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Metabolomic signature of exposure and response to citalopram/escitalopram in depressed outpatients.
Bhattacharyya, S, Ahmed, AT, Arnold, M, Liu, D, Luo, C, Zhu, H, Mahmoudiandehkordi, S, Neavin, D, Louie, G, Dunlop, BW, et al
Translational psychiatry. 2019;(1):173
Abstract
Metabolomics provides valuable tools for the study of drug effects, unraveling the mechanism of action and variation in response due to treatment. In this study we used electrochemistry-based targeted metabolomics to gain insights into the mechanisms of action of escitalopram/citalopram focusing on a set of 31 metabolites from neurotransmitter-related pathways. Overall, 290 unipolar patients with major depressive disorder were profiled at baseline, after 4 and 8 weeks of drug treatment. The 17-item Hamilton Depression Rating Scale (HRSD17) scores gauged depressive symptom severity. More significant metabolic changes were found after 8 weeks than 4 weeks post baseline. Within the tryptophan pathway, we noted significant reductions in serotonin (5HT) and increases in indoles that are known to be influenced by human gut microbial cometabolism. 5HT, 5-hydroxyindoleacetate (5HIAA), and the ratio of 5HIAA/5HT showed significant correlations to temporal changes in HRSD17 scores. In the tyrosine pathway, changes were observed in the end products of the catecholamines, 3-methoxy-4-hydroxyphenylethyleneglycol and vinylmandelic acid. Furthermore, two phenolic acids, 4-hydroxyphenylacetic acid and 4-hydroxybenzoic acid, produced through noncanconical pathways, were increased with drug exposure. In the purine pathway, significant reductions in hypoxanthine and xanthine levels were observed. Examination of metabolite interactions through differential partial correlation networks revealed changes in guanosine-homogentisic acid and methionine-tyrosine interactions associated with HRSD17. Genetic association studies using the ratios of these interacting pairs of metabolites highlighted two genetic loci harboring genes previously linked to depression, neurotransmission, or neurodegeneration. Overall, exposure to escitalopram/citalopram results in shifts in metabolism through noncanonical pathways, which suggest possible roles for the gut microbiome, oxidative stress, and inflammation-related mechanisms.
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The Experience Sampling Method-Evaluation of treatment effect of escitalopram in IBS with comorbid panic disorder.
Vork, L, Mujagic, Z, Drukker, M, Keszthelyi, D, Conchillo, JM, Hesselink, MAM, van Os, J, Masclee, AAM, Leue, C, Kruimel, JW
Neurogastroenterology and motility. 2019;(1):e13515
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Abstract
BACKGROUND Confirming treatment response in clinical trials for irritable bowel syndrome (IBS) is challenging, due to the lack of biomarkers and limitations of the currently available symptom assessment tools. The Experience Sampling Method (ESM) might overcome these limitations by collecting digital assessments randomly and repeatedly during daily life. This study evaluated differences in change in abdominal pain between real-time (ie, ESM) and retrospective (ie, Gastrointestinal Symptom Rating Scale [GSRS] and an end-of-day symptom diary) measurements, using data of an RCT on escitalopram vs placebo in patients with IBS and comorbid panic disorder. METHODS Twenty-nine IBS patients with comorbid panic disorder were included in a 6-month RCT. The GSRS, diary, and ESM were completed at baseline (t = 0) and after 3 (t = 3) and 6 months (t = 6). Linear mixed models were used. KEY RESULTS Experience Sampling Method analyses revealed a significant interaction between escitalopram and time, and ESM abdominal pain scores were 1.4 points lower in the escitalopram group compared to placebo at t = 6 (on a 1-to-7 scale; P = 0.021). When including the interaction with momentary anxiety, the reduction in abdominal pain scores in escitalopram vs placebo was even more pronounced for higher levels of anxiety. Average GSRS- and end-of-day abdominal pain scores were not significantly different between escitalopram and placebo at t = 3 and 6. CONCLUSIONS & INFERENCES Real-time ESM has the potential to capture treatment response more sensitively compared to a retrospective end-of-day GI symptom diary and the GSRS, by taking into account day-to-day symptom variability as well as momentary factors that might moderate treatment effect, such as anxiety.
