A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression

2021 ◽  
Vol 13 (597) ◽  
pp. eabe1376
Author(s):  
Peter Nagele ◽  
Ben J. Palanca ◽  
Britt Gott ◽  
Frank Brown ◽  
Linda Barnes ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Depressive Symptoms ◽  
Major Depression ◽  
Rating Scale ◽  
Similar Efficacy ◽  
Comparable Efficacy ◽  
Crossover Fashion ◽  
Phase 2 ◽  
Treatment Resistant ◽  
Phase 2 Trial

Nitrous oxide at 50% inhaled concentration has been shown to improve depressive symptoms in patients with treatment-resistant major depression (TRMD). Whether a lower concentration of 25% nitrous oxide provides similar efficacy and persistence of antidepressant effects while reducing the risk of adverse side effects is unknown. In this phase 2 clinical trial (NCT03283670), 24 patients with severe TRMD were randomly assigned in a crossover fashion to three treatments consisting of a single 1-hour inhalation with (i) 50% nitrous oxide, (ii) 25% nitrous oxide, or (iii) placebo (air/oxygen). The primary outcome was the change on the Hamilton Depression Rating Scale (HDRS-21). Whereas nitrous oxide significantly improved depressive symptoms versus placebo (P = 0.01), there was no difference between 25 and 50% nitrous oxide (P = 0.58). The estimated differences between 25% and placebo were −0.75 points on the HDRS-21 at 2 hours (P = 0.73), −1.41 points at 24 hours (P = 0.52), −4.35 points at week 1 (P = 0.05), and −5.19 points at week 2 (P = 0.02), and the estimated differences between 50% and placebo were −0.87 points at 2 hours (P = 0.69), −1.93 points at 24 hours (P = 0.37), −2.44 points at week 1 (P = 0.25), and −7.00 points at week 2 (P = 0.001). Adverse events declined substantially with dose (P < 0.001). These results suggest that 25% nitrous oxide has comparable efficacy to 50% nitrous oxide in improving TRMD but with a markedly lower rate of adverse effects.

scholarly journals Nitrous Oxide for Treatment-Resistant Major Depression: A Proof-of-Concept Trial

2015 ◽  
Vol 78 (1) ◽  
pp. 10-18 ◽  
Author(s):  
Peter Nagele ◽  
Andreas Duma ◽  
Michael Kopec ◽  
Marie Anne Gebara ◽  
Alireza Parsoei ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Major Depression ◽  
Proof Of Concept ◽  
Treatment Resistant

FC10-02 - Ghrelin affects sleep, secretion of cortisol and growth hormone and psychopathology in patients with major depression

2011 ◽  
Vol 26 (S2) ◽  
pp. 1865-1865
Author(s):  
M. Kluge ◽  
P. Schüssler ◽  
M. Dresler ◽  
D. Schmidt ◽  
A. Yassouridis ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Depressive Symptoms ◽  
Major Depression ◽  
Rem Sleep ◽  
Rating Scale ◽  
Well Being ◽  
Somatotropic Axis ◽  
Healthy Humans ◽  
Antidepressant Effects ◽  
Time Awake

IntroductionGhrelin showed antidepressant-like effects in mice. Furthermore, ghrelin influences sleep and the activity of hypothalamic-pituitary-adrenal (HPA) and somatotropic axis in healthy humans as indicated by increased cortisol and growth hormone (GH) plasma levels. Both sleep and the activity of these endocrine axes are disturbed in depression.ObjectiveTo study the effect of ghrelin on psychopathology, sleep and secretion of cortisol and GH in patients with major depression.MethodsDepressive symptoms as assessed by a validated self rating scale (’Befindlichkeits-Skala’, [well-being scale]), secretion profiles of cortisol and GH and sleep-EEGs were determined in 14 unmedicated patients with major depression (7 women) twice, receiving 50 μg ghrelin or placebo at 2200, 2300, 0000, and 0100 hours.ResultsOverall, depressive symptoms did not change significantly after ghrelin administration (placebo: 37 ± 8; ghrelin: 33 ± 10, p = 0.178). However, there was an improvement at trend level in men (placebo: 36 ± 9 to ghrelin: 30 ± 9, p = 0.093) but not in women. In men, ghrelin was associated with less time awake (placebo: 149.0 ± 11.1; ghrelin: 88.0±12.2 min, p = 0.029) and more non-REM sleep (placebo: 263.2 ± 24.1; ghrelin: 304.9 ± 14.1 min, p = 0.027), in women with less REM sleep (placebo: 108.6 ± 15.7; ghrelin: 74.1 ± 13.8 min, p = 0.031) and longer REM latency (placebo: 49.9 ± 6.5; ghrelin: 85.6 ± 14.1 min, p = 0.019). In both sexes, ghrelin caused strong transient increases of GH and cortisol.ConclusionOur study may provide an initial indication that ghrelin can exert antidepressant effects in patients with major depression. Ghrelin strongly affected sleep and secretion of GH and cortisol in a partly different way as previously reported in healthy subjects.

