Frontal Alpha Asymmetry and Its Modulation by Monoaminergic Neurotransmitters in Depression.

Frontal alpha asymmetry (FAA) is an electroencephalography (EEG) measure that quantifies trait-like left versus right hemisphere lateralization in alpha power. Increased FAA indicates relatively greater left than right frontal cortex activation and is associated with enhanced reward-related approach behaviors rather than avoidance or withdrawal. Studies dating back several decades have often suggested that having greater FAA supports enhanced positive affect and protection against major depressive disorder (MDD), whereas having greater right frontal activation (i.e., reduced FAA) is associated with negative affect and risk for MDD. While this hypothesis is widely known, a number of other studies instead have found increased FAA in MDD, or evidence that either leftward or rightward bias in FAA is associated with depression. Here we briefly review the literature on leftward or rightward lateralization in FAA in MDD, and find much evidence that MDD is not always characterized by reduced FAA. We also review the limited literature on FAA and monoaminergic neurotransmitter systems, including pharmacologic agents that act on them. Studies of serotonin in particular provide genetic and pharmacologic evidence for modulation of FAA, where some of these data may suggest that serotonin reduces FAA. In a synthesis of the collective literature on FAA and the monoamines, we suggest that serotonin and norepinephrine may differentially affect FAA, with serotonin tending to promote right frontal activation and norepinephrine biased toward left frontal activation. These putative differences in frontal lateralization may influence MDD phenotypes or potential subtypes of the disorder, and suggest pharmacologic treatment strategies.

Effects of selective serotonin reuptake inhibitors on endocrine system (Review).

Selective serotonin reuptake inhibitors (SSRIs) are typically prescribed for treating major depressive disorder (MDD) due to their high efficacy. These drugs function by inhibiting the reuptake of serotonin [also termed 5-hydroxytryptamine (5-HT)], which raises the levels of 5-HT in the synaptic cleft, leading to prolonged activation of postsynaptic 5-HT receptors. Despite the therapeutic benefits of SSRIs, this mechanism of action also disturbs the neuroendocrine response. Hypothalamic-pituitary-adrenal (HPA) axis activity is strongly linked to both MDD and the response to antidepressants, owing to the intricate interplay within the serotonergic system, which regulates feeding, water intake, sexual drive, reproduction and circadian rhythms. The aim of the present review was to provide up-to-date evidence for the proposed effects of SSRIs, such as fluoxetine, citalopram, escitalopram, paroxetine, sertraline and fluvoxamine, on the endocrine system. For this purpose, the literature related to the effects of SSRIs on the endocrine system was searched using the PubMed database. According to the available literature, SSRIs may have an adverse effect on glucose metabolism, sexual function and fertility by dysregulating the function of the HPA axis, pancreas and gonads. Therefore, considering that SSRIs are often prescribed for extended periods, it is crucial to monitor the patient closely with particular attention to the function of the endocrine system.

[Pharmacogenomic and pharmacometabolomic biomarkers of the efficacy and safety of antidepressants: focus on selective serotonin reuptake inhibitors]. / Farmakogenomnye i farmakometabolomnye biomarkery effektivnosti i bezopasnosti antidepressantov: fokus na selektivnye ingibitory obratnogo zakhvata serotonina.

The efficacy and safety of psychopharmacotherapy with antidepressants is of great medical importance. The search for clinical and biological predictors for choosing the optimal psychopharmacotherapy with antidepressants is actively underway all over the world. Research is mainly devoted to searching for associations of polymorphic gene variants with the efficacy and safety of therapy. However, information about a patient's genetic polymorphism is often insufficient to predict the efficacy and safety of a drug. Modern research on the personalization of pharmacotherapy should include, in addition to genetic, phenotypic biomarkers. This is important because genotyping, for example, cannot accurately predict the actual metabolic activity of an isoenzyme. To personalize therapy, a combination of methods is required to obtain the most complete profile of the efficacy and safety of the drug. Successful treatment of depression remains a challenge, and inter-individual differences in response to antidepressants are common. About half of patients with depressive disorders do not respond to the first attempt at antidepressant therapy. Serious side-effects of antidepressant pharmacotherapy and discontinuation of treatment due to their intolerance are associated with ineffective therapy. This review presents the results of the latest studies of «omics¼ biomarkers of the efficacy and safety of antidepressants.

