Selective Serotonin Reuptake Research Articles

Advances in Therapeutics to Alleviate Cognitive Decline and Neuropsychiatric Symptoms of Alzheimer's Disease.

Dementia exists as a 'progressive clinical syndrome of deteriorating mental function significant enough to interfere with activities of daily living', with the most prevalent type of dementia being Alzheimer's disease (AD), accounting for about 80% of diagnosed cases. AD is associated with an increased risk of comorbidity with other clinical conditions such as hypertension, diabetes, and neuropsychiatric symptoms (NPS) including, agitation, anxiety, and depression as well as increased mortality in late life. For example, up to 70% of patients diagnosed with AD are affected by anxiety. As aging is the major risk factor for AD, this represents a huge global burden in ageing populations. Over the last 10 years, significant efforts have been made to recognize the complexity of AD and understand the aetiology and pathophysiology of the disease as well as biomarkers for early detection. Yet, earlier treatment options, including acetylcholinesterase inhibitors and glutamate receptor regulators, have been limited as they work by targeting the symptoms, with only the more recent FDA-approved drugs being designed to target amyloid-β protein with the aim of slowing down the progression of the disease. However, these drugs may only help temporarily, cannot stop or reverse the disease, and do not act by reducing NPS associated with AD. The first-line treatment options for the management of NPS are selective serotonin reuptake inhibitors/selective noradrenaline reuptake inhibitors (SSRIs/SNRIs) targeting the monoaminergic system; however, they are not rational drug choices for the management of anxiety disorders since the GABAergic system has a prominent role in their development. Considering the overall treatment failures and side effects of currently available medication, there is an unmet clinical need for rationally designed therapies for anxiety disorders associated with AD. In this review, we summarize the current status of the therapy of AD and aim to highlight novel angles for future drug therapy in our ongoing efforts to alleviate the cognitive deficits and NPS associated with this devastating disease.

Factors Associated with Depressive and Anxiety Symptom Trajectories Across Pregnancy and Postpartum in Selective Serotonin Reuptake Inhibitor‐Treated Individuals

ObjectiveThe primary purpose of this article is to identify factors that are associated with worsening mood and anxiety trajectories across the perinatal period among pregnant individuals receiving treatment with a selective‐serotonin reupdate inhibitor.MethodsThis secondary analysis of primary data from the original article, Trajectories of Depressive and Anxiety Symptoms Across Pregnancy and Postpartum in Selective Serotonin Reuptake Inhibitor‐Treated Women, explores if number of lifetime episodes of depression as characterized in the Mini‐International Neuropsychiatric Interview, elevated maternal adverse childhood experiences (ACE) score, or specific obstetric or neonatal factors from the Peripartum Events Scale (PES) were associated with membership in trajectory groups with the highest symptom burden.ResultsNo difference in ACE scores or obstetric or neonatal factors were associated with membership in the trajectory groups using Wilcoxon rank sum tests and bi‐variable logistic regression. The trajectory group with the highest anxiety symptom burden experienced more lifetime episodes of depression compared to other groups (odds ratio = 1.17, 95% confidence intervals, 1.02–1.34, p = 0.03).ConclusionsCongruent with other studies, we found a high prevalence of co‐occurring mood and anxiety symptoms and that past episodes of depression remain an important historical risk factor for perinatal symptom burden. This reinforces that past experiences of depression increase not only the risk of future symptoms but also higher symptom burden during antidepressant treatment.

Palliative care and end of life care in decompensated cirrhosis.

Palliative care and end of life care in decompensated cirrhosis.

