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1.
Lancet Psychiatry. 2020 Jan;7(1):2-3. doi: 10.1016/S2215-0366(19)30476-6.

Putting deep brain stimulation for depression in a wider perspective.

Author information

1
Department of Psychiatry, Amsterdam Neuroscience, Amsterdam Universitair Medische Centra, University of Amsterdam, Amsterdam 22660, Netherlands; Amsterdam Brain and Cognition, Amsterdam, Netherlands. Electronic address: i.o.bergfeld@amsterdamumc.nl.
PMID:
31860453
DOI:
10.1016/S2215-0366(19)30476-6
[Indexed for MEDLINE]
Icon for Elsevier Science
2.
Epidemiol Psychiatr Sci. 2019 Dec 16;29:e79. doi: 10.1017/S2045796019000751.

Esketamine for treatment resistant depression: a trick of smoke and mirrors?

Author information

1
Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, University of Verona, Verona, Italy.

Abstract

In March 2019, the US Food and Drug Administration (FDA) approved a nasal spray formulation of esketamine for the treatment of resistant depression in adults. Esketamine is the S-enantiomer of ketamine, an FDA-approved anaesthetic, known to cause dissociation and, occasionally, hallucinations. While ketamine has not been approved for depression in the USA or in any other country, it has been used off-label in cases of severe depression. This commentary critically reviewed the evidence on esketamine submitted to the FDA, aiming to draw implications for clinical practice, research and regulatory science.

KEYWORDS:

Esketamine; FDA; evidence-based medicine; regulatory policies; treatment-resistant depression

PMID:
31841104
DOI:
10.1017/S2045796019000751
[Indexed for MEDLINE]
Icon for Cambridge University Press
3.
Psychiatr Hung. 2019;34(4):393-402.

[How we see the development of clinical trials from the investigators' side?]

[Article in Hungarian]

Author information

1
Semmelweis Egyetem Pszichiatriai és Pszichoterapias Klinika, Budapest, Hungary, E-mail: bitter.istvan@med.semmelweis-univ.hu.

Abstract

This is a discussion paper on research in clinical pharmacology in the field of psychiatry. In addition to other factors the decline in discovery and development of new drugs in the field of psychiatry and the developments and growing complexity in the field of clinical trial technology, including outsourcing and risk based monitoring, reduced the number of young clinical researchers interested in this important field. The challenges posed by the restructuring within the pharmacological industry - including digitalization - should induce changes in the structure and in the processes of clinical pharmacology research and in the training of clinical research staff members. The approval of esketamine nasal spray for treatment resistant depression by the FDA and the results of research with psychedelics call for more education and training in this specific field.

PMID:
31767799
[Indexed for MEDLINE]
4.
Psychiatr Danub. 2019 Sep;31(Suppl 3):585-590.

Short-term ketamine administration in treatment-resistant depression: focus on cardiovascular safety.

Author information

1
Department of Psychiatry, Faculty of Medicine, Medical University of Gdańsk, Dębinki St. 7 build. 25, 80-952 Gdańsk, Poland.

Abstract

Ketamine is an anaesthetic and analgesic agent that demonstrates the antidepressive effect in major depression. Several administrations routes, dosing schemas and esketamine are investigated in basic and clinical research with particular focus on treatment-resistant depression (TRD) where drug demonstrates its efficacy where very limited alternatives are available. The majority of ketamine studies in TRD treatment reported no serious adverse events regardless the administration route or regimen. However, the most commonly observed adverse events following ketamine administration in antidepressive doses include general, psychotomimetic, dissociative and hemodynamic ones. The side effects are mild or moderate, well-tolerated and transient. This paper discusses the risks regarding cardiovascular safety in MDD patients in short-term ketamine administration with particular focus on the effect on blood pressure and adverse drug reactions mitigation measures. The increase in systolic (SBP) and diastolic (DBP) blood pressure is dose-dependent and begins shortly after administration peaking at around 30 to 50 minutes with SBP and DBP rise from 10% to 50% above predose values and resolving at approximately 2 to 4 hours after the dose administration. These changes generally are primarily asymptomatic. The elevations in SBP and DBP are observed on each dosing day with multiple administration schema. The treatment with ketamine and esketamine is contradicted in subjects at risk of an increase in blood pressure or intracranial pressure. The current evidence indicates the blood pressure should be assessed prior to dosing with ketamine and hypertensive individuals shall receive effective lifestyle/pharmacologic management prior to treatment. Blood pressure should be monitored after dose administration until blood pressure returns to acceptable levels. If blood pressure remains elevated acute blood pressure management shall be delivered. In patients experiencing symptoms of hypertensive crisis immediate emergency care must be provided. The unmet need for improved pharmacotherapies for TRD means the use of ketamine and esketamine is warranted therapeutic option in patients who fail to achieve a sustained remission of depressive symptoms with drugs with monoamine-based mechanisms of action. Adequate safety measures must be applied when using ketamine/esketamine in TRD subjects with particular focus on somatic comorbidities as the transient drug effect on cardiovascular system is demonstrated and of clinical significance.