scholarly journals Additional intranasal oxytocin to escitalopram improves depressive symptoms in resistant depression: An open trial

2015 ◽  
Vol 30 (1) ◽  
pp. 65-68 ◽  
Author(s):  
G. Scantamburlo ◽  
M. Hansenne ◽  
V. Geenen ◽  
J.J. Legros ◽  
M. Ansseau
Keyword(s):  
Depressive Symptoms ◽  
Rating Scale ◽  
Open Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Hamilton Depression Rating Scale ◽  
Resistant Depression ◽  
Synthetic Oxytocin

AbstractThe aim of this open trial was to assess the antidepressant/anxiolytic effects of oxytocin used as an adjunct to antidepressant in treatment-resistant depression. Fourteen patients, who have not responded to 40 mg of escitalopram, received intranasal synthetic oxytocin during 4 weeks, in association with antidepressant. This is the first open trial study suggesting OT in association with escitalopram significantly reduced scores on Hamilton Depression Rating Scale.

Clinical and neurocognitive characteristics associated with treatment-resistant depression

2017 ◽  
Vol 41 (S1) ◽  
pp. S542-S542 ◽  
Author(s):  
G. Serafini ◽  
G. Adavastro ◽  
G. Canepa ◽  
C. Conigliaro ◽  
M. Pompili ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Early Onset ◽  
Rating Scale ◽  
Color Word ◽  
Late Onset ◽  
Anxiety Symptoms ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Interference Test ◽  
Resistant Depression

IntroductionTreatment resistant depression (TRD) is a disabling condition associated with a relevant psychosocial impairment worldwide.ObjectivesThis exploratory study is aimed to evaluate the main clinical and neurocognitive characteristics in a sample of 21 subjects admitted to the Psychiatric Clinic of University of Genoa as inpatients between 2015 and 2016 and diagnosed with TRD according to Thase and Rush staging method.MethodsPatients have been assessed using the Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale, and Clinical Global Impression (CGI). The Continuous Performance Test (CPT), Trial Making Test (TMT-A/B), Stroop Color Word Interference Test, Verbal Fluency Test, and Rey auditory-verbal learning test (RAVLT) have been administered as well.ResultsSubjects with early-onset (< 50 years) depression had a longer illness duration, higher depressive episodes and more impaired performance at RAVLT while individuals with late-onset (> 50 years) depression showed a higher severity of depressive symptoms and more anxiety symptoms. Depressive symptoms were positively associated with anxiety (r = 0.82; P = 0.00) and negatively with TMT-A/B (r = −0.56, P = 0.01), Stroop Color Word Interference Test (r = −0.72, P = 0.005 and r = −0.616, P = 0.008), and RAVLT (r = −0.60; P = 0.02) performances. According to regression analyses, anxiety symptoms were the only significant predictor of depression severity (P = 0.02).ConclusionsEarly-onset depression is associated with more disability and worse neurocognitive performance whereas late-onset depression is linked to more anxiety symptoms and more depressive symptoms severity. Clinicians should closely monitor patients with TRD for the presence of anxiety symptoms that may represent a significant risk factor of poorer long-term outcome.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Base excision repair (BER) inhibitor TRC 102 (Methoxyamine) combined with pemetrexed (PEM)-based chemo-radiation (CRT) for locally advanced non-squamous non-small cell lung cancer (NS-NSCLC): Results of a phase I trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9027-9027
Author(s):  
Tithi Biswas ◽  
Afshin Dowlati ◽  
Charles Kunos ◽  
John Pink ◽  
Nancy Oleinick ◽  
...  
Keyword(s):  
Excision Repair ◽  
Locally Advanced ◽  
Chemotherapy Resistance ◽  
Stage Iv ◽  
Similar Efficacy ◽  
Primary Objective ◽  
Phase 2 ◽  
Abasic Sites ◽  
Phase 2 Trial ◽  
Base Excision