Association between the loudness dependence of auditory evoked potential, serotonergic neurotransmission and treatment outcome in patients with depression

Previous studies have suggested that the loudness dependence of auditory evoked potential (LDAEP) is associated with the effectiveness of antidepressant treatment in patients with major depressive disorders (MDD). Furthermore, both LDAEP and the cerebral serotonin 4 receptor (5-HT4R) density is inversely related to brain serotonin levels.We included 84 patients with MDD and 22 healthy controls to examined the association between LDAEP and treatment response and its association with cerebral 5-HT4R density. Participants underwent both EEG and 5-HT4R neuroimaging with [11C]SB207145 PET. Thirty-nine patients with MDD were re-examined after 8 weeks of treatment with selective serotonin reuptake inhibitors/serotonin noradrenaline reuptake inhibitor (SSRI/SNRI).We found that the cortical source of LDAEP was higher in untreated patients with MDD compared to healthy controls (p=0.03). Prior to SSRI/SNRI treatment, subsequent treatment responders had a negative association between LDAEP and depressive symptoms and a positive association between scalp LDAEP and symptom improvement at week 8. This was not found in source LDAEP. In healthy controls, we found a positive correlation between both scalp and source LDAEP and cerebral 5-HT4R binding but that was not observed in patients with MDD. We did not see any changes in scalp and source LDAEP in response to SSRI/SNRI treatment.These results support a theoretical framework where both LDAEP and cerebral 5-HT4R are indices of cerebral 5-HT levels in healthy individuals while this association seems to be disrupted in MDD. The combination of the two biomarkers may be useful for stratifying patients with MDD.Clinical Trials Registration:https://clinicaltrials.gov/ct2/show/NCT02869035?draw=1Registration number: NCT0286903.

A study of molecular docking of l-tryptophan ligand as a compound in pineapples and bananas binding with the human serotonin transporter (SERT)

Introduction: Low mood condition is related to a low level of brain serotonin. An early sign of depression with low mood symptoms is generally treated with psychotropic drugs that work as selective serotonin reuptake and monoamine oxidase (MAO) inhibitors (one of which is sertraline), to increase serotonin levels in the brain. There are some concerns regarding side effects available medication like serotonin syndrome, suicidality and aggressive behavior. Thus, development of alternative herbal products made from a combination of pineapple and banana extract with less side effect and its potential affinity with serotonin regulation is important. Aim of the study: To determine potential herbal rich (banana and pineapple) of L-tryptophan and potential active compounds interaction with the human serotonin transporter. Method: In the present study, using in silico molecular docking techniques, the active compound of banana and pineapple and its potential interaction with human serotonin transporter were assed. Docking study explored the bioactive compounds interactions with specific target like catechin, dopamine, epigallocatechin, gallic acid, L-tryptophan, malvidin, norepinephrine, pelargonidin, peonidin, and serotonin. Molecular docking simulations were performed using AutoDock 4.2 software. The docking method was validated first by re-docking sertraline (nature ligand) in a complex with PDB ID: 6AWO against the target receptor (SERT). Result: The molecular docking results had showed that L-tryptophan, peonidin, and catechin could bind to esential amino acid residues in the binding pocket, with binding affinity -5.69, -8.63, -8.24 kcal/mol respectively. Conclusion: L-tryptophan, peonidin, and catechin are the most promising compounds that have good potency as anti-depressant agents through SERT inhibitory activity. This compounds in bananas and pineapples have the potential to affect serotonin transporter receptors that play a role in mood and behavior.

Co-prescribing of Central Nervous System-Active Medications for COPD Patients: Impact on Emergency Room Visits and Hospitalization.

Anxiety and chronic pain are common comorbidities in patients with chronic obstructive pulmonary disease (COPD), which are frequently managed with benzodiazepines (BZDs) and opioids, respectively. The purpose of this study was to determine whether different combinations of opioids, BZD, and their substitutes-gabapentinoids (GABA) and selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs)-are associated with lower risk of acute respiratory events in COPD patients with co-occurring chronic pain and anxiety. This retrospective cohort study used a nationally representative sample of Medicare beneficiaries with COPD, chronic pain, and anxiety. Patients were grouped based on drug combination (opioid + BZD/Z-hypnotics, opioid + GABA, opioid + SSRI/SNRI, BZD/Z-hypnotics + GABA, BZD/Z-hypnotics + SSRI/SNRI, GABA + SSRI/SNRI, or ≥3 drugs). The primary outcome was emergency room (ER) visit or hospitalization due to acute respiratory events assessed up to 180 days following initiation of drug combination. Overdose secondary to central nervous system (CNS)-related drugs was also assessed up to 180 days following initiation of drug combination. The drug combination opioid + GABA was associated with decreased risk for ER visit (hazard ratio [HR] = 0.73; 95% CI = 0.61-0.87) and hospitalization (HR = 0.69; 95% CI = 0.55-0.85). Opioid + SSRI/SNRI also showed decreased risk for ER visit (HR = 0.84; 95% CI = 0.71-0.99). There was no significant difference in risk for CNS-related drug overdose among different drug combinations compared with opioid + BZD/Z-hypnotics. Opioids in combination with GABA and SSRI/SNRI demonstrate relatively lower risk for acute respiratory events among patients with COPD and comorbid chronic pain and anxiety. The findings emphasize the need for multimodal management in this vulnerable population.

