Weeks Of Sertraline Research Articles

Patterns of Pretreatment Reward Task Brain Activation Predict Individual Antidepressant Response: Key Results From the EMBARC Randomized Clinical Trial

BackgroundThe lack of biomarkers to inform antidepressant selection is a key challenge in personalized depression treatment. This work identifies candidate biomarkers by building deep learning predictors of individual treatment outcomes using reward processing measures from functional magnetic resonance imaging, clinical assessments, and demographics. MethodsParticipants in the EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study (n = 222) underwent reward processing task-based functional magnetic resonance imaging at baseline and were randomized to 8 weeks of sertraline (n = 106) or placebo (n = 116). Subsequently, sertraline nonresponders (n = 37) switched to 8 weeks of bupropion. The change in Hamilton Depression Rating Scale was measured after treatment. Reward processing, clinical measurements, and demographics were used to train treatment-specific deep learning models. ResultsThe predictive model for sertraline achieved R2 of 48% (95% CI, 33%–61%; p < 10−3) in predicting the change in Hamilton Depression Rating Scale and number-needed-to-treat (NNT) of 4.86 participants in predicting response. The placebo model achieved R2 of 28% (95% CI, 15%–42%; p < 10−3) and NNT of 2.95 in predicting response. The bupropion model achieved R2 of 34% (95% CI, 10%–59%, p < 10−3) and NNT of 1.68 in predicting response. Brain regions where reward processing activity was predictive included the prefrontal cortex and cerebellar crus 1 for sertraline and the cingulate cortex, caudate, orbitofrontal cortex, and crus 1 for bupropion. ConclusionsThese findings demonstrate the utility of reward processing measurements and deep learning to predict antidepressant outcomes and to form multimodal treatment biomarkers.

A robust and reproducible connectome fingerprint of ketamine is highly associated with the connectomic signature of antidepressants.

Over the past decade, various N-methyl-D-aspartate modulators have failed in clinical trials, underscoring the challenges of developing novel rapid-acting antidepressants based solely on the receptor or regional targets of ketamine. Thus, identifying the effect of ketamine on the brain circuitry and networks is becoming increasingly critical. In this longitudinal functional magnetic resonance imaging study of data from 265 participants, we used a validated predictive model approach that allows the full assessment of brain functional connectivity, without the need for seed selection or connectivity summaries. First, we identified a connectome fingerprint (CFP) in healthy participants (Cohort A, n = 25) during intravenous infusion of a subanesthetic dose of ketamine, compared to normal saline. We then demonstrated the robustness and reproducibility of the discovered ketamine CFP in two separate healthy samples (Cohort B, n = 22; Cohort C, n = 18). Finally, we investigated the ketamine CFP connectivity at 1-week post treatment in major depressive disorder patients randomized to 8 weeks of sertraline or placebo (Cohort D, n = 200). We found a significant, robust, and reproducible ketamine CFP, consistent with reduced connectivity within the primary cortices and within the executive network, but increased connectivity between the executive network and the rest of the brain. Compared to placebo, the ketamine CFP connectivity changes at 1 week predicted response to sertraline at 8 weeks. In each of Cohorts A-C, ketamine significantly increased connectivity in a previously identified antidepressant CFP. Investigating the brain connectivity networks, we successfully identified a robust and reproducible ketamine biomarker that is related to the mechanisms of antidepressants.

Pretreatment Reward Sensitivity and Frontostriatal Resting-State Functional Connectivity Are Associated With Response to Bupropion After Sertraline Nonresponse

