Weekly Breaking Research Updates, June 22, 2015

Weekly Breaking Research Updates, June 22, 2015

Weekly Breaking Research Updates

Scientific breakthroughs happen every day!  In an effort to help our patients stay up to speed on the most cutting edge treatment options available for them, our scientists monitor current research and publish weekly research updates.  The title of each article below is a link to the full study report.  If you’d like to make an appointment with Dr. Hanna to discuss your treatment options, please contact us.

 

Ketamine

 

Ketamine and Phencyclidine: the good, the bad and the unexpected

D Lodge, MS Mercier – British Journal of Pharmacology, 2015

ABSTRACT: The history of ketamine and phencyclidine from their development as potential

clinical anaesthetics, through drugs of abuse and animal models of schizophrenia to

potential rapidly acting antidepressants is reviewed. The discovery in 1983 of the NMDA

 

Intra‐and postoperative low‐dose ketamine for adolescent idiopathic scoliosis surgery: a randomized controlled trial

R Minoshima, S Kosugi, D Nishimura, N Ihara, H Seki… – Acta Anaesthesiologica …, 2015

Background In this randomized controlled trial, we examined whether intra-and

postoperative infusion of low-dose ketamine decreased postoperative morphine

requirement and morphine-related adverse effects as nausea and vomiting after scoliosis

 

Period Prevalence of Ketamine-Propofol Admixture “Ketofol” in the Operating Room among Anesthesia Providers at an Academic Medical Center

AN Olson, WR Rao, ME Marienau, NJ Smischney – Medical Science Monitor, 2015

BACKGROUND: The primary aim of this study was to determine the period prevalence of the

single-syringe ketamine-propofol admixture used for sedation and induction among

anesthesia providers during a 5-year period before and after educational sessions

 

Electrochemiluminescence immunosensor for ketamine detection based on polyamidoamine-coated carbon dot film

Q Li, W Tang, Y Wang, J Di, J Yang, Y Wu – Journal of Solid State Electrochemistry, 2015

Abstract In this work, we reported the synthesis of water-soluble carbon dots (CDs) by a one-

step hydrothermal synthetic route using polyamidoamine (PAMAM) as platform and

passivant, where the formation of CDs capped with PAMAM and the surface passivation

 

Letter to the editor: When what you see might not be what you get: prudent considerations of anesthetics for murine echocardiography

J Wu, J You, S Wang, Y Ye, X Wang, J Jia, Y Zou – American Journal of Physiology- …, 2015

In their well- designed experiments, the authors compared four popular an- esthetic regimens

(ketamine-xylazine, ketamine alone, avertin, and isoflurane) used in mice during

echocardiographic mea- surement, with conscious state as a reference.

 

Ketamine promotes inflammation through increasing TLR4 expression in RAW264. 7 cells

C Meng, Z Liu, G Liu, L Fu, M Zhang, Z Zhang, H Xia… – Journal of Huazhong …, 2015

Summery Ketamine (KTM), a N-methyl-D-aspartate (NMDA) receptor antagonist, was found

to has an anti-inflammatory effect, but some patients suffered from exacerbated pro-

inflammatory reactions after anesthesia with KTM. The present study was aimed to

 

The effect of NMDA receptor antagonists and antidepressants on resting state in major depressive disorder

A Dutta – 2015

fMRI ; major depressive disorder ; resting state ; antidepressant ; lanicemine ; ketamine ; citalopram

; anterior cingulate cortex ; NMDA ; glutamate. Ketamine and other NMDA antagonists have

improved MDD symptoms within 24 hours though the effects are short lasting.

 

Assessing Measures of Suicidal Ideation in Clinical Trials with a Rapid-Acting Antidepressant

ED Ballard, DA Luckenbaugh, EM Richards, TL Walls… – Journal of Psychiatric …, 2015

Received 22 April 2015, Revised 21 May 2015, Accepted 5 June 2015, Available online 16 June

2015. Highlights. • Clinical trials of ketamine and suicide will require appropriate measurement. •

We compared several suicide assessment measures in ketamine clinical trials. •

 

d-Cycloserine

AR Durrant, U Heresco-Levy – Encyclopedia of Psychopharmacology, 2015

of this concept became evident during the last decade when robust antidepressant effects

emerging within 2–4 h and lasting up to more than 2 weeks were obtained and replicated fol-

lowing intravenous administration of single sub-anesthetic doses of ketamine (Krystal et al.

 

Depression: Response and Remission

SD Østergaard, GI Papakostas, M Fava – Encyclopedia of Psychopharmacology, 2015

of this concept became evident during the last decade when robust antidepressant effects

emerging within 2–4 h and lasting up to more than 2 weeks were obtained and replicated fol-

lowing intravenous administration of single sub-anesthetic doses of ketamine (Krystal et al.

 

Is pre-emptive administration of ketamine a significant adjunction to intravenous morphine analgesia for controlling postoperative pain? A randomized, double-blind, …

A Fiorelli, A Mazzella, B Passavanti, P Sansone… – … and Thoracic Surgery, 2015

OBJECTIVES To evaluate if the pre-emptive administration of ketamine would potentiate the

effect of intravenous morphine analgesia in the management of post-thoracotomy pain.

METHODS This was a unicentre, double-blind, placebo-controlled, parallel-group,

 

Kappa-Opioid Agonists

E Opioid – 2015

It is considered a precancerous condition. Ketamine Synonyms Ketalar; Ketaset Definition

Ketamine is an FDA-approved medication for induction and maintenance of anesthesia

in adults. It is a phencyclidine derivative first synthetized in 1962.

 

Investigation of the effects of stress on some liver enzymes (AST, ALT, ALP) in rats.

YG Gencer, A Çınar, B Comba – Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 2015

was applied intraperitoneally (ip) to the experimental group. After 3 h, blood samples

were collected from both groups under ketamine anaesthesia, using appropriate

techniques. The control group serum AST, ALT, ALP values

 

Back to the Future: Are Tumor-Targeting Bacteria the Next-Generation Cancer Therapy?

RM Hoffman – Gene Therapy of Solid Cancers, 2015

7. Anesthetic reagents (ketamine, xylazine, acepromazine maleate). 8. Kanamycin. 9. Nair. 10.

1. Four-week-old female mice were anesthetized by a ketamine mixture (10 μl ketamine HCL,

7.6 μl xylazine, 2.4 μl acepromazine maleate, and 10 μl H 2 O) via sc injection.

 

[PDF] The Protective Effect of Melatonin vs. Vitamin E in the Ischemic/Reperfused Skeletal Muscle in the Adult Male Rat Model

EA Mohamed – J Cytol Histol S, 2015

All surgical procedures were performed under anesthesia with IP injection of

Ketamine hydrochloride (Ketame, Egyptian Int. Co. After 2 hours of reperfusion, the

rats were sacrificed by Ketamine hydrochloride (100 mg/kg) [10].

 

[PDF] CORM2 protects from myocardial ischemia reperfusion injury via modulation of the inflammatory response and apoptosis

NR Hadi, FG Al-Amran, KA Muhsin, A Taher – Journal of Advanced Pharmacy …, 2015

2% vials (RompunTM, Bayer AG, Leverkusen, Germany), ketamine (Hikma, Jordan), ethanol

(Fluka, Switzerland) and normal saline (KSA). Rat (IL-1β), (IL- Surgical LAD ligation The rats were

anesthetized by intraperitoneal injection with a mixture of ketamine and xylazine in a

 

[HTML] Long-term correlation of the electrocorticogram as a bioindicator of brain exposure to ionizing radiation

LAA Aguiar, IMS Silva, TS Fernandes, RA Nogueira – Brazilian Journal of Medical and …, 2015

The irradiation was carried out with the animals anesthetized with 10 mg/kg xylazine and 75

mg/kg ketamine administered intraperitoneally. To record the ECoG, animals were anesthetized

with 10 mg/kg xylazine and 75 mg/kg ketamine administered intraperitoneally.