Eye disorders associated with selective serotonin reuptake inhibitors: a real-world disproportionality analysis of FDA adverse event reporting system.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are widely used in depression and other psychiatric disorders. Despite their efficacy, there is a growing concern about the risk of eye disorders. This study aims to explore the potential correlation between eye disorders and SSRIs utilizing real-world data. RESEARCH DESIGN AND METHODS: The data were extracted from the US FDA Adverse Event Reporting System database from 2004Q1 to 2023Q3. The analysis focused on the clinical characteristics, the ranking of adverse reactions, the time-to-onset, and the severity proportion of SSRI-related eye disorders. RESULTS: Our analysis revealed that SSRIs were significantly associated with eye disorders, with a higher risk of vision blurred with escitalopram, angle closure glaucoma with citalopram, and photopsia with paroxetine. The most common eye disorders were vision blurred, visual impairment, mydriasis, etc. Most of these adverse events occurred within the first 30 days of treatment. The reported incidence of severe eye disorders was 38.6% for SSRIs, with fluoxetine exhibiting the highest rate at 45.9%. CONCLUSION: Our study demonstrates a significant association between SSRIs and the risk of eye disorders. These findings provide crucial insights for clinicians when prescribing SSRIs and underscore the need to monitor eye health in patients receiving these medications.

Impact of trazodone once-a-day on quality of life and functional recovery in adults with major depressive disorder: A prospective, observational study.

BACKGROUND: Health-related quality of life (HRQL) is an important goal for patients with major depressive disorder (MDD), but whether antidepressants improve HRQL in these patients is unclear. Here, we describe the real-world effects of trazodone once-a-day (TzOAD) and selective serotonin reuptake inhibitor (SSRI) treatments on HRQL and functioning in adults with MDD. METHODS: This 8-week prospective, observational, open-label, multicenter study was conducted in adults with moderate or severe MDD for whom TzOAD or SSRI were prescribed as monotherapy. The primary outcome was life enjoyment and satisfaction assessed via the patient-reported Quality-of-Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) from baseline to week 8. Secondary outcomes included change in Q-LES-Q-SF from baseline to weeks 1 and 2; severity of depressive symptoms using the Montgomery Åsberg Depression Rating Scale (MADRS) and sleep disturbance via the PROMIS SF-SD 8b questionnaire at weeks 1, 2, and 8; and overall functioning via the Sheehan Disability Scale (SDS), hedonic capacity using the Snaith-Hamilton Pleasure Scale (SHAPS), and cognitive dysfunction using the Perceived Deficits Questionnaire (PDQ-5) at baseline and week 8. RESULTS: The study included 208 adults with MDD (mean [SD] age = 50.2 [14.3] years; 68.6% female; 98.4% White). Life enjoyment and satisfaction improved from baseline to week 8 for both treatment groups: Q-LES-Q-SF mean (SD) scores were 27.5 (20.4) for the SSRI group and 39.0 (22.1) for the TzOAD group. Depressive symptoms and sleep disturbances also reduced from baseline to week 8: MADRS (SSRI, -15.7 [8.3]; TzOAD, -21.0 [9.8]); PROMIS SF-SD 8b (SSRI, -9.9 [12.6]; TzOAD, -22.0 [12.6]). Mean change scores in Q-LES-Q-SF, MADRS, and PROMIS SF-SD 8b improved as early as week 1 in both groups. Mean scores also improved from baseline to week 8 on SDS (SSRI, -9.2 [7.4]; TzOAD, -14.3 [7.5]), SHAPS (SSRI, -6.6 [4.3]; TzOAD, -8.3 [4.4]), and PDQ-5 (SSRI, -5.8 [4.5]; TzOAD, -7.7 [5.0]). CONCLUSIONS: In adults with MDD who received TzOAD or SSRIs, overall and individual HQRL domains improved rapidly and in parallel with improvements in depressive symptoms, with a slightly greater improvement observed in the TzOAD group.

Neuropathological implication of high blood bilirubin in patients and model rats with depression.