BackgroundStandard guidelines recommend selective serotonin reuptake inhibitors as first-line antidepressants for adults with major depressive disorder, but success is limited and patients who fail to benefit are often switched to non–selective serotonin reuptake inhibitor agents. This study investigated whether brain- and behavior-based markers of reward processing might be associated with response to bupropion after sertraline nonresponse. MethodsIn a two-stage, double-blinded clinical trial, 296 participants were randomized to receive 8 weeks of sertraline or placebo in stage 1. Individuals who responded continued on another 8-week course of the same intervention in stage 2, while sertraline and placebo nonresponders crossed over to bupropion and sertraline, respectively. Data from 241 participants were analyzed. The stage 2 sample comprised 87 patients with major depressive disorder who switched medication and 38 healthy control subjects. A total of 116 participants with major depressive disorder treated with sertraline in stage 1 served as an independent replication sample. The probabilistic reward task and resting-state functional magnetic resonance imaging were administered at baseline. ResultsGreater pretreatment reward sensitivity and higher resting-state functional connectivity between bilateral nucleus accumbens and rostral anterior cingulate cortex were associated with positive response to bupropion but not sertraline. Null findings for sertraline were replicated in the stage 1 sample. ConclusionsPretreatment reward sensitivity and frontostriatal connectivity may identify patients likely to benefit from bupropion following selective serotonin reuptake inhibitor failures. Results call for a prospective replication based on these biomarkers to advance clinical care.

Could EEG Help Predict Antidepressant Response?

Could EEG Help Predict Antidepressant Response?

Maintenance Antipsychotic Lowers Risk of Psychotic Depression Relapse

Maintenance Antipsychotic Lowers Risk of Psychotic Depression Relapse

Sertraline Effects on Striatal Resting-State Functional Connectivity in Youth With Obsessive-Compulsive Disorder: A Pilot Study

Foundational knowledge on neural circuitry underlying pediatric obsessive-compulsive disorder (OCD) and how it changes during standard treatment is needed to provide the basis for conceptualization and development of novel targeted treatments. This study explored the effects of sertraline, a selective serotonin reuptake inhibitor, on resting-state functional connectivity in cortico-striatal-thalamic-cortical circuits in pediatric OCD. Medication-free youths with OCD (n= 14) and healthy controls (n= 14) were examined at baseline and 12 weeks with resting-state functional magnetic resonance imaging. Between scan sessions, participants with OCD received 12 weeks of sertraline. For each scan, seed-based whole-brain resting-state functional connectivity analyses were conducted with 6 striatal seeds. Analysis of variance examined the interaction between group and time on striatal connectivity, including cluster-based thresholding to correct for multiple tests. Connectivity changes within circuits identified in group analyses were correlated with clinical change. Two significant group-by-time effects in the OCD group showed increased striatal connectivity from baseline to 12 weeks compared with controls. Circuits demonstrating this pattern included the right putamen with the left frontal cortex and insula and the left putamen with the left frontal cortex and pre- and post-central cortices. Increase in connectivity in the left putamen circuit was significantly correlated with clinical improvement on the Children's Yale-Brown Obsessive-Compulsive Scale score (r=-0.58, p= .03). Sertraline appears to affect specific striatal-based circuits in pediatric OCD, and these changes in part could account for clinical improvement. Future work is needed to confirm these preliminary findings, which would facilitate identification of circuit-based targets for novel treatment development. Effects of Sertraline on Brain Connectivity in Adolescents with OCD; https://clinicaltrials.gov/; NCT02797808.

2.59 Changes in Resting-State Functional Connectivity After Twelve Weeks of Sertraline in Youth With Obsessive-Compulsive Disorder (OCD)

2.59 Changes in Resting-State Functional Connectivity After Twelve Weeks of Sertraline in Youth With Obsessive-Compulsive Disorder (OCD)

Deep Brain Stimulation for Treatment-Resistant Depression

Brian did reasonably well for about 3 years, with occasional worsening of depressive symptoms but generally with good functioning, when he developed his current major depressive episode. This was his most severe episode to date, with active suicidal ideation with a plan (but no immediate intent) to shoot himself. Over the next year, he had a number of treatments, among them multiple antidepressant medications, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, mirtazapine, tricyclic antidepressants, and tranylcypromine, as well as augmentation with lithium, thyroid hormone, buspirone, atypical antipsychotics, anticonvulsants, stimulants, light therapy, and ongoing psychotherapy. No treatment was able to achieve remission or a persistent clinically signifi cant reduction in symptoms. Given his degree of treatment resistance and continued overall deterioration, including increased suicidal ideation, he was referred for ECT. He achieved a good response (50%‐60% symptom reduction) with eight highdose right unilateral ECT treatments. ECT was delivered concurrently with ongoing medications, and attempts were made to optimize medications during and after ECT. However, Brian relapsed in about 6 weeks, and repeat ECT (including four right unilateral and eight bitemporal treatments delivered concurrently with ongoing medications) was unsuccessful in achieving signifi cant symptom reduction but was associated with notable cognitive impairment.

