An Open Study of Sertraline in Patients with Major Depression who Failed to Respond to Moclobemide

Objectives: The aim of this study is to evaluate the efficacy and tolerability of sertraline in patients with major depression who have failed to respond to an adequate trial of moclobemide. Method: Sixty-three patients with major depression who had discontinued moclobemide within the last 6 weeks due to lack of efficacy were recruited from multiple psychiatric services in Victoria and Queensland. After a wash-out period, patients were treated with sertraline 50 mg once daily for 4 weeks. If there was an insufficient response, the dose was titrated upwards to a maximum of 200 mg/day, with 2 weeks at each dosage level. By the end of the study, patients had received a fixed dose of sertraline for 8 weeks. The main outcome measures were the 17-item Hamilton Rating Scale for Depression (HAMD) and Clinical Global Impression (CGI) scales. Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI). Results: Of the 62 intention-to-treat patients enrolled, 48 (77%) responded to sertraline (i.e. experienced ≥ 50% reduction in HAMD total score from baseline and had a final HAMD score of ≤ 17). Fifty-four (87%) patients were at least ‘minimally improved’ on the CGI scale. There were also significant improvements in mean total MADRS and BDI scores. Sertraline was well tolerated. Adverse events were reported by 84% of patients, but only 5% withdrew due to adverse events. Conclusions: This study shows that patients with major depression who have failed to respond to moclobemide can generally be treated successfully with sertraline.

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Donepezil for mild cognitive impairment in Parkinson’s disease

Scientific Reports ◽

10.1038/s41598-021-84243-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kyoungwon Baik ◽

Seon Myeong Kim ◽

Jin Ho Jung ◽

Yang Hyun Lee ◽

Seok Jong Chung ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Treatment Group ◽

Outcome Measures ◽

Rating Scale ◽

Secondary Outcome ◽

Control Group ◽

Significant Difference

AbstractWe investigated the efficacy of donepezil for mild cognitive impairment in Parkinson’s disease (PD-MCI). This was a prospective, non-randomized, open-label, two-arm study. Eighty PD-MCI patients were assigned to either a treatment or control group. The treatment group received donepezil for 48 weeks. The primary outcome measures were the Korean version of Mini-Mental State Exam and Montreal Cognitive Assessment scores. Secondary outcome measures were the Clinical Dementia Rating, Unified Parkinson’s Disease Rating Scale part III, Clinical Global Impression scores. Progression of dementia was assessed at 48-week. Comprehensive neuropsychological tests and electroencephalography (EEG) were performed at baseline and after 48 weeks. The spectral power ratio of the theta to beta2 band (TB2R) in the electroencephalogram was analyzed. There was no significant difference in the primary and secondary outcome measures between the two groups. However, the treatment group showed a significant decrease in TB2R at bilateral frontotemporoparietal channels compared to the control group. Although we could not demonstrate improvements in the cognitive functions, donepezil treatment had a modulatory effect on the EEG in PD-MCI patients. EEG might be a sensitive biomarker for detecting changes in PD-MCI after donepezil treatment.

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Long-term improvements following a residential combined physical and psychological programme for chronic low back pain

BMJ Open Quality ◽

10.1136/bmjoq-2020-001068 ◽

2021 ◽

Vol 10 (2) ◽

pp. e001068

Author(s):

Shaun Wellburn ◽

Cormac G Ryan ◽

Andrew Coxon ◽

Alastair J Dickson ◽

D John Dickson ◽

...

Keyword(s):

