scholarly journals Racemic ketamine as an alternative to electroconvulsive therapy for unipolar depression. A randomized, open-label, non-inferiority trial. (KetECT)

2021 ◽  
Author(s):  
Joakim Ekstrand ◽  
Christian Fattah ◽  
Marcus Persson ◽  
Tony Cheng ◽  
Pia Nordanskog ◽  
...  
Keyword(s):  
Adverse Events ◽  
Electroconvulsive Therapy ◽  
Rating Scale ◽  
Unipolar Depression ◽  
Treatment Session ◽  
Maximal Effect ◽  
Open Label ◽  
Final Treatment ◽  
Racemic Ketamine ◽  
Fast Acting

Abstract BACKGROUND Ketamine has emerged as a fast-acting and powerful antidepressant, but no head to head trial has been performed, Here, ketamine is compared to electroconvulsive therapy (ECT), the most effective therapy for depression. METHODS Hospitalized patients with unipolar depression were randomized (1:1) to thrice-weekly racemic ketamine (0.5 mg/kg) infusions or ECT, in a parallel, open-label, non-inferiority study. The primary outcome was remission (Montgomery Åsberg Depression Rating Scale [MADRS] score ≤10). Secondary outcomes included adverse events (AEs), time to remission and relapse. Treatment sessions (maximum of twelve) were administered until remission or maximal effect was achieved. Remitters were followed for twelve months after the final treatment session. RESULTS 186 inpatients were included and received treatment. Among patients receiving ECT 63% remitted, compared to 46% receiving ketamine infusions (p=0.026; difference 95% CI 2%, 30%). Both ketamine and ECT required a median of six treatment sessions to induce remission. Distinct adverse events (2015) were associated with each treatment. Serious and long-lasting AE, including cases of persisting amnesia, were more common with ECT, while treatment emergent AE led to more dropouts in the ketamine group. Among remitters, 70% and 63%, with 57 and 61 median days in remission, relapsed within twelve months in the ketamine and ECT group respectively (p=0.52). CONCLUSION Remission and cumulative symptom reduction following multiple racemic ketamine infusions in severely ill patients (age 18-85) in an authentic clinical setting suggest that ketamine, despite being inferior to ECT, can be a safe and valuable tool in treating unipolar depression.

Lamotrigine augmentation in treatment-resistant unipolar depression: A comprehensive meta-analysis of efficacy and safety

2019 ◽  
Vol 33 (6) ◽  
pp. 700-713 ◽  
Author(s):  
Kah Kheng Goh ◽  
Chun-Hsin Chen ◽  
Yi-Hang Chiu ◽  
Mong-Liang Lu
Keyword(s):  
Adverse Events ◽  
Rating Scale ◽  
Meta Analysis ◽  
Unipolar Depression ◽  
Severe Illness ◽  
Discontinuation Rate ◽  
Efficacy And Safety ◽  
Treatment Resistant ◽  
Chinese Studies ◽  
Hamilton Rating Scale

Objective: Augmentation strategies are commonly applied when an individual is unresponsive to antidepressant monotherapy. Lamotrigine is currently considered at best only as second line augmentation for treatment-resistant unipolar depression while its clinical efficacy and safety profiles remain inconclusive. We intended to assess the therapeutic effects and safety profiles of lamotrigine augmentation in patients with treatment-resistant unipolar depression by conducting a meta-analysis. Methods: MEDLINE, Embase, EBSCO, Cochrane, Web of Science, Scopus, Wanfang and Ariniti databases were searched. Coprimary outcomes, including changes in severity of depression and response rate, were measured in this study. Secondary outcomes were defined as the safety profile of the intervention, including reported discontinuation rate and adverse events. Results: Eight double-blinded randomized controlled trials with 677 patients overall were included. Significant improvements in Hamilton Rating Scale for Depression scores and response rates were shown in lamotrigine augmentation groups compared with control groups, of which the pooled result of six Chinese studies showed positive effects of Hamilton Rating Scale for Depression improvement while the pooled result of two non-Chinese studies was statistically non-significant. Patients with more severe illness and longer duration of illness were more effectively treated with lamotrigine augmentation. The magnitude of depression improvement after lamotrigine augmentation was higher in patients treated with selective serotonin reuptake inhibitors than those treated with serotonin-norepinephrine reuptake inhibitors. Lamotrigine augmentation is well-tolerated in terms of all-cause discontinuation rate and adverse events. Conclusions: Lamotrigine augmentation may serve as a possible choice for patients with treatment-resistant unipolar depression and further trials are warranted to clarify the optimal dosage of lamotrigine augmentation together with the treatment duration and safety over time.