PMID:
31488795
[Indexed for MEDLINE]
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5.
Psychiatr Danub. 2019 Sep;31(Suppl 3):530-533.

Short-term ketamine administration in treatment-resistant depression patients: focus on adverse effects on the central nervous system.

Author information

1
Department of Psychiatry, Faculty of Medicine, Medical University of Gdańsk, Dębinki St. 7 build. 25, 80-952 Gdańsk, Poland, aswlodarczyk@gmail.com.

Abstract

Major depressive disorder (MDD) is a recurrent, incapacitating psychiatric illness which will be the second most disabling disease worldwide by the year 2020. There is a rising promise in a N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, which may be used in the treatment of resistant depression. Many of the studies are in favor of the drug, even in single dose application, with effects appearing in minutes to hours from administration. However, there is a need to evaluate the benefits and risks regarding psychomimetic, psychiatric, neurologic, and cognitive adverse effects of ketamine administration. The most distressing symptoms which appear most frequently during ketamine administration are dissociative symptoms, which can be quantified as a CNS adverse drug reaction. Results generally show that a single infusion of ketamine is efficacious and well-tolerated, while dissociative symptoms tend to abate within 2 hours after ketamine administration. As studies show single doses of ketamine should be definitely considered as an option in TRD patients with/without suicidal thoughts, even though it could not provide remission, or the effect could be temporary, but improving patients' quality of life by reducing depressive symptomatology should be a major asset while considering this particular procedure, particularly in inpatients.

PMID:
31488786
[Indexed for MEDLINE]
6.
Psychiatr Danub. 2019 Sep;31(Suppl 3):520-523.

Role of copper and ketamine in major depressive disorder - an update.

Author information

1
Department of Psychiatry, Faculty of Medicine, Medical University of Gdansk, Dębinki St. 7 build. 25, 80-952 Gdańsk, Poland, jslupski@gumed.edu.pl.

Abstract

Major depressive disorder is one of the most important psychiatric issues worldwide, with important prevalence of treatment-resistant depression (TRD). Non-monoaminergic agents are currently in the spotlight. Objective was to explore for information about mechanisms of action of ketamine, its connections with copper and possible importance for TRD treatment. There are at least few possible pathways for ketamine action in depression in which copper and other divalent ions may show a vital role. There is urgent need for more studies to gather information about correlation between ketamine, copper and antidepressive features of these agents.

PMID:
31488784
[Indexed for MEDLINE]
7.
Psychiatr Danub. 2019 Sep;31(Suppl 3):258-260.

Suicidality in treatment resistant depression: perspective for ketamine use.

Author information

1
Department of Psychiatry, Faculty of Medicine, Medical University of Gdańsk, Dębinki St. 7 build. 25, 80-952 Gdańsk, Poland, k.jakuszkowiak@gumed.edu.pl.

Abstract

Suicidal ideations or attempts in patients with major depressive disorder (MDD) are emergent conditions that require immediate treatment. Numerous therapeutic interventions to reduce suicide risk in psychiatric disorders are effective in long-term suicide prevention, but there is necessity of sufficient, rapid pharmacological treatment of suicidal risk in MDD. Ketamine, an N-methyl-D-aspartate (NMDA) antagonist, has been reported to have rapid antidepressant effect. Depressive symptoms, anxiety, hopelessness, suicidal ideation had decreased within hours after ketamine infusion. Ketamine's rapid symptoms relief and reduction of suicide thoughts has aroused growing interests in psychiatric association.