Low Back Pain ◽

Back Pain ◽

Outcome Measures ◽

Chronic Low Back Pain ◽

Rating Scale ◽

Secondary Outcome ◽

Low Back ◽

Residential Setting ◽

Wide Range

ObjectivesEvaluate the outcomes and explore experiences of patients undergoing a residential combined physical and psychological programme (CPPP) for chronic low back pain.DesignA longitudinal observational cohort design, with a parallel qualitative design using semistructured interviews.SettingResidential, multimodal rehabilitation.Participants136 adults (62 male/74 female) referred to the CPPP, 100 (44 male/56 female) of whom completed the programme, during the term of the study. Ten (2 male/8 female) participated in the qualitative evaluation.InterventionA 3-week residential CPPP.Outcome measuresPrimary outcome measures were the STarT Back screening tool score; pain intensity—11-point Numerical Rating Scale; function—Oswestry Disability Index (ODI); health status/quality of life—EQ-5D-5L EuroQol five-Dimension-five level; anxiety—Generalised Anxiety Disorder-7; depression—Patient Health Questionnaire-9. Secondary outcome measures were the Global Subjective Outcome Scale; National Health Service Friends and Family Test;.ResultsAt discharge, 6 and 12 months follow ups, there were improvements from baseline that were greater than minimum clinically important differences in each of the outcomes (with the sole exception of ODI at discharge). At 12 months, the majority of people considered themselves a lot better (57%) and were extremely likely (86%) to recommend the programme to a friend. The qualitative data showed praise for the residential nature of the intervention and the opportunities for interaction with peers and peer support. There were testimonies of improvements in understanding of pain and how to manage it better. Some participants said they had reduced, or stopped, medication they had been taking to manage their pain.ConclusionsParticipants improved, and maintained long term, beyond minimum clinically important differences on a wide range of outcomes. Participants reported an enhanced ability to self-manage their back pain and support for the residential setting.

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Methotrimeprazine versus haloperidol in palliative care patients with cancer-related nausea: a randomised, double-blind controlled trial

BMJ Open ◽

10.1136/bmjopen-2019-029942 ◽

2019 ◽

Vol 9 (9) ◽

pp. e029942 ◽

Cited By ~ 2

Author(s):

Janet Rea Hardy ◽

Helen Skerman ◽

Jennifer Philip ◽

Phillip Good ◽

David C Currow ◽

...

Keyword(s):

Palliative Care ◽

Outcome Measures ◽

Controlled Trial ◽

Response Rates ◽

Complete Response ◽

Response To Treatment ◽

Secondary Outcome ◽

Double Blind ◽

Intention To Treat ◽

Point Reduction

ObjectivesMethotrimeprazine is commonly used for the management of nausea but never tested formally against other drugs used in this setting. The aim was to demonstrate superior antiemetic efficacy.DesignDouble-blind, randomised, controlled trial of methotrimeprazine versus haloperidol.Setting11 palliative care sites in Australia.ParticipantsParticipants were >18 years, had cancer, an average nausea score of ≥3/10 and able to tolerate oral medications. Ineligible patients had acute nausea related to treatment, nausea for which a specific antiemetic was indicated, were about to undergo a procedure or had received either of the study drugs or a change in glucocorticoid dose within the previous 48 hours.InterventionsBased on previous studies, haloperidol was used as the control. Participants were randomised to encapsulated methotrimeprazine 6·25 mg or haloperidol 1·5 mg one time or two times per day and assessed every 24 hours for 72 hours.Main outcome measuresA ≥two-point reduction in nausea score at 72 hours from baseline. Secondary outcome measures were as follows: complete response at 72 hours (end nausea score less than 3), response at 24 and 48 hours, vomiting episodes, use of rescue antiemetics, harms and global impression of change.ResultsResponse to treatment at 72 hours was 75% (44/59) in the haloperidol (H) arm and 63% (36/57) in the methotrimeprazine (M) arm with no difference between groups (intention-to-treat analysis). Complete response rates were 56% (H) and 51% (M). In theper protocolanalysis, there was no difference in response rates: (85% (44/52) (H) and 74% (36/49) (M). Completeper protocolresponse rates were 64% (H) and 59% (M). Toxicity worse than baseline was minimal with a trend towards greater sedation in the methotrimeprazine arm.ConclusionThis study did not demonstrate any difference in response rate between methotrimeprazine and haloperidol in the control of nausea.Trial registration numberACTRN 12615000177550.

