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Effectiveness and Tolerability of Intranasal Esketamine in Treatment-Resistant Depression: Report of Two Clinical Cases
- A. Mercado-Rodríguez, C. Martín Requena, A. Cano Baena, I. Zorrilla Martínez, A. González-Pinto Arrillaga, L. Mar-Barrutia
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S824
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Introduction
Major depressive disorder (MDD) is a mental health disorder characterised by persistently low mood; anhedonia; feelings of worthlessness and guilt; altered appetite, weight and sleep and suicidal ideation. About one-third of patients do not respond to available antidepressants (AD). Treatment-resistant depression (TRD) is a clinical term used to define a lack of response to two or more AD in patients with MDD that do not respond to other lines of treatment either. TRD is associated with an increased risk of relapse, hospitalisation and suicide. Esketamine is a non-competitive NMDAR antagonist that acts as an antidepressant by modulating glutamatergic neurotransmission, disturbed in MDD patients. It has recently been approved by the European Commission as a fast-acting nasal spray therapy for depression and suicidal ideation after showing effectiveness in TRD patients (Papakostas et al. JCP 2020; 81 4).
ObjectivesThe aim of this study is to determine the effectiveness, safety and tolerability of intranasal esketamine in two TRD-diagnosed patients and to assess their clinical evolution.
MethodsA prospective study was conducted describing the evolution of two TRD patients treated with intranasal esketamine. We used The Hamilton Depression Rating Scale (HDRS) to quantify the severity of their symptoms and assess their recovery over time, analyzing the score change from baseline to endpoint as a primary outcome of the study. We also applied the Addensbrooke Cognitive Examination (ACE-III) as a tool to establish their cognitive condition before therapy and its evolution. Changes in dosage during treatment, adverse effects, time required for onset of action, clinical outcomes and other variables were also measured.
ResultsIntranasal esketamine was administered twice a week during the first 4-week induction phase and weekly during the following 6-month maintenance phase. Dosage of antidepressant was determined depending on each patient’s age and clinical evolution, being 56 mg the initial dose for case 1 (57 years old) and 28 mg for case 2 (71 years old). This antidepressant was effective in both patients in a fast-acting way, with the onset of action occuring within the first two weeks. During the course of treatment, the HDRS score significantly decreased, associated with improvement and remission of depressive symptoms. Cognitive performance got better in both cases. None of the patients discontinued treatment due to adverse effects or lack of efficacy.
ConclusionsOur data suggest that intranasal esketamine therapy is a good alternative in TRD patients, being effective, fast-acting and well-tolerated, with a manageable safety profile. Clinical stability was also observed in the medium-term follow-up after the end of treatment. This presents esketamine as a promising therapeutic and effective strategy in MDD patients who are either treatment-resistant or acutely suicidal.
Disclosure of InterestNone Declared
Suicidal behaviour and cognition: A systematic review with special focus on prefrontal deficits
- J. Fernández-Sevillano, A. González-Pinto, J. Rodríguez-Revuelta, S. Alberich-Mesa, L. González-Blanco, I. Zorrilla-Martínez, Á. Velasco, P. López-Pena, I. Abad-Acebedo, P.A. Saiz
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- Journal:
- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, p. S584
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Introduction
Suicidal behaviour and cognition: A systematic review with special focus on prefrontal deficits Introduction: Suicide is a major health concern worldwide, thus, identifying risk factors would enable a more comprehensive understanding and prevention of this behaviour. Neuropsychological alterations could lead to difficulties in interpreting and managing life events resulting in a higher risk of suicide.
ObjectivesObjective: Bibliographic review about the influence of neuropsychological deficits on suicidal behaviour.
MethodsMethod: A systematic literature search from 2000 to 2020 was performed in Medline (Pubmed), Web of Science, SciELO Citation Index, PsycInfo, PsycArticles and Cochrane Library databases regarding studies comparing cognition of attempters versus non-attempters that share same psychiatric diagnosis. Results: 1.885 patients diagnosed with an Affective Disorder (n = 1512) and Schizophrenia/ Schizoaffective Disorder (n = 373) were included.
ResultsIn general comparison, attention was found to be clearly dysfunctional. Regarding diagnosis, patients with Schizophrenia and previous history of suicidal behaviour showed a poorer performance in executive function. Patients with current symptoms of an Affective Disorder and a previous history of suicidal attempt had poorer performance in attention and executive function. Similarly, euthymic affective patients with history of suicidal behaviour had worse decision-making, attention and executive function performance compared to euthymic non-attempters.