PURPOSE: Elevated bilirubin levels have been associated with major depressive disorder (MDD); however, the exact impact of bilirubin on MDD and the underlying molecular mechanisms remain unclear. Here, we explored the influence of bilirubin on MDD and sought to identify the mechanisms via which bilirubin induces depressive-like behavior. PATIENTS AND METHODS: Forty patients who were diagnosed with MDD and received treatment with selective serotonin reuptake inhibitors (SSRIs) were included, with 43 healthy volunteers serving as controls. Clinical symptoms were evaluated using Hamilton depression rating scale-24 (HAMD-24) and the Hamilton anxiety rating scale. Serum concentrations of total bilirubin (TBIL) and indirect bilirubin (IBIL) were measured at baseline and after treatment using an automated biochemical analyzer. The connection between clinical symptoms and TBIL or IBIL was examined using Pearson correlation. Chronic restraint stress (CRS) was employed to generate a rat model of depression. TBIL, IBIL in rat serum were measured by ELISA. Reactive oxygen species (ROS) contents in rat hippocampal tissues were quantified by flow cytometry. The levels of microglial markers and the extent of neuronal damage in the rat hippocampus were assessed by immunofluorescence and transmission electron microscopy, respectively. RESULTS: Serum TBIL and IBIL levels were higher in patients with MDD than in the healthy controls. After treatment with SSRIs, the serum levels of TBIL and IBIL in MDD patients were significantly reduced. The levels of TBIL and IBIL were associated with HAMD-24 in MDD patients. Compared with the controls, the serum levels of TBIL, IBIL and the hippocampal ROS contents were elevated in CRS-exposed rats. Fluoxetine lowered inflammatory factor levels, mitigated oxidative stress. CONCLUSION: Our findings indicate a possible correlation between elevated serum bilirubin and depressive symptoms. Increases in ROS levels, along with neuronal damage, may represent pathological mechanisms underlying MDD.

Selective Serotonin Reuptake Inhibitors and Symptoms of Depression in Patients on Chronic Hemodialysis: A Systematic Review.

Objective: The use of selective serotonin reuptake inhibitors (SSRIs) is common among hemodialysis patients who receive treatment for depression. However, studies on the efficacy of SSRIs in patients on chronic hemodialysis are few and have led to conflicting results. The present systematic review aims to evaluate, in randomized, controlled studies (RCSs), the efficacy of SSRI administration in reducing symptoms of depression in patients on chronic hemodialysis when compared with placebo or psychological interventions. Method: Research was run on December 2023 in the following databases: Ovid MEDLINE (1985 to present); Ovid EMBASE (1985 to present); Cochrane Library (Wiley); and PubMed (1985 to present). The primary outcome was the frequency and severity of the symptoms of depression assessed through the Beck Depression Inventory (BDI) or the Hamilton Depression Rating Scale (HAMD). The secondary outcome was the prevalence of adverse events. Results: Seven studies totaling 433 patients were included. The number of patients in each individual study ranged from 13 to 120. The length of studies ranged from 8 weeks to 6 months. Heterogeneous data precluded informative meta-analysis. Three studies compared sertraline with a placebo. Of these, two demonstrated that sertraline was better than the placebo in reducing the symptoms of depression while one showed no statistically significant differences between sertraline and the placebo. One study, comparing fluoxetine with a placebo showed that the symptoms of depression did not differ significantly at 8 weeks. In another study, escitalopram administration led to a significantly greater reduction in the Hamilton Depression Rating Scale score compared to a placebo, as well as in the Hamilton Anxiety Rating Scale score. In one study, citalopram and psychological interventions were both effective in reducing the symptoms of depression and anxiety and, in another study, sertraline was modestly more effective than CBT at 12 weeks in reducing the symptoms of depression. Conclusions: SSRIs may be effective in reducing the symptoms of depression in patients on chronic hemodialysis. SSRI administration, at the dosage used in the studies included in the present systematic review, seems safe in most hemodialysis patients. However, the paucity of studies and the limited number of patients included in the trials may suggest that further randomized, controlled studies are needed to determine if SSRIs may be used routinely in daily clinical practice in such a population.

Sertraline, citalopram and paroxetine in lactation: passage into breastmilk and infant exposure.

