A Clinical Rationale for Assessing the Impact of Childhood Sexual Abuse on Adjunctive Subcutaneous Esketamine for Treatment-Resistant Depression.
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SUBMITTER: Magalhaes EJM
PROVIDER: S-EPMC8415867 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Serotonin transporter (SERT) inhibitors treat depression by elevating brain extracellular 5-hydroxytryptamine (5-HTExt). However, only one-third of patients respond adequately. Treatment-resistant depression (TRD) is a major unmet need. Interestingly, elevating 5-HTExt beyond what is achieved by a SERT inhibitor appears to treat TRD. Adjunctive administration of 5-hydroxytryptophan (5-HTP) safely elevates 5-HTExt beyond the SERT inhibitor effect in humans; however, 5-HTP cannot be a clinically viable drug because of its poor pharmacokinetics. A slow-release (SR) delivery mode would be predicted to overcome the pharmacokinetic limitations of 5-HTP, substantially enhancing the pharmacological action and transforming 5-HTP into a clinically viable drug. Animal studies bear out this prediction. Thus, adjunct 5-HTP SR could be an important new treatment for TRD. Here, we review the clinical and preclinical evidence for this treatment.
| S-EPMC5728156 | biostudies-literature
Project description:ImportanceApproximately one-third of patients with major depressive disorder (MDD) do not respond to available antidepressants.ObjectiveTo assess the efficacy, safety, and dose-response of intranasal esketamine hydrochloride in patients with treatment-resistant depression (TRD).Design, setting, and participantsThis phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study was conducted in multiple outpatient referral centers from January 28, 2014, to September 25, 2015. The study consisted of 4 phases: (1) screening, (2) double-blind treatment (days 1-15), composed of two 1-week periods, (3) optional open-label treatment (days 15-74), and (4) posttreatment follow-up (8 weeks). One hundred twenty-six adults with a DSM-IV-TR diagnosis of MDD and history of inadequate response to 2 or more antidepressants (ie, TRD) were screened, 67 were randomized, and 60 completed both double-blind periods. Intent-to-treat analysis was used in evaluation of the findings.InterventionsIn period 1, participants were randomized (3:1:1:1) to placebo (n = 33), esketamine 28 mg (n = 11), 56 mg (n = 11), or 84 mg (n = 12) twice weekly. In period 2, 28 placebo-treated participants with moderate-to-severe symptoms were rerandomized (1:1:1:1) to 1 of the 4 treatment arms; those with mild symptoms continued receiving placebo. Participants continued their existing antidepressant treatment during the study. During the open-label phase, dosing frequency was reduced from twice weekly to weekly, and then to every 2 weeks.Main outcomes and measuresThe primary efficacy end point was change from baseline to day 8 (each period) in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score.ResultsSixty-seven participants (38 women, mean [SD] age, 44.7 [10.0] years) were included in the efficacy and safety analyses. Change (least squares mean [SE] difference vs placebo) in MADRS total score (both periods combined) in all 3 esketamine groups was superior to placebo (esketamine 28 mg: -4.2 [2.09], P = .02; 56 mg: -6.3 [2.07], P = .001; 84 mg: -9.0 [2.13], P < .001), with a significant ascending dose-response relationship (P < .001). Improvement in depressive symptoms appeared to be sustained (-7.2 [1.84]) despite reduced dosing frequency in the open-label phase. Three of 56 (5%) esketamine-treated participants during the double-blind phase vs none receiving placebo and 1 of 57 participants (2%) during the open-label phase had adverse events that led to study discontinuation (1 event each of syncope, headache, dissociative syndrome, and ectopic pregnancy).Conclusions and relevanceIn this first clinical study to date of intranasal esketamine for TRD, antidepressant effect was rapid in onset and dose related. Response appeared to persist for more than 2 months with a lower dosing frequency. Results support further investigation in larger trials.Trial registrationclinicaltrials.gov identifier: NCT01998958.