Trajectories of Depressive and Anxiety Symptoms Across Pregnancy and Postpartum in Selective Serotonin Reuptake Inhibitor-Treated Women.

ObjectiveTracking perinatal mood and anxiety disorders is championed by the American Psychiatric Association and the International Marcé Society for Perinatal Mental Health. We conducted this study to examine trajectories of monthly depressive and anxiety symptoms through pregnancy and postpartum.MethodsThis is a prospective longitudinal observational cohort study of pregnant women interviewed at baseline (≤18th gestational week), every four weeks through delivery and at 6 and 14 weeks postpartum at three urban academic medical centers (N = 85) and a single rural health center (N = 3) from 2016 to 2020. Pregnant women had at least one prior episode of major depressive disorder, were not in a current episode, and were treated with sertraline, fluoxetine, citalopram, or escitalopram. Of 192 women screened, 88 (46%) women enrolled, and 77 (88%) women completed the postpartum follow‐up. Symptom trajectories were generated with scores from the Edinburgh Postnatal Depression Scale, the Quick Inventory of Depressive Symptoms, the Generalized Anxiety Disorder Scale, 7‐item, and the Patient‐Reported Outcomes Measurement Information System Global Health measure. A semi‐parametric, group‐based mixture model (trajectory analysis) was applied.ResultsThree relatively stable depression trajectories emerged, described as Minimal, Mild, and Subthreshold, in each group across pregnancy. Two of the four anxiety trajectories were stable, including Asymptomatic and Minimal, while the third, termed Breakthrough, was ascending with increasing symptoms and the fourth trajectory, described as Mild, had descending symptoms.ConclusionsScreening for anxiety with depression for pregnant women will yield a comprehensive view of psychiatric symptoms and treatment targets in perinatal women.

Identification and Management of Night Eating Syndrome in the Adolescent and Young Adult Population.

Objective: Night eating syndrome (NES) is a lesser-known eating disorder that can lead to significant morbidity in adults. However, there is little research into the condition and its comorbidities in the adolescent and young adult population. We sought to compile the existing literature on NES in university student populations to aid health care providers in identifying and treating the condition and its symptoms before it causes adverse health outcomes.Methods: We conducted a review of the literature from 2003 to present with no limitations using PubMed and Google Scholar. Search terms were night eating syndrome AND student, yielding 23 articles that were deemed relevant to the review. A manual search of the literature using only night eating syndrome was performed to identify any additional studies not included in the initial search. This search yielded an additional 4 articles of interest, including those related to treatment options. A total of 25 studies were included in the final review.Results: Adolescent patients exhibiting conditions including depression, eating disorders, insomnia, and high levels of stress should be monitored for the development of night eating symptoms. Children of mothers with NES should also be monitored during adolescence, as this confers a higher risk. Interestingly, increased body mass index is not associated with NES in adolescence. Patients that are identified as being at risk should have their comorbid conditions managed medically, while those diagnosed with NES can potentially be treated with cognitive-behavioral therapy and/or selective serotonin reuptake inhibitors.Conclusions: NES is a clinical entity that requires further investigation, especially concerning adolescents and the development of symptoms during the transition into adulthood. More research is needed on the treatment of the syndrome, as several treatments have been studied but none are US Food and Drug Administration approved.

