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Article ; Online: Ropinirole Augmentation for Depression: A Randomized Controlled Trial Pilot Study.

Gershon, Ari A / Amiaz, Revital / Shem-David, Haim / Grunhaus, Leon

2018 Volume 39, Issue 1, Page(s) 78–81

Abstract: Objective: Evidence both from animal and human studies suggests a role for dopaminergic pathways in the treatment of depression. Ropinirole, a selective agonist of dopamine D2/D3, is in use for the treatment of parkinsonism. Preliminary evidence ... ...

Abstract	Objective: Evidence both from animal and human studies suggests a role for dopaminergic pathways in the treatment of depression. Ropinirole, a selective agonist of dopamine D2/D3, is in use for the treatment of parkinsonism. Preliminary evidence suggests that such agonists might be useful as antidepressants. We tested whether an add-on ropinirole is an effective in depressed patients. Methods: We conducted a double-blind, randomized, placebo-controlled trial of add-on ropinirole in depressed patients unresponsive to at least one antidepressant. We recruited 32 unipolar and bipolar patients who remained depressed (modified 21-item Hamilton Depression Rating Scale) despite at least 4 weeks of treatment with an adequate dose of antidepressant medication. Patients received either 2 mg of oral ropinirole or placebo twice daily added on to their current medication and were evaluated weekly for 7 weeks using the Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale. Results: No difference in primary or secondary outcome measures was detected between the treatment and control groups. Discussion: These results differ from previous studies and are unexpected in light of theoretical considerations. This may indicate that there are differences in pharmacological activity between ropinirole and other dopaminergic agents such as pramipexole.
MeSH term(s)	Antidepressive Agents/administration & dosage ; Antidepressive Agents/therapeutic use ; Depression/drug therapy ; Dopamine Agonists/therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Humans ; Indoles/administration & dosage ; Indoles/therapeutic use ; Male ; Middle Aged ; Pilot Projects
Chemical Substances	Antidepressive Agents ; Dopamine Agonists ; Indoles ; ropinirole (030PYR8953)
Language	English
Publishing date	2018-11-29
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	604631-9
ISSN	1533-712X ; 0271-0749
ISSN (online)	1533-712X
ISSN	0271-0749
DOI	10.1097/JCP.0000000000000984
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Article ; Online: Application of Machine Learning Models to Biomedical and Information System Signals From Critically Ill Adults.

Lilly, Craig M / Kirk, David / Pessach, Itai M / Lotun, Gurudev / Chen, Ofer / Lipsky, Ari / Lieder, Iris / Celniker, Gershon / Cucchi, Eric W / Blum, James M

Chest

2023

Abstract: Background: Machine learning (ML)-derived notifications for impending episodes of hemodynamic instability and respiratory failure events are interesting because they can alert physicians in time to intervene before these complications occur.: Research ...

Abstract	Background: Machine learning (ML)-derived notifications for impending episodes of hemodynamic instability and respiratory failure events are interesting because they can alert physicians in time to intervene before these complications occur. Research question: Do ML alerts, telemedicine system (TS)-generated alerts, or biomedical monitors (BMs) have superior performance for predicting episodes of intubation or administration of vasopressors? Study design and methods: An ML algorithm was trained to predict intubation and vasopressor initiation events among critically ill adults. Its performance was compared with BM alarms and TS alerts. Results: ML notifications were substantially more accurate and precise, with 50-fold lower alarm burden than TS alerts for predicting vasopressor initiation and intubation events. ML notifications of internal validation cohorts demonstrated similar performance for independent academic medical center external validation and COVID-19 cohorts. Characteristics were also measured for a control group of recent patients that validated event detection methods and compared TS alert and BM alarm performance. The TS test characteristics were substantially better, with 10-fold less alarm burden than BM alarms. The accuracy of ML alerts (0.87-0.94) was in the range of other clinically actionable tests; the accuracy of TS (0.28-0.53) and BM (0.019-0.028) alerts were not. Overall test performance (F scores) for ML notifications were more than fivefold higher than for TS alerts, which were higher than those of BM alarms. Interpretation: ML-derived notifications for clinically actioned hemodynamic instability and respiratory failure events represent an advance because the magnitude of the differences of accuracy, precision, misclassification rate, and pre-event lead time is large enough to allow more proactive care and has markedly lower frequency and interruption of bedside physician work flows.
Language	English
Publishing date	2023-11-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1032552-9
ISSN	1931-3543 ; 0012-3692
ISSN (online)	1931-3543
ISSN	0012-3692
DOI	10.1016/j.chest.2023.10.036
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Article: Validation of an Automatic Tagging System for Identifying Respiratory and Hemodynamic Deterioration Events in the Intensive Care Unit.