 

[HTML] The Anti-Tumor Effects of Adipose Tissue Mesenchymal Stem Cell Transduced with HSV-Tk Gene on U-87-Driven Brain Tumor

SM de Melo, S Bittencourt, EG Ferrazoli, CS da Silva… – PLOS ONE, 2015

The animals were anesthetized via the ip injection of a ketamine (100 mg/kg) and xylazine

(10 mg/kg) solution (Syntec, 1356009 and 1720407) and fastened to a stereotaxic

instrument (David Kopf) equipped with a mouse adapter (Enlaup).

 

[HTML] Intrarectal Lidocaine-Diltiazem-Meperidine Gel for Transrectal Ultrasound Guided Prostate Biopsy

F Imani, Y Moghaddam, RS Moharari, F Etezadi… – Anesthesiology and Pain …, 2015

4, 6) or bupivacaine as a single agent (7). These latter studies have suggested that rectal

administration of lidocaine gel is a safe, simple modality, without any discomfort for patients (8).

Not only local anesthetic agents but also intravenous anesthetic drugs (ketamine) (9) or

 

[PDF] Alcohol Withdrawal Syndrome: Improving Outcomes Through Early Identification And Aggressive Treatment Strategies

AF Pizon – 2015

Page 1. June 2015 Volume 17, Number 6 Authors Joseph H. Yanta, MD Medical

Toxicology Fellow, Division of Medical Toxicology, Dept. of Emer- gency Medicine,

University of Pittsburgh Medical Center, Pittsburgh, PA Greg

 

Radiofrequency Ablation (RFA)

 

Use of Contact Force Sensing Technology During Radiofrequency Ablation Reduces Recurrence of Atrial Fibrillation: A Systematic Review and Meta-Analysis

MR Afzal, J Chatta, A Samanta, S Waheed… – Heart Rhythm, 2015

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Comparison of Surgical Resection and Radiofrequency Ablation for Hepatocellular Carcinoma: Take Care Not to Neglect Radiofrequency Technic and Device.

A Hocquelet, M Montaudon, P Balageas, N Frulio… – Annals of Surgery, 2015

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your privacy and will not share your personal information without your express consent. For more

information, please refer to our Privacy Policy. Skip Navigation Links Home >

 

Effect of different ablation settings on acute complications using the novel irrigated multipolar radiofrequency ablation catheter (nMARQ)

T Deneke, P Müller, P Halbfaß, A Szöllösi, M Roos… – Journal of Cardiovascular …, 2015

Background: Single-shot ablation devices for pulmonary vein isolation (PVI) in patients with

symptomatic atrial fibrillation (AF) have been increasingly used in clinical practice. Objective:

A novel mapping-system integrated irrigated multipolar circular ablation catheter (nMARQ)

 

Long-Term Effects of Ganglionated Plexi Ablation on Electrophysiological Characteristics and Neuron Remodeling in Target Atrial Tissues in a Canine Model

X Wang, M Zhang, Y Zhang, X Xie, W Wang, Z Li… – Circulation: Arrhythmia and …, 2015

Long-Term Effects of Ganglionated Plexi Ablation on Electrophysiological Characteristics and

Neuron Remodeling in Target Atrial Tissues in a Canine Model. Atrial electrophysiological

characteristics were examined before ablation, immediately and continuously after ablation.

 

… to Letter From Bisbal et al Regarding,“Repeat Left Atrial Catheter Ablation: Cardiac Magnetic Resonance Prediction of Endocardial Voltage and Gaps in Ablation

JL Harrison, C Sohns, NW Linton, R Karim, SE Williams… – Circulation: Arrhythmia and …, 2015

Tolosana JM,; Arbelo E,; de Caralt TM,; Perea RJ,; Brugada J,; Mont L. CMR-guided

approach to localize and ablate gaps in repeat AF ablation procedure. JACC Cardiovasc

Imaging . 2014;7:653–663. doi: 10.1016/j.jcmg.2014.01.014.

 

Pulmonary vein stenosis after pulmonary vein isolation using duty-cycled unipolar/bipolar radiofrequency ablation guided by intracardiac echocardiography

S Asbach, F Schluermann, L Trolese, M Langer… – Journal of Interventional …, 2015

Purpose Concerning rates of pulmonary vein (PV) stenosis were reported following PV

isolation (PVI) with a circular pulmonary vein ablation catheter (PVAC). As this may depend

on intraprocedural imaging, we evaluated the incidence of PV stenosis in patients

 

Atrioventricular Block During Slow Pathway Ablation Entirely Preventable?

H Chen, M Shehata, W Ma, J Xu, J Cao, E Cingolani… – Circulation: Arrhythmia and …, 2015

In a small percentage of cases of AVNRT, it may be necessary to ablate within the CS

with larger atrial potentials, however, ablation at the roof of the proximal CS carries

a high risk of AV nodal block during radiofrequency application.

 

Is There Still a Role for CFAE Ablation in Addition to Pulmonary Vein Isolation in Patients with Paroxysmal and Persistent Atrial Fibrillation? A Meta-Analysis of 1,415 …

R Providência, PD Lambiase, N Srinivasan, GG Babu… – Circulation: Arrhythmia and …, 2015

Is There Still a Role for CFAE Ablation in Addition to Pulmonary Vein Isolation in Patients with

Paroxysmal and Persistent Atrial Fibrillation? We aimed to assess the impact of CFAE ablation

in addition to pulmonary vein isolation (PVI) in patients undergoing ablation for AF.

 

Real-Time Contact Force Measurement A Key Parameter for Controlling Lesion Creation With Radiofrequency Energy

DC Shah, M Namdar – Circulation: Arrhythmia and Electrophysiology, 2015

Low CF values are also advisable in the vicinity of already ablated sites, where the for the

acquisition of reliable mapping information and achievement of stable ablation lesions 183 gs)

as area under curve (red hatched zone) during short duration of radiofrequency (RF) energy

 

Atrioventricular Nodal Block With Atrioventricular Nodal Reentrant Tachycardia Ablation

SJ Asirvatham, WG Stevenson – Circulation: Arrhythmia and Electrophysiology, 2015

a relatively slow stable, junctional rhythm with consistent stable retrograde atrial conduction during

radiofrequency application. of energy delivery, junctional rhythm may not be seen despite adequate

slow pathway ablation, and the operator may be inclined to ablate at more

 

[HTML] Near-infrared spectroscopy integrated catheter for characterization of myocardial tissues: preliminary demonstrations to radiofrequency ablation therapy for atrial …

RP Singh-Moon, CC Marboe, CP Hendon – Biomedical Optics Express, 2015

Abstract Effects of radiofrequency ablation (RFA) treatment of atrial fibrillation can be limited

by the ability to characterize the tissue in contact. Parameters obtained by conventional

catheters, such as impedance and temperature can be insufficient in providing

 

A Phase 2, Open-Label, Randomized Study of Pexa-Vec (JX-594) Administered by Intratumoral Injection in Patients with Unresectable Primary Hepatocellular …

CJ Breitbach, A Moon, J Burke, TH Hwang, DH Kirn – Gene Therapy of Solid Cancers, 2015

Download Protocol (725 KB). Abstract. Primary liver cancer (hepatocellular carcinoma; HCC)

in patients not eligible for surgery or transplant is currently treated by locoregional therapeutic

approaches, including trans-arterial chemoembolization and radiofrequency ablation.

 

[PDF] Feasibility and efficacy of helical tomotherapy in cirrhotic patients with unresectable hepatocellular carcinoma

CM Huang, MY Huang, JY Tang, SC Chen, LY Wang… – World Journal of Surgical …, 2015

Several other treatment modalities for patients with unresectable HCC, including percutaneous

ethanol injection (PEI), radiofrequency ablation (RFA), and transcatheter arterial

chemoembolization (TACE), seem to be more effective in smaller tumors and are contraindicated

 

The Wolf-Parkinson-White ECG Pattern-Assessing the Mortality Risk

E Posan – Journal of Insurance Medicine, 2015

32. MANAGEMENT. Radiofrequency Ablation Therapy With pacing maneuvers, the accessory

pathway properties are defined, potential tachycardias are induced, accurate mapping (localization)

of the accessory pathway is achieved and radiofrequency ablation is employed.