PMID:
31488737
[Indexed for MEDLINE]
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8.
Psychiatr Danub. 2019 Sep;31(Suppl 3):252-257.

The immunomodulatory effect of ketamine in depression.

Author information

1
Department of Physiopathology, Medical University of Gdańsk, Ul. Dębinki 7, 80-210 Gdańsk, Poland, lukasz.szalach@gumed.edu.pl.

Abstract

Major depression is one of the most frequent psychiatric conditions. Despite many available treatment methods, more than 30% of patients do not achieve remission, even after trying several antidepressants and augmentation strategies. S-enantiomer of ketamine, well-known anesthetic and analgesic, has been recently approved by Food and Drug Administration in the intranasal form as a new generation antidepressant. However, the mechanism in which ketamine reduces depressive symptoms in treatment-resistant depression patients is still not completely understood. There are several theories explaining how ketamine might reduce depressive symptoms, which have been described in detail; one of them is immunomodulatory effect of ketamine, according to the inflammatory theory of depression. In the review authors present and summarize studies showing ketamine effect on human immune system ex vivo and in vitro, including changes in cytokine levels, number, ratio and activity of various immune cell population and the correlation with clinical improvement in depressive symptoms. Most of the results confirm the anti-inflammatory effect of ketamine. There are only a few studies in the population of patients suffering from depression receiving ketamine, focused on correlation between immunological changes and clinical outcome of the therapy; further studies of that area are neccesary for understanding the immunomodulatory effect of ketamine in depression.

PMID:
31488736
[Indexed for MEDLINE]
9.
Expert Opin Pharmacother. 2019 Nov;20(16):1925-1933. doi: 10.1080/14656566.2019.1654457. Epub 2019 Aug 20.

Brexpiprazole for treatment-resistant major depressive disorder.

Author information

1
Neuroscience, Reproductive Science and Dentistry, Federico II University of Naples , Naples , Italy.
2
Department of Psychiatry, Villa Camaldoli Alma Mater SpA , Naples , Italy.
3
Department of Mental Health, ASL NOVARA , Borgomanero , Italy.
4
National Health Care System, Mazzini Hospital , Teramo , Italy.

Abstract

Introduction:Treatment-resistant depression (TRD), seldom interchangeably referred to as 'depression inadequately responding to the standard antidepressant drug,' carries a significant burden. The atypical antipsychotics represent a popular augmentation strategy for antidepressant-resistant depression, although their efficacy/safety profiles vary across different agents and presentations of depression. Areas covered: This review appraises the evidence supporting the use of brexpiprazole augmentation for major depressive disorder (MDD) adults showing an inadequate response to standard antidepressants, covering the related regulatory affairs, and essential pharmacology. Expert opinion: Brexpiprazole is a 'third-generation' antipsychotic featuring dopaminergic D2 and serotonergic 5-HT1A partial agonism approved by the U.S. Food and Drug Administration for the treatment of MDD, besides schizophrenia in adults. The clinical trials leading to the extended approval of brexpiprazole rely on the definition of 'inadequate response' to antidepressants, which seems to poorly represent the most severe cases of TRD seen in clinical practice. TRD definitions appraised in the literature are likewise inconsistent and questionable from a clinical-standpoint. Compared to aripiprazole, brexpiprazole has lower D2 intrinsic activity, although the latter features a more potent serotonergic 5-HT2A antagonism. The actual propensity of brexpiprazole to induce akathisia and tardive dyskinesia warrants assessment by ad-hoc designed long-term, controlled trials.

KEYWORDS:

Brexpiprazole; atypical antipsychotic; augmentation; treatment-resistant depression

PMID:
31431092
DOI:
10.1080/14656566.2019.1654457
[Indexed for MEDLINE]
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10.
Medicine (Baltimore). 2019 Aug;98(31):e16674. doi: 10.1097/MD.0000000000016674.