Objectives: This study aimed to investigate the plasma and breastmilk concentrations for sertraline, citalopram and paroxetine for assessment of the Milk/Plasma (M/P) ratio and Absolute Infant Dose (AID), and to determine actual infant drug exposure through breastfeeding. Subsequently, informed recommendations will be formulated regarding the advisability of breastfeeding in women undergoing treatment with the three most widely used antidepressants. Methods: A pharmacokinetic study in lactating women and their infants using sertraline, citalopram or paroxetine was performed. Paired breastmilk and plasma samples and single point infant plasma samples were collected to determine antidepressant concentrations. An Area Under the Curve (AUC) based approach with the trapezoidal rule was used to calculate M/P ratios and AID for all three antidepressants by combining all measured concentrations for the same dose. Results: Thirty-seven lactating women and their infants participated in this study. 111 paired breastmilk and plasma samples and 37 single point infant plasma samples were collected. Detectable concentrations of sertraline, citalopram and paroxetine were present in all breastmilk samples. For sertraline and citalopram M/P ratio is above one, indicating higher breastmilk than plasma concentrations, however, drug exposure by breastmilk did not lead to detectable plasma drug levels in any of the 15 infants for sertraline, for nine (out of 13) infants for citalopram and for eight (out of nine) infants for paroxetine. Conclusion: Given the well-known benefits of breastfeeding, our findings support breastfeeding of infants by mothers who are taking sertraline, citalopram or paroxetine is safe. Sertraline and paroxetine are the preferred antidepressants during breastfeeding, reaching mostly undetectable infant drug levels.

Serotonin syndrome controversies: A need for consensus.

Serotonin syndrome (SS) is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system. Although more than seven decades have passed since the first description of SS, it is still an enigma in terms of terminology, clinical features, etiology, pathophysiology, diagnostic criteria, and therapeutic measures. The majority of SS cases have previously been reported by toxicology or psychiatry centers, particularly in people with mental illness. However, serotonergic medications are used for a variety of conditions other than mental illness. Serotonergic properties have been discovered in several new drugs, including over-the-counter medications. These days, cases are reported in non-toxicology centers, such as perioperative settings, neurology clinics, cardiology settings, gynecology settings, and pediatric clinics. Overdoses or poisonings of serotonergic agents constituted the majority of the cases observed in toxicology or psychiatry centers. Overdose or poisoning of serotonergic drugs is uncommon in other clinical settings. Patients may develop SS at therapeutic dosages. Moreover, these patients may continue to use serotonergic medications even if they develop mild to moderate SS due to several reasons. Thus, the clinical presentation (onset, severity, and clinical features) in such instances may not exactly match what toxicologists or psychiatrists observe in their respective settings. They produce considerable diversity in many aspects of SS. However, other experts discount these new developments in SS. Since SS is a potentially lethal illness, consensus is required on several concerns related to SS.

Effects of antidepressants on brain structure and function in patients with obsessive-compulsive disorder: A review of neuroimaging studies.

Obsessive-compulsive disorder (OCD) affects 2-3% of people worldwide. Although antidepressants are the standard pharmachological treatment of OCD, their effect on the brain of individuals with OCD has not yet been fully clarified. We conducted a systematic search on PubMed, Scopus, Embase, and Web of Science to explore the effects of antidepressants on neuroimaging findings in OCD. Thirteen neuroimaging investigations were included. After antidepressant treatment, structural magnetic resonance imaging studies suggested thalamic, amygdala, and pituitary volume changes in patients. In addition, the use of antidepressants was associated with alterations in diffusion tensor imaging metrics in the left striatum, the right midbrain, and the posterior thalamic radiation in the right parietal lobe. Finally, functional magnetic resonance imaging highlighted possible changes in the ventral striatum, frontal, and prefrontal cortex. The small number of included studies and sample sizes, short durations of follow-up, different antidepressants, variable regions of interest, and heterogeneous samples limit the robustness of the findings of the present review. In conclusion, our review suggests that antidepressant treatment is associated with brain changes in individuals with OCD, and these results may help to deepen our knowledge of the pathophysiology of OCD and the brain mechanisms underlying the effects of antidepressants.