Utilization of Experimental Design for the Establishment and Optimization of RP-HPLC Method for the Estimation of Two Selective Serotonin Reuptake Inhibitors/benzodiazepines Combinations in the Presence of their Related Compounds

Background: Design of experiment (DOE) is considered the most powerful tool to identify factors that affect variation and improve the response by tuning these factors. In the present work, DOE was applied to establish an innovative, sensitive and precise HPLC method for the simultaneous determination of Escitalopram oxalate, Paroxetine hydrochloride hemihydrate and Clonazepam in presence of their related compounds in drug substance and drug products. Methods: Buffer molarity, % organic modifier (acetonitrile content) at the beginning/end of the gradient, flow rate at the beginning/end of the gradient, pH of the mobile phase, and column temperature were screened using Plackett-Burman design (PBD) model. The main effect plot showed that % organic modifier at the beginning/end of gradient and flow rate at the beginning of gradient were statistically significant variables influencing peaks resolution (p<0.05). Box-Behnken design (BBD) was then used as an optimization model in order to achieve the highest possible resolution with the least possible experimental trials through studying the interaction and quadratic effects of these three factors. Finally, the optimum condition for predicated peak resolution could be achieved by the desirability function. Results: After optimization, chromatographic separation was attained on Agilent Zorbax SB C18 (4.6×250mm, 5µm) column using gradient elution of mobile phase: (A) potassium dihydrogen phosphate (pH 2.7; 0.025M) and (B) acetonitrile at ambient column temperature with the last eluted compound at less than 17 min. The flow rate was maintained at 1/2.3 mLmin-1 with UV detection at 245/210 nm using time programming. Conclusion: The optimized chromatographic method was used for stability indicating assay of the cited drugs in presence of their related compounds according to ICH Q2R1 guidelines.

Association of co-prescribing of opioid and benzodiazepine substitutes with incident falls and fractures among older adults: a cohort study

ObjectiveExamine the association between the co-prescribing of opioids, benzodiazepines, gabapentinoids (pregabalin and gabapentin) and selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitors (SSRI/SNRIs) in different combinations and the risk of...

Periodontal status and the efficacy of the first-line treatment of major depressive disorder.

ObjectivesThe efficacy of treatment of major depressive disorder (MDD) is not satisfactory. Systemic inflammation may play an important role in MDD pathogenesis and treatment outcomes. Periodontal disease is the systemic inflammatory condition. Its prevalence may be as high as 45%. We aimed to assess the association of periodontal status with the outcome of 3‐month first‐line treatment of MDD with selective serotonin reuptake inhibitors.Material and MethodsWe performed the prospective cohort study during 2018/2019 at Psychiatric Hospital “Sveti Ivan,” Croatia, on a consecutive sample of 43 patients. The outcome was the MDD symptoms severity measured using the Hamilton Depression Rating Scale‐17. The periodontal status was indicated by the clinical attachment loss (CAL).ResultsBaseline periodontal status had a nonlinear significant and clinically relevant association with the MDD treatment outcome (R 2 change of the quadratic term = 0.12; p = 0.027). In patients with good baseline periodontal status the severity of MDD symptoms was significantly improved. When the value of CAL was ≥4.44 mm, indicating the worse periodontal status, further increase in baseline CAL was associated with the worsening of MDD treatment outcomes independently of the baseline depression severity and 14 sociodemographic and clinical predictors of treatment outcome.ConclusionsPeriodontal healthcare is accessible, and should be utilize in an integrative, multidisciplinary approach not only for the sake of psychiatric patients' quality of life and prevention of periodontal disease, but for the sake of the outcomes of psychiatric treatment as well.

The prevalence and risk factors of potentially inappropriate medication use in older Chinese inpatients with multimorbidity and polypharmacy: a cross-sectional study

