Rev Chilena Infectol.
2005 Jun;22(2):141-6. Epub 2005 May 12.
[Search of amantadine-resistance in influenza A strains isolated
in Santiago, Chile, 2001-2002.]
[Article in Spanish]
Fehlmann P E, Le Corre P N, Abarca V K, Godoy M P, Montecinos P L,
Veloz B A, Ferres G M.
Amantadine has been used for prevention and treatment of influenza A
infection. It blocks the proton through the M2 ion channel. Drug-resistant
viruses appear quickly when this therapy is used. Single amino acids changes
in the H2 protein can confer resistance, being the most frequent one in
position 31. Different methods to detect resistant strains have been described.
The objectives were to determine the existence of amantadine resistance
of influenza A strains isolated in a virologic laboratory in Santiago,
Chile, between 2001-2002, and to validate a new molecular method to detect
resistant strains. A PCR restriction fragment length polymorphism analysis
was employed for the detection of resistant viruses. In 31 processed strains
no mutation in the position 31 was found. This result supports that amantadine
resistance is very low or absent in Chile. This could be explained by
a limited use of this drug in the study population. This method could
be used as a monitoring system to survey resistant viruses.
Biochem Biophys Res Commun. 2005 Jun 3;331(2):621-9.
Amantadine inhibits hepatitis A virus internal ribosomal entry
site-mediated translation in human hepatoma cells.
Kanda T, Yokosuka O, Imazeki F, Fujiwara K, Nagao K, Saisho
H.
Safety and Health Organization, Chiba University, 1-33 Yayoicho, Inage-ku,
Chiba 263-8522, Japan; Department of Medicine and Clinical Oncology, Graduate
School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-0856,
Japan.
The effect of six drugs (amantadine, glycyrrhizin, ribavirin, ursodeoxycholic
acid, alcohol, and IFN) on HAV RNA translation from the HAV internal ribosomal
entry site (IRES) was investigated using a bicistronic reporter construct
containing HAV IRES as intragenic spacer. Huh-7 cells and derivatives
were transfected with in vitro transcripts, and the reporter gene activity
was determined. IFN suppressed both cap-dependent and HAV IRES-dependent
translation, while amantadine specifically inhibited HAV IRES-dependent
translation. In contrast to IFN, by reporter assay, amantadine did not
activate the interferon-stimulated response element (ISRE) or interferon
gamma-activated sequence (GAS)-associated pathways. Immunoblot analysis
revealed that amantadine had no effect on PKR and on IFN-regulatory factor-1
(IRF-1) expression. These findings demonstrated a novel antiviral effect
of amantadine against HAV with or without HCV infection.
Br J Pharmacol. 2005 Apr 18; [Epub ahead of print]
Effects of amantadine and budipine on antidepressant drug-evoked
changes in extracellular 5-HT in the frontal cortex of freely moving rats.
Owen JC, Whitton PS.
1Department of Pharmacology, The School of Pharmacy, 29-39 Brunswick
Square, London WC1N 1AX.
Evidence has recently suggested that NMDA receptors may play a role in
the aetiology and possible treatment of depression and that weak noncompetitive
NMDA receptor antagonists such as amantadine can synergize with conventional
antidepressants in a model of the illness.To try to obtain a neurochemical
rationale for these findings, we have studied the effects of acute and
chronic administration of amantadine or the related drug budipine on cortical
release of 5-hydroxytryptamine (5-HT) following the antidepressants reboxitine
(REB), paroxetine (PAROX) and clomipramine (CLOM) in freely moving rats
by using microdialysis.Acute administration of amantadine (40 mg kg(-1)),
budipine (10 mg kg(-1)), REB (10 mg kg(-1)), PAROX (10 mg kg(-1)) or CLOM
(10 mg kg(-1)) all failed to significantly alter extracellular 5-HT in
the cortex. However, when either amantadine or budipine was administered
30 min prior to any of the three antidepressants, a significant rise in
5-HT was observed.For chronic studies, the effects of the drugs were studied
at 4, 7, 14 and 21 days. Amantadine and budipine did not significantly
alter extracellular 5-HT at any time point. The three antidepressant drugs
all elicited a gradual increase in 5-HT, which became significant after
14 days and tended to plateau thereafter. When either amantadine (20 mg
kg(-1)) or budipine (5 mg kg(-1)) was coadministered with any of the three
antidepressants, two differences were seen compared with the effects of
the antidepressants alone. Firstly, the time required for significant
increases in cortical 5-HT was reduced with elevated levels now being
observed by 7 days. Secondly, the absolute magnitude of the increase in
extracellular 5-HT was markedly greater in these rats from day 7 until
the end of the experiment.If, as is widely considered, an increase in
extracellular 5-HT represents a critical step in the mechanism of action
of antidepressants, these data suggest that combined treatment with clinically
tolerated NMDA antagonists such as amantadine could reduce the delay in
therapeutic onset of antidepressants as well as possibly enhance their
efficacy.British Journal of Pharmacology advance online publication, 18
April 2005; doi:10.1038/sj.bjp.0706188.