 

[HTML] Congenital (in growing) osteoma skull in 20-day-old neonate

PG Devi, TS Venkatachalam, YV Sharma, MP Kumar – CHRISMED Journal of …, 2015

6. 7. Virayavanich W, Singh R, O’Donnell RJ, Horvai AE, Goldsby RE, Link TM. Osteoid osteoma

of the femur in a 7-month-old infant treated with radiofrequency ablation. Skeletal Radiol

2010;39:1145-9. Back to cited text no. 7. 8. McHugh JB, Mukherji SK, Lucas DR.

 

[PDF] Simulating and Optimizing the Response of a Sine Wave Finite state Machine with Timestamp Simulation Using Simulink

M Kalpna, MA Varma – International Journal of Research, 2015

[5.] Dagmara M. Dołęga, Jerzy Barglik, (2012) “Computer modeling and simulation of

radiofrequency thermal ablation“, COMPEL – The international journal for computation and

mathematics in electrical and electronic engineering, Vol. 31 Iss: 4, pp.1087 – 1095

 

[PDF] Coexistence of permanent junctional reciprocating tachycardia with rheumatic valvular disease; a case sucessfully treated with radiofrequency ablation

M Aydın, A Yıldız, M Yüksel, Y İslamoğlu

Abstract A seventeen years old female had presented with palpitation. On the

electrocardiography (ECG), long RP, narrow QRS tachycardia, inverted P waves in leads

D2, D3 and aVF were noticed. On transthoracic echocardiography, rheumatic mitral

 

[PDF] Macrophage Inflammatory Protein Derivative ECI301

T Radiotherapy

inhibition by ECI301 was not attributable to radiation alone but also shown to other factors such

as the heat generated from high-frequency alter- nating current, namely radiofrequency ablation

(RFA; ref. 5B), significant differences were ablated by the anti- HMGB1 antibody.

 

[PDF] Regenerative Injection Treatment in the Spine: Review and Case Series with Platelet Rich Plasma. J Stem Cells Res

D Aufiero, H Vincent, S Sampson, M Bodor – Rev & Rep, 2015

back or neck pain refractory to physical therapy, trigger point injections, medial branch blocks,

or radio- frequency ablation. There is scarce evidence supporting less commonly performed

non-surgical treatments for lumbar radiculopathy including pulsed radiofrequency to the

 

[HTML] Modern medicine-morcellation

SC Olmstead

abandoned as a surgical procedure? What about noninvasive treatment options that

leave the presumed fibroid inside the body, such as uterine artery embolization,

MRI-guided focused ultrasound, and radiofrequency ablation?

 

Chronic Regional Pain Syndrome (CRPS/RSD)

 

What outcome measures are commonly used for Complex Regional Pain Syndrome clinical trials? A systematic review of the literature

S Grieve, L Jones, N Walsh, C McCabe – European Journal of Pain, 2015

Background and objective. Complex Regional Pain Syndrome (CRPS) is a chronic pain condition,

often triggered by trauma to a limb and characterized by sensory, motor, autonomic and trophic

changes within the affected limb. 2.4 Classification of CRPS clinical trials.

 

[PDF] MIRROR THERAPY: A REVIEW OF EVIDENCES

A Najiha, J Alagesan, VJ Rathod, P Paranthaman – Int J Physiother Res, 2015

Three particular conditions that have been studied the most are stroke, CRPS and phantom

limb pain. MT was used in conditions like stroke, cerebral palsy (CP), complex regional pain

syndrome (CRPS), phantom limb pain (PL) and fracture rehabilitation.

 

Physical Therapy Treatment for Patients Diagnosed with Complex Regional Pain Syndrome

J Connole – 2015

Abstract. This case study and evidence-based research analyzes the effects of physical

therapy interventions on a patient diagnosed with type 1 complex regional pain

syndrome (CRPS) to determine the most beneficial treatments.

 

Hybrid short-term freeway speed prediction methods based on periodic analysis

Y Zou, X Hua, Y Zhang, Y Wang – Canadian Journal of Civil Engineering, 2015

Page 1. Hybrid short-term freeway speed prediction methods based on periodic

analysis By Yajie Zou, Ph.D. Research associate 133B More Hall, Box 352700

Department of Civil and Environmental Engineering University of

 

[HTML] Japanese MD Develops Nutritional Protocols for Gardasil/Cervarix HPV Vaccine Injury

LC Botha – 2015

subacute sclerosing panencephalitis; CRPS: Complex regional pain syndrome; POTS:

Postural orthostatic tachycardia syndrome; Anti-phospholipid antibody syndrome;

SLE: systemic lupus erythematosus; Rheumatoid arthritis;

 

The social behavior of children adopted from Russian Federation: a controlled study

C Caprin, L Ballarin, L Benedan, A Castelli – Psicologia clinica dello sviluppo, 2015

Nonostante nella ricerca si sia utilizzata la forma estesa per genitori dello strumento

(CRPS-R:L; Conners, validazione Italiana a cura di Nobile, Alberti e Zuddas, 2007), composta

da 80 item (valori di a com- presi fra 0.57 e 0.91 per i maschi e 0.58 e 0.89 per le femmine), in

 

A Review of the Use of Stellate Ganglion Block in the Treatment of PTSD

E Lipov, EC Ritchie – Current Psychiatry Reports, 2015

14. Lipov EG, Joshi JR, et al. A unifying theory linking the prolonged efficacy of the stellate

ganglion block for the treatment of chronic regional pain syndrome (CRPS), hot flashes,

and posttraumatic stress disorder (PTSD). Med Hypotheses.

 

Addiction Recovery in Services and Policy: An International Overview

A Laudet, D Best – Textbook of Addiction Treatment: International …, 2015

model is growing in popularity nationwide: in the past decade, growing concerns about substance

use on campus and federal agencies’ focus on building a community-based continuum of care

system for youths have fueled a fivefold increase in the number of CRPs, from four

 

[HTML] Related Products

R Frank

43. Canalith Repositioning Procedures. The recommended treatment for BPPV is a canalith

repositioning procedure (CRP). There are several CRPs described in the literature; the most

studied and used in the United States was first described by Epley in 1992.

 

Central habituation and distraction alter C‐fibre‐mediated laser‐evoked potential amplitudes

P Hüllemann, YQ Shao, G Manthey, A Binder, R Baron – European Journal of Pain, 2015

Skip to Main Content. Wiley Online Library. Log in / Register. Log In E-Mail

Address Password Forgotten Password? Remember Me.

 

Nuclear Medicine Imaging of Sport Injuries of the Wrist, Hand and Fingers

M Sathekge, FE Suleman, MD Velleman, R Clauss – Nuclear Medicine and …, 2015

Abductor pollicis longus. CRPS: Chronic regional pain syndrome. 1997 ). 24.7 Complex Regional

Pain Syndrome (Reflex Sympathetic Dystrophy, Sudeck’s Dystrophy). Complex regional pain

syndrome (CRPS) is one of the most challenging chronic pain conditions of the limbs.

 

The Child with a Painful Limp

J Robb – Paediatric Orthopaedic Diagnosis, 2015

There may be symptoms of psychological distress and further specialist evaluation may

reveal an underlying cause. Complex Regional Pain Syndrome (CRPS). Children with

CRPS type 1 affecting the lower limb often limp (Wilder et al. 1992 ).

 

Complex regional pain syndrome type I. An analysis of 7 cases in children

VP Stalla, CM Olaso, VK Almada, GG Rabelino – Neurología (English Edition), 2015

Complex regional pain syndrome (CRPS) is characterised by the presence of pain accompanied

by sensory, autonomic and motor symptoms, usually preceded by a lesio.