Combined treatment with reboxetine in depressed patients with no response to venlafaxine: a 6-week follow-up study

2007 ◽  
Vol 19 (5) ◽  
pp. 291-296 ◽  
Author(s):  
Cecilio Álamo ◽  
Francisco López-Muñoz ◽  
Gabriel Rubio ◽  
Pilar García-García ◽  
Antonio Pardo
Keyword(s):  
Adverse Events ◽  
Rating Scale ◽  
Combined Treatment ◽  
Open Label ◽  
Serious Adverse Events ◽  
Multicentric Study ◽  
Intent To Treat ◽  
Events Data ◽  
Clinical Global Impression Improvement

Objective:The purpose of present study was to evaluate the efficacy of the addition of reboxetine in patients that had not previously responded, or had done so only partially, over 6 weeks of conventional pharmacological treatment with venlafaxine.Methods:This open-label, prospective and multicentric study included 40 outpatients diagnosed with major depressive disorder according to the DSM-IV criteria. Efficacy was assessed using the 21-item Hamilton Depression Rating Scale (HAMD) and the Clinical Global Impression-Improvement (CGI-I). Safety was evaluated by recording spontaneously reported adverse events. Data were analysed on an intent-to-treat basis, using the last-observation-carried-forward method.Results:Mean HAMD reduction was 34.9% (P < 0.0001). The percentages of responders (≥50% reduction in HAMD) and patients considered as benefiting from complete remission (HAMD ≤ 10 points) at week 6 were 27.5 and 12.5%, respectively. By the end of the treatment, the score of CGI-I decreased 24.8% (P < 0.0001). Percentage of patient improving (CGI < 4 points) was 47.5%. The most common non-serious adverse events were constipation, nervousness, anxiety and insomnia.Conclusion:These findings suggest that the combined treatment of reboxetine and venlafaxine, in venlafaxine-resistant patients, may be an effective and well-tolerated strategy.

scholarly journals Accelerated intermittent theta burst as a substitute for patients needing electroconvulsive therapy during the COVID-19 pandemic: study protocol for an open-label clinical trial

2020 ◽  
Author(s):  
Daniel M. Blumberger ◽  
Zafiris J. Daskalakis ◽  
Fidel Vila-Rodriguez ◽  
David Boivin-Lafleur ◽  
Michelle S. Goodman ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Outcomes ◽  
Electroconvulsive Therapy ◽  
Relapse Prevention ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Unipolar Depression ◽  
High Dose ◽  
Treatment Schedule ◽  
Open Label ◽  
Theta Burst