ConclusionsPatients who have attempted suicide have a poorer neuropsychological functioning than non-attempters with a similar psychiatric disorder in attention and executive function. These alterations increase vulnerability for suicide.
Conflict of interestJessica Fernández-Sevillano is beneficiary of the Pre-PhD Training Programme of the Basque Government. Dr. Gonzalez-Pinto has received grants and served as consultant, advisor or CME speaker for the following entities: Almirall, AstraZeneca, Bristol-Myers
Oxidative stress, inflammation and cognitive impairment in first psychotic patients
- M. Martínez-Cengotitabengoa, J.C. Leza, S. Alberich, S. Barbeito, R. González-Oliveros, I. Zorrilla, I. de la Rosa, L. Celaya, S. Gubbini, A. González-Pinto
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- Journal:
- European Psychiatry / Volume 26 / Issue S2 / March 2011
- Published online by Cambridge University Press:
- 16 April 2020, p. 427
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Introduction
Both oxidative stress and the inflammatory chemokine MCP-1 have been linked to the pathophysiology of certain mental illnesses such as psychosis. There are previous studies in rats and dogs suggesting that oxidative stress can cause cognitive impairment.
ObjectivesTo correlate oxidative stress and the chemokine MCP-1 levels with cognitive impairment in first episode psychosis.
Methods28 patients with first episode psychosis and 28 healthy controls matched by sex and age were included in the study, who were given a battery of neurocognitive tests and we determined their blood levels of lipid peroxidation (TBARS), nitric oxide, total antioxidant status (TAS), glutathione, activity of enzymes catalase (CAT), glutathione peroxidase (cGPx) and superoxide dismutase (SOD) and the inflammatory chemokine MCP-1.
ResultsHealthy controls had better TAS than patients and increased activity of enzymes cGPx and CAT.
We found a statistically significant negative relationship between levels of MCP-1 and working memory, attention and verbal memory. At higher levels of chemokines, worse cognitive functioning in these areas.
Verbal memory was also negatively related, in a meaningful way, with nitric oxide levels in blood.
Likewise, we found that higher levels of glutathione correlated with better scores on the 3 tests performed of verbal fluency.
ConclusionsIn patients with a PEP, levels of certain markers of oxidative stress and inflammation are associated with poorer cognitive functioning.
Telemedicine and bipolar disorder
- A. García-Alocén, C. Bermudez-Ampudia, M. Martínez-Cengotitabengoa, I. González-Ortega, S. Ruiz de Azua, I. Zorrilla, P. Lopez, A. González-Pinto
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- Journal:
- European Psychiatry / Volume 33 / Issue S1 / March 2016
- Published online by Cambridge University Press:
- 23 March 2020, p. S121
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Show the efficacy of an innovate telemedicine psyeducational invention based on a psychoeducational intervention treatment with a group of bipolar patients.
ObjetivesTo assess the efficacy of an innovate telemedicine psyeducational treatment (TPT) based on a psychoeducational intervention (21 sessions) with an additional support through telemedicine which has 12 videos versus treatment as usual (TAU) based on psychiatry reviews. Specifically, the objective was to evaluate patients’ efficacy of psyeducational treatment with telemedicine (TPT) in the fuctionalitity, depressive symptoms and manic symptoms.
MethodsThirty-eight patients with bipolar disorder were included in the study and randomly distributed in the two groups. The telemedine treatment is performed through a www.puedoser.es web platform provided by Astra Zeneca. In the web platform is available forums, emails and digital-course with the sessions worked as a reminder. In order to assess the effectiveness of treatments, FAST scale was administered at baseline and 6 months after the intervention. To obtain the results we used coparative data analysis.
ResultsIn patients, we found a low daily functionality. The main issues were: interpersonal cognitive area (t = –2.611; P = 0.014) and interpersonal-area (t = –2.617; P = 0.014). We found, at baseline, that TPT group had worse overall results in daily functionality (t = –2.876; P = 0.008). After intervention, there is an improvement in the daily functionality of the TPT group. This improvement occurred in cognitive area (z = –3.24; P < 0.001), leisure area (z = –1.85; P = 0.065) and interpersonal area (z = –1.72; P = 0.086).