Jeddah, Danielle / Chen, Ofer / Lipsky, Ari M / Forgacs, Andrea / Celniker, Gershon / Lilly, Craig M / Pessach, Itai M

Healthcare informatics research

2021 Volume 27, Issue 3, Page(s) 241–248

Abstract: Objective: Predictive models for critical events in the intensive care unit (ICU) might help providers anticipate patient deterioration. At the heart of predictive model development lies the ability to accurately label significant events, thereby ... ...

Abstract	Objective: Predictive models for critical events in the intensive care unit (ICU) might help providers anticipate patient deterioration. At the heart of predictive model development lies the ability to accurately label significant events, thereby facilitating the use of machine learning and similar strategies. We conducted this study to establish the validity of an automated system for tagging respiratory and hemodynamic deterioration by comparing automatic tags to tagging by expert reviewers. Methods: This retrospective cohort study included 72,650 unique patient stays collected from Electronic Medical Records of the University of Massachusetts' eICU. An enriched subgroup of stays was manually tagged by expert reviewers. The tags generated by the reviewers were compared to those generated by an automated system. Results: The automated system was able to rapidly and efficiently tag the complete database utilizing available clinical data. The overall agreement rate between the automated system and the clinicians for respiratory and hemodynamic deterioration tags was 89.4% and 87.1%, respectively. The automatic system did not add substantial variability beyond that seen among the reviewers. Conclusions: We demonstrated that a simple rule-based tagging system could provide a rapid and accurate tool for mass tagging of a compound database. These types of tagging systems may replace human reviewers and save considerable resources when trying to create a validated, labeled database used to train artificial intelligence algorithms. The ability to harness the power of artificial intelligence depends on efficient clinical validation of targeted conditions; hence, these systems and the methodology used to validate them are crucial.
Language	English
Publishing date	2021-07-31
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2619923-3
ISSN	2093-369X ; 2093-3681
ISSN (online)	2093-369X
ISSN	2093-3681
DOI	10.4258/hir.2021.27.3.241
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Article ; Online: Applying Transcranial Magnetic Stimulation (TMS) Over the Dorsal Visual Pathway Induces Schizophrenia-like Disruption of Perceptual Closure.

Amiaz, Revital / Vainiger, Dana / Gershon, Ari A / Weiser, Mark / Lavidor, Michal / Javitt, Daniel C

Brain topography

2016 Volume 29, Issue 4, Page(s) 552–560

Abstract: Perceptual closure ability is postulated to depend upon rapid transmission of magnocellular information to prefrontal cortex via the dorsal stream. In contrast, illusory contour processing requires only local interactions within primary and ventral ... ...