Transplantation. 2005 Feb 15;79(3):325-9.
Triple antiviral therapy with amantadine for IFN-ribavirin nonresponders
with recurrent posttransplantation hepatitis C.
Bizollon T, Adham M, Pradat P, Chevallier M, Ducerf C, Baulieux
J, Zoulim F, Trepo C.
Hotel-Dieu 1, Lyon, France. thierry.bizollon@chu-lyon.fr
BACKGROUND: HCV reinfection after liver transplantation is universal
and has an accelerated course with a high risk of progression to cirrhosis.
It is now established that combination therapy with interferon (IFN) alpha
and ribavirin may achieve a sustained virological response in 20% of transplanted
patients. However, the optimal therapy for nonresponders remains an unresolved
issue. We conducted a pilot study to determine the efficacy and safety
of triple antiviral therapy in IFN-ribavirin nonresponders with recurrent
chronic hepatitis C. METHODS: Twenty-four nonresponders to the IFN-ribavirin
combination were enrolled in this pilot study. Patients were treated with
IFN-alpha (3 million units three times a week subcutaneously with ribavirin
[800-1,000 mg daily]) and amantadine 200 mg daily for 48 weeks. The primary
end point was the loss of HCV RNA 6 months after the end of treatment.
RESULTS: Median age was 50 years; 72% were men and 82% had genotype 1.
The median interval between the end of combination therapy and enrollment
was 11 months. Twenty-four patients started therapy, but five (21%) withdrew
due to side effects, including two with anemia.On an intent-to-treat basis,
18 patients (75%) had a biochemical response and 9 (37%) had a virologic
response at the end of triple antiviral therapy. Eight of these nine patients
(33%) had a sustained virological response. The mean METAVIR score improved
from A 2.2 F2.1 before treatment to A 1.2 F1.9 in sustained virological
responders. In virological nonresponders, inflammatory activity did not
change, but fibrosis worsened. Several patients required treatment with
erythropoietin for anemia. Triple therapy was well tolerated and neither
increased the frequency nor severity of side effects. CONCLUSION: Our
results show that triple antiviral therapy for 48 weeks induced a sustained
virological response in 33% of IFN-ribavirin nonresponders with recurrent
hepatitis C.
Minerva Gastroenterol Dietol. 2004 Mar;50(1):29-36.
Treatment of chronic hepatitis c.
Marcellin P, Asselah T, Ripault MP, Boyer N.
Unit of Hepatology, Claude Bernard Research Center on Viral Hepatitis,
INSERM U-481, Hospital Beaujon, Clichy, France. marcellin@bichat.inserm.fr
Since the discovering of the hepatitis C virus in 1989, the treatment of hepatitis C has considerably improved. Initially, with interferon alpha used as a single drug, the sustained virological response rate was below 20%. Then, with the use of combination therapy of interferon a with ribavirin, the response rate increased to 41%. More recently, combination of pegylated interferons with ribavirin give a response rate of about 54-63%. The long-term follow-up studies showed that sustained virological response is generally associated with clinical and histological improvement. The indication of therapy is mainly based on the results of the liver biopsy which is the best way to assess the prognosis of the liver disease. Therefore, treatment is indicated in patients with moderate or severe necroinflammation or fibrosis. The tolerability of combination therapy is relatively poor with a frequent flu-like syndrome and an impaired quality of life. Factors associated with a poor response to treatment are essentially genotype 1 and high viral load. To further improve the efficacy of therapy, different new drugs are under investigation (amantadine, cytokines). These drugs may be candidates for new combinations. In addition, intensive research is currently done for the development of inhibitors of viral enzymes (helicase, protease or polymerase) and anti-sense oligonucleotides, ribozymes and therapeutic vaccine.
