factors were assessed using Cox regression models. Results: A total of 1828 men were diagnosed with prostate cancer of whom 15% received antidepressants. The unadjusted hazard ratio of antidepressant prescription was 2.18 (95%CI, 1.92, 2.48) for men with prostate cancer and 1.27 (95%CI, 0.87, 1.85) for their partners, compared with cancer-free men and their partners, respectively. After adjusting for sociodemographic, lifestyle-related, and comorbidity factors, this risk was 2-fold to 4-fold increased among patients, but not significantly increased among partners. Significant risk factors among patients were curative and palliative treatment (vs. active surveillance and watchful waiting), nonlocalized disease, and short education. Conclusions: Men with prostate cancer have a higher risk of receiving antidepressant medication than cancer-free men. Clinical characteristics can help clinicians in identifying patients at a high risk of depression or anxiety. Implications for Cancer Survivors: Men with prostate cancer who experience symptoms of depression or anxiety should seek professional help early on. Patient education could aid in raising awareness and reducing the stigma associated with mental disorders. [ABSTRACT FROM AUTHOR]

Purpose: We sought to compare the effectiveness of physical exercise with that of treatment with antidepressant drugs routinely used in clinical practice, in terms of decreasing depressive symptomatology in patients aged ≥65 years who present with clinical criteria of a depressive episode.Methods: We conducted a randomized clinical trial in a primary care setting. A total of 347 patients aged ≥65 years with a clinically significant depressive episode were randomized to participation in a supervised physical exercise program or to receive antidepressant treatment by their general practitioners.Results: Intention-to-treat analysis showed that the cumulative incidence of improvement in depressive symptomatology (Montgomery-Åsberg Depression Rating Scale score <10) in the physical activity (PA) group after 1 month was not significantly different from that in the antidepressant treatment (AT) group. However, the proportion of those who showed improvement was significantly greater (P <.01) in the AT group (60.6% and 49.7%) compared to the PA group (45.6% and 32.9%) at the end of 3 and 6 months, respectively. The number of withdrawals was greater in the PA group (39.2% and 58.2%) compared to the AT group (22.6% and 40.0%) at 3 and 6 months, respectively, yet the proportion of participants with adverse side effects was greater in the AT group (8.9% vs 22.5%; P = .007).Conclusion: Although improvement was initially similar in both treatment groups, AT was superior in the medium term, despite giving rise to a greater number of adverse effects. [ABSTRACT FROM AUTHOR]

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The currently available clinical antidepressants can be classified into 13 different classes based on their mechanisms of action. These basic pharmacological concepts thoroughly elucidate and unravel the therapeutic actions and side effects of the wide range of antidepressants currently available. The two classical mechanisms are exhibited by tricyclic antidepressants (TCAs) and by monoamine oxidase inhibitors (MAOIs). Regarding the 11 relatively nonclassical antidepressants, the most widely prescribed agents are the selective serotonin reuptake inhibitors (SSRIs). The mechanisms of action for the other classes of antidepressants that exhibit additional actions on serotonergic neurotransmission are dual serotonin-norepinephrine reuptake inhibition (SNRI), serotonin receptors antagonism with serotonin reuptake inhibition (SARI), serotonin 5-HT1Aautoreceptor partial agonism with serotonin reuptake inhibition (SPARI), serotonin-norepinephrine reuptake inhibition and serotonin receptors antagonism antidepressant with potent antipsychotic D2 receptor blockade/antagonism (SNRISA with potent antipsychotic D2 receptor blockade/antagonism), norepinephrine reuptake inhibition with serotonin receptors antagonism (NRISA), noradrenergic α2-receptor antagonism with specific serotonergic receptors-2 and-3 antagonism (NASSA), and atypical antipsychotics that exhibit weak D2receptor antagonism with potently strong 5-HT2Areceptor blockade. Furthermore, the two classes that exhibit selective norepinephrine reuptake inhibition (NRI) and dual norepinephrine-dopamine reuptake inhibition (NDRI) define separate novel classes of antidepressants that have a direct action on the noradrenergic neurotransmission system but have no direct action on the serotonergic neurotransmission system, while the last remaining one class of N-methyl-D-aspartate-glutamatergic ionoceptor antagonist/inverse agonist/partial agonist also represents a separate novel class of antidepressants with a direct action on the excitatory glutamatergic neurotransmission system but no direct action on the serotonergic, noradrenergic, or dopaminergic neurotransmission systems. Lastly, this review remarkably advocates for the incorporation of the atypical antipsychotics and NMDA-glutamatergic ionoceptor antagonist/inverse agonist/partial agonist as new member classes of the antidepressant agents because of their clinically significant roles in the management of depression disorders.