Abstract	Perceptual closure ability is postulated to depend upon rapid transmission of magnocellular information to prefrontal cortex via the dorsal stream. In contrast, illusory contour processing requires only local interactions within primary and ventral stream visual regions, such as lateral occipital complex. Schizophrenia is associated with deficits in perceptual closure versus illusory contours processing that is hypothesized to reflect impaired magnocellular/dorsal stream. Perceptual closure and illusory contours performance was evaluated in separate groups of 12 healthy volunteers during no TMS, and during repetitive 10 Hz rTMS stimulation over dorsal stream or vertex (TMS-vertex). Perceptual closure and illusory contours were performed in 11 schizophrenia patients, no TMS was applied in these patients. TMS effects were evaluated with repeated measures ANOVA across treatments. rTMS significantly increased perceptual closure identification thresholds, with significant difference between TMS-dorsal stream and no TMS. TMS-dorsal stream also significantly reduced perceptual closure but not illusory contours accuracy. Schizophrenia patients showed increased perceptual closure identification thresholds relative to controls in the no TMS condition, but similar to controls in the TMS-dorsal stream condition. Conclusions of this study are that magnocellular/dorsal stream input is critical for perceptual closure but not illusory contours performance, supporting both trickledown theories of normal perceptual closure function, and magnocellular/dorsal stream theories of visual dysfunction in schizophrenia.
MeSH term(s)	Adult ; Case-Control Studies ; Female ; Humans ; Male ; Perceptual Closure ; Schizophrenia/physiopathology ; Transcranial Magnetic Stimulation ; Visual Pathways
Language	English
Publishing date	2016-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1078442-1
ISSN	1573-6792 ; 0896-0267
ISSN (online)	1573-6792
ISSN	0896-0267
DOI	10.1007/s10548-016-0487-1
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Article: Transcranial magnetic stimulation: a new tool in the fight against depression.

Grunhaus, Leon / Dannon, Pinhas N / Gershon, Ari A

Dialogues in clinical neuroscience

2011 Volume 4, Issue 1, Page(s) 93–103

Abstract: Since its introduction to the clinical realm in 1985, transcranial magnetic stimulation (TMS) has rapidly developed into a tool for exploring central nervous system function in both health and disease. The antidepressant effects of TMS were initially ... ...

Abstract	Since its introduction to the clinical realm in 1985, transcranial magnetic stimulation (TMS) has rapidly developed into a tool for exploring central nervous system function in both health and disease. The antidepressant effects of TMS were initially observed in 1993. Since then, a solid body of evidence has accumulated suggesting antidepressant effects for both slow TMS (sTMS) and repetitive TMS (rTMS). This review is divided into four parts. First, it addresses the basic concepts governing TMS, and then, second, it discusses the technical parameters involved in administering TMS. Knowledge of these parameters is necessary for understanding how TMS is administered, and how manipulation of the technique impacts on the results obtained. Third, we review the most relevant studies on the antidepressant effects of sTMS and rTMS published to date. Finally, we discuss cortical excitability and how the understanding of this basic neurophysiological function of cortical neurons can be used for monitoring the effects of TMS. In our discussion, we conclude that the time has arrived for TMS to be offered to depressed patients as a treatment.
Language	English
Publishing date	2011-10-28
Publishing country	France
Document type	Journal Article
ZDB-ID	2188781-0
ISSN	1294-8322
ISSN	1294-8322
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Article ; Online: Central nervous system effects of the histamine-3 receptor antagonist CEP-26401, in comparison with modafinil and donepezil, after a single dose in a cross-over study in healthy volunteers.

Baakman, Anne C / Zuiker, Rob / van Gerven, Joop M A / Gross, Nicholas / Yang, Ronghua / Fetell, Michael / Gershon, Ari / Gilgun-Sherki, Yossi / Hellriegel, Edward / Spiegelstein, Ofer

British journal of clinical pharmacology

2019 Volume 85, Issue 5, Page(s) 970–985

Abstract: Aims: In previous studies, the histamine-3 receptor antagonist CEP-26401 had a subtle effect on spatial working memory, with the best effect seen at the lowest dose tested (20 μg), and a dose-dependent disruption of sleep. In the current study, 3 low- ... ...

