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.
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.
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.
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.
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 dHepato-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.