Depression is a multifactorial disorder that affects millions of people worldwide, and none of the currently available therapeutics can completely cure it. Thus, there is a need for developing novel, potent, and safer agents. Recent medicinal chemistry findings on the structure and function of the serotonin 2A (5-HT2A) receptor facilitated design and discovery of novel compounds with antidepressant action. Eligible papers highlighting the importance of 5-HT2A receptors in the pathomechanism of the disorder were identified in the content-screening performed on the popular databases (PubMed, Google Scholar). Articles were critically assessed based on their titles and abstracts. The most accurate papers were chosen to be read and presented in the manuscript. The review summarizes current knowledge on the applicability of 5-HT2A receptor signaling modulators in the treatment of depression. It provides an insight into the structural and physiological features of this receptor. Moreover, it presents an overview of recently conducted virtual screening campaigns aiming to identify novel, potent 5-HT2A receptor ligands and additional data on currently synthesized ligands acting through this protein.

Opioid analgesics have been used for a long time in the treatment of acute and chronic pain. However, they have many side effects including tolerance development to a significant extent. Agomelatine, an atypical antidepressant, has been demonstrated to be effective in experimental studies on pain. However, the effect of agomelatine on morphine tolerance development and its mechanism of action are unknown. The antinociceptive effects of agomelatine, morphine and their combination were assessed in a mice model for painful diabetic neuropathy. The roles of glutamate ionotropic receptor N-methyl-D-aspartate (NMDA) type subunit-1 (GluN1) in raphe nucleus and periaqueductal gray (PAG) in the effect of agomelatine on neuropathic pain were also investigated in diabetic mice. Agomelatine (10 mg/kg), morphine (10 mg/kg) and agomelatine + morphine were administered intraperitoneally for 15 consecutive days (twice per day), and the analgesic responses were assessed at days 1, 3, 6, 9, 12 and 15 in healthy and diabetic mice. Real time polymerase chain reaction (RT-PCR) was used to determine the changes in GluN1 expression. The tolerance development for morphine was evident, started at 6th day and remained thereafter, but not for agomelatine. GluN1 in raphe nucleus and PAG was upregulated in morphine treated but not in agomelatine-treated groups. The combination of agomelatine with morphine alone causes outlasting analgesic effects of repeated treatment, which can be interpreted as attenuated tolerance. Moreover, we also pointed out for the first time the modulatory effects of agomelatine on GluN1 expression in raphe nucleus and PAG after chronic morphine treatment. Ca2+: Calcium; D2DR: Dopamine D2 receptor; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; GluN1: Glutamate ionotropic receptor N-methyl-D-aspartate type subunit-1; 5-HT: 5-hydroxytryptamine; i.p.: intraperitoneal injection; MPE: Maximal possible effect; MT: Melatonin; NMDA: N-methyl-D-aspartate; NMDAR1: NMDA receptors-1; PAG: Periaqueductal grey; PKCγ: Protein kinase C gamma; RT-PCR: Real time polymerase chain reaction; STZ: Streptozotocin [ABSTRACT FROM AUTHOR]