 

Vitamin C, Extremity Trauma and Surgery

N Shibuya, MR Agarwal, DC Jupiter – 2015

987 Abstract Complex regional pain syndrome (CRPS) is a devastating condition often seen

after extrem- ity injury and surgery. Efficacy and safety of vitamin C used to prevent CRPS are

discussed. List of Abbreviations CRPS Complex regional pain syndrome Introduction

 

Psychological Factors as Outcome Predictors for Spinal Cord Stimulation

T Bendinger, N Plunkett, D Poole, D Turnbull – Neuromodulation: Technology at the …, 2015

SCS trials were offered for the following indications: failed back surgery syndrome (FBSS),

refractory radiculopathy or peripheral neuropathy, complex regional pain syndrome (CRPS),

and refractory angina (at the beginning of observed period—since 2008, this indication is not

 

[PDF] The Role of Transitional Justice and Access to Justice in Conflict Resolution and Democratic Advancement

MF Moscati – 2015

year mandate. The Community Reconciliation Processes (CRPs) of Timor-Leste were created

with the specific aim of dealing with disputes between perpetrators into their communities. The

possibility of recourse to CRPs was established by the United Nations Transitional

 

Complex Regional Pain Syndrome in Children: a Multidisciplinary Approach and Invasive Techniques for the Management of Nonresponders

MJ Rodriguez‐Lopez, M Fernandez‐Baena, A Barroso… – Pain Practice, 2015

Complex regional pain syndrome (CRPS) is multifactorial condition with complex

pathogenesis characterized by spontaneous or stimulus-induced pain that is

disproportionate to the inciting event. It is also commonly accompanied

 

Analgesic response to intravenous ketamine is linked to a circulating microRNA signature in female complex regional pain syndrome patients

SR Douglas, BB Shenoda, RA Qureshi, A Sacan… – The Journal of Pain, 2015

Although ketamine is beneficial in treating complex regional pain syndrome (CRPS), a subset

of patients respond poorly to therapy. We investigated treatment-ind. Highlights. • We studied

ketamine treatment induced miRNA alterations in blood from CRPS patients. •

 

Peptide signalling during the pollen tube journey and double fertilization

LJ Qu, L Li, Z Lan, T Dresselhaus – Journal of Experimental Botany, 2015

In general, plant peptides can be categorized into two classes: secreted peptides and

non-secreted peptides. Secreted peptides can be further divided into two major classes:

cysteine-rich peptides (CRPs) and non-CRPs (NCRPs). CRPs are significantly larger peptides.

 

[HTML] Overexpression of the Arabidopsis thaliana signalling peptide TAXIMIN1 affects lateral organ development

J Colling, T Tohge, R De Clercq, G Brunoud, T Vernoux… – Journal of Experimental …, 2015

Two distinct classes of secreted peptides can be distinguished in plants: small post-translationally

modified peptides such as the CLAVATA3/ENDOSPERM SURROUNDING REGION (CLE) family,

and cysteine-rich peptides (CRPs), exemplified by the EPIDERMAL

 

METHODS OF MODULATING DRUG PLASMA LEVELS USING ERYTHROHYDROXYBUPROPION

H Tabuteau – US Patent 20,150,157,582, 2015

In some embodiments, a combination of dextromethorphan and an antidepressant, such as

bupropion, may be administered to relieve complex regional pain syndrome, such as complex

regional pain syndrome type I (CRPS-I), complex regional pain syndrome type 11 (CRPS-II

 

METHODS FOR THE SAFE ADMINISTRATION OF IMIDAZOLE OR IMIDAZOLIUM COMPOUNDS

H Tabuteau – US Patent 20,150,157,564, 2015

embodiments, an osteoclast inhibitor, such as a nitrogen-containing bisphosphonate, eg

zoledronic acid, ibandronic acid or minodronic acid, may be administered to relieve complex

regional pain syndrome, such as complex regional pain syndrome type I (CRPS-I), complex

 

Fibromyalgia

 

The Use of Polysymptomatic Distress Categories in the Evaluation of Fibromyalgia (FM) and FM Severity

F Wolfe, BT Walitt, JJ Rasker, RS Katz, W Häuser – The Journal of Rheumatology, 2015

Objective The polysymptomatic distress (PSD) scale is derived from variables used in the

2010 American College of Rheumatology (ACR) fibromyalgia (FM) criteria modified for

survey and clinical research. The scale is useful in measuring the effect of PSD over the

 

Association of different levels of depressive symptoms with symptomatology, overall disease severity, and quality of life in women with fibromyalgia

A Soriano-Maldonado, K Amris, FB Ortega… – Quality of Life Research, 2015

Purpose This study examined the associations of different levels of depression with pain,

sleep quality, fatigue, functional exercise capacity, overall fibromyalgia (FM) severity, and

health-related quality of life (HRQoL) in women with FM. Methods A total of 451 women

 

Fibromyalgia: Clinical Guidelines and Treatments

E Lawson, M Wallace – 2015

 

Major Classes of Medication for Treatment of Fibromyalgia

AM Kelly, K Mauer – Fibromyalgia: Clinical Guidelines and Treatments, 2015

 

Implications of proposed fibromyalgia criteria across other functional pain syndromes

N Egloff, R von Känel, V Müller, UT Egle… – Scandinavian Journal of …, 2015

Objectives: In 2010, the American College of Rheumatology (ACR) proposed new criteria for

the diagnosis of fibromyalgia (FM) in the context of objections to components of the criteria of

1990. The new criteria consider the Widespread Pain Index (WPI) and the Symptom

 

Omar I. Halawa and David A. Edwards

DA Edwards – Fibromyalgia: Clinical Guidelines and Treatments, 2015

 

Psychophysiological Methods

RH McAllister-Williams – Encyclopedia of Psychopharmacology, 2015

potential. Tramadol reduces pain substantially in osteoarthritis and fibromyalgia

(Bennett et al. 2003). Methadone below). There is evidence of a mild degree of benefit

in low back pain, fibromyalgia, and headaches. Anticonvulsant

 

PTSD and Fibromyalgia Syndrome: Focus on Prevalence, Mechanisms, and Impact

W Häusera, J Ablinb, B Walittc – 2015

Abstract The association between fibromyalgia syndrome (FMS) and posttraumatic stress

disorder (PTSD) is of growing interest in psychosocial research. The mechanisms by which

both disorders are interconnected are not well understood. The article presents an

 

Conditioned Pain Modulation: Neurophysiological, Cognitive, And Pharmacological Aspects

RR Nir, D Yarnitsky – Topics in Pain Management, 2015

The relevance of modulatory pain mechanisms in the clinical arena is represented through

cumulative research reporting impaired pain inhibition associated with pain disorders, particularly

fibromyalgia, irritable bowel syndrome, migraine, tension-type headache

 

Ryan D. McConn and Magdalena Anitescu

RD McConn – Fibromyalgia: Clinical Guidelines and Treatments, 2015

 

[HTML] Another dimension of pain

TH Khan – Anaesth Pain & Intensive Care, 2015

Pain Manag Nurs. 2013 Dec;14(4):368-78. [PubMed] doi: 10.1016/j.pmn.2011.08.001. Menzies

V, Taylor AG, Bourguignon C. Effects of guided imagery on outcomes of pain, functional status,

and self-efficacy in persons diagnosed with fibromyalgia. J Altern Complement Med.

 

[HTML] Pattern of irritable bowel syndrome and its impact on quality of life: A tertiary hospital based study from Kolkata on newly diagnosed patients of irritable bowel …

U Sinharoy, K Sinharoy, P Mukhopadhyay… – CHRISMED Journal of …, 2015

[6],[7],[8],[9] IBS can coexist with other functional disorders, most notably fibromyalgia, chronic

fatigue syndrome 10. 11. Aaron LA, Burke MM, Buchwald D. Overlapping conditions among

patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder.

 

[PDF] Disability Status, Disability Type, and Training as Predictors of Job Placement

J Stahl – 2015

Deafness Hearing, Communicating Deafness Neurological Memory, Speaking TBI, Multiple

Sclerosis, Fibromyalgia Developmental Reading, Writing, Speaking Autism, Williams Syndrome

Mental Neurological Memory, Speaking TBI, Multiple Sclerosis, Fibromyalgia

 

[HTML] Pilates for Fibromyalgia

DPT Tom Lavosky, C MDT

By Gabrielle Shirer As originally seen in the Fall 2006 edition of the Pilates Coreterly

According to the National Fibromyalgia Association, Fibromyalgia Syndrome (FMS) is an

increasingly recognized chronic pain illness characterized by widespread

 

New study by guidelines author dismisses risk of chronic Lyme disease

D Cameron

In addition, these patients were not more prone to developing fibromyalgia and/or chronic fatigue,

according to two additional papers by Dr. Wormser. [1]. And previous studies report there’s a

high risk of developing fibromyalgia after having Lyme disease.