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The Add-On Effect of Lactobacillus plantarum PS128 in Patients With Parkinson's Disease: A Pilot Study

Frontiers in Nutrition ◽

10.3389/fnut.2021.650053 ◽

2021 ◽

Vol 8 ◽

Author(s):

Chin-Song Lu ◽

Hsiu-Chen Chang ◽

Yi-Hsin Weng ◽

Chiung-Chu Chen ◽

Yi-Shan Kuo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Lactobacillus Plantarum ◽

Outcome Measures ◽

Rating Scale ◽

Controlled Trial ◽

Secondary Outcome ◽

Motor Deficits ◽

Motor Symptoms ◽

Non Motor Symptoms

Background:Lactobacillus plantarum PS128 (PS128) is a specific probiotic, known as a psychobiotic, which has been demonstrated to alleviate motor deficits and inhibit neurodegenerative processes in Parkinson's disease (PD)-model mice. We hypothesize that it may also be beneficial to patients with PD based on the possible mechanism via the microbiome-gut-brain axis.Methods: This is an open-label, single-arm, baseline-controlled trial. The eligible participants were scheduled to take 60 billion colony-forming units of PS128 once per night for 12 weeks. Clinical assessments were conducted using the Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr scale, and change in patient “ON-OFF” diary recording as primary outcome measures. The non-motor symptoms questionnaire, Beck depression inventory-II, patient assessment of constipation symptom, 39-item Parkinson's Disease Questionnaire (PDQ-39), and Patient Global Impression of Change (PGI-C) were assessed as secondary outcome measures.Results: Twenty-five eligible patients (32% women) completed the study. The mean age was 61.84 ± 5.74 years (range, 52–72), mean disease duration was 10.12 ± 2.3 years (range, 5–14), and levodopa equivalent daily dosage was 1063.4 ± 209.5 mg/daily (range, 675–1,560). All patients remained on the same dosage of anti-parkinsonian and other drugs throughout the study. After 12 weeks of PS128 supplementation, the UPDRS motor scores improved significantly in both the OFF and ON states (p = 0.004 and p = 0.007, respectively). In addition, PS128 intervention significantly improved the duration of the ON period and OFF period as well as PDQ-39 values. However, no obvious effect of PS128 on non-motor symptoms of patients with PD was observed. Notably, the PGI-C scores improved in 17 patients (68%). PS128 intervention was also found to significantly reduce plasma myeloperoxidase and urine creatinine levels.Conclusion: The present study demonstrated that PS128 supplementation for 12 weeks with constant anti-parkinsonian medication improved the UPDRS motor score and quality of life of PD patients. We suggest that PS128 could serve as a therapeutic adjuvant for the treatment of PD. In the future, placebo-controlled studies are needed to further support the efficacy of PS128 supplementation.Clinical Trial Registration:https://clinicaltrials.gov/, identifier: NCT04389762.

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An Open Study of Sertraline in Acute and Continuation Treatment of Depressed Out-Patients

Journal of International Medical Research ◽

10.1177/030006059702500604 ◽

1997 ◽

Vol 25 (6) ◽

pp. 340-353 ◽

Cited By ~ 3

Author(s):

B Van Houdenhove ◽

P Onghena ◽

M Flows ◽

F Janssen ◽

AR De Nayer ◽

...

Keyword(s):

Major Depression ◽

Open Study ◽

Acute Treatment ◽

Rating Scale ◽

Severity Of Illness ◽

Final Visit ◽

Clinical Global Impression Scale ◽

Scale Scores ◽

Insufficient Response ◽

Continuation Treatment

The efficacy and tolerability of sertraline in 422 out-patients with major depression (DSM-III-R) was evaluated in an open multicentre 8-month study. Patients received sertraline 50 mg/day; if there was insufficient response at week 4, the dose was increased to 100 mg/day. After 8 weeks, 68.6% of patients had responded (≥ 50% reduction in Montgomery Åsberg depression rating scale and clinical global impression scale scores of two or less (improvement of illness) and three or less (severity of illness); of patients receiving continuation treatment, 87.9% maintained at least a partial response at the final visit. The clinical response to the 50 mg/day dose was maintained throughout the acute treatment in 64% of patients. In all, 23% of the patients had mild or moderate drug-related gastrointestinal disturbances, which generally disappeared after 2 weeks. Only 8% of the patients withdrew because of side-effects. Just over half of the patients were taking other psychotropic drugs. Nevertheless the results of this open study are consistent with those of controlled studies in which sertraline was effective and well tolerated, in acute and continuation treatment for major depression, at 50 mg/day in most patients.

