Published Research - Pharmaceutical

[Aiken]

mackjergens--

I think the first article was about multiple drugs Jazz is working on, and JZP-7 is the one for RLS, not fluvoxamine maleate (a.k.a. Luvox).

I saw elsewhere that JZP-7 is a dopamine agonist of some sort.

[ViewsAskew]

I hoped so! I was just commenting on the "luvox" in the tagging on the html. Seemed weird to be tagged that way.

Thanks for looking deeper and clarifying my side-tracked comment.

[Aiken]

Ann--

Whoops! I just realized I made an off-by-one error when looking at posters' names. I actually should have addressed that last post to mackjergens, and now I have.

[ViewsAskew]

I think I inadvertantly started it, Aiken. Since I mentioned that it was weird to be in the coding of the link. Sorry I side tracked everyone.

[ViewsAskew]

Interesting possibilities for helping get our sleep clocks back on track:

http://www.websciences.org/cftemplate/N ... D=20068118

[SquirmingSusan]

Where do I get some?!!!

[Sojourner]

Regarding the link...Say what !

M.

[ViewsAskew]

Xenoport is close to final stages - from this article, it looks like they have finished testing, have shown efficacy, and are now going to the FDA to ask for marketing approval.

http://www.reuters.com/article/governme ... 4020080228

[ViewsAskew]

For those with renal failure:

http://www.theannals.com/cgi/content/ab ... ph.1K619v1

DISCUSSION: Memantine is cleared primarily through the kidneys and should be renally dosed. Drugs that interfere with elimination-that is, other drugs utilizing the organic cation transporter-2 in the tubule, such as trimethoprim, metformin, or imipramine-may lead to drug accumulation. Our patient, who had impaired renal function, developed severe myoclonus and delirium after trimethoprim was added to therapy with memantine. As there were no reports of myoclonus and delirium with this drug combination and because of the structural, pharmacologic, and pharmacokinetic similarities between the aminoadamantanes memantine and amantadine, we researched similar dual adverse effects reported with amantadine. Amantadine has led to the same adverse effects noted in our patient, not only in patients with renal impairment, but also in one patient when trimethoprim was added to a stable dose of amantadine.

CONCLUSIONS: This is the first reported case of a drug interaction between memantine and trimethoprim, which resulted in clinically significant myoclonus and delirium. Clinicians should be aware of this potential interaction, since there have been reports of this adverse effect with the use of amantadine. Because memantine chemically and pharmacologically resembles amantadine, it is quite possible that their toxicities are similar.

[ViewsAskew]

Here's some research about chronic pain, lack of sleep, daytime sleepiness, and opioids...

http://www.websciences.org/cftemplate/N ... D=20080725

OBJECTIVE: Sleep problems are common among patients with chronic pain (CP). Information on sleep problems and associated covariates in opioid-treated patients with CP is limited. The aim of this study was to assess the prevalence, characteristics, and risk factors of sleep and daytime sleepiness problems in this specific population. DESIGN: Cross-sectional. SETTING: Primary care outpatient clinics. PARTICIPANTS: Eight hundred and seventy six patients with CP treated with long-term opioids. MAIN OUTCOME MEASURES: Prestudy selected questionnaires: six questions from the Medical Outcomes Study Sleep Scale, Pain Inventory Survey, Pain Patient Profile, Substance Dependence Severity Scale, and medication log. RESULTS: Insomnia-type sleep problems and combined sleep and sleepiness problems were reported by 87 percent and 49 percent of the sample, respectively. Logistic regression analysis showed that depression (adjusted OR, aOR 2.8, 95% CI2.1-3.7) and pain severity (aOR 1.4, 95% CI 1.1-1.7) were the strongest independent predictors of sleep problems; only depression severity predicted daytime sleepiness (aOR 1.9, 95% CI 1.6-2.2) or combined sleep/sleepiness problems (aOR 2.2, 95% CI 1.8-2.5). Opioid dose was associated with a slight tendency toward unrefreshing sleep (aOR 1.2, 95% CI 1.0-1.4) and worse sleep maintenance (aOR 1.2, 95% CI 1.0-1.4), while use of long-acting opioids was associated with a trend toward increased napping (aOR 1.3, 95% CI 1.0-1.. CONCLUSIONS: Sleep and daytime sleepiness problems are common among opioid-treated primary care patients with CP and seem to be related mainly to depression and pain severity. Physicians caring for opioid-treated patients with CP may want to assess them for sleep disorders as a part of routine CP care.