Objective:We aimed to investigate the effects of a structured cognitive behavioral group therapy (CBGT) on weight loss, depression, anxiety, body image and self-esteem levels in women with obesity treatment and to show that cognitive behavioral therapy may also be effective in the treatment of obese women receiving antidepressant medication in our study. Methods: Fourteen sessions of CBGT were administered to 28 obese female patients who met inclusion criteria. Measurement and clinical scale application were made before and after the therapy. Six months after the therapy, the patients were asked about their weight by phone call. Sociodemographic Information Form, body mass index (BMI) monitoring, DSM-IV based Structured Clinical Interview, State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Short Form-36 (SF-36), and Symptom Check List-90 (SCL-90) were applied to the cases. Results: A statistically significant decrease in patients' weight and body mass index were found after 14 sessions of therapy (p<0,001). Statistically significant difference were found about the BDI (p=0,009), TAI (p=0,020), SCL-90 (p=0,001), SF-36 physical function (p=0.035), SF-36 general health (p=0.004), SF-36 social function (p=0.034) scores between the beginning and the end of the therapy. There was no statistically significant difference between the measurements of BMIs at the end of therapy and at the end of therapy. Conclusion: We can say that the method we applied with the findings obtained works. According to this, CBGT is a suitable treatment method for obese people in controlling BMI, providing psychological well-being and improving quality of life. [ABSTRACT FROM AUTHOR]

The phenomenon of drug-induced mania, i.e., a manic episode associated with the use of pharmacotherapy (in particular antidepressants) is well defined and described in groups of adult patients. The negative effect on the course of bipolar disorder has been confirmed. In the group of children and adolescents, this subject is still poorly known and rarely described because of controversies in diagnosing early-onset bipolar disorder. The authors present an overview of current research on this problem starting from case reports, through open studies to randomized trials. Because the results of studies are ambiguous, the main problems that hinder the formulation of objective conclusions and the most important directions for further research are also discussed. The authors also present current hypotheses on the phenomenon of drug-induced mania in children and adolescents to systematize knowledge on the subject and provide diagnostic help in everyday clinical work. In a group of children and adolescents, there is a need to differentiate the phenomenon of drug-induced mania depending on the basic disorder, because similarly to studies that concern adult patients this problem seems to occur more frequently in patients with bipolar disorder than in other psychiatric disorders. It seems that the diagnosis of drug-induced mania is possible in children and adolescents at the present stage of knowledge, however, the assessment of the prevalence of this phenomenon requires careful evaluation in further studies. [ABSTRACT FROM AUTHOR]