A statistical analysis plan for a randomized clinical trial to evaluate the efficacy and safety of ethosuximide in patients with treatment-resistant depression.

Jiang J1, Wang Z1,2,3, Dong Y4, Yang Y4,5, Ng CH6, Ma S4, Xu Y1,2,3, Hu H4,5, Hu S1,2,3.

Author information

1
Department of Psychiatry, the First Affiliated Hospital, College of Medicine, Zhejiang University.
2
The Key Laboratory of Mental Disorder's Management of Zhejiang Province.
3
Brain Research Institute of Zhejiang University.
4
Center for Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, School of Medicine, Interdisciplinary Institute of Neuroscience and Technology, Qiushi Academy for Advanced Studies.
5
Mental Health Center, School of Medicine, Zhejiang University, Hangzhou, China.
6
Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia.

Abstract

BACKGROUND AND OBJECTIVE:

A recent striking advance in the treatment of depression has been the finding of rapid antidepressant effects in over 70% of patients with treatment-resistant depression (TRD) using ketamine. However, the potential risk of addiction may limit its clinical use. Recent research revealed that blockade of N-methyl-D-aspartate receptor (NMDAR) dependent bursting activity in the lateral habenula (LHb) could mediate the fast antidepressant effects of ketamine. Further, LHb bursting plays an important role in the pathophysiology of depression that requires both NMDARs and low-voltage-sensitive T-type calcium channels (T-VSCCs). Ethosuximide, which is used to treat absence seizures, is a T-VSCCs inhibitor, may be a novel drug candidate for depression. The objective of this clinical trial is to investigate the efficacy and safety of ethosuximide in patients with TRD.

DESIGN:

The study is a single center, randomized, double-blind, placebo-controlled, parallel-group, two-stage clinical trial. Forty patients with TRD will be randomly assigned to Group A (treatment group) or Group B (control group). In the first stage ethosuximide or placebo will be given for 2 weeks. In the second stage, escitalopram (or another antidepressant if escitalopram has been used before) will be given for the next 4 weeks for all trial patients to ensure effective treatment. The primary outcome measure is the Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Secondary outcome measures include the Quick Inventory of Depressive Symptomatology-Self Report score, Hamilton Anxiety Rating Scale scores, individual scores of MADRS, and Young Mania Rating Scale scores. All these scales are measured at baseline and at each treatment visit. Two-way repeated measures analysis of variance is used to analyze the study outcomes.

DISCUSSION:

A statistical analysis plan is employed to enhance the transparency of the clinical trial and reduce the risks of outcome reporting bias and data-driven results.

PMID:
31374046
PMCID:
PMC6709087
DOI:
10.1097/MD.0000000000016674
[Indexed for MEDLINE]
Free PMC Article
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11.
Tijdschr Psychiatr. 2019;61(7):498-503.

[Lithium augmentation to monoamine oxidase-inhibitors in treatment-resistant depressive disorders: case report and overview of literature].

[Article in Dutch]

Abstract

Three patients suffering from a treatment-resistant depression were being treated with a monoamine oxidase (mao-)inhibitor and received lithium augmentation to achieve better recovery. One patient showed significant improvement of depressive symptoms within 24 hours, one patient showed very little respons and one patient did not respond at all. Literature research led to other casereports, where adding lithium to mao-inhibitors had also been effective. The growing amount of arguments of a positive effect of lithium augmentation to mao-inhibitors asks for more research to collect more evidence and a better understanding of this new, potentially effective treatment.

PMID:
31372971
[Indexed for MEDLINE]
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12.
Psychiatr Danub. 2019 Jun;31(2):148-156. doi: 10.24869/psyd.2019.148.

Amisulpride as an Augmentation Agent in Treatment Resistant Depression: A Case Series and Review of the Literature.