| S-EPMC5838571 | biostudies-literature
Project description:BackgroundPrevious studies have frequently reported a high prevalence of co-occurring anxiety and depression among people who experienced stressful events in childhood. However, few have noted the symptomatic relationship of this comorbidity among childhood sexual abuse (CSA) survivors. Therefore, this study's objectives were as follows: (1) to examine the relationship across symptoms between anxiety and depression among CSA survivors; (2) to compare differences between male and female network structures among CSA survivors.MethodsA total of 63 Universities and Colleges in Jilin Province, China, covered 96,218 participants in this study, a sub-set data of which met the criteria of CSA was analyzed with the network analysis. The Childhood Trauma Questionnaire-Short Form (CTQ-SF), measured CSA. Anxiety was measured by the seven-item Generalized Anxiety Disorder Scale (GAD-7), and depression was measured by the Patient Health Questionnaire (PHQ-9). The sex difference between anxiety and depression among CSA survivors was compared.Results3,479 college students reported the experience of CSA (CTQ-SF total scores ≥ 8), with a prevalence of 3.62% (95% CI: 3.50-3.73%). Among CSA survivors, control worry, sad mood, and energy were central and bridge symptoms of the anxiety and depression network. Meanwhile, male CSA survivors appeared to have a stronger correlation between guilt and suicide, but female CSA survivors seemed to have a stronger correlation between control worry and suicide. Moreover, the edge of control worry-relax-afraid was stronger in the male network, while the edge of restless-relax was stronger in the female network.ConclusionControl worry, sad mood, and energy are crucial to offer targeted treatment and to relieve anxiety and depression symptoms for CSA survivors. Guilt needs more attention for male CSA survivors, while control worry remains more important for female CSA survivors to reduce suicidal ideation and suicide attempts.
| S-EPMC10504753 | biostudies-literature
Project description:OBJECTIVE:Sexual abuse experienced in childhood and adolescence is associated with severity of posttraumatic stress disorder (PTSD), depressive symptoms, and emotion regulation difficulties. The current study examined the relationships among these factors in a sample of adolescents with sexual abuse-related PTSD. It was hypothesized that (a) self-perceived emotion regulation difficulties would predict severity of PTSD and depressive symptoms, and that (b) depressive symptoms would mediate the relationship between emotion regulation difficulties and PTSD. METHOD:Ninety treatment-seeking female adolescents with a history of sexual abuse were evaluated using the Child PTSD Symptom Scale-Interview and completed the Negative Mood Regulation Questionnaire and the Beck Depression Inventory as part of a baseline evaluation. RESULTS:Greater emotion regulation difficulties were associated with greater severity of PTSD and depressive symptoms. In addition, the relationship between emotion regulation difficulties and PTSD severity was mediated by depressive symptoms. However, the reverse was also true: the relationship between emotion regulation difficulties and depressive symptoms was mediated by PTSD symptoms. CONCLUSIONS:Mediation analyses showed that emotion regulation difficulties were associated with both PTSD and depressive symptoms rather than fitting a unidirectional model. These findings are consistent with and extend previous research and highlight the importance of emotion regulation in adolescent survivors of sexual abuse. (PsycINFO Database Record
| S-EPMC5756524 | biostudies-literature
Project description:In March 2019, the US Food and Drug Administration (FDA) approved a nasal spray formulation of esketamine for the treatment of resistant depression in adults. Esketamine is the S-enantiomer of ketamine, an FDA-approved anaesthetic, known to cause dissociation and, occasionally, hallucinations. While ketamine has not been approved for depression in the USA or in any other country, it has been used off-label in cases of severe depression. This commentary critically reviewed the evidence on esketamine submitted to the FDA, aiming to draw implications for clinical practice, research and regulatory science.