Background: This research was designed to investigate Algorithm Guided Treatment (AGT) and clinical traits for the prediction of antidepressant treatment outcomes in Chinese patients with major depressive disorder (MDD)., Methods: This study included 581 patients who had reached treatment response and 406 patients remained non-responded observed after three months of treatment. Sociodemographic factors, clinical traits, and psychiatric rating scales for evaluating therapeutic responses between the two groups were compared. Logistic regression analysis was adopted to determine the risk factors of unresponsive to antidepressant (URA) in MDD. Kaplan-Meier survival analysis was utilized to compare the therapeutic response between AGT and treatment as usual (TAU)., Results: Compared to the MDD responsive to antidepressant (RA) group, the URA group had significantly lower rates of the following clinical traits: married status, anxious distress, moderate to severe depressive symptoms, and higher rates of comorbidity ( p-value < 0.05). Logistic Regression Analysis showed that eight clinical traits from psychiatric rating scales, such as anxious characteristics, were correlated positively with URA, while the other eight symptoms, such as autonomic symptoms, were negatively correlated. Time to symptomatic remission was longer in TAU without statistically significant ( p-value  = 0.11) by log-rank testing., Conclusions: The factors may affect the therapeutic responses and compliance of patients, increasing the non-response risk for antidepressants. Therapeutic responses might be improved by increasing the clarification and elucidation of different symptom clusters of patients. Benefits on treatment response to AGT were not found in our study, indicating a one-size-fits-all approach may not work. Trial Registration: We registered as a clinical trial at the International Clinical Trials Registry Platform (No. NCT01764867) and obtained ethical approval 2012-42 from SMHC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: To assess whether neighbourhood deprivation is associated with exposure to an antidepressant drug treatment (ADT) and its quality among individuals diagnosed with unipolar depression and insured by the Quebec public drug plan.Method: We conducted an administrative database cohort study of adults covered by the Quebec public drug plan who were diagnosed with a new episode of unipolar depression. We assessed material and social deprivation using an area-based index. We considered exposure to an ADT as having ≥1 claim for an ADT within the 365 days following depression diagnosis. Among those exposed to ADT, ADT quality was assessed with 3 indicators: first-line recommended ADT, persistence with the ADT, and compliance with the ADT. Generalized linear models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (95% CI).Results: Of 100,432 individuals with unipolar depression, 65,436 (65%) were exposed to an ADT in the year following the diagnosis. Individuals living in the most materially deprived areas were slightly more likely to be exposed to an ADT than those living in the least deprived areas (aPR, 1.04; 95% CI, 1.03 to 1.06). The likelihoods of being exposed to a first-line ADT, persisting for the minimum recommended duration and complying with the ADT were independent of the deprivation levels.Conclusions: Neighbourhood deprivation was not associated with ADT quality among individuals insured by the Quebec public drug plan. It might be partly attributable to the public drug plan whose goal is to provide equitable access to prescription drugs regardless of income. [ABSTRACT FROM AUTHOR]

Purpose To assess the accuracy of using diagnostic codes from administrative data to infer treatment indications for antidepressants prescribed in primary care. Methods: Validation study of administrative diagnostic codes for 13 plausible indications for antidepressants compared with physician‐documented treatment indications from an indication‐based electronic prescribing system in Quebec, Canada. The analysis included all antidepressant prescriptions written by primary care physicians between January 1, 2003 and December 31, 2012 using the electronic prescribing system. Patient prescribed antidepressants were linked to physician claims and hospitalization data to obtain all diagnoses recorded in the past year. Results: Diagnostic codes had poor sensitivity for all treatment indications, ranging from a high of only 31.2% (95% CI, 26.8%‐35.9%) for anxiety/stress disorders to as low as 1.3% (95% CI, 0.0%‐5.2%) for sexual dysfunction. Sensitivity was notably worse among older patients and patients with more chronic comorbidities. Physician claims data were a better source of diagnostic codes for antidepressant treatment indications than hospitalization data. Conclusions: Administrative diagnostic codes are poor proxies for antidepressant treatment indications. Future work should determine whether the use of other variables in administrative data besides diagnostic codes can improve the ability to predict antidepressant treatment indications. [ABSTRACT FROM AUTHOR]