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-ß 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.

The anti-inflammatory effects of antidepressants on colitis.

Aim: Clomipramine (tricyclic antidepressant), Risperidone (a non-typical antidepressant), and Escitalopram (selective serotonin reuptake inhibitor antidepressant) might be good candidates for investigating the anti-colitis activity. Background: The incidence of depression with ulcerative colitis in patients has led to the use of antidepressants in their treatment. In addition to the antidepressant effect of these drugs, anti-inflammatory effects have also been reported. Methods: In this study, 36 rats were used 2 ml of 3% acetic acid solution rectally to show the colitis. Then, Clomipramine (25 mg/kg), Escitalopram (10 mg/kg), Prednisolone (5 mg/kg), Risperidone (2 mg/kg), and normal saline as the control was administered orally for six days. The levels of Tumor Necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and myeloperoxidase (MPO) were measured by Enzyme-linked immune sorbent assay (ELISA), and changes in the tissue pathology were investigated. Results: IL-6 level was significantly reduced after the administration of clomipramine and Prednisolone (p=0.025). Risperidone has significantly reduced MPO activity in colonic tissue (P=0.006). We did find no statistical decrease in MPO activity and TNF-α and IL-6 levels after consumption of Escitalopram (p>0.05). Conclusion: Clomipramine showed the best anti-inflammatory effect compared to Escitalopram and Risperidone. Therefore, clomipramine showed the best relieving effect on inflammation of ulcerative colitis in rats.

Antidepressant Sertraline Hydrochloride Inhibits the Growth of HER2+ AU565 Breast Cancer Cell Line through Induction of Apoptosis and Cell Cycle Arrest.

BACKGROUND: Drug repurposing in oncology promises a high impact on many patients through its ability to provide access to novel, fast-tracked treatments. Previous studies have demonstrated that depression may influence tumor progression. Anti-proliferative activity of certain antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), are reported in the literature. OBJECTIVE: This study was conducted to repurpose selective serotonin reuptake inhibitors (SSRIs) in treating breast cancers, and it merits the pursuit of drug repositioning in oncology. EXPERIMENTAL: Changes in cell morphology were studied using DAPI staining, and the Annexin V/PI method was employed for apoptotic analysis. The expression of specific genes involved in cancer progression was also analyzed via RT-PCR. Caspase-3 activation was observed through fluorometric assay. RESULTS: We have identified that sertraline hydrochloride most effectively inhibited the growth of breast cancer cell cells in vitro. Preliminary mechanistic studies demonstrated that the cytotoxicity of sertraline hydrochloride was possibly through the induction of apoptosis, as inferred from enhanced nuclear fragmentation, flow cytometric data, and caspase-3/7 activation. Gene expression analysis also showed an increased expression of proapoptotic Bax and a slight decrease in oncogene c-myc in the presence of sertraline hydrochloride. CONCLUSION: In conclusion, our data suggest that sertraline hydrochloride, an antidepressant, can potentially be used for the treatment of breast cancer.

Prescribing patterns in patients with obsessive-compulsive disorder: Retrospective, single-center study.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is marked by a high rate of treatment resistance. Patients are often left trialing medications within multiple drug classes with little response, causing heterogeneity to emerge in prescribing patterns. This analysis seeks to investigate the selection and dosing of the pharmacotherapy utilized, to portray an overview of prescribing trends in the United States. METHODS: This retrospective, single center, review of electronic medical records investigated the pharmacotherapy utilization of patients with a primary diagnosis of OCD. Two hundred and ninety-five patients who received OCD treatment at an urban, academic medical center were included in the study. Patients were included in the review if they were at least eighteen years of age and were assigned a diagnosis of OCD according to DSM-5 criteria. RESULTS: Psychotropic pharmacotherapy was integrated into the care of 93% of patients. Selective serotonin reuptake inhibitors were the most utilized medication class at 85% followed by benzodiazepines (47%) and second-generation antipsychotics (37%). Tricyclic antidepressants and first-generation antipsychotics were the two medication classes utilized the least at 13% and 2% respectively. Additionally, mood stabilizers and serotonin-norepinephrine reuptake inhibitors were utilized at rates of 8% and 16%, respectively. CONCLUSIONS: Evidence-based treatment guidelines are being followed with varying augmentation strategies widely prevalent, thus displaying the heterogeneity in treating OCD. A high rate of benzodiazepine utilization highlights a practice trend with potential ties to clinical factors, such as the latency to treatment effect of other first-line pharmacotherapies. Future prospective studies are required to determine the cultural, pharmacoeconomic and pharmacogenomic factors that contribute to the variation in prescribing practices and whether these variations influence treatment outcomes.