Time course of response to antidepressants: Predictive value of early improvement and effect of additional psychotherapy

Background The full response to antidepressant pharmacotherapy is evident only after several weeks, but considerable improvements may already be visible within the first two weeks. Little is known about the potential influence of additional psychotherapy on the speed of response to antidepressant treatment. We have analysed in more severely depressed inpatients treated with antidepressants i) the predictive value of early improvement for later response and ii) the impact of additional psychotherapy on the time course of response. Methods 124 patients with a major depression referred for hospitalized care were randomized to 5 weeks of sertraline (or amitriptyline as a second choice) plus either additional Interpersonal Psychotherapy modified for inpatients (IPT) or Clinical Management (CM). “Improvement” was defined as a decrease of ≥ 20% on the 17-item Hamilton Rating Scale for Depression (HAMD). “Onset of response” was defined as sustained improvement (without any subsequent increase in the HAMD) culminating in 50% decrease on the HAMD by week 5. Results Early improvement within two weeks was highly predictive of later stable response (≥ 50% decrease on the HAMD at weeks 4 and 5) or stable remission (HAMD score of ≤ 7 at weeks 4 and 5), irrespective of the type of medication or additional IPT or CM. Survival analysis of the ITT sample revealed that patients of the IPT group had a shorter time to “onset of response” than patients in the CM group (median: 12 vs. 30 days; p = 0.041, Log Rank). However, there was no significant difference in the time to onset of response, when more stringent conditions were used. Limitations Due to ethical restrictions a comparison with an untreated placebo group could not be performed. Conclusions Early improvement is highly predictive for later stable response or remission in more severely depressed inpatients. In combination therapy, the additional benefit of psychotherapy occurs at least as rapid as the response to antidepressants.

Augmentation of sertraline with prolonged exposure in the treatment of posttraumatic stress disorder

The present study was designed to determine whether augmenting sertraline with prolonged exposure (PE) would result in greater improvement than continuation with sertraline alone. Outpatient men and women with chronic PTSD completed 10 weeks of open label sertraline and then were randomly assigned to five additional weeks of sertraline alone (n = 31) or sertraline plus 10 sessions of twice-weekly PE (n = 34). Results indicated that sertraline led to a significant reduction in PTSD severity after 10 weeks but was associated with no further reductions after five more weeks. Participants who received PE showed further reduction in PTSD severity. This augmentation effect was observed only for participants who showed a partial response to medication.

Randomized, Double-Blind, Placebo-Controlled, Crossover Study of Sertraline (Zoloft) for the Treatment of Hot Flashes in Women with Early Stage Breast Cancer Taking Tamoxifen

We observed the relief of hot flashes in breast cancer survivors taking tamoxifen and treated with sertraline for depression. Our objective was to assess the effect of sertraline on the frequency and severity of hot flashes, mood status, and health-related quality of life. We used a randomized, double-blind, placebo-controlled, crossover study using 6 weeks of sertraline (50 mg each morning) versus placebo. Study participants were 62 breast cancer survivors from an oncology clinic in a tertiary care center on adjuvant tamoxifen reporting bothersome hot flashes. Patients were asked to keep a daily hot flash diary to record hot flash frequency and severity, from which hot flash scores (frequency x severity) were calculated. The Center for Epidemiologic Studies depression scale and Functional Assessment of Cancer Therapy--Breast (FACT-B) (at baseline, 6 weeks, and 12 weeks) were used to assess mood and quality of life. Sixty-two women were accrued. Forty-seven women (median age 53.9 years, range 36.6-77.1 years; 89% postmenopausal; 85.5% Caucasian) completed the first 6 weeks and 39 completed 12 weeks. The baseline daily hot flash frequency and score were 5.8 (standard deviation 4.1) and 11.5 (14.0), respectively. At the end of the first 6 weeks, hot flash frequency decreased by 50% in 36% of those taking sertraline compared to 27% taking placebo. In the crossover analysis, sertraline was significantly more effective than placebo: women crossing from placebo to sertraline had a decrease (-0.9 and -1.7) in hot flash frequency and score, whereas those crossing from sertraline to placebo had an increase (1.5 and 3.4) in hot flash frequency and score (p = 0.03 and 0.03). Forty-eight percent preferred the sertraline period, 11% preferred the placebo period, and 41% had no preference (p = 0.006). Measures of depression and quality of life were within normal range and did not change significantly within treatment groups. Sertraline decreases hot flashes in breast cancer survivors taking tamoxifen and women prefer sertraline to placebo. Further study of sertraline for the management of hot flashes is warranted.