BackgroundMultimorbidity and polypharmacy are common problems among the older population globally. They not only reduce the quality of life of older adults but also increase the prevalence of potentially inappropriate medication (PIM) use. This study aimed to examine the prevalence and the predictors of PIMs in hospitalized geriatric patients with multimorbidity and polypharmacy in Chengdu based on the 2015 American Geriatric Society Beers Criteria (2015 AGS Beers Criteria) and 2019 American Geriatric Society Beers Criteria (2019 AGS Beers Criteria).MethodsFrom 2016 to 2018, a cross-sectional study was conducted using electronic medical data from nine tertiary hospitals in Chengdu. The 2019 and 2015 AGS Beers Criteria were used to evaluate the PIM status of older inpatients (age ≥65 years), and logistic regression was used to identify the risk factors for PIM use.ResultsA total of 17,352 inpatients were included in the study between 2016 and 2018. The prevalence of PIM use based on the 2019 AGS Beers Criteria (72.54%) was slightly higher than that based on the 2015 AGS Beers Criteria (70.10%). Further, the prevalence of PIM use based on the 2019 AGS Beers Criteria showed an increasing trend, from 71.17% in 2016 to 73.39% in 2018. Logistic regression demonstrated that female, advanced age, and polypharmacy were positively associated with PIM use in older adults. The most frequently used PIMs in the inpatients were diuretics, benzodiazepines, non-steroidal anti-inflammatory drugs, antipsychotics, and selective serotonin reuptake inhibitors.ConclusionsThere is a high prevalence of PIM use in older inpatients with multimorbidity and polypharmacy in Chengdu. The 2019 AGS Beers Criteria is more sensitive for evaluating older adults in Chengdu than the 2015 AGS Beers Criteria. Further, based on the 2019 AGS Beers Criteria, the prevalence of PIM use is increasing year by year. Research on interventions rationing PIM use in the geriatric population in Chengdu are necessary in the future.

Depression treatment in women and men with bipolar affective disorder: a comparative study

Objective: to compare depression treatment efficacy with and without antidepressants (ADs) in men and women with bipolar affective disorder (BAD).Patients and methods. We enrolled 100 patients with BAD (F31.3–F31.5 according to ICD-10), including 50 women aged 33.0 [23.0; 50.2] years and 50 men aged 37.5 [29.5; 47.2] years using prospective and retrospective methods. Various antidepressants, normothymics, antipsychotics combinations were used to treat depression. We performed a comparative analysis of treatment efficacy with and without antidepressants in men and women subgroups. Clinical assessment at the baseline and the end of 1, 2, 4, 6-th week of therapy (or at discharge) included a specially developed clinical examination chart and the following psychometric scales: Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression – Severity of illness (CGI-S), Clinical Global Impression – Improvement (CGI-I).Results and discussion. Women tended to have a slower improvement in the condition compared to men. Maximum reduction in MADRS score and a CGI-I, CGI-S higher frequency of clinical improvement and remission was observed in men and women who did not receive antidepressants than patients who did not receive antidepressants. When BAD type was included in the analysis, in patients treated with antidepressants, transient symptoms of the opposite pole occurred in 24.7% of patients of both sexes with bipolar affective I disorder (BAD I) and in 16.8% with bipolar affective II disorder (BAD II). There were no significant gender differences in patients with BAD I, while women predominated in BAD II group (22.5% compared to 7.8% men). No significant treatment-emergent affective switch was observed with tricyclic antidepressants and selective serotonin and norepinephrine reuptake inhibitors in both groups (21; 16.7; 16.7% in men and 28; 21.8; 12.5% in women, respectively). The assessment of intermission revealed that women were significantly more likely to have shorter periods between phases (42% compared to 22% in men). In addition, women were significantly more likely to have shorter periods between phases (42% compared to 22% in men) when the intermission duration was included in the analysis. In some patients with severe depression and infective first-line therapy (anticonvulsants and atypical antipsychotics), antidepressants prescription can increase treatment effectiveness. However, several factors should be considered, such as BAD type and variant, depression severity, treatment-emergent affective switch in history, and gender.Conclusion. A decision about antidepressants' dosage and treatment duration requires a dynamic follow-up of the patient in order to discontinue the antidepressants as fast as possible and decrease the risk of treatment-emergent affective switch and shortening of remission period.

Risk of Bleeding Associated with Antidepressant Drugs: The Competitive Impact of Antithrombotics in Quantitative Signal Detection.