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A phase I study evaluating COM701 monotherapy and in combination with nivolumab in patients with advanced solid malignancies.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.5_suppl.tps23 ◽

2020 ◽

Vol 38 (5_suppl) ◽

pp. TPS23-TPS23

Author(s):

Ryan J. Sullivan ◽

Emerson A. Lim ◽

Manish Sharma ◽

Dale Randall Shepard ◽

Amita Patnaik ◽

...

Keyword(s):

Antitumor Activity ◽

Adverse Events ◽

Outcome Measures ◽

Dose Level ◽

Study Design ◽

Phase 1 ◽

Performance Status ◽

Secondary Outcome ◽

Tumor Growth Inhibition ◽

Solid Malignancies

TPS23 Background: COM701 is a novel 1st-in-class monoclonal antibody that binds with high affinity to poliovirus receptor related immunoglobulin domain containing (PVRIG) blocking its interaction with its ligand, PVRL2. In preclinical experiments inhibition of PVRIG alone and in combination with a PD-1 inhibitor leads to activation of T cells in the tumor microenvironment generating an anti-tumor immune response leading to tumor growth inhibition. Novel checkpoint therapies are needed for the treatment of patients with advanced malignancies. We hypothesized that COM701 monotherapy and in combination with nivolumab will be safe and tolerable and demonstrate preliminary antitumor activity in pts with advanced solid malignancies. Methods: This ongoing phase 1 study (NCT03667716) is evaluating the safety and tolerability of escalating doses of COM701 monotherapy IV Q3 or Q4 weekly and in combination with nivolumab 360 mg IV Q3 weekly or 480 mg IV Q4 weekly. Key Inclusion Criteria: Age ≥18 yrs, histologically or cytologically confirmed advanced solid malignancy and has exhausted all available standard therapy, ECOG performance status 0-1, prior ICI permissible. Key Exclusion Criteria: Symptomatic interstitial lung disease or inflammatory pneumonitis, untreated or symptomatic central nervous system metastases. Primary outcome measures are the incidence of adverse events and dose-limiting toxicities (21-day or 28-day DLT window), pharmacokinetics of COM701 and to identify the maximum tolerated dose and/or the recommended dose for expansion. Key secondary outcome measures are to characterize the immunogenicity and preliminary antitumor activity of COM701 as monotherapy and in combination with nivolumab. Study Design: Hybrid accelerated titration and 3+3 study design. Statistical Considerations: Adverse events graded as per CTCAE v4.03, responses as per RECIST v1.1. Analyses of all study objectives are descriptive and hypothesis generating. As of the date of this submission dose level 8 of COM701 monotherapy and dose level 3 of the combination arm are open to enrollment. Updated data will be presented at the conference. Clinical trial information: NCT03667716.

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Efficacy of Citalopram in the prevention of recurrent depression in elderly patients: Placebo-controlled study of maintenance therapy

The British Journal of Psychiatry ◽

10.1192/bjp.181.1.29 ◽

2002 ◽

Vol 181 (1) ◽

pp. 29-35 ◽

Cited By ~ 62

Author(s):

René Klysner ◽

Jesper Bent-Hansen ◽

Hanne L. Hansen ◽

Marianne Lunde ◽

Elisabeth Pleidrup ◽

...

Keyword(s):

Major Depression ◽

Elderly Patients ◽

Rating Scale ◽

The Elderly ◽

Term Treatment ◽

Fixed Dose ◽

Controlled Study ◽

Recurrence Time ◽

Long Term Treatment

BackgroundThe highly recurrent nature of major depression in the young and the elderly warrants long-term antidepressant treatment.AimsTo compare the prophylactic efficacy of citalopram and placebo in elderly patients; to evaluate long-term tolerability of citalopram.MethodOut-patients, ⩾65 years, with unipolar major depression (DSM – IV: 296.2 x or 296.3 x) and Montgomery – Åsberg Depression Rating Scale score ⩾22 were treated with citalopram 20–40 mg for 8 weeks. Responders continued on their final fixed dose of citalopram for 16 weeks before randomisation to double-blind treatment with citalopram or placebo for at least 48 weeks.ResultsNineteen of the 60 patients using citalopram v. 41 of the 61 patients using placebo had recurrence. Time to recurrence was significantly different between citalopram— and placebo-patients, in favour of citalopram (log-rank test, P < 0.0001). Long-term treatment was well tolerated.ConclusionsLong-term treatment with citalopram is effective in preventing recurrence of depression in the elderly and is well tolerated.