The present contribution aims to design new-generation bar adsorptive microextraction (BAμE) devices that promote an innovative and much better user-friendly analytical approach. The novel BAμE devices were lab-made prepared having smaller dimensions by using flexible nylon-based supports (7.5 × 1.0 mm) coated with convenient sorbents (≈ 0.5 mg). This novel advance allows effective microextraction and back-extraction (‘only single liquid desorption step’) stages as well as interfacing enhancement with the instrumental systems dedicated for routine analysis. To evaluate the achievements of these improvements, four antidepressant agents (bupropion, citalopram, amitriptyline and trazodone) were used as model compounds in aqueous media combined with liquid chromatography (LC) systems. By using an N -vinylpyrrolidone based-polymer phase good selectivity and efficiency were obtained. Assays performed on 25 mL spiked aqueous samples, yielded average recoveries in between 67.8 ± 12.4% (bupropion) and 88.3 ± 12.1% (citalopram), under optimized experimental conditions. The analytical performance also showed convenient precision (RSD < 12%) and detection limits (50 ng L −1 ), as well as linear dynamic ranges (160–2000 ng L −1 ) with suitable determination coefficients ( r 2  > 0.9820). The application of the proposed analytical approach on biological fluids showed negligible matrix effects by using the standard addition methodology. From the data obtained, the new-generation BAμE devices presented herein provide an innovative and robust analytical cycle, are simple to prepare, cost-effective, user-friendly and compatible with the current LC autosampler systems. Furthermore, the novel devices were designed to be disposable and used together with negligible amounts of organic solvents (100 μL) during back-extraction, in compliance with the green analytical chemistry principles. In short, the new-generation BAμE devices showed to be an eco-user-friendly approach for trace analysis of priority compounds in biological fluids and a versatile alternative over other well-stablished sorption-based microextraction techniques. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Administrative claim databases are increasingly being used to study the safety of medication exposures during pregnancy. These studies are restricted to live births due to a reliance on algorithms for estimating gestational age that are based on codes associated with live delivery. Conditioning on live birth may induce selection bias when studying the effect of a drug on a pregnancy complication if fetal death is a competing risk for the complication or is caused by the complication. Methods: We simulated a population of 100,000 pregnancies and estimated the impact of selection bias on relative estimates for the effect of antidepressant exposure on the outcome of preeclampsia. We assumed that the exposure, outcome, and covariates increased the risk of fetal loss. Results: A downward bias in the risk ratio was consistently observed when conditioning on live births. When an unmeasured covariate was assumed to be a common cause of fetal death, antidepressant use, and preeclampsia, the direction of bias varied depending on the strength of the confounding relationship coupled with the selection bias. Despite the very low prevalence of stillbirth, the strength of the relationship between antidepressant use and stillbirth had a substantial impact on bias. Conclusions: Conditioning on live birth can be problematic when studying pregnancy complications. Simple quantitative selection bias analysis in populations restricted to live births may not fully account for selection bias. [ABSTRACT FROM AUTHOR]

Background: Some individuals with major depressive disorder do not experience a remission even after one or more adequate treatment trials. In some others who experience remission, it happens at variable times. This study sought to estimate the prevalence of nonremission in a large sample of patient participating in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial and to identify correlates of nonremission and time to remission among remitters.Methods: Using data from 3,606 participants of STAR*D, the study used cure regression modeling to estimate nonremission and jointly model correlates of nonremission and time to remission among the remitters.Results: Overall, 14.7% of the STAR*D participants were estimated to be nonremitters. Among remitters, the rate of remission declined over time. Greater severity, poorer physical health, and poor adherence with treatments were associated with both nonremission and a longer time to remission among the remitters in multivariable analyses, whereas unemployment, not having higher education, and longer duration of current episode were uniquely associated with nonremission; whereas, treatment in specialty mental health settings, poorer mental health functioning, and greater impairment in role functioning with a longer time to remission among remitters.Conclusion: Poor treatment adherence and poor physical health appear to be common risk factors for both nonremission and longer time to remission, highlighting the importance of integrated care models that address both medical and mental healthcare needs and interventions aimed at improving treatment adherence. [ABSTRACT FROM AUTHOR]

Background: Antidepressant use has increased exponentially in recent decades, mostly due to long continuation. Aim: To assess the effectiveness of a tailored recommendation to withdraw antidepressant treatment. Design & setting: Randomised controlled trial in primary care (PANDA study) in the Netherlands Method: Long-term antidepressant users (≥9 months) were selected from GPs prescription databases. Patients were diagnosed with the Composite International Diagnostic Interview (CIDI). Long-term users without indication for maintenance treatment (overtreatment) were selected. The intervention consisted of disclosure of the current psychiatric diagnosis combined with a tailored treatment recommendation. Patients were followed for 12 months. Results: The study included 146 participants from 45 family practices. Of the 70 patients in the intervention group, 34 (49%) did not comply with the advice to stop their antidepressant medication. Of the 36 (51%) patients who agreed to try, only 4 (6%) succeeded. These figures were consistent with the control group, where 6 (8%) of the 76 patients discontinued antidepressant use successfully. Patients who were recommended to discontinue their antidepressant medication reported a higher relapse rate than the control group (26% versus 13%, P = 0.05). Conclusion: Changing inappropriate long-term antidepressant use is difficult.