Brain Inj. 2004 Dec;18(12):1309-18.
Amantadine for neurobehavioural deficits following delayed post-hypoxic
encephalopathy.
Arciniegas DB, Frey KL, Anderson CA, Brousseau KM, Harris SN.
Brain Injury Rehabilitation Unit, Spalding Rehabilitation Hospital,
Aurora, CO, USA. david.arciniegas@uchsu.edu
Delayed post-hypoxic encephalopathy is an uncommon but potentially debilitating consequence of hypoxic-ischemic brain injury. This condition is characterized by delayed neurological deterioration days-to-weeks after an initial partial or complete recovery from hypoxic-ischemic brain injury. The course of recovery from this condition is highly variable, ranging from rapid and fatal progression over several weeks to delayed but occasionally complete recovery. There are no reports describing neurorehabilitative, including neuropharmacologic, interventions for persons with persistent neurological and/or neurobehavioural deficits following delayed post-hypoxic encephalopathy. This study describes the case of a 24-year old male who developed delayed post-hypoxic encephalopathy following an unintentional methadone and diazepam overdose and who demonstrated cognitive and neurobehavioural improvements during treatment with amantadine HCl hydrochloride in a single-case, open-label design. A brief review of the literature regarding this condition, its treatment and suggestions for further study are presented.
Pol J Pharmacol. 2004 Nov-Dec;56(6):735-42.
Effects of joint administration of imipramine and amantadine in
patients with drug-resistant unipolar depression.
Rogoz Z, Dziedzicka-Wasylewska M, Daniel WA, Wojcikowski J, Dudek D, Wrobel
A, Zieba A.
Department of Pharmacology, Institute of Pharmacology, Polish Academy
of Sciences, Smetna 12, PL 31-343 Krakow, Poland. rogoz@if-pan.krakow.pl.
The paper describes the effect of amantadine (AMA) supplementation on
imipramine (IMI) therapy in patients (with treatment-resistant unipolar
depression) who fulfilled DSM IV criteria for major depression. Twelve
patients were enrolled to the study on the basis of history of their illness
and therapy. Following 2 weeks of washout period, the patients were treated
with IMI twice daily (100-150 mg/day) for 6 weeks, and then AMA was introduced
(twice daily, 100-150 mg/day) and administered jointly with IMI for further
6 weeks. Thereafter, AMA was withdrawn, and the patients were treated
with IMI alone for 2 weeks. Hamilton Depression Rating Scale (HDRS) and
Beck Depression Inventory (BDI) were used to assess efficacy of antidepressant
therapy. IMI changed neither HDRS nor BDI score after 3 or 6 weeks of
treatment when compared with washout (before treatment). AMA supplementation
significantly reduced both HDRS and BDI scores after 3- or 6-week supplementation.
AMA augmentation of IMI treatment was beneficial and lasted even after
AMA withdrawal. Moreover, pharmacokinetic data indicate that AMA did not
influence significantly the plasma concentration of the IMI and its metabolite,
desipramine, in the patients during joint treatment with AMA and IMI,
what suggests the lack of pharmacokinetic interaction. These results suggest
that joint therapy with IMI and AMA may be successful in the treatment-resistant
unipolar depression.
Semin Liver Dis. 2004;24 Suppl 2:89-95.
Role of amantadine and other adjuvant therapies in the treatment
of hepatitis C.
Brillanti S.
University of Bologna, Bologna, Italy.
There is room for improvement in the treatment of chronic hepatitis C with standard interferon (IFN) alfa. In the search for treatment adjuvants, the antiviral compound ribavirin has been found to significantly increase sustained virological response. Despite this improvement, the rate of "cure" remains low at approximately 40%, thus stimulating the search for additional adjuvants. In 1997, it was suggested that amantadine monotherapy could be used successfully to treat patients with chronic hepatitis C who had previously failed IFN alfa therapy, but ensuing studies could not support these findings. Instead, researchers have studied amantadine as an adjuvant to either IFN alfa alone or IFN alfa plus ribavirin, and promising results have been published. In this article, the author reviews the role of amantadine alone or as part of combination therapy regimens for chronic hepatitis C and briefly looks at the use of other agents as potential adjuvants.