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Premenstrual Dysphoric Disorder.
Lanza di Scalea, T, Pearlstein, T
The Medical clinics of North America. 2019;(4):613-628
Abstract
Premenstrual dysphoric disorder (PMDD) comprises emotional and physical symptoms and functional impairment that lie on the severe end of the continuum of premenstrual symptoms. Women with PMDD have a differential response to normal hormonal fluctuations. This susceptibility may involve the serotonin system, altered sensitivity of the GABAA receptor to the neurosteroid allopregnanalone, and altered brain circuitry involving emotional and cognitive functions. Serotonin reuptake inhibitors are considered the first-line treatment. Second-line treatments include oral contraceptives containing drospirenone, other ovulation suppression methods, calcium, chasteberry, and cognitive-behavioral therapy.
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Facets of shared decision-making on drug treatment for adults with an eating disorder.
Himmerich, H, Bentley, J, Lichtblau, N, Brennan, C, Au, K
International review of psychiatry (Abingdon, England). 2019;(4):332-346
Abstract
Shared decision-making (SDM) means that clinicians and the patient make decisions about the treatment together. Regarding drug treatment in eating disorders (EDs), such decisions may include psychopharmacological treatment for the ED itself, medications for potential co-morbid psychiatric disorders, pharmacological strategies to alleviate the health consequences of an ED, or 'pro re nata' (PRN) medication which is given in acute care when required. Decisions regarding drug treatment in EDs should be specific in terms of the active pharmacological substance, its dose, its route of administration, and the duration of treatment. Decisions should be made with regard to the specific health risks of patients with EDs and the entire treatment approach, and should take alternative measures, additional therapies, and specific combinations of therapies into account. The differences in the expectations of patients, carers, and clinicians towards drug treatment, the lack of specific suggestions in clinical practice guidelines, and the lack of approved psychopharmacological treatment options make SDM necessary, but also a challenge. However, SDM may be limited due to the patient's impaired insight or limited capacity due to the ED. Thus, the legal framework must be taken into consideration.
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The influence of sertraline on depressive disorder after traumatic brain injury: A meta-analysis of randomized controlled studies.
Gao, C, Fu, Q, Chen, P, Liu, Z, Zhou, Q
The American journal of emergency medicine. 2019;(9):1778-1783
Abstract
BACKGROUND Sertraline showed some potential in alleviating depressive disorder after traumatic brain injury. This systematic review and meta-analysis was conducted to investigate the efficacy of sertraline on the treatment of depressive disorder after traumatic brain injury. METHODS The databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched for collecting the randomized controlled trials (RCTs) regarding the efficacy of sertraline for traumatic brain injury. RESULTS This meta-analysis included five RCTs. The initial use of sertraline was within 8 weeks after traumatic brain injury. Compared with control group for traumatic brain injury, sertraline treatment showed no significant improvement on Hamilton Depression Rating Scale (HAM-D) (standard mean difference (Std. MD) = -0.08; 95% confidence interval (CI) = -0.45 to 0.28; P = 0.65), anxiety score (Std. MD = 0.08; 95% CI = -0.32 to 0.48; P = 0.69), aggression score (Std. MD = -0.12; 95% CI = -0.56 to 0.32; P = 0.59), or quality of life (QOL) score (Std. MD = -0.06; 95% CI = -0.49 to 0.37; P = 0.78). There was no statistical difference of diarrhea (risk ratio (RR) = 0.85; 95% CI = 0.92 to 3.71; P = 0.08), dizziness (RR = 1.15; 95% CI = 0.57 to 2.31; P = 0.70), dry mouth (RR = 2.44; 95% CI = 0.43 to 13.89; P = 0.32), nausea or vomiting (RR = 1.17; 95% CI = 0.37 to 3.70; P = 0.79) between sertraline group and control group. CONCLUSIONS Sertraline showed no obvious benefits for the relief of depressive disorder after traumatic brain injury.
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Drug Treatment of Trichotillomania (Hair-Pulling Disorder), Excoriation (Skin-picking) Disorder, and Nail-biting (Onychophagia).