Objective: Despite the recognized anti-inflammatory potential of heterocyclic antidepressants, the mechanisms concerning their modulating effects are not completely known. Thus, we evaluated the anti-inflammatory effect of amitriptyline, clomipramine, and maprotiline and the possible modulating properties of these drugs on neutrophil migration and mast cell degranulation. Methods: The hind paw edema and air-pouch models of inflammation were used. Male Wistar rats were treated with saline, amitriptyline, clomipramine or maprotiline (10, 30, or 90 mg/kg, per os [p.o.]) 1 h before the injection of carrageenan (300 μg/0.1 mL/paw) or dextran (500 μg/0.1 mL/paw). Then, edema formation was measured hourly. Neutrophil migration to carrageenan (500 μg/pouch) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) (10-6 M/mL/pouch) was also investigated in 6-day-old air-pouch cavities. Compound 48/80-induced mast cell degranulation was assessed in the mesenteric tissues of antidepressant-treated rats. Results: All tested antidepressants prevented both carrageenan- and dextran-induced edema. The anti-inflammatory effect of these drugs partially depends on the modulation of neutrophil migration, since they significantly counteracted the chemotactic response of both carrageenan and fMLP (p < 0.01). Furthermore, amitriptyline, clomipramine and maprotiline inhibited compound 48/80-induced mast cell degranulation (p < 0.001). Conclusions: These results suggest an important anti-inflammatory role of heterocyclic antidepressants, which is dependent on the modulation of neutrophil migration and mast cell stabilization.

Objectives An evidence base for the treatment of mania and bipolar depression with psychotic symptoms is lacking. Nevertheless, clinicians may have a preference for treating episodes of bipolar disorder with or without psychotic symptoms in different ways, which is likely to reflect notions of differential efficacy of treatments between these subtypes. This study aimed to investigate whether the psychopharmacological treatment of psychotic and non-psychotic episodes of mania and bipolar depression, respectively, differs in clinical practice. Methods We conducted a register-based study assessing the psychopharmacological treatment of all individuals receiving their first diagnosis of mania or bipolar depression between 2010 and 2012. The psychopharmacological treatment within 3 months following the time of diagnosis was considered. Potential differences in psychopharmacological treatment between the psychotic and non-psychotic subtypes of mania and bipolar depression, respectively, were investigated by means of Pearson's χ2 test and logistic regression adjusted for sex and age at diagnosis of bipolar disorder. Results A total of 827 patients were included in the analyses. The adjusted odds ratio ( aOR) for treatment with an antipsychotic was 1.71 (95% confidence interval [CI]: 1.18-2.48, P<.01) for psychotic mania and 3.89 (95% CI: 1.95-7.76, P<.001) for psychotic bipolar depression. The aOR for treatment with the combination of an antipsychotic and an anticonvulsant was 1.60 (95% CI: 1.06-2.43, P<.05) for psychotic mania. The aOR for treatment with the combination of an antipsychotic and an antidepressant was 2.50 (95% CI: 1.43-4.37, P<.01) for bipolar psychotic depression. Conclusions It would be of interest to conduct studies evaluating whether antipsychotics represent the superior pharmacological treatment for psychotic mania and psychotic bipolar depression. [ABSTRACT FROM AUTHOR]

