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"Depression - drug therapy"
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Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial
AbstractObjectiveTo confirm the rapid onset anti-suicidal benefits of ketamine in the short term and at six weeks, overall and according to diagnostic group.DesignProspective, double blind, superiority, randomised placebo controlled trial.SettingSeven French teaching hospitals between 13 April 2015 and 12 March 2019.Eligibility criteria for participantsAged 18 or older with current suicidal ideation, admitted to hospital voluntarily. Exclusion criteria included a history of schizophrenia or other psychotic disorders, substance dependence, and contraindications for ketamine.Participants156 participants were recruited and randomised to placebo (n=83) or ketamine (n=73), stratified by centre and diagnosis: bipolar, depressive, or other disorders.InterventionTwo 40 minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) were administered at baseline and 24 hours, in addition to usual treatment.Main outcome measuresThe primary outcome was the rate of patients in full suicidal remission at day 3, according to the scale for suicidal ideation total score ≤3. Analyses were conducted on an intention-to-treat basis.ResultsMore participants receiving ketamine reached full remission of suicidal ideas at day 3 than those receiving placebo: 46 (63.0%) of 83 participants in the ketamine arm and 25 (31.6%) of 73 in the placebo arm (odds ratio 3.7 (95% confidence interval 1.9 to 7.3), P<0.001). This effect differed according to the diagnosis (treatment: P<0.001; interaction: P=0.02): bipolar (odds ratio 14.1 (95% confidence interval 3.0 to 92.2), P<0.001), depressive (1.3 (0.3 to 5.2), P=0.6), or other disorders (3.7 (0.9 to 17.3, P=0.07)). Side effects were limited. No manic or psychotic symptom was seen. Moreover, a mediating effect of mental pain was found. At week 6, remission in the ketamine arm remained high, although non-significantly versus placebo (69.5% v 56.3%; odds ratio 0.8 (95% confidence interval 0.3 to 2.5), P=0.7).ConclusionsThe findings indicate that ketamine is rapid, safe in the short term, and has persistent benefits for acute care in suicidal patients. Comorbid mental disorders appear to be important moderators. An analgesic effect on mental pain might explain the anti-suicidal effects of ketamine.Trial registrationClinicalTrials.gov NCT02299440.
Journal Article
Depression During Pregnancy and Postpartum
Depression is a common complication of pregnancy and the postpartum period. There are multiple risk factors for peripartum mood disorders, most important of which is a prior history of depression. Both depression and antidepressant medications confer risk upon the infant. Maternal depression has been associated with preterm birth, low birth weight, fetal growth restriction, and postnatal cognitive and emotional complications. Antidepressant exposure has been associated with preterm birth, reductions in birth weight, persistent pulmonary hypertension, and postnatal adaptation syndrome (PNAS) as well as a possible connection with autism spectrum disorder. Paroxetine has been associated with cardiac malformations. Most antidepressant medications are excreted in low levels in breast milk and are generally compatible with breastfeeding. The use of antidepressants during pregnancy and postpartum must be weighed against the risk of untreated depression in the mother.
Journal Article
Trends in prevalence and treatment of antepartum and postpartum depression in the United States: Data from the national health and nutrition examination survey (NHANES) 2007 to 2018
(1) To assess the prevalence of depression and treatment rates in antepartum and postpartum women compared to a control group of reproductive-age women over a 12-year period, and (2) To determine demographic characteristics associated with depression.
National Health and Nutrition Examination Survey data (2007-2018) were used. 5412 controls, 314 antepartum women, and 455 postpartum women were analyzed. Outcomes included depression prevalence, defined as moderate to severe depressive symptoms measured by Patient Health Questionnaire-9 (PHQ-9) scores ≥10 or self-reported antidepressant use; and treatment, defined as antidepressant prescription and/or mental health care services in the past 12 months. Multivariable logistic regression adjusted for age, insurance, race/ethnicity, education, and marital status estimated odds ratios and 95% confidence intervals.