[ViewsAskew]

Zolpidem...improved sleep!

http://www.websciences.org/cftemplate/N ... D=20080724

Polysomnographic study of intermittent zolpidem treatment in primary sleep maintenance insomnia.
PARRINO L, SMERIERI A, GIGLIA F, MILIOLI G, DE PAOLIS F, TERZANO MG.
Clin Neuropharmacol 2008;31(1):40-50.
Sleep Disorders Center, Department of Neuroscience, University of Parma, Italy


BACKGROUND AND PURPOSE: Treatment of chronic insomnia with nightly hypnotics is efficacious, but discontinuation is recommended after 1 month, less than the average disease duration. This study was undertaken to determine the efficacy of intermittent administration. PATIENTS AND METHODS: A double-blind study was carried out on 8 patients (age, 32.8 +/- 9 years; 3 men) with primary sleep maintenance insomnia longer than 1 month. Polysomnography of conventional sleep parameters, cyclic alternating patterns (CAPs), and arousals was performed. Perception of sleep quality was assessed on a visual analog scale. After an adaptation night, baselines were recorded followed by 6 consecutive nights of alternating treatment with zolpidem (10 mg) or placebo. RESULTS: Significant improvements on baseline values (P < 0.0001) were observed on all 3 active treatment nights for total sleep time, sleep efficiency, CAP time, CAP rate, subtype A2, arousals, and arousal index. Deep non-rapid eye movement sleep increased with the second and third doses of active treatment (P < 0.0001). Rapid eye movement sleep increased during the last 3 polysomnographic recordings (P < 0.014). Sleep quality (visual analog scale) improved on all nights after the initial dose of active treatment (P < 0.0001). There was no evidence of rebound insomnia with placebo. CONCLUSIONS: Intermittent treatment with zolpidem in primary insomnia patients improves CAP parameters and arousals, as well as sleep duration and quality, in the absence of rebound insomnia.

[ViewsAskew]

Wow...not sure if this is believable when they use the words "cured" but for those wanting to try acupuncture, this may offer some help:

http://www.websciences.org/cftemplate/N ... D=20080776


[Observation on therapeutic effect of acupuncture on restless legs syndrome]
WU YH, SUN CL, WU D, HUANG YY, CHI CM.
Zhongguo Zhen Jiu 2008;28(1):27-9.
Shandong Provincial Jimo Municipal Hospital of TCM, Shandong 266200, China. doctorwu6@126.com


OBJECTIVE: To compare therapeutic effects of acupuncture combined with TDP radiation and western medicine on restless legs syndrome. METHODS: One hundred and fifty-eight cases of restless legs syndrome were randomly divided into an observation group and a control group, 79 cases in each group. The treatment group were treated with acupuncture at Shenshu (BL 23), Dachangshu (BL 25), Guanyuanshu (BL 26), Zhibian (BL 54), Taixi (KI 3), etc., and TDP radiation. The control group were treated with L-Dopa. Clinical observation was made for 30 days. RESULTS: In the observation group, 42 cases were cured, 30 cases were effective and 7 cases were ineffective with a total effective rate of 91.1%; in the control group no case was cured, 24 cases were effective and 55 cases were ineffective with a total effective rate of 30.4%, with a significant difference between the two groups in the total effective rate. CONCLUSION: Acupuncture combined with TDP radiation has a better therapeutic effect on restless legs syndrome.

[ViewsAskew]

http://www.neurology.org/cgi/content/short/70/18/1620

Low-dose hydrocortisone in the evening modulates symptom severity in restless legs syndrome
M. Hornyak, MD, A. Rupp, D. Riemann, PhD, B. Feige, M. Berger and U. Voderholzer, MD
From the Center for Sleep Research and Sleep Medicine, Department of Psychiatry and Psychotherapy, University Medical Center, Freiburg, Germany.