Sani, G, Gualtieri, I, Paolini, M, Bonanni, L, Spinazzola, E, Maggiora, M, Pinzone, V, Brugnoli, R, Angeletti, G, Girardi, P, et al
Current neuropharmacology. 2019;(8):775-786
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Abstract
BACKGROUND Trichotillomania (TTM), excoriation (or skin-picking) disorder and some severe forms of onychophagia are classified under obsessive-compulsive and related disorders. There are different interacting neurotransmitter systems involved in the pathophysiology of impulse-control disorders, implicating noradrenaline, serotonin, dopamine, opioid peptides and glutamate, hence investigators focused on drugs able to act on these transmitters. Our aim was to critically review the efficacy of the drugs employed in impulse-control disorders. METHODS We searched for controlled drug trials to treat TTM, excoriation, and/or nail-biting six databases (PubMed, Cochrane, Scopus, CINAHL, PsycINFO/PsycARTICLES, and Web of Science), using the search strategy: (trichotillomania OR "excoriation disorder" OR "face picking" OR "skin picking" OR "hair pulling" OR onychophagia OR "nail-biting") AND drug treatment on 12 March 2018 for all databases. We followed in our method of identifying relevant literature the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS SSRIs and clomipramine are considered first-line in TTM. In addition, family members of TTM patients are often affected by obsessive-compulsive spectrum disorders. Other drugs used in the treatment of TTM are lamotrigine, olanzapine, N-Acetylcysteine, inositol, and naltrexone. CONCLUSION The treatment of TTM, excoriation disorder and nail-biting is still rather disappointing. Conjectures made from preclinical studies and the relative pathophysiological hypotheses found poor confirmations at a clinical level. There is a need for further studies and the integration of pharmacological and psychotherapeutic. Our results point to the need of integrating personalised medicine principles in the treatment of these patients.
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Combination Therapy of Serotonin Reuptake Inhibitors and Memantine for Obsessive- Compulsive Disorder: A Meta-Analysis of Double-Blind, Randomized, Placebo-Controlled Trials.
Kishi, T, Matsuda, Y, Iwata, N
Journal of Alzheimer's disease : JAD. 2018;(1):43-48
Abstract
We performed a meta-analysis to determine whether combination therapy with serotonin reuptake inhibitors (SRIs) and memantine (MEM) was beneficial for the treatment of obsessive- compulsive disorder. This study included three double-blind, randomized, placebo-controlled trials. MEM+SRI was superior to placebo+SRI with regard to response rate [primary outcome, n = 97; risk ratio = 0.22; 95% confidence intervals (CI) = 0.12-0.42; p < 0.00001; I2 = 0%; number needed to treat = 2], the Yale- Brown Obsessive- Compulsive Scale total [standardized mean difference (SMD) = - 4.56; 95% CI = - 8.50, - 0.62; p = 0.02], obsession subscale (SMD = - 4.39; 95% CI = - 5.94, - 2.85; p < 0.00001), and compulsion subscale score (SMD = - 4.60; 95% CI = - 7.64, - 1.55; p = 0.003). No significant differences in any safety outcome were found between the groups.
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A Systematic Review of Psychological and Pharmacological Treatments for Adjustment Disorder in Adults.
O'Donnell, ML, Metcalf, O, Watson, L, Phelps, A, Varker, T
Journal of traumatic stress. 2018;(3):321-331
Abstract
Adjustment disorder is a common psychiatric disorder, yet knowledge of the efficacious treatments for adjustment disorder is limited. In this systematic review, we aimed to examine psychological and pharmacological interventions that target adjustment disorder in adults to determine which interventions have the best evidence for improving adjustment disorder symptoms. We performed database searches for literature published between January 1980 and September 2016 and identified studies that included both a sample majority of individuals diagnosed with adjustment disorder and findings on adjustment disorder symptom outcomes. There were 29 studies that met the inclusion criteria for qualitative synthesis; the majority of studies (59%) investigated psychological therapies rather than pharmacological treatments (35%). The range of psychological therapies tested was diverse, with the majority containing cognitive behavioral therapy (CBT) components (53%), followed by three studies that were psychodynamic-related, three studies that were behavioral therapy-based, and two studies that involved relaxation techniques. We rated individual studies using a modified National Health and Medical Research Council quality and bias checklist and then used the Grading of Recommendations Assessment, Development and Evaluation (GRADE; Grade Working Group, 2004) system to rate the overall quality of the evidence. Despite several randomized controlled trials, the quality of the evidence for positive effects of all psychological and pharmacological treatments on symptoms of adjustment disorder was ranked as low to very low. Future high-quality research in the treatment of adjustment disorder has the potential to make a significant difference to individuals who struggle to recover after stressful events.
