| 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 Thereafter, AMA was withdrawn, and the patients were treated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. |
| GENERIC NAME: amantadine
BRAND NAME: Adamantan-Viregyt, Symmetrel
DRUG CLASS AND MECHANISM: Amantadine is a synthetic (man-made)
anti-viral drug that can inhibit the replication of viruses in cells.
To prevent a viral infection, the drug should be present before exposure
to the virus. Clearly, this is not practical for most viral infections.
It was initially used to prevent influenza A during flu season, and, if
given within 24 to 48 hours of the onset of flu symptoms, to decrease
the severity of the flu. Later amantadine was found to cause improvement
in the symptoms of Parkinson's disease. Amantadine's mechanism of action
in Parkinson's disease is not fully understood. Its effects may be related
to its ability to augment (amplify) the effects of dopamine, a neurotransmitter
in the brain, that is reduced in Parkinson's disease. Amantadine is less
effective than levodopa in Parkinson's disease but can offer additional
benefit when taken with levodopa. Amantadine was approved by the FDA in
1966.
PREPARATIONS: Amantadine is available as 100mg soft
gelatin capsules and as a syrup containing 50mg per each teaspoon.
STORAGE: Store at room temperature between 15 and 30°C
(59 and 86°F).
PRESCRIBED FOR: Amantadine is used for the prevention
or treatment of infections with influenza A virus, especially for individuals
at high-risk such as immunosuppressed patients and nursing home residents.
It should not be used as a substitute for vaccination. Amantadine also
is used for control of the symptoms of Parkinson's disease.
DOSING: Amantadine is taken once or twice daily with
or without food. If it causes an upset stomach, it can be taken with food.
For treatment of influenza, amantadine should be started within 24 to
48 hours after the onset of signs or symptoms and should be continued
for 24 to 48 hours after the disappearance of signs or symptoms. To prevent
influenza, amantadine should be started as soon as possible after exposure
to the influenza virus and continued for at least 10 days.
Persons with reduced kidney function and elderly persons may need lower
doses (or less frequent doses).
DRUG INTERACTIONS: Amantadine adds to the sedating effects
alcohol and other sedating drugs such as the benzodiazepine class of anti-anxiety
drugs (e.g., Valium, Ativan, Klonopin, Xanax, Ambien), the tricyclic class
of antidepressants (e.g., Elavil, Tofranil, Norpramin), dicyclomine (Bentyl),
certain antihistamines (Benadryl, Vistaril, Atarax, Tavist), opiate agonists
(e.g., Dilaudid; Vicodin; Percocet; Codeine) and certain antihypertensive
medications (e.g., Catapres, Inderal). Such combinations can cause dizziness,
confusion, lightheadedness, fainting, or dizziness upon standing.
Since amantadine amplifies the actions of dopamine in the brain, drugs
which block the effects of dopamine should be avoided in persons taking
amantadine when amantadine is used for the treatment of Parkinson's disease.
Such drugs include haloperidol (Haldol), metoclopramide (Reglan), and
phenothiazines, e.g., thioridazine (Mellaril) or triflupromazine (Stelazine).
The use of the diuretics hydrochlorothiazide or triamterene (Dyazide;
Maxzide) with amantadine can reduce the kidney's ability to eliminate
amantadine. This can lead to high levels of amantadine in the blood and
amantadine-associated toxicity.
PREGNANCY: No well-controlled studies have been done
in pregnant women to evaluate amantadine's safety. Physicians may choose
to use amantadine during pregnancy when the potential benefits outweigh
the potential but unknown risks to the fetus.
NURSING MOTHERS: Amantadine is excreted into breast
milk in low concentrations. Although no information is available on the
effects in infants, the manufacturer recommends that amantadine be used
cautiously in nursing mothers.
SIDE EFFECTS: The most frequent side effects associated
with amantadine include dizziness, loss of coordination, inability to
sleep, and nervousness, nausea, and vomiting. All of these side effects
have been reported to occur in about 1 in 20 persons. Effects can appear
after a few hours or several days of therapy. Less common side effects
include headache, irritability, nightmares, depression, confusion, drowsiness,
and hallucinations, weakness, amnesia, slurred speech, diarrhea, constipation,
and loss of appetite, and discolorations in the eye.
Caution! Before starting
to take this medicine, it is vital that you should consult your doctor!
Do not use it on your own initiative, without medical advice. |