 

[HTML] Evolution of Skin Temperature after the Application of Compressive Forces on Tendon, Muscle and Myofascial Trigger Point

MF Magalhães, AV Dibai-Filho, EC de Oliveira Guirro… – PLOS ONE, 2015

of musculoskeletal, tendon or nervous injuries in the upper limb, history of fracture in the upper

limb, use of painkillers, anti-inflammatory drugs or muscle relaxants during the previous week,

presence of systemic or neuromuscular diseases, and medical diagnosis of fibromyalgia

 

[HTML] Rejuvenate With Stem Cells

R Schilling – 2015

literature. This combination (laser activated, intravenous mesenchymal injection) has

the potential for being useful for a multitude of chronic illnesses like fibromyalgia,

MS, generalized arthritis, just to mention a few. Mesenchymal

 

[PDF] Regenerative Injection Treatment in the Spine: Review and Case Series with Platelet Rich Plasma. J Stem Cells Res

D Aufiero, H Vincent, S Sampson, M Bodor – Rev & Rep, 2015

Positive results for Prolotherapy have been published for a variety of conditions including lateral

epicondylosis [21], osteoarthritis [22], sacroiliac joint pain [23], chondromalacia patellae [24],

fibromyalgia [25], chronic groin pain [26] and Osgood-Schlatter disease [27].

 

[PDF] APPROVAL SHEET

M Holman – 2015

Page 14. Effect of US and Graston on Muscle Contraction 11 plantar fasciitis,

patellofemoral disorders, fibromyalgia, scar tissue, and trigger finger. 13 The Graston

Technique allows for controlled application of friction massage to the

 

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N Patient, C Forms

There are many symptoms that can lead the person with fibromyalgia syndrome (FMS)

and/or chronic myofascial pain (CMP) to your office. Research indicates that fibromyalgia

may increase the risk of cardiovascular disease (Curtis, O’Keefe Jr 2002).

Treating Chronic Pain With Ketamine

Treating Chronic Pain With Ketamine

Treating Chronic Pain With Ketamine

treatment

By Christine Lin, Epoch Times

NEW YORK—As human beings, we instinctively avoid pain—the sting of nettles, the burn of a hotplate, the pinching of door hinges. Pain is useful because it communicates immediate danger and helps us keep out of it. However, some pain is chronic, as neuropathic pain often is.Neuropathic pain derives from the central nervous system or peripheral nervous system. It is pain that comes from the nerves, as opposed to common muscular aches and arthritic pain. Sometimes it is triggered by traumatic accidents.

In support forums, patients suffering from neuropathic pain describe their symptoms as “burning all over,” “shooting pains in the arms and legs,” “agony,” and “unbearable.” Many of them recount their experiences in seeking relief “frustrating,” that they’ve “tried everything,” or that “not one doctor can give me an answer.”

Neuropathic pain, as a broad category of conditions that include neuralgia, phantom limb syndrome, complex regional pain syndrome (CRPS), and central pain syndrome, is a little-understood realm in medicine. We don’t always know its causes. And current treatment methods are mediocre at best.

Even its occurrence rate among the general population is hard to discern.

In 2008, a study of neuropathic pain incidences in the Dutch population found it has an annual incidence of almost 1 percent of the general population and affects women and middle-aged persons more often.

A 2005 survey of three U.K. cities puts the rate at 8 percent, while a 2006 one conducted in France came up with 5 percent.

Chronic pain affects more than day-to-day functioning. A study last year published in the Journal of Neuroscience found that people with chronic back pain or CRPS have smaller hippocampi than healthy people.

The hippocampus plays a crucial role in processing information, memory, and spatial navigation.

Current Treatments Hit-or-Miss

While researchers are slowly forming a better idea of what causes neuropathic pain, the research has been hard to translate into medical practice, leaving many patients feeling hopeless. Part of the reason is that there are likely a variety of causes that depend on the patient’s history of injury, lifestyle, and drug history.

Tricyclic antidepressants and anticonvulsants are the common, first-line drugs used to treat neuropathic pain.

According to a 2005 study, http://www.ncbi.nlm.nih.gov/pubmed/15910402 tricyclic antidepressants will give relief to one in every two to three patients with peripheral neuropathic pain, which is superior to serotonin noradrenaline reuptake inhibitors (SNRIs), which are successful in one in every four to five, and selective serotonin reuptake inhibitors (SSRIs), good for one in every seven patients.

Anticonvulsants have not been found to be more effective than tricyclic antidepressants with an efficacy rate about the same as that of SNRIs.

Emerging Treatment

Patients who fail to find relief may have a new treatment option to turn to.

A 2006 study in the American Journal of Therapeutics http://www.rsds.org/pdfsall/Webster_Walker.pdf found that 85 percent of neuropathic pain patients who underwent outpatient ketamine infusion saw improvements in their conditions. Just over half of the study participants reported continued relief one month after discontinuing treatment.

Known more popularly for its abuse as a club drug, ketamine has been recognized and used for several decades as an anesthetic. It works to stop the transmission of pain by blocking N-methyl-D-aspartate (NMDA) receptors. Recent research has identified hyperactivity of these receptors as a possible factor in generating neuropathic pain.

Few medical establishments in the United States administer ketamine infusions. While it does not cure neuropathic pain conditions, treatment can put the patient into remission long enough to give the nervous system a chance to repair itself.

Despite the drug itself being inexpensive, the cost of ketamine infusion runs the gamut, from $200 to $2,000 per session in outpatient clinics.

Very rarely, hospitals offer it as an in-patient option, which, factoring in all overhead, runs an average of $25,000 for a five-day course of treatment, according to American RSD Hope, an association of neuropathic pain sufferers. However, a Web search revealed that none of the country’s largest medical institutions currently offers the therapy as more than part of clinical research.

Outpatient options are more cost-effective but take several hours a day, for a week or so.

Dr. Glen Z. Brooks, who runs a ketamine infusion clinic in New York, first offers an initial session to see if the patient responds. If it’s positive, Brooks recommends a series of six more treatments over the next eight days, either consecutively or every other day. Following that, the patient may return for single treatments for maintenance as needed. Typically, doctors charge $200 to $1,000 for each session.

Brooks, trained as an anesthesiologist, treats patients by referral only.

From March 2012, his practice was offering anesthesia-assisted opiate detox. It was during this time he discovered ketamine’s benefits on pain.

“Some of my patients were addicted to pain medications because they were having problems with chronic pain,” he said. “I noticed that if during their eight-hour detox procedure I added ketamine into the infusion, there were often dramatic improvements on their chronic pain following detox.”

In September 2012, he changed his practice over to ketamine therapy entirely, and sees patients with treatment-resistant depression and neuropathic pain.

“It stops the transmission of pain from the body to the spine and to the brain, and gives the system the chance to reboot,” said Brooks.

Of CRPS patients, he said, 80 percent see dramatic reduction in their pain with lasting improvement, and 20 percent do not.

Ketamine: Reinventing Chronic Pain Management

Ketamine: Reinventing Chronic Pain Management

Ketamine: Reinventing Chronic Pain Management

womawithdoctors

 

Author: Jeannette Y. Wick, RPh, MBA, FASCP

For patients who respond poorly or incompletely to opioids, ketamine may be the answer. In the middle of the past century, phencyclidine hydrochloride—called PCP or angel dust on the street—was developed to be a safe, effective anesthetic that did not cause cardiovascular and respiratory depression. However, its propensity to cause convulsions at high doses and long-lasting psychoactive side effects during emergence from anesthesia destroyed its potential.

Ketamine—a PCP derivative—was synthesized in 1963 and was tested on 20 prison volunteers in 1965. One-tenth as potent as PCP, ketamine was intended to induce anesthesia like PCP, but with greater specificity and fewer side effects.

.1 The FDA approved it in 1970, and its widespread use in the Vietnam conflict theater catapulted its popularity

.2 Today, ketamine is used less and less in the operating suite

.3 Although ketamine’s psychomimetic side effects are milder than those of PCP, they can be problematic (Table 12-10).