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Pharmacotherapy for the treatment of depression in patients with alzheimer's disease: a treatment-resistant depressive disorder.
Lozupone, M, La Montagna, M, D'Urso, F, Piccininni, C, Sardone, R, Dibello, V, Giannelli, G, Solfrizzi, V, Greco, A, Daniele, A, et al
Expert opinion on pharmacotherapy. 2018;(8):823-842
Abstract
INTRODUCTION Pharmacotherapy for the treatment of depressive disorders in Alzheimer's Disease (AD) represents a clinical challenge. pharmacological options are often attempted after a period of watchful waiting (8-12 weeks). monoaminergic antidepressant drugs have shown only modest or null clinical benefits, maybe because the etiology of depressive symptoms in ad patients is fundamentally different from that of nondemented subjects. AREAS COVERED The following article looks at the selective serotonin reuptake inhibitor sertraline, which is one of the most frequently studied antidepressant medications in randomized controlled trials (RCTs). It also discusses many other pharmacological approaches that have proven to be inadequate (antipsychotics, acetylcholinesterase inhibitors, anticonvulsants, hormone replacement therapy) and new drug classes (mainly affecting glutamate transmission) that are being studied for treating depression in AD. It also gives discussion to the phase II RCT on the alternative drug S47445 and the potential effect on cognition of the multimodal antidepressant vortioxetine in older depressed patients. Finally, it discusses the N-methyl-D-aspartate antagonist ketamine. EXPERT OPINION The present RCT methodologies are too disparate to draw firm conclusions. Future studies are required to identify effective and multimodal pharmacological treatments that efficiently treat depression in AD. Genotyping may boost antidepressant treatment success.
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Pretreatment and early-treatment cortical thickness is associated with SSRI treatment response in major depressive disorder.
Bartlett, EA, DeLorenzo, C, Sharma, P, Yang, J, Zhang, M, Petkova, E, Weissman, M, McGrath, PJ, Fava, M, Ogden, RT, et al
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2018;(11):2221-2230
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Abstract
To date, there are no biomarkers for major depressive disorder (MDD) treatment response in clinical use. Such biomarkers could allow for individualized treatment selection, reducing time spent on ineffective treatments and the burden of MDD. In search of such a biomarker, multisite pretreatment and early-treatment (1 week into treatment) structural magnetic resonance (MR) images were acquired from 184 patients with MDD randomized to an 8-week trial of the selective serotonin reuptake inhibitor (SSRI) sertraline or placebo. This study represents a large, multisite, placebo-controlled effort to examine the association between pretreatment differences or early-treatment changes in cortical thickness and treatment-specific outcomes. For standardization, a novel, robust site harmonization procedure was applied to structural measures in a priori regions (rostral and caudal anterior cingulate, lateral orbitofrontal, rostral middle frontal, and hippocampus), chosen based on previously published reports. Pretreatment cortical thickness or volume did not significantly associate with SSRI response. Thickening of the rostral anterior cingulate cortex in the first week of treatment was associated with better 8-week responses to SSRI (p = 0.010). These findings indicate that frontal lobe structural alterations in the first week of treatment may be associated with long-term treatment efficacy. While these associational findings may help to elucidate the specific neural targets of SSRIs, the predictive accuracy of pretreatment or early-treatment structural alterations in classifying treatment remitters from nonremitters was limited to 63.9%. Therefore, in this large sample of adults with MDD, structural MR imaging measures were not found to be clinically translatable biomarkers of treatment response to SSRI or placebo.