BackgroundTo date, disproportionality analysis has been unable to demonstrate the increased bleeding risk associated with antidepressant drugs, especially selective serotonin reuptake inhibitors.ObjectiveWe hypothesised that a potential signal for an increased bleeding risk may be mitigated by the effects of agents other than antidepressant drugs that are strongly associated with haemorrhages, especially antithrombotics. In addition, we investigated if the use of more specific search terms of the Medical Dictionary for Regulatory Activities facilitates the detection of signals.MethodsPharmacovigilance data from the Uppsala Monitoring Centre were used to calculate substance-specific reporting odds ratios (RORs) for all types of bleeding and gastrointestinal bleeding. Reporting odds ratios were calculated with and without antithrombotic comedication.ResultsRegarding any type of bleeding, no signals were found in association with antidepressant drugs. Concerning upper gastrointestinal bleeding, signals were found related to citalopram (ROR: 1.56 [95% confidence interval 1.11–2.20]) and escitalopram (ROR: 1.52 [95% confidence interval 1.03–2.25]). After removal of reports related to antithrombotics, these signals could no longer be detected, but a new signal related to St. John’s Wort associated with haemorrhages was found (ROR: 1.50 [95% confidence interval 1.21–1.86]).ConclusionsAntithrombotics seem unlikely to have a major impact on the detection of the bleeding risk of antidepressant drugs. The different categorisation of adverse drug reactions regarding the strength of a causal relationship between a drug and an event in the database may be relevant for this negative finding.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-021-00260-9.

Determining the Efficacy of Electronic Cognitive Behavioral Therapy for Generalized Anxiety Disorder Compared to Pharmaceutical Interventions: Protocol for a Quasi-Experimental Study.

BackgroundGeneralized anxiety disorder (GAD) is an extremely prevalent and debilitating mental health disorder. Currently, the gold standard treatment for GAD is cognitive behavioral therapy (CBT) and/or pharmacotherapy. The most common medications used to treat GAD are selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors. While CBT is the gold standard treatment for GAD, it is costly, time-consuming, and often inaccessible. Fortunately, the electronic delivery of CBT (e-CBT) has emerged as a promising solution to address these barriers. e-CBT has shown to offer comparable results to in-person CBT while improving accessibility for patients and time efficiency for clinicians.ObjectiveThis study aims to investigate the treatment efficacy of e-CBT compared to and in conjunction with pharmacotherapy for GAD.MethodsThis study will use a quasi-experimental design to allow patients the freedom to choose which treatment modality they would like to receive. Participants with a diagnosis of GAD will be enrolled in 1 of 3 possible treatment arms: (1) e-CBT, (2) medication, or (3) a combination of e-CBT and medication. The e-CBT program will include a 12-week psychotherapy program delivered through the Online Psychotherapy Tool—a secure, cloud-based, digital mental health platform. The treatment efficacy of e-CBT will be compared with that of medication alone and medication in combination with e-CBT.ResultsThe study received ethics approval in April 2019 and participant recruitment began in June 2019. Participant recruitment has been conducted through social media advertisements, physical advertisements, and physician referrals. To date, 146 participants (e-CBT: n=53; medication: n=49; combination: n=44) have been recruited. Data collection is expected to conclude by June 2021, and data analysis is expected to be completed by October 2021. Linear regression (for continuous outcomes) and binomial regression (for categorical outcomes) analysis will be conducted using interpretive qualitative methods.ConclusionsIf either the efficacy of e-CBT is shown to be comparable to that of medication or the effects of both treatments are augmented when used in tandem, these findings could have major implications on the mental health care system. e-CBT is a more accessible and affordable treatment that could increase mental health care capacity 4-fold if proven viable.Trial RegistrationClinicalTrials.gov NCT04478526; https://clinicaltrials.gov/ct2/show/NCT04478526International Registered Report Identifier (IRRID)DERR1-10.2196/27772

Drug utilization study in patients visiting psychiatric OPD in tertiary care hospital