Depression prevalence was 20.2% in controls (95% CI 18.5-21.9), 9.7% in antepartum (6.3-14.1), and 12.8% in postpartum women (9.3-17.1). Mental health care service utilization increased for postpartum women in 2017-2018 (22.0%, 10.6-37.7). In those with depression, control and postpartum groups had similar treatment rates (70%, p = 0.894) compared to antepartum women (51%, p = 0.051). Antidepressant use was the most common treatment reported in all groups. Those who were married or had private insurance had the lowest depression rates in their respective categories. After adjusting for confounders, antepartum and postpartum women had lower odds of depression compared to controls. When the outcome was PHQ-9 ≥ 10 alone, these associations persisted.
In a nationally representative sample, depression prevalence was lower in perinatal women compared to reproductive-age controls, and treatment rates were lowest in antepartum women with prevalent depression. Mental health care services may have increased for postpartum women due to the US Preventive Services Task Force 2016 recommendations, which endorsed psychotherapy for postpartum women. Even so, antidepressants were the most reported treatment among perinatal women, despite psychotherapy being the first-line recommended treatment for this population.
Journal Article
Developmental Fluoxetine Exposure Normalizes the Long-Term Effects of Maternal Stress on Post-Operative Pain in Sprague-Dawley Rat Offspring
Early life events can significantly alter the development of the nociceptive circuit. In fact, clinical work has shown that maternal adversity, in the form of depression, and concomitant selective serotonin reuptake inhibitor (SSRI) treatment influence nociception in infants. The combined effects of maternal adversity and SSRI exposure on offspring nociception may be due to their effects on the developing hypothalamic-pituitary-adrenal (HPA) system. Therefore, the present study investigated long-term effects of maternal adversity and/or SSRI medication use on nociception of adult Sprague-Dawley rat offspring, taking into account involvement of the HPA system. Dams were subject to stress during gestation and were treated with fluoxetine (2×/5 mg/kg/day) prior to parturition and throughout lactation. Four groups of adult male offspring were used: 1. Control+Vehicle, 2. Control+Fluoxetine, 3. Prenatal Stress+Vehicle, 4. Prenatal Stress+Fluoxetine. Results show that post-operative pain, measured as hypersensitivity to mechanical stimuli after hind paw incision, was decreased in adult offspring subject to prenatal stress alone and increased in offspring developmentally exposed to fluoxetine alone. Moreover, post-operative pain was normalized in prenatally stressed offspring exposed to fluoxetine. This was paralleled by a decrease in corticosteroid binding globulin (CBG) levels in prenatally stressed offspring and a normalization of serum CBG levels in prenatally stressed offspring developmentally exposed to fluoxetine. Thus, developmental fluoxetine exposure normalizes the long-term effects of maternal adversity on post-operative pain in offspring and these effects may be due, in part, to the involvement of the HPA system.
Journal Article
Recurrence of depression in the perinatal period: Clinical features and associated vulnerability markers in an observational cohort
Antidepressant medication is commonly used for the prevention of depression recurrence in the perinatal period, yet it is unknown what vulnerability markers may play a role in recurrence. The objective of the current study was to provide a descriptive overview of the associated characteristics of women who experienced a perinatal recurrence of depression despite ongoing antidepressant use, and further, to identify clinically measurable vulnerability markers associated with recurrence.
Eighty-five pregnant women with a history of depression who used antidepressants (e.g. Selective Serotonin Reuptake Inhibitors or Serotonin and Noradrenaline Reuptake Inhibitors) at the start of the study were included. Clinical features, including information on psychiatric history and antidepressant use, were collected throughout the perinatal period (in this study defined as the period between 12 weeks of pregnancy untill three months postpartum). The clinical features of women experiencing recurrence of depression were described in detail. To identify vulnerability markers associated with recurrence of depression, we performed exploratory univariable logistic regression analyses.
Eight women (9.4%) experienced a recurrence of depression; two during pregnancy and six in the first 12 weeks postpartum. All women with recurrence of depression had first onset of depression during childhood or adolescence and had at least 2 psychiatric co-morbidities. Identification of vulnerability markers associated with recurrence of depression yielded associations with depressive symptoms around 16 weeks of pregnancy (OR 1.28, 95%CI 1.08-1.52), number of psychiatric co-morbidities (OR 1.89, 95%CI 1.16-3.09) and duration of antidepressant use (OR 1.01, 95%CI 1.00-1.02).