Abstract	Aims: In previous studies, the histamine-3 receptor antagonist CEP-26401 had a subtle effect on spatial working memory, with the best effect seen at the lowest dose tested (20 μg), and a dose-dependent disruption of sleep. In the current study, 3 low-dose levels of CEP-26401 were compared with modafinil and donepezil. Methods: In this double-blind, placebo- and positive-controlled, randomized, partial 6-way cross-over study, 40 healthy subjects received single doses of placebo, CEP-26401 (5, 25 or 125 μg) or modafinil 200 mg or donepezil 10 mg. Pharmacokinetic and pharmacodynamic measurements were performed predose and at designated time points postdose. Results: The main endpoint between-errors of the spatial working memory-10-boxes task only improved for the 125 μg dose of CEP-26401 with a difference of 2.92 (confidence interval [CI] -1.21 to 7.05), 3.24 (CI -1.57 to 8.04) and 7.45 (CI 2.72 to 12.19) for respectively the 5, 25 and 125 μg dose of CEP-26401, -1.65 (CI -0.572 to 1.96) for modafinil and - 3.55 (CI -7.13 to 0.03) for donepezil. CEP-26401 induced an improvement of adaptive tracking, saccadic peak velocity and reaction time during N-back, but a dose-related inhibition of sleep and slight worsening of several cognitive parameters at the highest dose. CEP-26401 significantly changed several subjective visual analogue scales, which was strongest at 25 μg, causing the same energizing and happy feeling as modafinil, but with a more relaxed undertone. Discussion: Of the doses tested, the 25 μg dose of CEP-26401 had the most optimal balance between favourable subjective effects and sleep inhibition. Whether CEP-26401 can have beneficial effects in clinical practice remains to be studied.
MeSH term(s)	Adolescent ; Adult ; Brain/drug effects ; Brain/physiology ; Cognition/drug effects ; Cognition/physiology ; Cognitive Dysfunction/drug therapy ; Cohort Studies ; Cross-Over Studies ; Donepezil/administration & dosage ; Donepezil/pharmacokinetics ; Dose-Response Relationship, Drug ; Double-Blind Method ; Female ; Healthy Volunteers ; Histamine Antagonists/administration & dosage ; Histamine Antagonists/pharmacokinetics ; Humans ; Male ; Memory/drug effects ; Memory/physiology ; Middle Aged ; Modafinil/administration & dosage ; Modafinil/pharmacokinetics ; Pyridazines/administration & dosage ; Pyridazines/pharmacokinetics ; Pyrrolidines/administration & dosage ; Pyrrolidines/pharmacokinetics ; Reaction Time/drug effects ; Reaction Time/physiology ; Receptors, Histamine H3/metabolism ; Sleep/drug effects ; Sleep/physiology ; Young Adult
Chemical Substances	Histamine Antagonists ; Pyridazines ; Pyrrolidines ; Receptors, Histamine H3 ; Donepezil (8SSC91326P) ; Modafinil (R3UK8X3U3D) ; 6-(4-(3-(2-methylpyrrolidin-1-yl)propoxy)phenyl)-2H-pyridazin-3-one (WH7ISP34KA)
Language	English
Publishing date	2019-03-14
Publishing country	England
Document type	Clinical Trial, Phase I ; Comparative Study ; Journal Article ; Randomized Controlled Trial
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.13885
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Article: Naltrexone augmentation in OCD: a double-blind placebo-controlled cross-over study.

Amiaz, Revital / Fostick, Leah / Gershon, Ari / Zohar, Joseph

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

2008 Volume 18, Issue 6, Page(s) 455–461

Abstract: Current treatments for Obsessive Compulsive Disorder (OCD) rely primarily on serotonergic mechanisms. However, approximately 30% of patients do not respond to serotonin reuptake inhibitors and remain chronically ill. Given the behavioral similarities ... ...