Author information

1
Department of Psychiatry, General Hospital Steyr, 4400 Steyr, Austria, h.rittmannsberger@aon.at.

Abstract

Amisulpride (AMS) in low dosage has been used effectively for treatment of dysthymia. Yet there is a dearth of reports on its use as an augmentation agent in therapy-resistant depression. We deal with this issue presenting case reports and a review of the literature. The addition of 50 mg amisulpride (AMS) to antidepressant therapy in seven patients with depression at different stages of treatment resistance, one of them a case of recurrent brief depression, is described in this report. Augmentation with AMS led to a profound improvement in psychopathology in most patients. The only side effects were elevation of prolactin levels and occasional weight gain. In most cases, improvement occurred early, after only 1-2 weeks of treatment. In some patients, reduction or cessation of AMS led to an immediate and intense recurrence of depressive symptoms that resembled a withdrawal syndrome. Further investigations into the clinical utility and the mode of action of AMS as an augmentation agent are warranted.

PMID:
31291218
DOI:
10.24869/psyd.2019.148
[Indexed for MEDLINE]
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13.
Tijdschr Psychiatr. 2019;61(6):411-420.

[Consensus statement on the application of rTMS in depression in the Netherlands and Belgium].

[Article in Dutch]

Abstract

Since 2017, repetitive transcranial magnetic stimulation (rTMS) has become eligible for reimbursement for the treatment of therapy-resistant depression in the Dutch healthcare system.<br/> AIM: To initiate a guideline in the Netherlands and Belgium for the safe and effective application of rTMS for the treatment of depression.<br/> METHOD: Based on literature review, existing guidelines and consensus among Dutch rTMS experts, recommendations were developed regarding the implementation of rTMS as a treatment of depression. All available evidence was weighed and discussed among all co-authors and recommendations were reached by consensus among the group.<br/> RESULTS: rTMS targeting the dorsolateral prefrontal cortex (DLPFC) should be seen as a first choice in the treatment of depression using high-frequency rTMS (left) or, as an alternative, low-frequency rTMS (right). Stimulation protocols should use more than 1000 pulses per session for an average of 20-30 sessions, offered in 2-5 sessions per week. Contraindications for rTMS include epilepsy, intracranial presence of (magnetisable) metals, pacemaker and cochlear implant.<br/> CONCLUSION: rTMS, performed by competent professionals is an effective and safe treatment for depression.

PMID:
31243751
[Indexed for MEDLINE]
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14.
J Manag Care Spec Pharm. 2019 Jul;25(7):823-835. doi: 10.18553/jmcp.2019.25.7.823.

Economic Burden of Treatment-Resistant Depression on the U.S. Health Care System.

Author information

1
1 Boston Health Economics, Boston, Massachusetts.
2
2 Alkermes, Waltham, Massachusetts.
3
3 Columbia University Medical Center, New York, New York.

Abstract

BACKGROUND:

Treatment-resistant depression (TRD), defined as episodes of depression that do not respond to ≥ 2 lines of adequate depression therapy, is associated with a high economic burden. Although the economic burden of TRD is reported elsewhere, its exact magnitude and current value is uncertain due to differences in methodology in TRD identification.

OBJECTIVE:

To compare all-cause health care resource utilization (HCRU) and associated health care payments among patients with TRD and those with depression but without TRD, using administrative claims data.

METHODS:

This retrospective cohort study used data from the Truven Health MarketScan Commercial and Medicare Supplemental Databases (October 1, 2008-September 30, 2016). All patients were aged ≥ 18 years, newly diagnosed with depression (≥ 1 inpatient admission or ≥ 2 outpatient visits with a primary or secondary depression diagnosis), and newly treated with depression therapy. The population included patients with and without TRD. Patients with TRD were defined as having been treated with ≥ 3 courses of depression therapy within a 360-day period (initiation of the third course served as the TRD index date), while patients without TRD (non-TRD) were defined as having been treated with 2 courses of depression therapy. TRD and non-TRD cohorts were matched using propensity scores. Using the TRD index date of their matched TRD pair, non-TRD patients were assigned a simulated index date following second-line therapy. Eligible TRD and non-TRD patients were continuously enrolled from a 12-month baseline period before the first course of therapy through a 12-month follow-up period beginning with the TRD index date and simulated index date, respectively. Annual all-cause HCRU and associated payments (2016 U.S. dollars) were assessed in aggregate and by place of service during the follow-up period and were compared between the matched cohorts using nonparametric Wilcoxon signed-rank tests.