Drugs. 2004;64(18):2031-46.
Antiviral therapy for influenza : a clinical and economic comparative
review.
Schmidt AC.
Department of Paediatrics, Charite University Hospital, Berlin, Germany.
Each year influenza epidemics cause a considerable burden of disease. Vaccination against influenza A and B viruses has been and remains the cornerstone of influenza prevention, but antiviral therapy can serve as an important adjunct to vaccination in controlling the impact of the disease. Two classes of drugs are currently licensed in a large number of countries for the treatment of influenza. The M2 ion channel blockers or amantadanes (amantadine and rimantadine) are specific inhibitors of influenza A virus replication, whereas the neuraminidase inhibitors (zanamivir and oseltamivir) are active against influenza A and B viruses. Readily transmissible drug-resistant viruses develop frequently during amantadane treatment but not during neuraminidase inhibitor treatment. In this review, efficacy and safety data from randomised controlled trials are evaluated to gain an understanding of what we can and cannot expect from antiviral treatment. All four drugs shorten the course of influenza disease by approximately 1 day and relieve symptoms to some extent, but there is still uncertainty as to whether antiviral therapy leads to a reduction of serious complications and hospitalisation. The results of cost-effectiveness analyses are very diverse, in part because of differences in methodology but also because there is no consensus on what probabilities to assign to the key risks and benefits that form the basis of these studies. Consensus statements by advisory bodies in England and Germany recommend neuraminidase inhibitors for the therapy of influenza in high-risk individuals such as people over 65 years or under 2 years, and individuals with chronic cardiovascular, pulmonary or renal disease, diabetes mellitus or immunosuppression. However, there is no agreement as to whether antiviral therapy can be generally recommended for otherwise healthy children and adults. The availability of safe and effective antiviral therapy options should be kept in mind by the practising clinician, while more specific recommendations and policy formulation will depend on additional efficacy data that include frequency of complications and hospitalisation as outcome measures.
J Hepatol. 2004 Sep;41(3):462-73.
Evaluation of amantadine in chronic hepatitis C: a meta-analysis.
Deltenre P, Henrion J, Canva V, Dharancy S, Texier F, Louvet
A, De Maeght S, Paris JC, Mathurin P.
Services d'Hepato-Gastroenterologie, Hopital Huriez, CHRU Lille, France.
BACKGROUND/AIMS: The benefit of amantadine combination therapy, either with interferon (IFN) alone (double therapy) or with ribavirin and IFN (triple therapy) is unknown. METHODS: We analyzed the effect of amantadine on the end-of-treatment virological response and the sustained response using meta-analysis of 31 randomized controlled trials. RESULTS: Overall analysis revealed a significant effect of amantadine. Triple therapy was the best regimen for improving the sustained response (mean difference: 8.4%, 95% CI: 2.4-13.8%, P=0.002). In subgroup analysis, amantadine did not have a significant effect upon naive patients or relapsers. In non-responders, combination therapy with amantadine was associated with a significant effect on the sustained response (mean difference: 8.3%, 95% CI: 1.9-14.6%, P=0.01). In sensitivity analysis, double therapy did not improve virological responses. Conversely, triple therapy tended to improve the end-of-treatment virological response and was associated with a significant effect upon the sustained response (mean difference: 12.7%, 95% CI: 3.8-21.6%, P=0.005). CONCLUSIONS: Combination therapy with amantadine is of no effect upon naive patients or relapsers. In non-responders, triple therapy with amantadine improved the sustained response. New randomized controlled trials are required to confirm this meta-analysis.
Cochrane Database Syst Rev. 2004;(3):CD001169.
Amantadine and rimantadine for preventing and treating influenza
A in adults.
Jefferson T, Deeks JJ, Demicheli V, Rivetti D, Rudin M.
Health Reviews Ltd, Via Adige 28a, Anguillara Sabazia, Roma, Italy,
00061.