Abstract Background Treatment resistant depression (TRD) is one of the leading causes of disability in Canada and is associated with significant societal costs. Repetitive transcranial magnetic stimulation (rTMS) is an approved, safe, and well-tolerated intervention for TRD. In the setting of the COVID-19 pandemic, reducing the number of visits to the clinic is a potential approach to significantly minimize exposure and transmission risks to patients. This can be accomplished by administering multiple treatment sessions in a single day, using an rTMS protocol known as accelerated intermittent theta burst stimulation (aiTBS). The objective of this novel study is to assess the feasibility, acceptance and clinical outcomes of a practical high-dose aiTBS protocol, including tapering treatments and symptom-based relapse prevention treatments, in patients with unipolar depression previously responsive to electroconvulsive therapy (ECT) or patients warranting ECT due to symptom severity. Methods All patients with unipolar depression referred to the brain stimulation service at the Centre for Addiction and Mental Health (CAMH) who warrant ECT will be offered screening to assess for eligibility to enroll in this trial. This open label, single group trial consists of 3 phases. In the acute treatment phase, treatment will occur 8 times daily for 5 days a week, until symptom remission is achieved or a maximum of 10 days of treatment. In the tapering phase, treatments will be reduced to 2 treatment days per week for 2 weeks, followed by 1 treatment day per week for 2 weeks. Patients will then enter the symptom-based relapse prevention phase including virtual check-ins and a treatment schedule based on symptom level. Remission, response and change in scores on several clinical measures from baseline to the end of the acute, tapering and relapse prevention phases represent the clinical outcomes of interest. Discussion Findings from this novel clinical trial may provide support for the use of aiTBS, including tapering treatments and symptom-based relapse prevention treatments, as a safe and effective alternative intervention for patients needing ECT during the COVID-19 pandemic. Trial registration Clinicaltrials.gov: NCT04384965

scholarly journals An Open-Label, 8-Week Study of Safety and Efficacy of Pimavanserin Treatment in Adults with Parkinson’s Disease and Depression

2020 ◽  
Vol 10 (4) ◽  
pp. 1751-1761
Author(s):  
Daryl DeKarske ◽  
Gustavo Alva ◽  
Jason L. Aldred ◽  
Bruce Coate ◽  
Marc Cantillon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adverse Events ◽  
Reuptake Inhibitor ◽  
Adjunctive Therapy ◽  
Rating Scale ◽  
Depression Scale ◽  
System Organ Class ◽  
Hamilton Depression Scale ◽  
Open Label

Background: Many patients with Parkinson’s disease (PD) experience depression. Objective: Evaluate pimavanserin treatment for depression in patients with PD. Methods: Pimavanserin was administered as monotherapy or adjunctive therapy to a selective serotonin reuptake inhibitor or serotonin/noradrenaline reuptake inhibitor in this 8-week, single-arm, open-label phase 2 study (NCT03482882). The primary endpoint was change from baseline to week 8 in Hamilton Depression Scale–17-item version (HAMD-17) score. Safety, including collection of adverse events and the Mini-Mental State Examination (MMSE) and Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS III) scores, was assessed in patients who received ≥1 pimavanserin dose. Results: Efficacy was evaluated in 45 patients (21 monotherapy, 24 adjunctive therapy). Mean (SE) baseline HAMD-17 was 19.2 (3.1). Change from baseline to week 8 (least squares [LS] mean [SE]) in the HAMD-17 was –10.8 (0.63) (95% CI, –12.0 to –9.5; p < 0.0001) with significant improvement seen at week 2 (p < 0.0001) and for both monotherapy (week 8, –11.2 [0.99]) and adjunctive therapy (week 8,–10.2 [0.78]). Most patients (60.0%) had ≥50% improvement at week 8, and 44.4% of patients reached remission (HAMD-17 score ≤7). Twenty-one of 47 patients experienced 42 treatment-emergent adverse events; the most common by system organ class were gastrointestinal (n = 7; 14.9%) and psychiatric (n = 7; 14.9%). No negative effects were observed on MMSE or MDS-UPDRS Part III. Conclusion: In this 8-week, single-arm, open-label study, pimavanserin as monotherapy or adjunctive therapy was well tolerated and associated with early and sustained improvement of depressive symptoms in patients with PD.

scholarly journals Open-label phase 3 study of diclofenac conjugated to hyaluronate (diclofenac etalhyaluronate: ONO-5704/SI-613) for treatment of osteoarthritis: 1-year follow-up

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yoshihiro Nishida ◽  
Kazuyuki Kano ◽  
Taiki Osato ◽  
Takayuki Seo
Keyword(s):  
Adverse Events ◽  
Joint Pain ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Open Label ◽  
Phase 3 ◽  
X Ray ◽  
Knee Oa ◽  
Pain Scores ◽  
X Ray Imaging