Antidepressant nonadherence and sexual dysfunction among young adult males: the cross-sectional YAMAN study.

PURPOSE: Selective serotonin reuptake inhibitors are associated with high rates of nonadherence and sexual dysfunction, yet the correlation between these findings in young adult men is poorly characterized. We aimed to evaluate if young adult men are less willing to adhere to antidepressant treatment due to intolerable side effects, such as sexual dysfunction. METHODS: Deidentified, compensated survey that assessed baseline demographics, PHQ-8 and GAD-7 scores, attitudes towards antidepressant medication side effects, and perceptions of antidepressant medications including selective serotonin reuptake inhibitors, bupropion, and mirtazapine. RESULTS: From 665 delivered surveys, 505 respondents completed their survey (response rate: 76%), of which 486 were included for final analysis. After seeing common side effect profiles, our sample's willingness to take sexual function-sparing agents, such as bupropion or mirtazapine, was significantly greater than selective serotonin reuptake inhibitors (p < 0.001), with no significant difference between bupropion and mirtazapine (p = 0.263). The negative influence of erectile dysfunction and anorgasmia scored significantly higher than other common antidepressant side effects like weight gain, nausea, and dry mouth (range: p < 0.001, p = 0.043). With the exception of insomnia, participants indicated that experiencing sexual dysfunction while taking an antidepressant medication would lead to nonadherence at a significantly higher frequency than any other side effect assessed (range: p < 0.001, p = 0.005). CONCLUSION: The risk of experiencing sexual side effects when taking antidepressants could lead young adult men to become nonadherent to these medications. Strategies to augment the effectiveness of antidepressants, such as shared decision-making and the use of sexual function-sparing agents, are critical.

Off-label higher doses of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder: Safety and tolerability.

OBJECTIVE: To examine the long-term safety and tolerability of off-label high-dose serotonin reuptake inhibitors (OLHD-SRIs) in the treatment of obsessive-compulsive disorder (OCD). METHODS: A retrospective longitudinal study was performed on 105 randomly selected outpatients diagnosed with OCD and were treated with OLHD-SRIs for at least 6 months. Patients received sertraline >200 mg/day, escitalopram >20 mg/day, fluvoxamine >300 mg/day, and fluoxetine >60 mg/day, combined with exposure and response prevention therapy. Patients were divided into three dosing groups: sertraline equivalent dose (SED) ≤ 200 mg/day (n = 26, 24.7%), 201-400 mg/day (n = 51, 48.5%) and 401-650 mg/day (n = 28, 26.6%). Safety and tolerability were assessed with an electrocardiogram, blood biochemistry, complete blood count, and side-effects monitoring. RESULTS: SED ranged from 100 to 650 mg/day and the mean duration of OLHD-SRI treatment was 20.8 months. The most common side-effects reported were sexual dysfunction (n = 36, 34%), weight gain (n = 28, 27%), sedation (n = 27, 26%), hyperhidrosis (n = 20, 19%), and tremor (n = 11, 10%). Abnormal ECG was documented in one patient, and another patient experienced a first-time seizure, whereas elevated liver enzymes were seen in 4.8% of the sample (n = 5). None of the patients had serotonin syndrome or drug-induced liver injury. Side-effects did not differ among the three dosing groups. CONCLUSION: OLHD-SRIs appear to be safe and well tolerated in OCD patients in SED ≤ 650 mg/day doses and the side-effects did not differ between the three dosing groups.

Greater Apathy Associated With Selective Serotonin Reuptake Inhibitor Use in Parkinson's Disease.