Screen Shot 2015-06-09 at 4.02.20 PM

Recreational abuse has dogged ketamine since its approval. Abusers have injected, inhaled, and smoked ketamine, revealing characteristics of the drug that would otherwise remain unknown. Researchers hypothesize that abusers may develop tolerance because ketamine induces liver enzymes.11 Abusers rarely experience withdrawal, instead reporting a sensation called the K-hole—a constellation of visual hallucinations, dissociation, and out-of-body, and sometimes, near-death experiences. Heavy, prolonged ketamine use can cause cognitive and psychological impairment.4,12-15

Up to one-third of chronic ketamine abusers develop dose-dependent urinary tract symptoms within weeks to years: lower urinary tract irritation (vesicopathy), hydroureter, and hemorrhagic or ulcerative cystitis.13,16,17

The symptom etiology remains unclear, but may be direct toxic damage, immune system activation, or the effect of unknown bacteria.16,18

Long-term complications include hepatotoxicity (jaundice, itching, or elevated liver enzyme levels, especially in alcoholic patients) and/or cholangiopathy.19,20

Some long-term abusers develop corneal edema.21

These complications reverse after cessation of ketamine use.17,20,21

Clinically, the most common side effects of ketamine are inebriation, mental alteration, headache, hypertension, and altered liver enzymes.22

Newer, cleaner drugs or biologics are replacing ketamine in the operative suite. Yet ketamine is finding a new place in clinical therapy. Ketamine, an N-methyl-D-aspartate (NMDA)–receptor antagonist, is becoming an option for perioperative pain management among patients with opioid tolerance, acute hyperalgesia, and chronic neuropathic pain.1

NMDA Receptors

NMDA receptors are 1 of 3 glutamategated ion receptors. Gated by a magnesium ion, they normally open only briefly to allow calcium ions and other cations to enter the cell. Calcium activates second- messenger systems, causing neuronal hyperactivity.1,22-24 NMDA receptors may be involved in neuronal survival and maturation, synaptic plasticity, and memory. Abnormal NMDA function may cause neurologic disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, depression, epilepsy, multiple sclerosis, Parkinson’s disease, and schizophrenia.25 Unrelenting NMDA receptor excitation allows continuous calcium influx into the cell and creates hyperexcitability. This presents clinically as opioid tolerance, hyperalgesia, and allodynia.22,26,27

Ketamine is the most potent clinically available, uncompetitive, open-channel NMDA-receptor blocker (it only works if the receptor is activated and the channel is open). Ketamine depresses the thalamus and limbic systems, preventing central nervous system centers from receiving or processing sensory input. This creates anesthesia, analgesia, and amnesia, and sometimes unpleasant psychomimetic effects or emergence phenomena.23,28,29

Sympathetic cardiovascular stimulation caused by ketamine is unique among intravenous anesthetics: it inhibits neuronal catecholamine reuptake, thereby increasing heart rate, cardiac output, and systemic and pulmonary blood pressure.30,31 Theoretically, ketamine use should be avoided in patients with prolonged QT syndrome.32 Ketamine inhibits neuronal serotonin reuptake, causing an emesis that is reversed by 5-HT–receptor blockers.33,34

What Route?

To minimize adverse events associated with ketamine use, researchers are examining the use of administration routes other than intravenous. Oral ketamine, as an injectable liquid or a compounded product, is subject to hepatic first-pass metabolism and is less effective than parenteral doses. It also lacks a clear dose-response relationship.22,35 Some study results suggest that the oral route leads to few side effects.36 Topical formulations of ketamine or ketamine with other potential analgesics has been used for managing several painful conditions (eg, pelvic pain, pruritus) with mixed results.22,37-39

Managing Pain

Ketamine use in pain management evolved from its perioperative use. Perioperative pain is expected, but may have physical or psychological consequences that delay rehabilitation and prolong hospitalization.1 Most surgeons use opioids to treat postoperative pain and supplement with regional anesthesia, other analgesics, and adjuvant agents as needed.1,23,40 Some patients respond poorly or incompletely to opioids; ketamine may help these patients.26,27,41

In low doses, NMDA-receptor antagonists can provide analgesia and circumvent opioid-related tolerance, hyperalgesia, and allodynia.10,23,40 Randomized, placebo-controlled, double-blind clinical trials (RCTs) have found that perioperative subanesthetic doses of ketamine added to opioid analgesia improved pain scores and reduced opioid consumption by approximately 30% to 50%. Ketamine was given as an intermittent low-dose intravenous bolus or a continuous infusion. It reduced opioid-related nausea and vomiting and added no additional significant adverse effects.42,43

Ketamine can also be given with morphine patient-controlled analgesia, contributing a morphine-sparing effect. Patients with chronic neuropathic pain, opioid dependence or tolerance, and acute hyperalgesia seem to benefit more.42,43 Low-dose ketamine administered before the surgical incision can lead to better analgesia for 24 hours after surgery.1 Most studies report no significant increase in psychomimetic adverse effects when ketamine is added to morphine.42,43

Sickle Cell Crisis and Chronic Noncancer Pain

Acute sickle cell disease creates severe pain with a neuropathic element. Several published guidelines recommend using opioids as first-line treatment, but some patients are unresponsive to even high opioid doses. Rapidly escalating opioid doses may induce acute tolerance and opioid-induced hyperalgesia.29,44 Case studies (but no RCTs) indicate that adding a low-dose ketamine infusion to opioids can improve pain in sickle cell disease.44 Usually, NMDA receptors activate continually only after a severe, sustained painful stimulus allows sufficient glutamate release. This is why ketamine may be useful as an adjuvant in several types of chronic central and peripheral neuropathic pain (Table 223,45,46).

Several of ketamine’s properties may prevent chronic pain from developing:

Dampening of nociception
Prevention or attenuation of hyperalgesia, allodynia, and tolerance
Attenuating central sensitization and windup phenomenon from repeated noxious stimuli when previously nonpainful stimuli become exaggerated and painful23,40

Clinicians have used short-term subanesthetic doses of ketamine to treat neuropathic pain.45 Scheduled infusions over several days can improve pain scores in patients with chronic pain; a few studies report pain relief persisting for weeks following treatment, indicating that ketamine may be disease modifying.46

Cancer Pain

Limited but increasing data support ketamine use in refractory cancer pain. Adding a small dose of ketamine to opioid therapy in a patient with opioid tolerance, called burst therapy, can improve pain management.12,47 Patients on highdose opioids whose cancer pain has a neuropathic component may respond to oral ketamine.48 Adding a small dose of ketamine to patient-controlled morphine seems to improve pain management, and some researchers are testing a ketamine mouthwash for mucositis.49,50

Endnote

Large, well-designed RCTs are needed to confirm the analgesic role of ketamine. Most studies suggest, and experts believe, that ketamine use should be reserved for patients in whom opioids, anticonvulsants, or antidepressants have failed.3,36 Because pain management is an off-label use for ketamine, clinicians should consult with field experts for dosing recommendations.