Abstract Background We evaluated the 1-year safety and efficacy of diclofenac etalhyaluronate (DF-HA), a diclofenac-conjugated hyaluronate, in patients with osteoarthritis (OA). Methods In this multi-centre, open-label, noncomparative phase 3 study in Japan, patients with a diagnosis of knee, shoulder, elbow, hip, or ankle OA received an intra-articular (IA) injection of DF-HA 30 mg every 4 weeks for 1 year (13 times in total). The safety outcomes included treatment-emergent adverse events (TEAEs) and target joint structural changes by X-ray imaging tests. Efficacy outcomes included joint pain scores on an 11-point numerical rating scale. Concomitant use of analgesics was not restricted. Results Overall, 166 eligible patients were enrolled, comprising knee OA (n = 126) and other OA (n = 40). All TEAEs were experienced by 126/166 patients (75.9%). The incidence of treatment-related TEAEs was not associated with the treatment period. No significant worsening of joint status was observed in X-ray imaging tests at week 52 or at last assessment. The mean joint pain scores (± standard deviation) were 5.9 ± 1.2, 4.9 ± 1.9, and 3.1 ± 2.3 at baseline, and weeks 2 and 52, respectively. Improvement of pain score was observed after the first injection and was maintained until week 52 regardless of knee OA or other joint OA. Conclusions Repeated IA injections of DF-HA every 4 weeks for 1 year were well tolerated with no clinically significant adverse events indicating they might lead to the long-term improvement of OA symptoms. DF-HA might be a useful treatment for patients with OA. Trial registration number JapicCTI-183855 (First registered date: 6th February 2018).

Electroconvulsive therapy in elderly - a preliminary study

2016 ◽  
Vol 33 (S1) ◽  
pp. s230-s230
Author(s):  
C. Agostinho ◽  
M. Duarte ◽  
R. Alves ◽  
I. Cunha ◽  
A.M. Batista
Keyword(s):  
Electroconvulsive Therapy ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Severe Depression ◽  
Unipolar Depression ◽  
Normal Range ◽  
Significant Difference ◽  
The Mean ◽  
Preliminary Study ◽  
Competing Interest

IntroductionStudies with electroconvulsive therapy (ECT) in elderly focus mainly on the assessment of possible side effects on the cognitive functioning; there are few studies that evaluate the effectiveness.ObjectiveEvaluate the effectiveness of this treatment in the population over 65 years.AimsPerform a preliminary study to evaluate the response to ECT of ≥ 65 years patients with depression.MethodsWe carry out a descriptive study based on patients treated in the last 10 years in the ECT Unit of Centro Hospitalar Psiquiátrico de Lisboa.ResultsOur initial sample consisted of 457 patients. We select patients aged ≥ 65 years with depression, and with complete data, including electroconvulsive parameters, and initial and final Hamilton Rating Scale for Depression (HRSD) scores (n = 59). Of this, 81.36% (n = 48) had unipolar depression, and 18.64% (n = 11) had bipolar depression. In the first group, the mean variation between the initial and final scores in HRSD was 13.88 points, and 27.10% (n = 13) of the patients ended the treatment in the normal range of HRSD score. In the second group, the mean variation was 12.82, and 63.60% (n = 7) ended the treatment in the normal range of HRSD. Considering the initial and final HRSD scores, it appears that unipolar depression group presents higher values (severe depression) (P < 0.05). When we compare the mean variation between the initial and final HRSD scores, we didn’t observe a statistically significant difference between the two groups. There was a clinical improvement in both.ConclusionsThe acute treatment with ECT appears to improve depressive symptoms in bipolar and unipolar depression, when considering an elderly population.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Open-Label Adjunctive Topiramate in the Treatment of Unstable Bipolar Disorder