Background: The illness due to psychiatric diseases and behavioral disorders is enormous, but it remains under represented by conventional public health statistics; which mainly targets mortality more than morbidity or dysfunction. The drug utilization study was conducted to find out problems and provide feedback to prescribers so as to create awareness about irrational use of drugs. This study was conducted in psychiatry outpatient department (OPD) of a tertiary care hospital.Methods: A prospective, observational and cross-sectional study was conducted in Department of Pharmacology in collaboration with department of psychiatry in a tertiary care hospital. Patients fulfilling the inclusion criteria visiting psychiatric OPD from 01 October 2018 to 31 December 2018 period of 3 months were enrolled in the study. Assessment of the prescriptions was done as per the ICD-10 criteria and World Health Organization-indicators for rational use of drugs (WHO-INRUD).Results: Among total 390 prescriptions; 71.54% was males and 28.46% were females. All the drugs were oral formulations. The burden of diseases are depression 35.89%, anxiety 20.51%, schizophrenia 18.97% and bipolar disorder 11.28% and other psychiatric diseases were 13.33%. Olanzapine was the most common drug which was prescribed followed by alprazolam. Total 1,140 drugs were prescribed out of which 86.32% was psychotropic drug and 13.68% were other like vitamin B-complex, analgesics, anta-acids, antibiotics and NSAIDS. The Most common prescribed class was atypical antipsychotics 26.31% followed by benzodiazepines 20.26%, antipsychotics 19.74%, tricyclic antidepressants 8.16%, anticonvulsants 9.21%, antiepileptics 2.37% and lastly selective serotonin reuptake inhibitors.Conclusions: Atypical antipsychotics was most commonly prescribed drug followed by benzodiazepines. All the drugs were prescribed by their generic names which suggests awareness among prescribers regarding WHO policies for generic prescribing.

Duloxetine (DL) in treatment of oxaliplatin-induced peripheral neuropathy (PN).

195 Background: Oxaliplatin is commonly used to treat many GI cancers, especially colorectal (CRC), pancreatic (PC), and gastric (GC); however, peripheral neuropathy (PN) is the dose-limiting toxicity. Duloxetine (DL) is a second-generation selective serotonin and norepinephrine reuptake inhibitor (SNRI) used for the treatment of depression, anxiety, PN-associated with diabetes or ongoing pain due to medical conditions such as fibromyalgia. In this retrospective study, we evaluated the role of DL in reduction of oxaliplatin-induced neuropathy. Methods: Patients with GI cancers receiving oxaliplatin-based chemotherapy regimens from Nov 2016 to Nov 2019 were included. Patients with pre-existing PN from other etiologies such as diabetes, alcoholism, autoimmune disease, infections, hereditary, etc. were excluded. Neurological evaluations were performed serially before initiating DL and every 4 weeks thereafter according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. DL was given at 30 mg by mouth (PO) once daily and if tolerated after 3 days, was escalated to 60 mg once daily. Response was calculated to include number of patients with stable PN, improved PN, or no benefit. Adverse toxicities were graded. Results: 53 patients with median age of 53 years (range: 38 – 72) received DL for oxaliplatin-induced PN during treatment of GI cancers (CRC: 40%, PC:30%, GC: 10%, others: 10%). Improvement in PN from higher to lower grades was witnessed at 2 weeks in only 4 patients. At 4 week of DL, 3/53 (6%) patients improved from G3 PN to G2, 6/53 (11%) from G3 to G1, and 28/53 (52.8%) from G2 to G1, 14/53 (26%) and 2/53 (4%) had stable G3 and G2 PN respectively. At 8 week of DL, 10/53 (19%) of patients improved from G3 to G2, 3/53 (6%) from G2 to G1, 23/53 (43%) from G1 to G0, while 11/53 (21%), 2/53 (4%) and 4/53 (8%) remained stable at G1, G2 and G3 respectively. Overall DL resulted in a response rate of 89% and stable PN in 11%. 5 patients had to stop DL due to G3 drowsiness, insomnia, dry mouth and headache. Overall, DL was well-tolerated with majority of toxicities in G1-2 grade: dizziness (15%), drowsiness (11%), sexual side effects (11%), dry mouth (11%), insomnia (8%), headache (8%). In addition to PN, DL helped in improving depression in 50% of these patients and decreased the pain score in an additional 23%. Conclusions: DL resulted in a clinically significant improvement in PN-induced by oxaliplatin with manageable toxicity profile. Additionally, DL also improved depression and pain score. DL may be considered as an option in ameliorating PN in these patients, however, caution must be taken about DL and other drugs interaction. Our study warrants a prospective randomized trial to study the effectiveness of DL in treating oxaliplatin-induced PN. Moreover, cost effectiveness of DL in concurrently improving PN, depression and pain needs to be studied as well.