| S-EPMC8061126 | biostudies-literature
Project description:Treatment-resistant depression (TRD) is a challenge for psychiatrists, even after more than seven decades since the first antidepressants were used in clinical practice. Non-monoaminergic-based drugs with antidepressant properties have been developed, but to date, only esketamine and brexanolone have been approved for TRD and postpartum depression, respectively. A narrative review on the efficacy and safety of esketamine in the main categories of depressive disorders has been conducted through four electronic databases (Pubmed, Cochrane, EMBASE and Clarivate/Web of Science) The primary objective of the present review was to find evidence that may support the usefulness of esketamine for patients diagnosed with TRD as well as data about its potential adverse effects in the short and long term. A total of 14 papers were reviewed, and their results support the recommendation of esketamine for treatment of TRD as an add-on to antidepressants, but more data is needed in order to assess its long-term efficacy and safety. It must also be mentioned that there have been a few trials which did not report a significant effect on the severity of depressive symptoms with esketamine in TRD, therefore, caution is indicated for patients initiated on this adjuvant agent. There has been insufficient data to formulate specific guidelines about esketamine administration because evidence about favorable or negative prognostic factors of this treatment has been lacking, and the duration of its administration has not been unanimously accepted. Novel directions for research have been identified, especially in the case of patients with TRD and substance use disorders, geriatric or bipolar depression or in major depression with psychotic features.
| S-EPMC9922941 | biostudies-literature
Project description:IntroductionWe assessed the correlation between childhood maltreatment (CM) and severity of depression in an elderly unipolar Treatment-Resistant Depression (TRD) sample.MethodsPatients were enrolled from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centres.ResultsOur sample included 96 patients (33% of the overall cohort) aged 60 years or above, with a mean age of 67.2 (SD = 5.7). The majority of the patients were female (62.5%). The Montgomery and Asberg Depression Rating Scale (MADRS) and Quick Inventory Depression Scale-Self Report (QIDS-SR) mean scores were high, 28.2 (SD = 7.49) [MADRS score range: 0-60; moderate severity≥20, high severity≥35] and 16.5 (SD = 4.94) [IDS-SR score range: 0-27; moderate severity≥11, high severity≥16], respectively. Mean self-esteem scores were 22.47 (SD = 6.26) [range 0-30]. In an age- and sex-adjusted model, we found a positive correlation between childhood trauma (CTQ scores) and depressive symptom severity [MADRS (β = 0.274; p = 0.07) and QIDS-SR (β = 0.302; p = 0.005) scores]. We detected a statistically significant correlation between physical abuse and depressive symptom severity [MADRS (β = 0.304; p = 0.03) and QIDS-SR (β = 0.362; p = 0.005) scores]. We did not observe any significant correlation between other types of trauma and depressive symptom severity. We showed that self-esteem (Rosenberg scale) mediated the effect of physical abuse (PA) on the intensity of depressive symptoms [MADRS: b = 0.318, 95% BCa C.I. [0.07, 0.62]; QIDS-SR: b = 0.177, 95% BCa C.I. [0.04, 0.37]]. Preacher & Kelly's Kappa Squared values of 19.1% (k2 = 0.191) and 16% (k2 = 0.16), respectively for the two scales, indicate a moderate effect.ConclusionTo our knowledge, this is the first study conducted in a geriatric TRD population documenting an association between childhood trauma (mainly relating to PA) and the intensity of depressive symptoms.
| S-EPMC8057608 | biostudies-literature
Project description:The objective of this review is to summarize the literature (and to the extent possible, report the magnitude and direction of the association) concerning history of childhood sexual abuse (CSA) and depression or depressive symptoms among pregnant and postpartum women. Publications were identified through literature searches of seven databases (PubMed, EMBASE, PyscINFO, CINAHL, Web of Science, BIOSIS, and Science Direct) using keywords including "child abuse," "depression," "pregnancy," "prenatal," "pregnancy," and "postpartum." The literature search yielded seven eligible studies on the prenatal period and another seven studies on the postpartum period. All but one prenatal study observed statistically significant positive associations of CSA with depression or depressive symptoms during pregnancy. Findings on the association of CSA with postpartum depression or depressive symptoms were inconsistent; pooled unadjusted and adjusted odds ratios were 1.82 (95 % confidence interval (CI) 0.92, 3.60) and 1.20 (95 % CI 0.81, 1.76). In sum, findings suggest a positive association of history of CSA with depression and depressive symptoms in the prenatal period. Findings on the postpartum period were inconsistent. Clinical and public health implications of evidence from the available literature are discussed, as are desirable study design characteristics of future research.