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A phase I study evaluating COM701 in patients with advanced solid tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.8_suppl.tps40 ◽

2019 ◽

Vol 37 (8_suppl) ◽

pp. TPS40-TPS40

Author(s):

Drew W. Rasco ◽

Kyriakos P. Papadopoulos ◽

Adeboye H. Adewoye ◽

John Hunter ◽

Denise Ramsey ◽

...

Keyword(s):

Antitumor Activity ◽

Adverse Events ◽

Solid Tumors ◽

Outcome Measures ◽

Standard Therapy ◽

Checkpoint Inhibitors ◽

Locally Advanced ◽

Secondary Outcome ◽

Tumor Growth Inhibition ◽

Single Subject

TPS40 Background: Novel checkpoint therapies are needed for the treatment of patients who relapse/refractory to treatment with checkpoint inhibitors. COM701 is a novel first-in-class humanized IgG4 monoclonal antibody that binds with high affinity to poliovirus receptor related immunoglobulin domain containing (PVRIG) blocking its interaction with it's ligand, PVRL2. We have demonstrated in preclinical experiments that inhibition of PVRIG leads to activation of T cells in the tumor microenvironment generating an anti-tumor immune response leading to tumor growth inhibition. We hypothesize that COM701 will be safe and tolerable and demonstrate antitumor activity in pts with R/R solid tumors. Methods: NCT03667716 is an ongoing open-label first-in-human phase 1 study in pts with R/R solid tumors. The initial part of this study will evaluate the safety and tolerability of escalating doses of COM701 monotherapy IV Q3 weekly. Key Inclusion Criteria: Age ≥18 yrs, histologically or cytologically confirmed, locally advanced or metastatic solid malignancy and has exhausted all the available standard therapy or is not a candidate for the available standard therapy, ECOG performance status 0-1, prior anti-PD-1, anti-PD-L1, anti-CTLA-4, OX-40, CD137. Key Exclusion Criteria: Active autoimmune disease requiring systemic therapy in the last 2 years prior to the first dose of COM701, symptomatic interstitial lung disease or inflammatory pneumonitis, untreated or symptomatic central nervous system metastases. Primary outcome measures are the incidence of adverse events and dose-limiting toxicities (21-day DLT window), pharmacokinetics of COM701 and to identify the maximum tolerated dose and/or the recommended dose for expansion. Secondary outcome measures are to characterize the immunogenicity and preliminary antitumor activity of COM701. Study Design: Accelerated titration design consisting of single subject cohorts has been implemented for the initial cohorts. Statistical Considerations: Adverse events graded as per CTCAE v4.03, responses as per RECIST v1.1. The analyses of all study objectives will be descriptive and hypothesis generating. As of the date of this submission a third single subject dose cohort has been filled.

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Postoperative Effects of Continuous Dexmedetomidine Infusion During Gynecological Laparoscopy: A Randomized, Placebo-Controlled, Double-Blind, Single Center Clinical Trial

10.21203/rs.3.rs-19402/v1 ◽

2020 ◽

Author(s):

SiYuan Liu ◽

Binbin Wang ◽

Yongtao Gao ◽

Xingguo Xu

Keyword(s):