The progress and development of antidepressants

Major depressive disorder is a common emotional mood disorder disease, which mainly manifests as depression, cognitive impairment, weakened volition activities, loss of appetite, and sleep disorders. Depression is a common mental disorder affecting more than 264 million people worldwide. There are many antidepressant drugs in clinic, e.g., tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin (5-HT) reuptake inhibitors and selective norepinephrine (NA) reuptake inhibitors. Although great progress has been made in the research of new antidepressant drugs, the current clinical use of drugs still has many shortcomings, e.g., the unmet efficiency, slow onset of action, and multiple adverse reactions, which are difficult to meet the requirements of the increasing number of the depressed patients. This article mainly focuses on the development process of antidepressant drugs and compares their effects. Specifically, the N-methyl-D-aspartate receptor as a new antidepressant has a good effect, which is worthy of further study. These results shed light for providing a research idea for the study of new antidepressants.

Hypocretinergic interactions with the serotonergic system regulate REM sleep and cataplexy

Loss of muscle tone triggered by emotions is called cataplexy and is the pathognomonic symptom of narcolepsy, which is caused by hypocretin deficiency. Cataplexy is classically considered to be an abnormal manifestation of REM sleep and is treated by selective serotonin (5HT) reuptake inhibitors. Here we show that deleting the 5HT transporter in hypocretin knockout mice suppressed cataplexy while dramatically increasing REM sleep. Additionally, double knockout mice showed a significant deficit in the buildup of sleep need. Deleting one allele of the 5HT transporter in hypocretin knockout mice strongly increased EEG theta power during REM sleep and theta and gamma powers during wakefulness. Deleting hypocretin receptors in the dorsal raphe neurons of adult mice did not induce cataplexy but consolidated REM sleep. Our results indicate that cataplexy and REM sleep are regulated by different mechanisms and both states and sleep need are regulated by the hypocretinergic input into 5HT neurons.

Effectiveness of Vortioxetine on Emotional Blunting in Patients with Major Depressive Disorder with inadequate response to SSRI/SNRI treatment

IntroductionInadequate treatment response and emotional blunting are common challenges with selective serotonin reuptake inhibitors/serotonin-noradrenaline reuptake inhibitors (SSRIs/SNRIs) for major depressive disorder (MDD). We investigated the effectiveness of vortioxetine on emotional blunting in patients with partial response to treatment with SSRIs/SNRIs. MethodsPatients with MDD who experienced a partial response to SSRI/SNRI monotherapy at adequate dose for ≥6 weeks were switched to 8 weeks of vortioxetine treatment 10-20 mg/day (Study NCT03835715). Key inclusion criteria were Montgomery-Åsberg Depression Rating Scale (MADRS) total score >21 and <29, current major depressive episode <12 months, Oxford Depression Questionnaire (ODQ) total score ≥50, and confirmation of emotional blunting by standardized screening question. Emotional blunting was assessed by ODQ and depressive symptoms by MADRS. Other outcomes assessed included motivation and energy (Motivation and Energy Inventory [MEI]), cognitive performance (Digit Symbol Substitution Test [DSST]), and overall functioning (Sheehan Disability Scale [SDS]). ResultsAt week 8, patients (N=143) had improved by -29.8 points (p<0.0001) in ODQ total score; 50% reported no emotional blunting in response to standardized screening question. Significant improvements were observed on the DSST, MEI, and SDS at all time points assessed, and 47% of patients were in remission (MADRS total score ≤10) at week 8. The most common treatment-emergent adverse events included nausea, headache, dizziness, vomiting, and diarrhea. LimitationsNo prospective phase before medication switch. ConclusionVortioxetine 10-20 mg effectively improved emotional blunting, overall functioning, motivation and energy, cognitive performance, and depressive symptoms in patients with MDD with partial response to SSRI/SNRI therapy and emotional blunting.