ConclusionsThe psychoeducational program combined with telemedicine shows to be more effective than TAU in the improvement of general patient functioning in bipolar disorder patients.
Disclosure of interestThe authors have not supplied their declaration of competing interest.
Evolution of inflammatory dysregulation and oxidative stress in patients with first episode of mania
- S. García, P. López Peña, I. Zorrilla, A. García-Alocen, M. Martínez-Cengotitabengoa, C. Bermúdez-Ampudia, K.S. Mac-Dowell, S. Rodríguez, J.C. Leza, A. González-Pinto
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- Journal:
- European Psychiatry / Volume 33 / Issue S1 / March 2016
- Published online by Cambridge University Press:
- 23 March 2020, p. S331
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Introduction
Recent studies have focused on the imbalance in inflammatory and antioxidant pathways as possible causes of the underlying neurodegenerative processes in bipolar disorder. Thus, the study of these pathways in first episodes of mania (FEM) can increase knowledge about this issue.
AimTo compare plasma concentrations of pro-inflammatory (MCP-1, PGE2, TNFα) and oxidative parameters (TAS, NO2 and TBARS) between controls and FEM patients and to analyze the evolution of these parameters in patients from baseline to 6 months assessment time.
MethodsThis study included 44 FEM patients and 79 healthy controls, aged 18 to 40. Blood samples were available for controls at baseline and for patients at baseline and 6 months after. TAS and TBARS were measured using non-EIA assay kits, N02 was measured with Griess method and PGE2, MCP-1 and TNFα with ELISA kits.
ResultsAt baseline, TAS was significantly lower in patients than in controls and TBARS, MCP-1 and TNFα were significantly higher in patients. Among patients, TAS and MCP1 were lower at 6 months than at the illness onset and PGE2 and NO2 were significantly higher than at baseline.
ConclusionPatients presented an increased oxidative damage and also a higher activation of pro-inflammatory pathways than healthy controls at baseline. After 6 months their level of oxidative stress continue increased. Pro-inflammatory parameters decreased overtime (MCP-1 and TNF α) but PGE2, increased surprisingly. This can be due to the fact that antipsychotics are not able to completely reverse baseline inflammation.
Disclosure of interestThe authors have not supplied their declaration of competing interest.
First bipolar episode and functionality: Relation with depressive symptoms and inflammation levels
- M. Martinez-cengotitabengoa, C. Bermudez-ampudia, M.P. Lopez, A. Garcia-alocen, I. Gonzalez-ortega, I. Zorrilla, A. Gonzalez-pinto
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- Journal:
- European Psychiatry / Volume 33 / Issue S1 / March 2016
- Published online by Cambridge University Press:
- 23 March 2020, pp. S122-S123
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Introduction
It is important to make an early and effective intervention from the first bipolar episode. The presence of depressive symptoms in the course of a manic episode could influence negatively the evolution and the prognosis of the patient. Inflammation and oxidative stress are also related with functionality.
ObjectivesTo explore the relationship between depressive symptoms during a first episode of mania, inflammatory parameters and patient functionality during the follow-up.
MethodWe included in the study 92 are patients with a first manic episode and 92 matched healthy controls. We compared 13 inflammatory/oxidative stress parameters measured at baseline (TFNα, IL6, PGE2, MCP1, TBARS, NO2, SOD, CAT, GSHTOT, GSSG, GSHfree, GPx, TAS) between both groups. Between patients, 46 presented pure mania (PM) (no depressive symptoms) and 46 mixed mania (MM) (with depressive symptoms). We explored the influence of inflammatory factors in functionality, exploring differences between PM and MM. To measure patients’ general functioning one year after illness onset, we used the Functional Assessment Short Test (FAST).
ResultsWe found significant differences in TFNα, MCP1 and TBARS (higher in patients) and in SOD, GSHtot, GSSG, GSHfree, GPx and TAS levels (lower in patients). Only In MM group, there was a significant influence of SOD and GSHfree in FAST scores suggesting that a higher antioxidant levels at baseline the patient functionality improves one year after.
ConclusionsSome parameters of oxidative stress at baseline are related with patient's functionality one year after the first episode of mania, but only when mania debuts with depressive symptons simultaneously.
Disclosure of interestThe authors have not supplied their declaration of competing interest.