Adverse Events ◽

General Anesthesia ◽

Outcome Measures ◽

Normal Saline ◽

Saline Group ◽

Secondary Outcome ◽

Double Blind ◽

Gynecological Laparoscopy ◽

Blood Pressures ◽

Group D

Abstract Background: Dexmedetomidine(DEX) has proven to be an effective adjuvant to anesthetics owing to its sympatholytic, analgesic, and sedative properties. This study was designed to investigate the postoperative effects of continuous DEX infusion during gynecological laparoscopy and to evaluate the safety of this treatment. Methods: Sixty patients undergoing selective gynecological laparoscopy with general anesthesia were randomly assigned into DEX group (group D )and normal saline group (group N). DEX was infused at 0.5ug/kg/h during anesthesia maintenance in group D while normal saline was infused at the same rate in group N. The primary outcome measures were heart rate and blood pressure at extubation, 1, 2, 3, 4, 5, 6, 7, 8, 12, 24 and 48 hours after operation, NRS scores at 1, 2, 3 ,4, ,8,12,24 hours after surgery and OAA/S scores after extubation. The secondary outcome measures were time to extubation, propofol and remifentanil dosage during anesthesia, postoperative adverse events, and postoperative hospital stay.Results: Systolic and diastolic blood pressures were lower in group D at extubation when compared with group N (P<0.05), but not different at the first postoperative hour or after. HR was lower both at extubation and the first postoperative hour in group D (P<0.05). NRS scores were lower in patients given DEX both at rest and movement at the first postoperative hour (P<0.05). Time to extubation and OAA/S scores after extubation were not different between groups. Postoperative respiratory depression, shivering and pruritus didn’t occur in this research. There were no significant differences in the incidence rate of postoperative adverse events or postoperative hospital stay between the groups.Conclusions: Continuous infusion of DEX during gynecological laparoscopy provided better hemodynamic stability at extubation and the effects on HR continued until 1 hour after operation. DEX administration was associated with lower NRS scores at the first postoperative hour without excessive sedation. DEX is a useful and safe adjuvant for general anesthesia during gynecological laparoscopy.

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Abstract P148: Safety And Efficacy Of Edaravone Dexborneol Versus Edaravone Alone For The Treatment Of Acute Ischemic Stroke Patients With Hypertention: Analysis From Taste Trial

Hypertension ◽

10.1161/hyp.78.suppl_1.p148 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Jie Xu ◽

Yongjun Wang

Keyword(s):

Ischemic Stroke ◽

Adverse Events ◽

Acute Ischemic Stroke ◽

Medical History ◽

Functional Outcomes ◽

Group Versus ◽

Phase Iii ◽

Secondary Outcome ◽

Serious Adverse Events ◽

Intention To Treat

Background and Aims: Evidenced by TASTE phase III trial, 90-day good functional outcomes favored the edaravone dexborneol group versus edaravone group when administered within 48 hours after Acute Ischemic Stroke (AIS). The present study aimed to investigate the effects of edaravone dexborneol versus edaravone in AIS patients with hypertension medical history. Methods: This study was a subgroup analysis of the TASTE trial with hypertension medical history. The primary outcome was the proportion of patients with modified Rankin Scale (mRS) score ≤1 on day 90 after randomization. The secondary outcome was the mRS score on day 90. The safety endpoints were the incidences of adverse events, serious adverse events and deaths. Analyses were by intention to treat. Results: We included 767 AIS patients with hypertension (390 in edaravone dexborneol group, 377 in edaravone group) in this analysis. Among them, 252 (64.62%) in edaravone dexborneol group versus 199 (52.79%) in edaravone group reached mRS score ≤1 on D90, revealing significantly higher proportion of mRS score ≤1 on D90 in edaravone dexborneol group (OR 1.63 [95% CI, 1.22-2.18]; P<0.001). Significant differences occurred between two groups in mRS score on D90 ([OR 1.32 [95% CI, 1.02-1.72]; P=0.038). The safety outcomes indicated that the two groups were similar in incidences of adverse events (366 [93.85%] versus 352 [93.37%], p=0.787), serious adverse events (48 [12.31%] versus 34 [9.02%], p=0.1405) and number of deaths (6 [1.54%] versus 4 [1.06%], p=0.56). Conclusion: This analysis demonstrated that AIS patients with hypertension receiving edaravone dexborneol had better functional outcomes than those with edaravone, which provided evidences for the clinical application of edaravone dexborneol in AIS patients with hypertension. Keywords: Edaravone dexborneol, Acute ischemic stroke, Hypertension, mRS score

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