OBJECTIVE: Apathy, a motivational disorder, is common in Parkinson's disease (PD) and often misdiagnosed as depression. Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with increased apathy in adolescents and adults with depression. Based on observations that serotonin may downregulate dopaminergic systems, we examined the relationship between apathy and SSRI use in individuals with PD. METHODS: Medications, mood/motivation scales, and clinical data were collected from a convenience sample of 400 individuals with PD. Depression and apathy were measured using the Beck Depression Inventory-II (BDI-Il) and the Apathy Scale (AS). Antidepressant medications were grouped by mechanism type. RESULTS: Of the 400 PD patients, 26% were on SSRIs. On standard mood/motivation scales, 38% of the sample exceeded clinical cut-offs for apathy and 28% for depression. Results of hierarchical regression analyses revealed that SSRIs were the only antidepressant that were significantly associated with higher apathy scores (ß = .1, P = .02). Less education (ß = -.1, P = .01) worse cognition (ß = -.1, P = .01), and greater depressive symptoms (ß = .5, P < .001) were also significant predictors of apathy. CONCLUSION: These findings suggest that use of SSRIs, but not other antidepressants, is associated with greater apathy in PD. Given the interactive relationship between serotonin and dopamine, the current findings highlight the importance of considering apathy when determining which antidepressants to prescribe to individuals with PD. Similarly, switching a SSRI for an alternative antidepressant in individuals with PD who are apathetic may be a potential treatment for apathy that needs further study.

Effect of l-arginine compared to placebo on sexual function in women with major depressive disorder: a randomized controlled trial.

BACKGROUND: While some evidence suggests that l-arginine may improve sexual function and alleviate depression, it has not been investigated in women with depression to assess both its effects on the depression and sexual function concurrently. METHODS: Patients who had received a diagnosis of major depressive disorder, as determined by predetermined inclusion and exclusion criteria, were enrolled in this triple-blind clinical trial. Patients were divided into two groups: group A, received L-arginine 1 gram twice daily, and group B, received a placebo for four weeks. They were evaluated at baseline, after four and eight weeks with the Hamilton Depression Rating Scale (HDRS), and Rosen's questionnaire or Female Sexual Function Index (FSFI). RESULTS: A decrease in the severity of depression was observed in all patients, which was determined due to Hamilton's questionnaire (P-value < 0.001). During the time in group A, FSFI increased. Based on the FSFI questionnaire, they had improvement in some domains, including the lubrication index and orgasm index, which significantly changed in the eighth week compared to the baseline (P-value < 0.05). However, these two indicators did not change statistically significantly compared to the placebo group. CONCLUSION: L-arginine supplementation can improve sexual function, particularly lubrication and orgasm, and mood in women with depression, with minimal side effects observed. Additional research is necessary to validate these results by examining the effects of higher dosages, extended durations, and larger populations of depressed patients. TRIAL REGISTRATION: Iranian Registry of Clinical Trial: IRCT20100127003210N26.

Reduced Bioavailability of Antidepressants for the Management of Generalized Anxiety Disorder Following Bariatric Surgery: A Case Study.

Bariatric surgery is a commonly performed procedure for patients who have failed to achieve weight loss through medical and lifestyle interventions. However, the altered gastrointestinal anatomy resulting from the surgery can significantly impact the bioavailability of antidepressants in patients with generalized anxiety disorder, potentially leading to uncontrolled anxiety symptoms. This case report describes a patient with generalized anxiety disorder who underwent Roux-en-Y gastric bypass surgery and subsequently experienced increased anxiety symptoms due to poor antidepressant bioavailability. The patient's medication was adjusted to a sublingual formulation, resulting in improved anxiety control and reduced side effects. Healthcare providers should be aware of the potential impact of bariatric surgery on medication absorption and closely monitor patients with generalized anxiety disorder for potential psychiatric medication-related complications postoperatively. The use of alternative routes of administration, such as sublingual medication, may be beneficial in improving drug bioavailability and managing anxiety symptoms. Creating awareness in primary care offices about poor drug absorption and using alternatives such as the sublingual route of administration to achieve optimal systemic delivery requires a multifaceted approach involving education and training for healthcare providers as well as patient education to ensure they are informed and engaged in their own care. By implementing these strategies, primary care providers can improve patient outcomes and prevent unnecessary referrals to specialists.