Ms. Wick is a visiting professor at the University of Connecticut.
References
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2. Mathew SJ, Shah A, Lapidus K, et al. Ketamine for treatment resistant unipolar depression: current evidence. CNS Drugs. 2012;26:189-204.
3. Hardy JR, Spruyt O, Quinn SJ, Devilee LR, Currow DC. Implementing practice change in chronic cancer pain management: clinician response to a phase III study of ketamine. Intern Med J. 2014;44(6):586-591.
4. Aroni F, Iacovidou N, Dontas I, et al. Pharmacological aspects and potential new clinical applications of ketamine: reevaluation of an old drug. J Clin Pharmacol. 2009;49:957-964.
5. Morgan CJ, Curran HV; Independent Scientific Committee on Drugs. Ketamine use: a review. Addiction. 2012;107:27-38.
6. Benitez-Rosario MA, Feria M, Salinas-Martin A, et al. A retrospective comparison of the dose ratio between subcutaneous and oral ketamine. J Pain Symptom Manage. 2003;25:400-402.
7. Ryu HG, Lee CJ, Kim YT, et al. Preemptive low-dose epidural ketamine for preventing chronic postthoracotomy pain: a prospective, double-blinded, randomized, clinical trial. Clin J Pain. 2011;27:304-308.
8. Barros GA, Miot HA, Braz AM, et al. Topical (S)-ketamine for pain management of postherpetic neuralgia. An Bras Dermatol. 2012;87:504-505.
9. Chong C, Schug SA, Page-Sharp M, et al. Development of a sublingual/oral formulation of ketamine for use in neuropathic pain: preliminary findings from a three-way randomized, crossover study. Clin Drug Investig. 2009;29:317-324.
10. Weber F, Wulf H, Gruber M, et al. S-ketamine and S-norke-tamine plasma concentrations after nasal and i.v. administration in anesthetized children. Paediatr Anaesth. 2004;14:983-988.
11. Reich DL, Silvay G. Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesth. 1989;36:186-197.
12. Loftus RW, Yeager MP, Clark JA, et al. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology. 2010;113:639-646.
13. Chen CH, Lee MH, Chen YC, et al. Ketamine-snorting associated cystitis. J Formos Med Assoc. 2011;110:787-791.
14. Schönenberg M, Reichwald U, Domes G, et al. Effects of peritraumatic ketamine medication on early and sustained posttraumatic stress symptoms in moderately injured accident victims. Psychopharmacology. 2005;182:420-425.
15. Morgan CJ, Muetzelfeldt L, Curran HV. Consequences of chronic ketamine self-administration upon neurocognitive function and psychological wellbeing: a 1-year longitudinal study. Addiction. 2010;105:121-133.
16. Wood D, Cottrell A, Baker SC, et al. Recreational ketamine: from pleasure to pain. BJU Int. 2011;107:1881-1884.
17. Middela S, Pearce I. Ketamine-induced vesicopathy: a literature review. Int J Clin Pract. 2011;65:27-30.
18. Chu PS, Ma WK, Wong SC, et al. The destruction of the lower urinary tract by ketamine abuse: a new syndrome? BJU Int. 2008;102:1616-1622.
19. Bell RF. Ketamine for chronic noncancer pain: concerns regarding toxicity. Curr Opin Support Palliat Care. 2012;6:183-187.
20. Seto WK, Ng M, Chan P, et al. Ketamine-induced cholangiopathy: a case report. Am J Gastroenterol. 2011;106:1004-1005.
21. Wai M, Chan W, Zhang A, et al. Long-term ketamine and ketamine plus alcohol treatments produced damages in liver and kidney. Hum Exp Toxicol. 2012;31:877-886.
22. Azari P, Lindsay DR, Briones D, Clarke C, Buchheit T, Pyati S. Efficacy and safety of ketamine in patients with complex regional pain syndrome: a systematic review. CNS Drugs. 2012;26:215-228.
23. Visser E, Schug SA. The role of ketamine in pain management. Biomed Pharmacother. 2006;60:341-348.
24. Wollmuth LP, Sobolevsky AI. Structure and gating of the glutamate receptor ion channel. Trends Neurosci. 2004;27:321-328.
25. Lipton SA. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat Rev Drug Discov. 2006;5:160-170.
26. Rodríguez-Muñoz M, Sánchez-Blázquez P, Vicente-Sánchez A, et al. The mu-opioid receptor and the NMDA receptor associate in PAG neurons: Implications in pain control. Neuro-psychopharmacology. 2012;37:338-349.
27. Orser BA, Pennefather PS, MacDonald JF. Multiple mechanisms of ketamine blockade of N-methyl-D-aspartate receptors. Anesthesiology. 1997;86:903-917.
28. Bhutta AT. Ketamine: a controversial drug for neonates. Semin Perinatol. 2007;31:303-308.
29. Zempsky WT, Loiselle KA, Corsi JM, et al. Use of low-dose ketamine infusion for pediatric patients with sickle cell disease-related pain: a case series. Clin J Pain. 2010; 26:163-167.
30. Craven R. Ketamine. Anaesthesia. 2007;62:48-53.
31. Waxman K, Shoemaker WC, Lippmann M. Cardiovascular effects of anesthetic induction with ketamine. Anesth Analg. 1980;59:355-358.
32. Mikesell CE, Atkinson DE, Rachman BR. Prolonged QT syndrome and sedation: a case report and a review of the literature. Pediatr Emerg Care. 2011;27:129-131.
33. McNulty JP, Hahn K. Compounded oral ketamine. Int J Pharm Compd. 2012;16:364-368.
34. Nishimura M, Sato K. Ketamine stereoselectively inhibits rat dopamine transporter. Neurosci Lett. 1999;274:131-134.
35. Blonk MI, Koder BG, van den Bemt PM, Huygen FJ. Use of oral ketamine in chronic pain management: a review. Eur J Pain. 2010;14:466-472.
36. Hocking G, Cousins MJ. Ketamine in chronic pain management: an evidence based review. Anesth Analg. 2003;97:1730-1739.
37. Kopsky DJ, Keppel Hesselink JM, Bhaskar A, Hariton G, Romanenko V, Casale R. Analgesic effects of topical ketamine [published online May 22, 2014]. Minerva Anestesiol.
38. Poterucha TJ, Murphy SL, Rho RH, et al. Topical amitriptyline-ketamine for treatment of rectal, genital, and perineal pain and discomfort. Pain Physician. 2012;15:485-488.
39. Poterucha TJ, Murphy SL, Sandroni P, et al. Topical amitriptyline combined with topical ketamine for the management of recalcitrant localized pruritus: a retrospective pilot study. J Am Acad Dermatol. 2013;69:320-321.
40. De Kock MF, Lavand’homme PM. The clinical role of NMDA receptor antagonists for the treatment of postoperative pain. Best Pract Res Clin Anaesthesiol. 2007;21:85-98.
41. Kaneria A. Opioid-induced hyperalgesia: when pain killers make pain worse [published online June 4, 2014]. BMJ Case Rep.
42. Bell RF, Dahl JB, Moore RA, et al. Perioperative ketamine for acute postoperative pain. Cochrane Database Syst Rev. 2010:CD004603.
43. Laskowski K, Stirling A, McKay WP, et al. A systematic review of intravenous ketamine for postoperative analgesia. Can J Anaesth. 2011;58:911-923.
44. Neri CM, Pestieau SR, Darbari DS: Low-dose ketamine as a potential adjuvant therapy for painful vaso-occlusive crises in sickle cell disease. Paediatr Anaesth. 2013;23:684-689.
45. Bell RF. Ketamine for chronic non-cancer pain. Pain. 2009;141:210-214.
46. Noppers I, Niesters M, Aarts L, et al. Ketamine for the treatment of chronic non-cancer pain. Expert Opin Pharmacother. 2010;11:2417-2429.
47. Ben-Ari A, Lewis MC, Davidson E. Chronic administration of ketamine for analgesia. J Pain Palliat Care Pharmacother. 2007;21:7-14.
48. Sear JW. Ketamine hepato-toxicity in chronic pain management: another example of unexpected toxicity or a predicted result from previous clinical and pre-clinical data? Pain. 2011;152:1946-1947.
49. White MC, Hommers C, Parry S, Stoddart PA. Pain management in 100 episodes of severe mucositis in children. Paediatr Anaesth. 2011;21:411-416.
50. Ryan AJ, Lin F, Atayee RS. Ketamine mouthwash for mucositis pain. J Palliat Med. 2009;12:989-991.

IV Ketamine Rapidly Effective in PTSD

IV Ketamine Rapidly Effective in PTSD

Action Points

PTSDa2

  • Patients with moderate to severe post-traumatic stress disorder (PTSD) symptoms showed rapid and substantial relief with a single intravenous dose of ketamine in a pilot randomized trial.
  • Note that dissociative symptoms were the main psychiatric adverse effects associated with ketamine, which peaked 40 minutes after dosing and were no longer detectable at the 2-hour mark.

Patients with moderate to severe post-traumatic stress disorder (PTSD) symptoms showed rapid and substantial relief with a single intravenous dose of ketamine in a pilot randomized trial, researchers said.

In the first day after treatment, mean scores on the Impact of Event Scale-Revised (IES-R) fell to 14 from 46 at baseline following the IV ketamine infusion, whereas IV midazolam given to the same patients in the crossover trial led to a drop in IES-R scores from 48 to 25.