Implementing adequate risk assessment in pregnant women who use antidepressants can help identify predictors for recurrence of depression in future studies and thus ultimately lead to improved care.
Journal Article
Screening for depression in hemodialysis patients: Associations with diagnosis, treatment, and outcomes in the DOPPS
Screening for depression in hemodialysis patients: Associations with diagnosis, treatment, and outcomes in the DOPPS.
Depressive symptoms and depression are the most frequent psychologic problems reported by hemodialysis patients. We assessed the prevalence of depressive symptoms and physician-diagnosed depression, their variations by country, and associations with treatment by antidepressants among hemodialysis patients. We also assessed whether depressive symptoms were independently associated with mortality, hospitalization, and dialysis withdrawal.
The sample was represented by 9382 hemodialysis patients randomly selected from dialysis centers of 12 countries enrolled in the Dialysis Outcomes and Practice Patterns Study (DOPPS II). Depressive symptoms were assessed by the short version of the Center for Epidemiological Studies Depression Screening Index (CES-D), using ≥10 CES-D score as the cut-off value.
Overall prevalence of physician-diagnosed depression was 13.9%, and percentage of CES-D score ≥10 43.0%. While the smallest prevalence of physician-diagnosed depression was observed in Japan (2.0%) and France (10.6%), the percentage of CES-D score ≥10 in these counties was similar to the whole sample. Patients on antidepressants also varied by country, 34.9% and 17.3% among those with physician-diagnosed depression and CES-D scores ≥10, respectively. In Cox models adjusted for several comorbidities, CES-D scores ≥10 were associated with significantly higher relative risks (RR) of death (RR = 1.42; 95% CI = 1.29 to 1.57), hospitalization (RR = 1.12; 95% CI = 1.03 to 1.22), and dialysis withdrawal (RR = 1.55; 95% CI = 1.29 to 1.85).
The data suggest that depression is underdiagnosed and undertreated among hemodialysis patients. CES-D can help identify hemodialysis patients who are at higher risk of death and hospitalization. Interventions should target these patients with the goal to improve survival and reduce hospitalizations.
Journal Article
Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression
Psilocybin is being studied for use in treatment-resistant depression.
In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits).
A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups.
In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).
Journal Article
Depression in sleep disturbance: A review on a bidirectional relationship, mechanisms and treatment
Sleep disturbance is the most prominent symptom in depressive patients and was formerly regarded as a main secondary manifestation of depression. However, many longitudinal studies have identified insomnia as an independent risk factor for the development of emerging or recurrent depression among young, middle‐aged and older adults. This bidirectional association between sleep disturbance and depression has created a new perspective that sleep problems are no longer an epiphenomenon of depression but a predictive prodromal symptom. In this review, we highlight the treatment of sleep disturbance before, during and after depression, which probably plays an important role in improving outcomes and preventing the recurrence of depression. In clinical practice, pharmacological therapies, including hypnotics and antidepressants, and non‐pharmacological therapies are typically applied. A better understanding of the pathophysiological mechanisms between sleep disturbance and depression can help psychiatrists better manage this comorbidity.
Journal Article
Celecoxib in Treatment of Postpartum Depression: A Case Report
Postpartum depression (PPD) impairs mother-infant interaction and has negative effects on the child’s emotional, behavioral, and cognitive skills. There is considerable evidence to suggest that inflammation plays a role in the pathogenesis of depression. Controlled trials indicate that celecoxib has antidepressant effects in patients with major depressive disorder. A 34-year-old woman with mild to moderate PPD received a celecoxib capsule twice a day. This treatment has not been reported in previous studies and is novel in clinical practice. The patient was assessed using the Hamilton Depression Rating Scale (HDRS). Moreover, levels of brain-derived neurotrophic factor (BDNF) and inflammatory cytokines were measured at baseline and at the end of celecoxib therapy. This case suggests that celecoxib can improve depressive symptoms in patients with mild to moderate PPD. No adverse effects occurred during follow-up.
Journal Article