9027 Background: About 35% of all NSCLC presents with locally advanced disease and chemo-radiation results in 5-year OS of only ~31%. PEM-platinum combination is approved in stage IV NSCLC and has similar efficacy to platinum-etoposide in stage 3 NSCLC and a favorable toxicity profile (Proclaim trial). TRC102 is an oral small molecule inhibitor of BER. TRC102 potentiates the cytotoxicity of antimetabolites and alkylators and reverses chemotherapy resistance by rapidly and covalently binding to chemotherapy-induced abasic sites in DNA. TRC102 increased radio-sensitization by PEM of NSCLC cell lines and H1299 and A549 xenografts. Methods: Between 11/2015 and 5/2019, 15 patients were enrolled in a 3+ 3 design: 12 with stage III and 3 with oligometastatic stage IV NS-NSCLC. The primary objective was to determine dose-limiting toxicities (DLT’s) and recommended Phase 2 dose (RP2D) of TRC102 in combination with PEM, cisplatin and radiotherapy. Secondary objectives were to assess toxicity, tumor response and PFS at 6 months. Based on pre-clinical data, PEM-TRC102 was given on day 1, and cisplatin/radiotherapy was initiated on day 3. This schedule was duplicated on day 21 and day 23 of the second cycle. After completion of radiotherapy, two additional cycles of PEM-cisplatin were given. Toxicities were assessed by NCI CTACAE version 4 and 5. Results: Median patient age was 69 years (45-79) and median follow up was 16.6 months (3.1-38.6). There were no DLTs or grade 5 toxicity. Hematologic and GI toxicities were the most common adverse events (Table) and radiation pneumonitis was not seen. The RP2D of TRC102 was 200 mg when given with cisplatin/radiotherapy and PEM. Of 15 evaluable patients, 3 had CR (20%) and 12 had PR (80%). The 2-year PFS rate was 49%. Conclusions: PEM-TRC102 combined with cisplatin/radiotherapy in non-squamous NSCLC was safe and well tolerated, and did not cause safety signals beyond those expected from CRT. Preliminary response data and PFS in this cohort was encouraging. A phase 2 trial, integrating post-CRT immunotherapy with this aggressive DNA-damaging regimen is warranted. Clinical trial information: NCT02535325. [Table: see text]

A Double-Blind, Multicentre Study of Paroxetine and Maprotiline in Major Depression

1996 ◽  
Vol 41 (4) ◽  
pp. 239-244 ◽  
Author(s):  
Ulrich Schnyder ◽  
Annemarie Koller-Leiser
Keyword(s):  
Side Effects ◽  
Major Depression ◽  
Rating Scale ◽  
Similar Efficacy ◽  
Nonsignificant Trend ◽  
Double Blind ◽  
Treatment Groups ◽  
Hopkins Symptom Checklist ◽  
Psychiatric Rating ◽  
Psychiatric Rating Scale

Objective: This study was performed to compare the clinical efficacy, side effects, and safety of paroxetine and maprotiline, the latter being the most frequently prescribed antidepressant in Switzerland. Method: Seventy-one patients (in and outpatients) with major depression were randomly allocated to treatment with paroxetine (20 to 40 mg daily) or with maprotiline (50 to 150 mg daily). Efficacy was measured by means of the Hamilton Psychiatric Rating Scale for Depression, the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression, and the Hopkins Symptom Checklist. Results: The 2 components showed a similar efficacy. The adverse effect profile was comparable in the 2 treatment groups, although the findings showed a nonsignificant trend pointing in the direction of lower side effects with paroxetine. Conclusion: In the moderate dose regimens tested, the 2 components seemed to be of similar efficacy, with comparable profiles of side effects and safety.