Abstract	Current treatments for Obsessive Compulsive Disorder (OCD) rely primarily on serotonergic mechanisms. However, approximately 30% of patients do not respond to serotonin reuptake inhibitors and remain chronically ill. Given the behavioral similarities between some of the compulsive behaviors in OCD and addiction, we hypothesized that the opioid antagonist naltrexone might attenuate compulsions in OCD as well. The effect of naltrexone augmentation to SRI was compared to placebo in 10 OCD outpatients who had not responded to an adequate dose of SSRI or clomipramine for at least 2 months. Participants underwent 5 weeks of treatment with naltrexone or placebo (and 1 week of tapering) in a randomized, double-blind, cross-over design. Patients were evaluated weekly using the Y-BOCS, CGI, HAM-A, and MADRS scales. A two-way repeated measures MANOVA revealed no significant effect for Y-BOCS. However, while receiving naltrexone, patients had significantly higher scores on CGI, MADRS and HAM-A as compared to placebo. The lack of significant findings on OC symptoms could be due to either ceiling effect or alternatively, due to a non-specific exacerbation on anxiety and depression but not on OC symptoms.
MeSH term(s)	Adolescent ; Adult ; Aged ; Clomipramine/therapeutic use ; Cross-Over Studies ; Double-Blind Method ; Drug Synergism ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Naltrexone/therapeutic use ; Narcotic Antagonists/therapeutic use ; Obsessive-Compulsive Disorder/drug therapy ; Psychiatric Status Rating Scales ; Serotonin Uptake Inhibitors/therapeutic use
Chemical Substances	Narcotic Antagonists ; Serotonin Uptake Inhibitors ; Naltrexone (5S6W795CQM) ; Clomipramine (NUV44L116D)
Language	English
Publishing date	2008-06
Publishing country	Netherlands
Document type	Clinical Trial ; Journal Article ; Randomized Controlled Trial
ZDB-ID	1082947-7
ISSN	1873-7862 ; 0924-977X
ISSN (online)	1873-7862
ISSN	0924-977X
DOI	10.1016/j.euroneuro.2008.01.006
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Article: Dopamine D2-like receptors and the antidepressant response.

Gershon, Ari A / Vishne, Tali / Grunhaus, Leon

Biological psychiatry

2007 Volume 61, Issue 2, Page(s) 145–153

Abstract: Converging lines of evidence suggest a role for the mesolimbic dopamine system in the response to somatic antidepressant therapies. Here, we review evidence suggesting that antidepressant treatments of different types share the effect of increasing the ... ...

Abstract	Converging lines of evidence suggest a role for the mesolimbic dopamine system in the response to somatic antidepressant therapies. Here, we review evidence suggesting that antidepressant treatments of different types share the effect of increasing the sensitivity of dopamine D2-like receptors in the nucleus accumbens, clinical studies suggesting that activation of these receptors has antidepressant efficacy, as well as relevant imaging and genetic data on the role of this system in the antidepressant response. We then attempt to reconcile this data with evidence of a common target of antidepressant drugs in the cyclic adenosine monophosphate (cAMP) response element binding protein-brain-derived neurotrophic factor (CREB-BDNF) pathway in a model that suggests potential directions for future inquiry.
MeSH term(s)	Animals ; Antidepressive Agents/pharmacology ; Brain-Derived Neurotrophic Factor/physiology ; Cyclic AMP Response Element-Binding Protein/physiology ; Depressive Disorder/physiopathology ; Dopamine/physiology ; Humans ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/physiopathology ; Receptors, Dopamine D2/drug effects ; Receptors, Dopamine D2/physiology ; Synaptic Transmission/drug effects ; Synaptic Transmission/physiology
Chemical Substances	Antidepressive Agents ; Brain-Derived Neurotrophic Factor ; Cyclic AMP Response Element-Binding Protein ; Receptors, Dopamine D2 ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2007-01-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2006.05.031
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Article ; Online: A randomized controlled trial of allopurinol vs. placebo added on to antipsychotics in patients with schizophrenia or schizoaffective disorder.

Weiser, Mark / Gershon, Ari A / Rubinstein, Katya / Petcu, Camelia / Ladea, Maria / Sima, Dorina / Podea, Delia / Keefe, Richard S E / Davis, John M

Schizophrenia research

2012 Volume 138, Issue 1, Page(s) 35–38

Abstract: Adenosine agonists produce behavioral effects similar to dopamine antagonists, hence increasing adenosine levels might improve symptoms of schizophrenia. This hypothesis is supported by three single-site studies indicating that allopurinol, which ... ...