Background Patients with an antidepressant drug treatment (ADT) report unmet needs and a significant proportion stop their ADT prematurely. Community pharmacists can play a key role in supporting these patients. Objective To explore the perspectives of various leaders in health care about the current and potential contributions of community pharmacists to patients on ADT. Setting The province of Quebec (Canada). Method We conducted a qualitative descriptive exploratory study using interviews among leaders who were involved in health care services, pharmaceutical services, physician and pharmacist education, as well as patient and healthcare professional associations. Verbatim transcripts of interviews were analyzed using computer-assisted thematic analysis. Main outcome measure Perspectives about the contributions of community pharmacists to patients on ADT. Results Interviews revealed that pharmacists are perceived to be accessible drug experts whose particular strengths are their thorough knowledge of drugs, their commitment to ensure ADT safety and tolerability, as well as their commitment to inform and support patients. Leaders trained in pharmacy or representatives of pharmacy organizations had concrete expectations for pharmacists' increased involvement in monitoring ADT adherence and efficacy. They extensively discussed the regulatory and organizational changes required to enhance this role. Leaders also stated that, in addition to patients, health care teams could benefit from pharmacists' expertise and support. Conclusion Participating key informants perceived the need for enhanced pharmacist monitoring of ADT adherence and efficacy. They also expressed their openness to an increased collaboration between health care teams and pharmacists. [ABSTRACT FROM AUTHOR]

Aims:To analyse trends in depression diagnoses and antidepressant use according to age and gender. Methods:Nationwide cohort study including all women and men of 10–49 years living in Denmark during 2000–2013. The Psychiatric Registry and Prescription Registry provided data on depression diagnoses and antidepressant medication, respectively. Incidence rates as well as 1-year prevalence rates were calculated. Results:The incidence and 1-year prevalence rates of depression diagnoses increased during 2000–2013. The women/men rates were 2.0 for both 1-year prevalence of depressions diagnoses and antidepressant use. For adolescent girls, the absolute increase was 3 per 1000 for depression diagnoses and 8 per 1000 for first use of antidepressants, compared to boys who had an increase of 1.1 and 3 per 1000, respectively. Before puberty, boys and girls had almost the same incidence rates of both depression diagnoses and antidepressant use throughout the period. After puberty, girls had significantly higher incidence rates than boys, and experienced during the study period a steeper increase than boys. According to age, the girls/boys incidence rate ratio of a depression diagnosis increased from 0.8 in the 10–11 year age group to 2.7 at age 12–19 years and hereafter decreased with increasing age to 1.5 at age 45–49. Conclusions:Depression diagnosed and first use of antidepressants increased more for girls of 12–19 years than for boys during 2000–2013, and the incidences were similar for girls and boys before puberty, but higher after puberty for girls. [ABSTRACT FROM PUBLISHER]

Background: Despite an increasingly recognized relationship between depression and smoking, little is known about how smoking influences antidepressant response and treatment outcomes. The aim of this study was to systematically review the evidence of the impact of smoking on new-generation antidepressants with an emphasis on the pharmacokinetic perspective. Methods: We present a systematic review of clinical trials comparing the serum levels of new-generation antidepressants in smokers and nonsmokers. Data were obtained from MEDLINE/PubMed, Embase, and other sources. Risk of bias was assessed for selection, performance, detection, attrition, and reporting of individual studies. Results: Twenty-one studies met inclusion criteria; seven involved fluvoxamine, two evaluated fluoxetine, sertraline, venlafaxine, duloxetine or mirtazapine, and escitalopram, citalopram, trazodone and bupropion were the subject of a single study. No trials were found involving other common antidepressants such as paroxetine or agomelatine. Serum levels of fluvoxamine, duloxetine, mirtazapine and trazodone were significantly higher in nonsmokers compared with smokers. Conclusions: There is evidence showing a reduction in the concentration of serum levels of fluvoxamine, duloxetine, mirtazapine and trazodone in smoking patients as compared to nonsmokers. The evidence regarding other commonly used antidepressants is scarce. Nonetheless, smoking status should be considered when choosing an antidepressant treatment, given the risk of pharmacokinetic interactions. [ABSTRACT FROM AUTHOR]