Address correspondence and reprint requests to Dr. Magdolna Hornyak, Interdisciplinary Pain Center, Breisacher Strasse 64, D-79106 Freiburg, Germany magdolna.hornyak@uniklinik-freiburg.de

Background: Circadian symptom manifestation in the evening and night is one of the main characteristics of restless legs syndrome (RLS). Although the inverse temporal course of corticosteroid rhythm and RLS symptom severity is obvious, this relationship has yet to be studied. We investigated the effect of late-evening application of exogenous cortisol (hydrocortisone) on sensory leg discomfort (SLD), one of the main complaints of patients with RLS.

Methods: Ten untreated patients with idiopathic RLS participated in the study. Change of SLD was rated on a visual analogue scale during the 60 minutes resting period of the so-called Suggested Immobilization Test. Patients received either hydrocortisone 40 mg or placebo (saline) IV in random order in a double-blind crossover design, with 1 week between the experiments.

Results: Severity of SLD was lower during hydrocortisone infusion than during placebo (p = 0.032). Though blind to the experimental condition, 5 of the 10 patients experienced improvement in symptoms during hydrocortisone administration, but no patient felt an amelioration during the placebo condition.

Conclusions: Our data indicate a probable physiologic relationship between evening and early night hour restless legs syndrome symptom increase and low cortisol level.


Abbreviations: ANOVA = analysis of variance; HPA = hypothalamic-pituitary-adrenal axis; PLMW = periodic leg movements during the resting wake state; PSG = polysomnography; RLS = restless legs syndrome; SIT = suggested immobilization test; SLD = sensory leg discomfort.

[ViewsAskew]

A variant of modafinil - I wonder why? It doesn't say if it's tolerated better, has less side effects, less expensive, whatever unless I'm missing it...


http://www.websciences.org/cftemplate/N ... D=20081187

Armodafinil: a new treatment for excessive sleepiness.
LANKFORD DA.
Expert Opin Investig Drugs 2008;17(4):565-73.
Sleep Disorders Center of Georgia, 5505 Peachtree Dunwoody Road, Suite 380, Atlanta, GA 30342, USA. alankford@sleepsciences.com

BACKGROUND: Armodafinil is a wake-promoting agent developed by Cephalon that was approved in mid-2007 for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea and shift work disorder. It is the R-enantiomer of the compound modafinil. Like modafinil, the mechanism of action for armodafinil is not fully characterized. OBJECTIVE: To determine what data are available to support the potential use of armodafinil in clinical settings. METHODS: There are limited data on armodafinil available in the public domain, particularly in regard to chemistry and pharmacokinetics/dynamics. Data were reviewed from refereed journals, scientific presentations, and published labeling. RESULTS/CONCLUSION: Clinical trials demonstrated efficacy and safety profiles that were similar to those of the parent compound with wake promotion sustained throughout the day. The longer duration of effect has the potential for improved patient response and compliance but this will require further study. The primary commercial challenge may be the future availability of generic modafinil.

[ViewsAskew]

Hmmm - treatment of refractory RLS

http://www.websciences.org/cftemplate/N ... D=20081191

Control of medically refractory restless legs syndrome with intrathecal morphine: case report.
ROSS DA, NARUS MS, NUTT JG.
Neurosurgery 2008;62(1):E263; discussion E263.
Medford Neurological Clinic, Medford, Oregon 97504, USA. drdoom867@yahoo.com

OBJECTIVE: Restless legs syndrome is now widely recognized and is usually successfully treated with medication. Occasionally, it may be severe and refractory to medication. Intrathecal opiates have been previously described to be useful in this situation in a single report. CLINICAL PRESENTATION: We report the successful use of low-dose intrathecal morphine in a severe case of restless legs syndrome refractory to medication. TECHNIQUE: The surgery was complicated by extreme restlessness in the recovery room resulting in withdrawal or breakage of the catheter on multiple occasions. Relief of symptoms was lost with each catheter malfunction. We describe the possible origin of this complication and a solution to the problem resulting in the successful control of symptoms for 7 months since the last surgery. CONCLUSION: Intrathecal opiates for restless legs syndrome are currently considered investigational, but we hope, with this second report of the efficacy of low-dose intrathecal narcotics in this condition, to stimulate further investigation of this treatment modality.