Diurnal variation of cerebrospinal fluid hypocretin-1 (Orexin-A) levels in control and depressed subjects

Background Hypocretins, excitatory neuropeptides at monoaminergic synapses, appear to regulate human sleep-wake cycles. Undetectable cerebrospinal fluid hypocretin-1 levels are seen in narcolepsy, which is frequently associated with secondary depression. Shortened rapid eye movement latency is observed in both narcolepsy and depression. Cerebrospinal fluid hypocretin-1 levels have not been reported in mood disorders. Methods We examined hypocretin-1 levels in 14 control and 15 depressed subjects. Cerebrospinal fluid was drawn continuously in supine subjects for 24 hours with an indwelling intrathecal catheter under entrained light-dark conditions. Depressed subjects were studied before and after 5 weeks of sertraline (n = 10, three nonresponders) or bupropion (n = 5, two nonresponders). Results Hypocretin-1 levels varied slightly (amplitude 10%) but significantly across the diurnal cycle in control subjects, with amplitude significantly reduced in depression (3%). Levels were lowest at midday, surprising for a hypothetically wake-promoting peptide. Mean hypocretin levels trended higher in depressive than in control subjects. Hypocretin-1 levels decreased modestly but significantly after sertraline (−14%) but not bupropion. Conclusions Our results are consistent with previous physiologic findings in depression indicating dampened diurnal variations in hypocretin-1. The finding that sertraline but not bupropion slightly decreased cerebrospinal fluid hypocretin-1 indicates a serotoninergic influence on hypocretin tone.

Long-term sertraline treatment and peripheral biochemical markers in female depressed patients

Serotonergic system is implicated in the pathogenesis of depression. Peripheral biochemical markers, platelet serotonin (5-HT) and platelet monoamine oxidase (MAO) activity were determined spectrofluorimetrically at baseline and after 4 and 24 weeks of sertraline (a selective serotonin reuptake inhibitor (SSRI)) treatment in 15 female nonsuicidal, nonpsychotic patients with major depression and compared with 15 drug-free healthy women. The aim of the study was to determine the effects of 4 and 24 weeks of sertraline treatment on platelet 5-HT concentration and platelet MAO activity in depressed patients subdivided according to the treatment response into remitters, responders and nonresponders after 4 and 24 weeks of sertraline treatment based on the 70%, 50–69% and <49% reductions in baseline Montgomery–Asperg Depression Rating Scale (MADRS) scores, respectively. Platelet 5-HT concentration was significantly lower in all depressed patients at baseline than in healthy subjects. Among patients, platelet 5-HT concentration or platelet MAO activity did not differ before treatment. There was no significant correlation between MADRS scores and peripheral biochemical markers. The limitation of the study was in a small number of patients, but its advantage was in a long-term (24 weeks) follow-up of both patients and healthy controls. Our results show that long-term sertraline treatment induced remission and response in 87% patients, decreased platelet 5-HT concentration after 4 and 24 weeks of treatment and decreased platelet MAO activity after 24 weeks and suggest that pretreatment values of platelet 5-HT and platelet MAO might not predict therapeutic outcome to sertraline treatment in female depressed patients.