2005 ◽  
Vol 50 (7) ◽  
pp. 415-422 ◽  
Author(s):  
Roger S McIntyre ◽  
Rosanna Riccardelli ◽  
Carin Binder ◽  
Vivek Kusumakar
Keyword(s):  
Bipolar Disorder ◽  
Adverse Events ◽  
Rating Scale ◽  
Vital Signs ◽  
Mood Stabilizers ◽  
Open Label ◽  
Young Mania ◽  
Satisfaction With Treatment ◽  
The Mean ◽  
Intent To Treat

Objective: To assess open-label adjunctive topiramate in the treatment of outpatients with unstable bipolar disorder (BD). Method: Outpatients with DSM-IV–defined BD (I or II) exhibiting mood instability were enrolled in this 16-week, open-label, multicentre study. Topiramate was added to existing mood stabilizers and other psychotropic treatments. The primary effectiveness measure was the Clinical Global Impression of Severity (CGI-S) scale; other scales included the Young Mania Rating Scale (YMRS) and the Montgomery–Asberg Depression Rating Scale (MADRS). Safety assessments included monitoring adverse events, measuring tremor, monitoring vital signs and weight, and laboratory indices. We also evaluated patient satisfaction with treatment. Results: A total of 109 patients were enrolled. Intent-to-treat analysis showed significant improvement from baseline in the CGI-S, YMRS, and MADRS, starting at Week 2 ( P < 0.001), with further accrual of benefit between Week 2 and Week 16 ( P < 0.001). The mean modal dosage of topiramate during the stable dosing period was 180 mg daily. There was a mean 1.8 kg decrease in patient weight from topiramate initiation to Week 16 ( P < 0.001). Topiramate was well tolerated by most patients; 11% withdrew from the study owing to adverse events. We noted a significant reduction in the mean severity score for preexisting tremor by Week 8 of treatment ( P < 0.005); no notable changes in vital signs were observed. At Week 16, 50% of the patients were “completely satisfied” with topiramate treatment. Conclusions: Adjunctive topiramate treatment can reduce the severity of manic and depressive symptoms, as well as reducing tremor and weight in outpatients with BD I or II.

Safety, tolerability and efficacy of a rapid dose escalation of quetiapine in bipolar I mania: the FATIMA study

2009 ◽  
Vol 21 (3) ◽  
pp. 125-132 ◽  
Author(s):  
Eric Constant ◽  
Arlette Seghers ◽  
Enio Ranalli ◽  
Vincent Ryckmans ◽  
Phillippe Snauwaert ◽  
...  
Keyword(s):  
Adverse Events ◽  
Adverse Drug Reactions ◽  
Dose Escalation ◽  
Rating Scale ◽  
Vital Signs ◽  
Severity Of Illness ◽  
Manic Episode ◽  
Drug Reactions ◽  
Open Label ◽  
Young Mania

Objective:The FATIMA study (FAst TItration of quetiapine fumarate in bipolar I MAnia) evaluated the safety, tolerability and efficacy of a rapid dose escalation of quetiapine in acutely ill bipolar I patients experiencing a manic episode.Methods:In an open-label, phase II pilot study, 29 patients aged 18 years or older, hospitalised with a bipolar I manic episode, received quetiapine twice daily for 21 days. Quetiapine was administered at 200, 400, 600, then 800 mg/day on the first 4 days, with flexible dosing (400–800 mg/day) subsequently. The primary endpoint was the proportion of patient dropouts because of adverse drug reactions during the first 7 days. Secondary safety assessments included incidences of adverse drug reactions and significant changes in vital signs. Efficacy assessments included Young Mania Rating Scale (YMRS) and Clinical Global Impressions Severity of Illness (CGI-S) score changes from day 1 to day 21.Results:Twenty patients (69%) completed the study. No patients withdrew as a result of drug-related adverse events (AEs) during the first 7 days. Twenty-three patients reported 58 adverse events, and most of the adverse events were mild or moderate. No clinically relevant abnormalities in vital signs were reported. Mean YMRS and CGI-S scores decreased significantly from baseline to day 21 (p < 0.001). Response and remission rates were 78 and 70%, respectively, at the end of the study.Conclusion:Rapid dose escalation of quetiapine to 800 mg/day over 4 days was well tolerated and effective in reducing symptoms within 5 days in acutely ill bipolar I patients with a manic episode.