BACKGROUND: Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but these drugs are not widely used due to a lack of knowledge of their potential value and concerns about possible adverse effects. OBJECTIVES: The objective of this review was to assess the effectiveness and safety ("effects") of amantadine and rimantadine in healthy adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2003), MEDLINE (January 1966 to November week 2, 2003), EMBASE (January 1990 to September 2003) and the reference lists of articles. We also contacted manufacturers, researchers and authors. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control antivirals or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults. DATA COLLECTION AND ANALYSIS: For prevention trials the numbers of participants with clinical influenza (influenza-like-illness or ILI), i.e. confirmed influenza A, and adverse effects were analysed. Analysis for treatment trials included the mean duration of fever and length of hospital stay, and the number of adverse effects. MAIN RESULTS: Amantadine prevented 25% of ILI cases (95% confidence interval (CI) 13% to 36%), and 61% of influenza A cases (95% CI 35% to 76%). Amantadine reduced duration of fever by one day (95% CI 0.7 to 1.3). Rimantadine demonstrated comparable effectiveness, but there were fewer trials and the results for prevention were not statistically significant. Both amantadine and rimantadine induced significant gastrointestinal adverse effects. Adverse effects of the central nervous system and study withdrawals were significantly more common with amantadine than rimantadine. REVIEWERS' CONCLUSIONS: Amantadine and rimantadine have comparable effectiveness in the prevention and treatment of influenza A in healthy adults, although rimantadine causes fewer adverse effects than amantadine.
J Gen Intern Med. 2004 Jun;19(6):662-8.
Amantadine therapy for chronic hepatitis C.
Smith JP, Riley TR 3rd, Devenyi A, Bingaman SI, Kunselman A.
Department of Medicine, Pennsylvania State College of Medicine, The
Milton S Hershey Medical Center, Hershey, PA 17033-0850, USA.
OBJECTIVE: Although treatment of hepatitis C has improved, up to 50% do not respond to standard therapy with interferon regimes or cannot tolerate the treatment due to side effects. The purpose of the present investigation was to evaluate the safety and effectiveness of the antiviral drug amantadine for the treatment of hepatitis C in those who had either previously failed interferon therapy or were not candidates for interferon. DESIGN: A prospective double-blind randomized placebo-controlled trial. SETTING: Outpatient research clinic of a teaching hospital. PATIENTS/PARTICIPANTS: One hundred fifty-two patients with confirmed hepatitis C with abnormal liver enzymes, detectable hepatitis C RNA in the blood, and abnormal liver histology by biopsy were randomized to receive treatment or placebo. MEASUREMENTS AND MAIN RESULTS: Patients received either amantadine 100 mg twice daily by mouth or placebo for 6 months. After 6 months, placebo-treated patients were crossed over and treated with amantadine for 6 months and amantadine-treated subjects received 6 additional months of therapy. Amantadine therapy resulted in a significant decline in serum alanine aminotransferase compared to placebo (P =.03). Nine percent cleared the virus at the end of therapy and 6.8% had a sustained virologic response 6 months after discontinuation of amantadine, but this was not statistically significant. Side effects were minimal, and the social quality of life survey improved with 12 months of amantadine (P =.02). CONCLUSIONS: Oral amantadine may provide a safe alternative treatment for those patients who are intolerant or unresponsive to interferon.
Drugs. 2004;64(12):1295-304.
Management of fatigue in patients with multiple sclerosis.
Zifko UA.
Klinik Pirawarth, Neurological Rehabilitation Centre, Kurhausstrasse
100, A-2222 Bad Pirawarth, Austria.
As long as no causal treatment is available for multiple sclerosis (MS), and as long as only some patients with MS respond to immunomodulators, symptomatic treatment is of paramount importance. Fatigue is the most common symptom of MS and is associated with a reduced quality of life. It is described as the worst symptom of their disease by 50-60% of patients.The first step in managing MS-related fatigue is identifying and eliminating any secondary causes. Primary fatigue syndrome can be alleviated with drug treatment in many cases. Modafinil has been shown to be effective in some studies, and amantadine is an alternative for patients who do not respond to or cannot tolerate modafinil. The nonpharmacological management of fatigue in MS includes inpatient rehabilitation and aerobic endurance exercise.This article describes the pathophysiology, diagnosis and treatment of MS-related fatigue--the most common symptom of MS.
Am J Gastroenterol. 2004 Jun;99(6):1099-104.
Amantadine therapy for chronic hepatitis C: a dose escalation
study.
Smith JP, Riley TR 3rd, Bingaman S, Mauger DT.
Department of Medicine, Pennsylvania State University College of Medicine,
The M.S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, USA.