The larger decline with ketamine versus midazolam was statistically significant, despite the small number of patients (29) who received both drugs, according to Adriana Feder, MD, of Icahn School of Medicine at Mt. Sinai in New York City, and colleagues writing in JAMA Psychiatry.

Some adverse psychiatric effects were seen with both drugs, and dissociative symptoms were especially prominent with ketamine. But these resolved within a few hours of dosing and neither manic nor psychotic symptoms presented, leading Feder and colleagues to call ketamine “safe and generally well-tolerated.”

Barbara Rothbaum, PhD, head of Emory University’s trauma and anxiety recovery program in Atlanta, told MedPage Today in an email that the study breaks new ground in PTSD treatment.

Ketamine has been shown to be helpful for depression and obsessive compulsive disorder, but this is the first time it has been shown to be helpful for PTSD,” said Rothbaum, who was not involved with the study.

Others in this field agreed that it was an important finding with strong clinical promise.

Steven Garlow, MD, also at Emory, said the drug, which is used a surgical anesthetic, is quite safe. “Midazolam and other sedative type agents represent greater physiological risk than does ketamine,” he told MedPage Today in an email. At the doses used in these psychiatric applications, Garlow said, the drug’s dissociative effects — which have led ketamine to become a drug of abuse — are not a serious problem.

“The key is whether ketamine has a long-term beneficial effect,” said Paul Schulz, MD, of the University of Texas Health Science Center in Houston, adding that, “in theory, subanesthetic doses of ketamine could be infused regularly.”

Garlow said his clinic had been treating depressed patients with ketamine on “weekly, biweekly, and triweekly” infusion schedules with good outcomes in about half the patients. The main obstacle has been necessity for frequent clinic visits to receive the IV treatments.

“The strong responders typically will invest in the weekly or biweekly inconvenience,” he said.

For the study, Feder and colleagues screened 57 adult patients and enrolled 41. Patients had to meet DSM-IV criteria for PTSD and score at least 50 on the Clinician-Administered PTSD Scale (CAPS) to be eligible. Patients with any history of psychotic or bipolar disorders were excluded, as were those with recent histories of alcohol misuse. Current anorexia or bulimia, any type of unstable mental illness, and current psychotropic medication use were exclusion criteria as well.

Participants were randomized to receive a single IV infusion of either 0.5 mg/kg of ketamine or 0.045 mg/kg of midazolam and were tested repeatedly over the next week. Two weeks after the first infusion, patients received an infusion of the other agent and were followed for another week.

Six patients did not receive the second infusion because they still showed sustained improvement of PTSD symptoms from the first dose, the researchers indicated. Four other patients left the study after the first dose: one because of delayed-onset sedation following ketamine infusion, one because of low baseline PTSD symptoms at the time of midazolam infusion, and two for administrative reasons.

Both drugs produced sharp drops in IES-R scores after the first infusion, but ketamine‘s was sharper — by 12.7 points (95% CI 2.5-22.8). The difference was slightly smaller at 8.6 points (95% CI 0.9-16.2) after the second infusion.

Reductions were seen in all three domains of the IES-R: intrusion, avoidance, and hyperarousal. The advantage of ketamine over midazolam was similar across all three, the researchers reported.

By day two after the infusions, IES-R scores began to rebound. However, at day seven, mean scores across the two infusions were still substantially lower than at baseline for both drugs (midazolam 33, ketamine 27).

Depression scores on the Montgomery-Asberg scale followed a roughly similar pattern, with an approximate 12-point drop during the first day with both drugs, from a baseline of about 22. Scores rose slowly over the succeeding days. At day seven after midazolam, mean depression scores had returned to baseline. On the other hand, the mean depression score after ketamine was 15 at day seven, still significantly below the baseline level.

Feder and colleagues reported that dissociative symptoms were the main psychiatric adverse effects associated with ketamine, which peaked 40 minutes after dosing and were no longer detectable at the 2-hour mark. However, one patient abruptly quit the study after receiving ketamine during the second infusion, apparently due to dissociative effects.

“No emergence of significant psychotic or manic symptoms was observed,” the researchers wrote.

Three patients needed beta-blockers to control blood pressure spikes during ketamine infusion. Other adverse effects seen during the first day that were more common with ketamine included blurred vision, dry mouth, restlessness, nausea and vomiting, and poor coordination.

The researchers said ketamine‘s precise mechanism of action for reducing PTSD symptoms was unknown. The drug antagonizes glutamate NMDA receptors; glutamate is believed to play a role in forming memories, including those of traumatic events. Thus, it is possible that the drug somehow disrupts the persistent fear and stress associated with such memories. Ketamine also has effects at the cellular level, boosting synaptic connections in the prefrontal cortex in rats, for example.

“If [the NMDA receptor] is involved in PTSD, that might suggest trials of other NMDA receptor antagonists, like memantine or dextromethorphan,” Schulz said.

Garlow said that drug companies have been looking at novel ketamine-like agents with “good bioavailability and less intoxicating properties,” as well as formulations that don’t require IV infusion.

Feder and colleagues acknowledged several limitations to the study: the small sample, the smaller number who received both infusions, and the lack of data on repeated dosing and potential interactions with other medications.

– John Gever
Deputy Managing Editor, Medpage Today

Listen to NPR’s report on Ketamine’s use for treating depression

Listen to NPR’s report on Ketamine’s use for treating depression

dep5

Lianne Milton/For NPR

Chris Stephens, 28, has been battling depression all of his life. At times he wouldn’t get out of bed for weeks. In January, he said his depression hadn’t returned since he started taking ketamine.

Chris Stephens, 28, has been battling depression all of his life. At times he wouldn’t get out of bed for weeks. In January, he said his depression hadn’t returned since he started taking ketamine.

Scientists say they have figured out how an experimental drug called ketamine is able to relieve major depression in hours instead of weeks.

Researchers from Yale and the National Institute of Mental Health say ketamine seems to cause a burst of new connections to form between nerve cells in parts of the brain involved in emotion and mood.

The discovery, described in Science, should speed development of the first truly new depression drugs since the 1970s, the researchers say.

“It’s exciting,” says Ron Duman, a a psychiatarist and neurobiologist at Yale University. “The hope is that this new information about ketamine is really going to provide a whole array of new targets that can be developed that ultimately provide a much better way of treating depression.”

Ketamine is an FDA-approved anesthetic. It’s also a popular club drug that can produce out-of-body experiences. Not exactly the resume you’d expect for a depression drug.

But a few years ago, researchers discovered that ketamine could help people with major depression who hadn’t responded to other treatments. What’s more, the relief came almost instantly.

The discovery “represents maybe one of the biggest findings in the field over the last 50 years,” Duman says.

beforeafter

A rat neuron before (top) and after (bottom) ketamine treatment. The increased number of orange nodes are restored connections in the rat’s brain.
Ronald Duman/Yale University

Depression is associated with a loss of so-called synaptic connections between nerve cells, Duman says. So he and other scientists began to study mice exposed to stresses that produce symptoms a lot like those of human depression.

The stressed mice lost connections in certain parts of the brain. But a dose of ketamine was able to “rapidly increase these connections and also to rapidly reverse the deficits that are caused by stress,” Duman says.

A team at the National Institute of Mental Health also has found evidence that ketamine works by encouraging synaptic connections.

It’s possible to see the change just by studying rodent brain cells with a microscope, says Carlos Zarate from the Mood and Anxiety Disorders Program at NIMH.

A healthy neuron looks like a tree in spring, he says, with lots of branches and leaves extending toward synaptic connections with other neurons. “What happens in depression is there’s a shriveling of these branches and these leaves and It looks like a tree in winter. And a drug like ketamine does make the tree look like one back in spring.”

And there’s also indirect evidence that ketamine is restoring synaptic connections in people, Zarate says.

His team studied 30 depressed patients who got ketamine. And they found changes in brainwave activity that indicated the drug had strengthened connections between neurons in areas of the brain involved in depression.

All of this research is intended to produce drugs that will work like ketamine, but without the hallucinations. And several of these alternative drugs are already being tried in people.

One of these drugs, called GLYX-13, has already been tested in two large groups of people — a key step toward FDA approval. The company that makes the drug, Naurex, says it will tell scientists how well GLYX-13 works at a meeting in December.

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