RESULTS:

The matched analysis included 800 patients in each cohort. For both cohorts, the mean age of patients was 39 years, and 60% were female. All clinical characteristics and all-cause HCRU were comparable at baseline. Compared with non-TRD patients, TRD patients had a significantly higher mean number of all-cause emergency department (ED) visits (0.29 vs. 0.24), outpatient visits (18.0 vs. 13.4), and prescriptions (30.0 vs. 24.0; all P < 0.05) during the 12-month follow-up period. The TRD cohort also had significantly higher mean total all-cause health care payments ($9,890 vs. $6,848; P < 0.001) and mean payments by place of service (ED: $518 vs. $408; outpatient: $3,603 vs. $2,585; pharmacy: $2,613 vs. $1,837; all P < 0.05) compared with the non-TRD cohort.

CONCLUSIONS:

In relation to propensity score-matched non-TRD patients, TRD patients used significantly more resources (ED visits, outpatient visits, and number of prescriptions) and had significantly higher overall health care payments. These results serve to highlight the unmet need in patients with TRD, suggesting that improved and more effective management of these patients may help reduce the economic burden of disease.

DISCLOSURES:

This study was funded by Alkermes. Sussman and Menzin, employees of Boston Health Economics, were paid consultants, and Olfson, an employee of Columbia University Irving Medical Center, was an unpaid consultant to Alkermes in connection with the study and development of this research article. O'Sullivan and Shah are employees of the study sponsor. Results from this analysis were first presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting in Boston, MA, on April 23-26, 2018.

PMID:
31232205
DOI:
10.18553/jmcp.2019.25.7.823
[Indexed for MEDLINE]
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16.
Am J Psychiatry. 2019 Jun 1;176(6):428-438. doi: 10.1176/appi.ajp.2019.19020172. Epub 2019 May 21.

Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study.

Author information

1
Janssen Research and Development, Beerse, Belgium (Popova); Janssen Research and Development, Titusville, N.J. (Daly, Lane, Lim, Hough, Manji, Drevets); the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Trivedi); Janssen Research and Development, Spring House, Pa. (Cooper); Janssen Canada, Toronto (Mazzucco); the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (Thase); the Department of Psychiatry, University of Alabama School of Medicine, Birmingham (Shelton); Clínica Universidad de Navarra, Pamplona, Spain (Molero); Institute of Neuroscience, University of Barcelona, Hospital Clinic, IDIBAPS, CIBERSAM, Barcelona, Spain (Vieta); Charité Universitätsmedizin Berlin, Berlin (Bajbouj); Janssen Research and Development, San Diego (Singh).

Erratum in

Abstract

OBJECTIVE:

About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants. This study compared the efficacy and safety of switching patients with treatment-resistant depression from an ineffective antidepressant to flexibly dosed esketamine nasal spray plus a newly initiated antidepressant or to a newly initiated antidepressant (active comparator) plus placebo nasal spray.

METHODS:

This was a phase 3, double-blind, active-controlled, multicenter study conducted at 39 outpatient referral centers. The study enrolled adults with moderate to severe nonpsychotic depression and a history of nonresponse to at least two antidepressants in the current episode, with one antidepressant assessed prospectively. Confirmed nonresponders were randomly assigned to treatment with esketamine nasal spray (56 or 84 mg twice weekly) and an antidepressant or antidepressant and placebo nasal spray. The primary efficacy endpoint, change from baseline to day 28 in Montgomery-Åsberg Depression Rating Scale (MADRS) score, was assessed by a mixed-effects model using repeated measures.

RESULTS:

Of 435 patients screened, 227 underwent randomization and 197 completed the 28-day double-blind treatment phase. Change in MADRS score with esketamine plus antidepressant was significantly greater than with antidepressant plus placebo at day 28 (difference of least square means=-4.0, SE=1.69, 95% CI=-7.31, -0.64); likewise, clinically meaningful improvement was observed in the esketamine plus antidepressant arm at earlier time points. The five most common adverse events (dissociation, nausea, vertigo, dysgeusia, and dizziness) all were observed more frequently in the esketamine plus antidepressant arm than in the antidepressant plus placebo arm; 7% and 0.9% of patients in the respective treatment groups discontinued study drug because of an adverse event. Adverse events in the esketamine plus antidepressant arm generally appeared shortly after dosing and resolved by 1.5 hours after dosing.