OBJECTIVES: Amantadine reduces liver transaminase levels in some patients with chronic hepatitis C at doses of 200 mg daily and may improve the sustained virological response (SVR) when given with interferon and ribavirin. The primary purpose of the present investigation was to study the safety and toxicity of higher doses of amantadine in subjects who previously failed or were intolerant to interferon. The secondary aim was to test the efficacy of higher dose of amantadine against hepatitis C. METHODS: An open-labeled prospective study was conducted starting with amantadine 200 mg daily and increasing to 500 mg daily while monitoring for safety, toxicity, and efficacy. An amantadine blood level exceeding 1,600 ng/ml was considered toxic requiring dose reduction. The patient's symptoms, laboratory tests, and quality of life were monitored. RESULTS: One hundred patients enrolled in the study. Normalization of alanine aminotransferase (ALT) for each dose was as follows: 200 mg (35%), 300 mg (49%), 400 mg (53%), and 500 mg (56%). The incidence of toxic amantadine plasma levels increased with dose, i.e., 200 mg (0%), 300 mg (6%), 400 mg (27%), and 500 mg (49%). The frequency and severity of arthralgias and fatigue improved at all dosages administered. No changes in the occurrence or severity of headache, insomnia, or depression were reported. Serious adverse events included myocardial infarction and suicide attempt. Other side effects included impotence, confusion, alopecia, and hoarseness. CONCLUSIONS: Amantadine given at a dose of 300 mg daily is safe, and significantly lowers ALT blood levels more than 200 mg daily. The enzyme response rate does not significantly improve above 300 mg, but toxicity increases.
Ann Pharmacother. 2004 Jul-Aug;38(7-8):1194-6.
Amantadine in the akinetic-rigid variant of Huntington's disease.
Magnet MK, Bonelli RM, Kapfhammer HP.
Karl-Franzens University Graz, Graz, Austria.
OBJECTIVE: To report the effects of amantadine on an akinetic-rigid variant of Huntington's disease (HD). CASE SUMMARY: We describe a 36-year-old woman with HD who was treated with intravenous amantadine for 5 days. The woman was evaluated with the Unified Huntington's Disease Rating Scale before and after treatment. Parkinsonism, bradykinesia, and dystonia improved significantly. DISCUSSION: Amantadine is a noncompetitive N-methyl d-aspartate receptor antagonist. It is mainly used in the treatment of Parkinson's disease, as it increases dopamine levels in the brain. This effect is said to ameliorate akinesia. Although the effect of amantadine on choreatic dystonia in HD has been reported in several studies, to the best of our knowledge, this is the first report of the ameliorative effects of amantadine on the rigid form of HD. Our patient showed improvements of gait, parkinsonism, and dystonia. Fine-motor tasks and eye movement did not change significantly. CONCLUSIONS: We suggest that amantadine treatment might be of value to patients with the akinetic-rigid variant of HD.
Psychosomatics. 2004 May-Jun;45(3):205-9.
Amantadine for executive dysfunction syndrome in patients with
dementia.
Drayton SJ, Davies K, Steinberg M, Leroi I, Rosenblatt A, Lyketsos
CG.
Department of Pharmacy, Johns Hopkins Hospital, Baltimore, MD 21287,
USA.
This article reports the results of an open uncontrolled chart review study of amantadine treatment for executive dysfunction syndrome in patients with dementia. All patients admitted to the neuropsychiatry or geriatric psychiatry inpatient units of Johns Hopkins Hospital in 2000 and 2001 who were treated empirically with amantadine for executive dysfunction syndrome were included in the review. Of the 30 patients whose cases were reviewed, 17 (57%) were at least "much improved," and most patients were discharged taking amantadine, suggesting that their physicians believed that they may have benefited from it. The medication was well tolerated in this frail group of patients. Most patients were taking one or more concurrent psychotropic medications, which may have contributed to the positive outcomes. Despite its limitations, this study offers preliminary data to support a controlled trial of amantadine in patients with executive dysfunction syndrome.
Neurol Neurochir Pol. 2003;37 Suppl 5:183-8.
[Treatment of Parkinson disease in patients with surgical problems]
[Article in Polish]
Sobolewski P.
Oddzial Neurologii, Samodzielny Publiczny Zespol Zakladow Opieki Zdrowotnej
w Sandomierzu.