scholarly journals Differential efficacy of escitalopram and nortriptyline on dimensional measures of depression

2009 ◽  
Vol 194 (3) ◽  
pp. 252-259 ◽  
Author(s):  
Rudolf Uher ◽  
Wolfgang Maier ◽  
Joanna Hauser ◽  
Andrej Marušič ◽  
Christine Schmael ◽  
...  
Keyword(s):  
Rating Scale ◽  
Unipolar Depression ◽  
Cognitive Symptoms ◽  
Measurement Scales ◽  
Open Label ◽  
Mixed Effect ◽  
Symptom Dimensions ◽  
Symptoms Of Depression ◽  
Therapeutic Drugs ◽  
Specific Effects

BackgroundTricyclic antidepressants and serotonin reuptake inhibitors are considered to be equally effective, but differences may have been obscured by internally inconsistent measurement scales and inefficient statistical analyses.AimsTo test the hypothesis that escitalopram and nortriptyline differ in their effects on observed mood, cognitive and neurovegetative symptoms of depression.MethodIn a multicentre part-randomised open-label design (the Genome Based Therapeutic Drugs for Depression (GENDEP) study) 811 adults with moderate to severe unipolar depression were allocated to flexible dosage escitalopram or nortriptyline for 12 weeks. The weekly Montgomery–Åsberg Depression Rating Scale, Hamilton Rating Scale for Depression, and Beck Depression Inventory were scored both conventionally and in a more novel way according to dimensions of observed mood, cognitive symptoms and neurovegetative symptoms.ResultsMixed-effect linear regression showed no difference between escitalopram and nortriptyline on the three original scales, but symptom dimensions revealed drug-specific advantages. Observed mood and cognitive symptoms improved more with escitalopram than with nortriptyline. Neurovegetative symptoms improved more with nortriptyline than with escitalopram.ConclusionsThe three symptom dimensions provided sensitive descriptors of differential antidepressant response and enabled identification of drug-specific effects.

Long-Term Safety and Effectiveness of Mixed Amphetamine Salts Extended Release in Adults With ADHD

CNS Spectrums ◽  
2005 ◽  
Vol 10 (S20) ◽  
pp. 16-25 ◽  
Author(s):  
Joseph Biederman ◽  
Thomas J. Spencer ◽  
Timothy E. Wilens ◽  
Richard H. Weisler ◽  
Stephanie C. Read ◽  
...  
Keyword(s):  
Adverse Events ◽  
Adult Adhd ◽  
Extended Release ◽  
Rating Scale ◽  
Vital Signs ◽  
Therapeutic Effects ◽  
Open Label ◽  
Dose Escalation Study ◽  
Double Blind

AbstractObjective: Assess the long-term safety and effectiveness of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype.Methods: A 24-month, open-label extension of a 4-week, multicenter, double-blind, placebo-controlled, parallel-group, forced–dose-escalation study of MAS XR in adults (≥ 18 years of age) with ADHD. The 223 enrolled subjects started treatment at 20 mgl day for 1 week, with subsequent titration up to 60 mgl day for optimal therapeutic effects. At monthly visits, efficacy was assessed based on the ADHD Rating Scale IV (ADHD-RS-N). Safety assessments included spontaneously reported adverse events, laboratory assessments, and monitoring of vital signs.Findings: ADHD symptoms significantly improved for all subjects as measured by change from baseline in mean ADHD-RS-IV total scores (-7.2±13.04 unit points; P<.001); this was sustained for up to 24 months. The most common treatment-related adverse events were dry mouth (43% of subjects reporting at least one occurrence), infection (33%), insomnia (32%), anorexia/decreased appetite (32%), headache (30%), and nervousness (26%). Most adverse events were mild to moderate in intensity.Conclusion: Treatment with MAS XR 20–60 mgl day for adult ADHD was generally well tolerated and was associated with sustained symptomatic improvement for up to 24 months.

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