Predictors of functioning in major depression

2017 ◽  
Vol 41 (S1) ◽  
pp. S325-S325
Author(s):  
M. Serra-Blasco ◽  
E. Aguilar ◽  
M. Vicent ◽  
G. Navarra ◽  
M.J. Portella ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Major Depression ◽  
Statistical Power ◽  
Rating Scale ◽  
Cognitive Domain ◽  
Neuropsychological Battery ◽  
Cognitive Difficulties ◽  
Mood Symptoms ◽  
Life Functioning ◽  
Competing Interest

IntroductionLife functioning difficulties are a relevant but undervalued consequence of major depression. Mood symptoms and cognitive deficits have a significant, and somehow independent, impact on them. Therefore, cognitive difficulties should be considered a potential target to improve patients’ functioning.AimsTo examine the degree in which objective and subjective cognition explain functional outcome.ObjectivesTo assess objective cognitive function (CF) with a neuropsychological battery and to measure subjective CF using measures of cognitive perception.MethodsNinety-nine patients with depression were assessed by age, sex and level of schooling. Depressive symptoms severity was measured by Hamilton Depression Rating Scale (HDRS-17). Objective CF consisted in the following cognitive domains: memory, attention, executive functioning and processing speed. Subjective CF was assessed with Perceived Deficit Questionnaire-Depression (PDQ-D). Functioning Assessment Short Test (FAST) was used to evaluate life functioning, excluding the cognitive domain. All the listed measures were included in a multiple regression analysis with FAST scores as dependent variable.ResultsThe regression model was significant (F1,98 = 67.484, P < 0.001) with an R of 0.825. The variables showing statistical power included (from higher to lower β-coefficient) HDRS-17 (β = 0.545, t = 8.453, P < 0.001), PDQ-D (β = 0.383, t = 6.047, P < 0.001) and DSST (β = −0.123, t = −1.998, P = 0.049).ConclusionsThe severity of depressive symptoms is the variable that best explains life functioning. Surprisingly, the second factor hindering it is the patients’ perception of their cognition. Current findings highlight the importance of correcting cognitive bias in order to improve functionality. However, results have to be taken cautiously as mood symptoms could partly explain the bias.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Dementia and Depression in Elderly Medical Inpatients

2000 ◽  
Vol 12 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Emese Linka ◽  
György Bartkó ◽  
Tamás Agárdi ◽  
Katalin Kemény
Keyword(s):  
Depressive Symptoms ◽  
Major Depression ◽  
Rating Scale ◽  
Depressive Symptomatology ◽  
Total Sample ◽  
Semistructured Interview ◽  
High Prevalence ◽  
Medical Inpatients ◽  
Dsm Iv ◽  
Hamilton Rating Scale

The purpose of this study was to examine the prevalence and correlation of cognitive impairments, major depression, and depressive symptoms among elderly medical inpatients, and to compare the degree of depressive symptomatology as well as cognitive deterioration in possible vascular dementia and possible Alzheimer's disease. In a department of internal medicine, 100 (36 male, 64 female) 65-year-old or older patients were examined by a semistructured interview, and assessed by the Hachinski Ischemic Scale, the Hamilton Rating Scale for Depression (HDS), and the Modified Mini-Mental State (MMMS) Examination. In our total sample, the MMMS total score was (±SD) 76.0 ± 15.5 and the HDS total score was (±SD) 12.0 ± 6.1. Based on DSM-IV criteria, major depression was established in 11 patients. Deterioration of cognitive functions was seen in 66 patients; cognitive impairment was mild in 30 patients, moderate in 19, and severe in 17. Forty-six patients had mild depressive symptoms and 27 had severe depressive symptoms. In summary, a high prevalence of cognitive dysfunction and depressive symptomatology was detected in our study, illustrating the importance of psychiatric care in elderly medical inpatients.

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