CONCLUSIONS:

Current treatment options for treatment-resistant depression have considerable limitations in terms of efficacy and patient acceptability. Esketamine is expected to address an unmet medical need in this population through its novel mechanism of action and rapid onset of antidepressant efficacy. The study supports the efficacy and safety of esketamine nasal spray as a rapidly acting antidepressant for patients with treatment-resistant depression.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02418585.

KEYWORDS:

Esketamine; Ketamine; Major Depressive Disorder; S-Ketamine; Treatment-Resistant Depression

Comment in

PMID:
31109201
DOI:
10.1176/appi.ajp.2019.19020172
[Indexed for MEDLINE]
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17.
Prog Neurol Surg. 2019;34:289-297. doi: 10.1159/000493076. Epub 2019 May 16.

Radiosurgery for Behavioral Disorders.

Author information

1
Ruber Internacional Hospital, Madrid, Spain, rob.martinez@telefonica.net.

Abstract

Psychiatric illnesses create great suffering for patients and the medical solution is sometimes limited. The experience observed after treating patients with obsessive-compulsive disorder (OCD), depression, and anorexia nervosa by Gamma Knife radiosurgery (GKRS) is presented. Ten patients with medically refractory OCD, 3 patients with depression resistant to medical treatment and electroconvulsive therapy, and 5 patients with refractory anorexia nervosa have been treated. Bilateral anterior capsulotomy has been performed to treat OCD and bilateral cingulotomy has been applied to treat severe depression and anorexia nervosa. The accumulated experience about treatment of OCD by GKRS is reviewed. In our experience, 70% of OCD patients achieved a full response. We observed a significant improvement in patients with depression and anorexia nervosa evidenced by the scales of assessment (mean reduction of 40% in the Beck Depression Inventory at 1-year follow-up and 40% average increase of body mass index at 6-month follow-up). No side effects have been observed. These procedures are effective in reducing obsession, compulsion, depression, and anxiety, improving the quality of life of the patients without side effects.

PMID:
31096225
DOI:
10.1159/000493076
[Indexed for MEDLINE]
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18.
J Consult Clin Psychol. 2019 May;87(5):433-445. doi: 10.1037/ccp0000391.

Personality and outcome in individuals with treatment-resistant depression-Exploring differential treatment effects in the Tavistock Adult Depression Study (TADS).

Author information

1
Research Department of Clinical, Educational and Health Psychology, University College London.
2
Faculty of Psychology and Educational Sciences, University of Leuven.

Abstract

OBJECTIVE:

Although research over the past decades has investigated the impact of the personality dimensions of dependency and self-criticism on treatment outcome, little is known of how these personality features influence responsiveness to treatment in patients with severe, chronic forms of depression.

METHOD:

The present study uses data from the Tavistock Adult Depression Study, a randomized controlled trial investigating the effectiveness of long-term psychoanalytic psychotherapy (LTPP) compared with treatment as usual (TAU) for individuals diagnosed with treatment-resistant depression. Patients were rated with the Anaclitic-Introjective Depression Assessment Q-sort, which distinguishes between two more maladaptive (Submissive and Dismissive) and two less maladaptive (Needy and Self-Critical) subdimensions of dependent or anaclitic and self-critical or introjective depression. Multilevel modeling was used to compare individuals' growth curves of depression severity as measured by the Hamilton Rating Scale for Depression over the 18-month treatment period and 2-year follow-up. Rates of clinically significant change were also determined.

RESULTS:

As expected, depressed patients with more maladaptive dependent and self-critical features did not benefit from LTPP or TAU. Patients with less maladaptive self-critical features benefited from both LTPP and TAU, while those with less maladaptive dependent features showed considerable gains from LTPP but not from TAU, with medium to large effect sizes.