The aim of the reports is to emphasize difficulty in treatment of Parkinson's disease in patients with surgical problems. Complex treatment of this patients is of major therapeutic challenge. The use of either soluble forms of levodopa, parenteral amantadine or apomorphine in the immediate postoperative period for patients unable to take oral antiparkinson drugs and early resumption of the oral antiparkinson drugs increases patients' comfort, may reduce serious postoperative complications and are the key points in the management of the patients.
J Neural Transm. 2004 Apr;111(4):511-4.
The outcome of patients with severe head injuries treated with
amantadine sulphate.
Saniova B, Drobny M, Kneslova L, Minarik M.
Department of Anaesthesiology and Intensive Medicine, Comenius University
and University Hospital, Martin, Slovak Republic.
OBJECTIVE: To compare our pilot therapeutic results of patients with severe head injury treated either with standard therapy alone or with standard therapy plus amantadine sulphate. DESIGN: Retrospective pilot study. SETTING: Intensive Care Unit (ICU), University Hospital. PATIENTS: All patients with severe head injury (GCS < 8) admitted to the ICU between January 1, 1999 and December 31, 2001. The patients were divided into two groups based on the fact, whether they did or did not receive amantadine sulphate included in standard therapy. Group 1 consisted of 41 patients of average age 42.12 +/- 16.8 years, of them 35 were males and 6 females. Group 2 included 33 patients of average age 43.91 +/- 18.45 years consisting of the 30 males and 3 females. INTERVENTION: Both groups were treated with the standard therapy of severe head injury accepted in our institution. In addition, group 1 patients received amantadine sulphate in a dose of 200 mg i.v. twice daily for 3 days, starting on day 3 of hospitalisation. The reason for amantadin sulphate administration was persistent comatos condition. MEASUREMENTS AND RESULTS: Glasgow Coma Scale in patients on admission (after resuscitation) and on discharge from the ICU and mortality rate were compared. In the group 1 the average income GCS was 4.47 +/- 2.26 and the average outcome GCS was 9.76 +/- 3.95. In the group 2 the average income GCS was 4.70 +/- 2.14 and the average outcome GCS was 5.73 +/- 3.57. In the amantadine sulphate group two patients out of 33 died (6.06%). There were 17 deaths (51.51%) out of 33 patients in the second control group. CONCLUSION: In the group of patients with severe brain injuries treated with standard therapy plus amantadine sulphate the outcome GCS was higher and the case fatality rate lower than in the group treated with standard therapy alone.
J Neurol Neurosurg Psychiatry. 2004 Jan;75(1):141-3.
Duration of amantadine benefit on dyskinesia of severe Parkinson's
disease.
Thomas A, Iacono D, Luciano AL, Armellino K, Di Iorio A, Onofrj
M.
Neurophysiopathology, Movement Disorders Centre, Department of Oncology
and Neuroscience, Universita G. D'Annunzio, Chieti-Pescara, Pescara, Italy.
BACKGROUND: Recent short-term studies suggested that amantadine (Ama)
might ameliorate dyskinesia in patients with Parkinson's disease. A double-blind
study programmed over 12 months was designed to assess the duration of
the antidyskinetic effect of amantadine on levodopa induced dyskinesia.
METHODS: 40 patients treated for 7.5 (2.2) years with levodopa (729.3
(199.4) mg/day) and dopaminoagonists, having peak dose or dyphasic dyskinesia
with or without pain, were assessed with the Unified Parkinson's Disease
Rating Scale subscale IV, Items 32-34, the Dyskinesia Rating Scale and
Investigator Global Assessment. Twenty patients received amantadine chloridrate
(100 mg) and 20 received a placebo. The Ama or placebo could be withdrawn
when scores indicated worsening of dyskinesia, after agreement with the
patient. RESULTS: After 15 days of amantadine treatment there was a reduction
by 45% in the total dyskinesia scores. All patients in the placebo group
were withdrawn in 1-3 months and all patients in the Ama group were withdrawn
in 3-8 months (p = 0.01, p<0.001). Ama withdrawal induced a rebound
with increase of dyskinesia by 10-20% in 11 patients. CONCLUSION: 300
mg amantadine reduces dyskinesia in Parkinson's disease by approximately
45% but the benefit lasted less than eight months.