| S-EPMC4565760 | biostudies-literature
Project description:Childhood and adolescent sexual abuse has been associated with subsequent (adult) sexual risk behavior, but the effects of force and type of sexual abuse on sexual behavior outcomes have been less well-studied. The present study investigated the associations between sexual abuse characteristics and later sexual risk behavior, and explored whether gender of the child/adolescent moderated these relations. Patients attending an STD clinic completed a computerized survey that assessed history of sexual abuse as well as lifetime and current sexual behavior. Participants were considered sexually abused if they reported a sexual experience (1) before age 13 with someone 5 or more years older, (2) between the ages of 13 and 16 with someone 10 or more years older, or (3) before the age of 17 involving force or coercion. Participants who were sexually abused were further categorized based on two abuse characteristics, namely, use of penetration and force. Analyses included 1177 participants (n=534 women; n=643 men). Those who reported sexual abuse involving penetration and/or force reported more adult sexual risk behavior, including the number of lifetime partners and number of previous STD diagnoses, than those who were not sexually abused and those who were abused without force or penetration. There were no significant differences in sexual risk behavior between nonabused participants and those who reported sexual abuse without force and without penetration. Gender of the child/adolescent moderated the association between sexual abuse characteristics and adult sexual risk behavior; for men, sexual abuse with force and penetration was associated with the greatest number of episodes of sex trading, whereas for women, those who were abused with penetration, regardless of whether the abuse involved force, reported the most episodes of sex trading. These findings indicate that more severe sexual abuse is associated with riskier adult sexual behavior.
| S-EPMC2042031 | biostudies-other
Project description:BACKGROUND:Although many meta-analyses have examined the association between childhood sexual abuse and subsequent outcomes, the scope, validity, and quality of this evidence has not been comprehensively assessed. We aimed to systematically review existing meta-analyses on a wide range of long-term psychiatric, psychosocial, and physical health outcomes of childhood sexual abuse, and evaluate the quality of the literature. METHODS:In this umbrella review, we searched four databases (PsycINFO, PubMed, Cumulative Index to Nursing and Allied Health Literature, and Global Health) from inception to Dec 31, 2018, to identify meta-analyses of observational studies that examined the association between childhood sexual abuse (before 18 years of age) and long-term consequences (after 18 years). We compared odds ratios (ORs) across different outcomes. We also examined measures of quality, including heterogeneity between studies and evidence for publication bias. This study is registered with PROSPERO, CRD42016049701. FINDINGS:We identified 19 meta-analyses that included 559 primary studies, covering 28 outcomes in 4?089?547 participants. Childhood sexual abuse was associated with 26 of 28 specific outcomes: specifically, six of eight adult psychiatric diagnoses (ORs ranged from 2·2 [95% CI 1·8-2·8] to 3·3 [2·2-4·8]), all studied negative psychosocial outcomes (ORs ranged from 1·2 [1·1-1·4] to 3·4 [2·3-4·8]), and all physical health conditions (ORs ranged from 1·4 [1·3-1·6] to 1·9 [1·4-2·8]). Strongest psychiatric associations with childhood sexual abuse were reported for conversion disorder (OR 3·3 [95% CI 2·2-4·8]), borderline personality disorder (2·9 [2·5-3·3]), anxiety (2·7 [2·5-2·8]), and depression (2·7 [2·4-3·0]). The systematic reviews for two psychiatric outcomes (post-traumatic stress disorder and schizophrenia) and one psychosocial outcome (substance misuse) met high quality standards. Quality was low for meta-analyses on borderline personality disorder and anxiety, and moderate for conversion disorder. Assuming causality, population attributable risk fractions for outcomes ranged from 1·7% (95% CI 0·7-3·3) for unprotected sexual intercourse to 14·4% (8·8-19·9) for conversion disorder. INTERPRETATION:Although childhood sexual abuse was associated with a wide range of psychosocial and health outcomes, systematic reviews on only two psychiatric disorders (post-traumatic stress disorder and schizophrenia) and one psychosocial outcome (substance misuse) were of a high quality. Whether services should prioritise interventions that mitigate developing certain psychiatric disorders following childhood abuse requires further review. Higher-quality meta-analyses for specific outcomes and more empirical studies on the developmental pathways from childhood sexual abuse to later outcomes are necessary. FUNDING:Wellcome Trust.
| S-EPMC7015702 | biostudies-literature