Sertraline maintenance treatment reduced relapse and dropouts in post-traumatic stress disorder

Davidson J, Pearlstein T, Londborg P, et al. Efficacy of sertraline in preventing relapse of posttraumatic stress disorder: results of a 28- week double-blind, placebo-controlled study . Am J Psychiatry2001...

Sertraline Pharmacokinetics and Dynamics in Adolescents

To determine the pharmacokinetics of sertraline in adolescents and assess its effect on a surrogate marker of serotonin transport. Pharmacokinetic parameters of a single 50-mg dose of sertraline were determined in 10 adolescents. Steady-state withdrawal kinetics were determined in 12 adolescents taking 50 mg/day and in 6 adolescents taking 100 to 150 mg/day. Platelet serotonin reuptake was measured before and after 2 weeks of daily 50-mg dosing. The mean steady-state half-life of 50 mg was significantly shorter (15.3 +/- 3.5 hours) than the single-dose half-life (26.7 +/- 5.2 hours; t = 6.4, p < .001) and the steady-state half-life at 100 to 150 mg/day (20.4 +/- 3.4 hours; t = 2.9, p = .01). Platelet serotonin reuptake was inhibited by 61 +/- 15% after approximately 2 weeks of sertraline 50 mg/day. The half-life of sertraline 50 mg becomes significantly shorter from the initial dose to steady-state, and many adolescents may benefit from twice-per-day dosing. The steady-state half-life increases as the dose increases. The moderate levels of platelet reuptake inhibition at 50 mg/day indicate that most adolescents may need sertraline doses higher than 50 mg/day to attain a therapeutic response.

Sertraline maintenance treatment reduced relapse and dropouts in post-traumatic stress disorder

(2001) Am J Psychiatry 158, 1974; Davidson J, Pearlstein T, Londborg P, et al. . Efficacy of sertraline in preventing relapse of posttraumatic stress disorder: results of a 28-week double-blind,...

Sertraline versus imipramine to prevent relapse in chronic depression

Background: Chronic depressions are common, disabling and under-treated, and long-term treatment is little studied. We report the continuation phase results from a long-term treatment study. Methods: After 12 weeks of acute phase treatment in a double-blind, randomized, parallel-group, multi-center trial of sertraline or imipramine, patients with chronic depression (≥2 years in major depression, or major depression superimposed on dysthymia) continued study drug for 16 weeks. Initially, 635 patients were randomized to sertraline or imipramine in a 2:1 ratio. Nonresponders after 12 weeks entered a 12-week double-blind crossover trial of the alternate medication. Entry into continuation treatment required at least a satisfactory response (partial remission) to initial or crossover treatment. Results: Of 239 acute or crossover responders to sertraline, 60% entered continuation in full remission and 40% with a partial remission. These proportions were identical for imipramine patients ( n=147). For both drug groups, over two-thirds of those entering in full remission retained it. For those entering in partial remission, over 40% achieved full remission. Patients requiring crossover treatment were less likely to maintain or improve their response during continuation treatment. The two drugs did not differ significantly in response distribution, drop out rates or discontinuation due to side effects during continuation treatment. Limitations: The absence of a placebo group constrains interpretation of our results, but chronic depressions have low placebo response rates. Conclusions: Most chronic depression patients who remit with 12 weeks of sertraline or imipramine treatment maintain remission during 16 weeks of continuation treatment. Most patients with a satisfactory therapeutic response (partial remission) after 12 weeks of treatment maintain it or further improve. Patients treated with imipramine experienced more side effects, but both drugs were well tolerated.

Sertraline for social phobia: a double-blind, placebo-controlled crossover study

The authors examined the efficacy of sertraline in the treatment of social phobia. In a double-blind crossover study, 12 outpatients were randomly assigned to 10 weeks of sertraline (50-200 mg/day, flexible dosing) and 10 weeks of placebo. A statistically significant improvement in scores on the Liebowitz Social Anxiety Scale was found with sertraline but not with placebo. There was no significant difference between scores obtained with computer- and clinician-administered versions of the Liebowitz Social Anxiety Scale, and the majority of patients preferred to be interviewed by the computer. Sertraline seems a safe and effective treatment for social phobia, and computer administration may be a preferable mode of assessment with socially phobic patients.