CONCLUSIONS:

Findings of this study are consistent with existing research suggesting the need to modify and tailor treatments in accordance with individuals' pretreatment personality features. Given the time and cost-intensive nature of longer-term treatment, this may be particularly important in patients with treatment-resistant depression. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

PMID:
30998046
DOI:
10.1037/ccp0000391
[Indexed for MEDLINE]
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19.
Rev Assoc Med Bras (1992). 2019 Mar;65(3):361-369. doi: 10.1590/1806-9282.65.3.361. Epub 2019 Apr 11.

Increased levels of plasma IL-1b and BDNF can predict resistant depression patients.

Author information

1
Dante Pazzanese Institute of Cardiology, São Paulo, SP, Brasil.
2
School of Pharmaceutical Science, University of São Paulo, São Paulo, SP, Brasil.

Abstract

BACKGROUND:

There is no strong evidence on the link between inflammatory profile and pattern of drug treatment response in depressive patients that could result in Coronary Artery Disease occurrence.

OBJECTIVE:

This study aimed to compare the subclinical atherosclerosis markers, inflammatory profile, and BDNF production in Resistant Depression (RD) or Bipolar Affective Disorder (BAD) patients under conventional treatment.

METHODS:

The population evaluated was comprised of 34 RD, 43 BAD, and 41 controls. Subclinical atherosclerosis markers were evaluated using ultrasonography, tomography, and exercise stress test. Plasma concentrations of TNFα, IL-1β, IL-6, and BDNF were measured using Luminex100™. The usCRP concentration was measured using turbidimetric immunoassay. IL1B, IL6, and TNFA expression were determined using TaqMan®. For the statistical analysis, the significance level was established at p<0.05.

RESULTS:

Concerning subclinical atherosclerosis markers, only O2 consumption was reduced in the BAD group (p = 0.001). Although no differences were found in gene expression, BDNF and IL-1β plasma concentration was increased in the RD group (p = 0.002 and p = 0.005, respectively) even with an antidepressant treatment, which suggests that these drugs have no effect in IL-1β secretion and that the inflammasome may play a role in therapy response.

CONCLUSION:

Taken together, both BDNF and IL-1β plasma concentrations could be used to the early identification of RD patients.

PMID:
30994834
DOI:
10.1590/1806-9282.65.3.361
[Indexed for MEDLINE]
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20.
Int J Psychiatry Clin Pract. 2019 Jun;23(2):122-127. doi: 10.1080/13651501.2018.1562077. Epub 2019 Mar 30.

Repetitive transcranial magnetic stimulation (rTMS) for depression: outcomes in a United Kingdom (UK) clinical practice.

Author information

1
a Innovation and Research Department , Northamptonshire Healthcare NHS Foundation Trust , Northampton , UK.
2
b Psychology Department, Faculty of Health and Society , University of Northampton , Northampton , UK.

Abstract

Objective: The aim of this paper is to present the outcomes data from the largest United Kingdom's (UK) National Health Service (NHS) clinical rTMS service treating treatment resistant depression (TRD). Methods: The study was a retrospective investigation of routinely collected data on patients receiving rTMS between 2015 and 2017. Measures used were the clinician-rated Clinical Global Impression (CGI) and Hamilton Depression Rating Scale (HAM-D), and patient rated Beck Depression Inventory (BDI). The outcome data of 73 patients with TRD were analysed. The sample included patients with co-morbid psychiatric diagnosis. Results: Response and remission rates, respectively, were 40.4% and 25.5% for the HAM-D; 35.6% and 20.8% for the BDI; and 51.1% and 52.1% for the CGI. Effect sizes were medium (0.54, 0.52 and 0.56, respectively). Conclusions: The results show that a UK-based clinical service achieves similar results to those published internationally and that clinical rTMS can have significant impact on symptoms of depression in many patients with TRD. Health services are under pressure to make financial savings, investment in rTMS could reduce the long-term treatment costs associated with TRD.

KEYWORDS:

Repetitive Transcranial Magnetic Stimulation (rTMS); naturalistic; service delivery; treatment-resistant depression

PMID:
30931656
DOI:
10.1080/13651501.2018.1562077
[Indexed for MEDLINE]
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