Abstract	Adenosine agonists produce behavioral effects similar to dopamine antagonists, hence increasing adenosine levels might improve symptoms of schizophrenia. This hypothesis is supported by three single-site studies indicating that allopurinol, which increases adenosine levels, improved symptoms in patients with schizophrenia. We performed a multi-center, 8-week RCT of allopurinol vs. placebo added to anti-psychotic medications in 248 patients with schizophrenia or schizoaffective disorder. Both groups showed improvement in the PANSS (effect size 1.13) and in clinical and cognitive measures. No difference was observed between groups in primary (t=0.01, p=0.992) or secondary outcome measures. These findings do not support allopurinol as a treatment for schizophrenia.
MeSH term(s)	Adenosine/metabolism ; Adult ; Allopurinol/therapeutic use ; Antipsychotic Agents/therapeutic use ; Drug Therapy, Combination ; Enzyme Inhibitors/therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Psychotic Disorders/drug therapy ; Schizophrenia/drug therapy ; Treatment Outcome ; Xanthine Oxidase/antagonists & inhibitors
Chemical Substances	Antipsychotic Agents ; Enzyme Inhibitors ; Allopurinol (63CZ7GJN5I) ; Xanthine Oxidase (EC 1.17.3.2) ; Adenosine (K72T3FS567)
Language	English
Publishing date	2012-06
Publishing country	Netherlands
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	639422-x
ISSN	1573-2509 ; 0920-9964
ISSN (online)	1573-2509
ISSN	0920-9964
DOI	10.1016/j.schres.2012.02.014
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Article: Transcranial magnetic stimulation in the treatment of depression.

Gershon, Ari A / Dannon, Pinhas N / Grunhaus, Leon

The American journal of psychiatry

2003 Volume 160, Issue 5, Page(s) 835–845

Abstract: Objective: Transcranial magnetic stimulation (TMS) is a noninvasive and easily tolerated method of altering cortical physiology. The authors evaluate evidence from the last decade supporting a possible role for TMS in the treatment of depression and ... ...

Abstract	Objective: Transcranial magnetic stimulation (TMS) is a noninvasive and easily tolerated method of altering cortical physiology. The authors evaluate evidence from the last decade supporting a possible role for TMS in the treatment of depression and explore clinical and technical considerations that might bear on treatment success. Method: The authors review English-language controlled studies of nonconvulsive TMS therapy for depression that appeared in the MEDLINE database through early 2002, as well as one study that was in press in 2002 and was published in 2003. In addition, the authors discuss studies that have examined technical, methodological, and clinical treatment parameters of TMS. Results: Most data support an antidepressant effect of high-frequency repetitive TMS administered to the left prefrontal cortex. The absence of psychosis, younger age, and certain brain physiologic markers might predict treatment success. Technical parameters possibly affecting treatment success include intensity and duration of treatment, but these suggestions require systematic testing. Conclusions: TMS shows promise as a novel antidepressant treatment. Systematic and large-scale studies are needed to identify patient populations most likely to benefit and treatment parameters most likely to produce success. In addition to its potential clinical role, TMS promises to provide insights into the pathophysiology of depression through research designs in which the ability of TMS to alter brain activity is coupled with functional neuroimaging.
MeSH term(s)	Aged ; Antidepressive Agents/therapeutic use ; Cerebral Cortex/physiology ; Cerebral Cortex/physiopathology ; Combined Modality Therapy ; Controlled Clinical Trials as Topic ; Depressive Disorder/physiopathology ; Depressive Disorder/therapy ; Electroconvulsive Therapy ; Electromagnetic Phenomena/instrumentation ; Electromagnetic Phenomena/methods ; Humans ; Middle Aged ; Psychiatric Status Rating Scales ; Transcranial Magnetic Stimulation/instrumentation ; Transcranial Magnetic Stimulation/therapeutic use ; Treatment Outcome
Chemical Substances	Antidepressive Agents
Language	English
Publishing date	2003-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	280045-7
ISSN	1535-7228 ; 0002-953X
ISSN (online)	1535-7228
ISSN	0002-953X
DOI	10.1176/appi.ajp.160.5.835
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