Weight loss abstract
A method of assisting weight loss involving the combined administration
of a rauwolfia alkaloid and at least one antidepressant, selected
from the groups consisting of aminoazoles, phenoxyphenylpropylamines,
and aminopropiophenones, in a daily regimen with the optional co-administration
of one or more sympathomimetic anorexic agents. In a typical embodiment
of this method, reserpine and trazodone are administered in a daily
regimen with diethylpropion, fenfluramine or both diethylpropion
and fenfluramine.
Weight loss claims
What is claimed is:
1. A method of assisting weight loss in a human in need thereof
which comprises administering to said human, over a sustained period
of time, both a rauwolfia alkaloid in the form of reserpine, and
at least one antidepressant selected from the group consisting of
trazodone, bupropion and fluoxetine in an administration regimen
sufficient to supply effective daily dosages thereof for assisting
weight loss.
2. The method of claim 1 wherein said antidepressant is trazodone
and both reserpine and trazodone are administered concomitantly.
3. The method of claim 1 wherein the daily dosage of reserpine
is between about 0.001 and about 0.01 milligram per kilogram of
human body weight.
4. The method of claim 1 wherein said antidepressant is trazodone
and the daily dosage of trazodone is between about 0.1 and about
6.0 milligram per kilogram of human body weight.
5. The method of claim 1 wherein said antidepressant is fluoxetine
and both reserpine and fluoxetine are administered concomitantly.
6. The method of claim 1 wherein the daily dosage of reserpine
is between about 0.001 and about 0.01 milligram per kilogram of
human body weight.
7. The method of claim 1 wherein said antidepressant is fluoxetine
and the daily dosage of fluoxetine is between about 0.1 and about
1.5 milligram per kilogram of human body weight.
8. The method of claim 1 wherein the rauwolfia alkaloid is reserpine,
and both trazodone and fluoxetine are administered, said reserpine,
trazodone, and fluoxetine being administered in a regimen sufficient
to supply effective daily dosages thereof for assisting weight loss.
9. The method of claim 1 wherein the rauwolfia alkaloid is reserpine,
and trazodone, bupropion, and fluoxetine are administered, said
reserpine, trazodone, bupropion and fluoxetine being administered
in a regimen sufficient to supply effective daily dosages thereof
for assisting weight loss.
10. The method of claim 1 wherein the rauwolfia alkaloid is reserpine,
and both trazodone and bupropion are administered, said reserpine,
trazodone, and bupropion being administered in a regimen sufficient
to supply effective daily dosages thereof for assisting weight loss.
Weight loss description
BACKGROUND OF THE INVENTION
The present invention pertains to a method of assisting weight
loss in patients which involves the administration of a unique combination
of pharmaceutically active ingredients to suppress appetite and
to a method of maintaining that weight loss by long term, chronic
administration of all or a portion of the components of this unique
combination.
While the causes of excess body weight and obesity are complex,
a common denominator in the overweight person's diet is a caloric
intake which exceeds his body's expenditure. A methodology which
combines dietary restriction with increased physical activity will
maximize potential weight loss. However, the obese patient has typically
developed eating and activity patterns which are counterproductive
to achieving weight reduction. One efficacious treatment of obesity
utilizes appetite suppressive drugs as adjuncts in a weight reduction
program. Thus increased compliance with and tolerance to a low-calorie
diet will often develop when an anorexic drug is prescribed for
the well-motivated patient. In many instances, however, the use
of an anorexic agent may produce undesired side effects or its effect
may diminish over a period of time.
DETAILED DESCRIPTION
The present invention pertains to a method of assisting weight
loss in patients through the administration of a unique combination
of pharmaceutically active ingredients to suppress appetite. In
particular, the present invention involves the concomitant administration
of effective amounts of a rauwolfia alkaloid and at least one antidepressant
selected from the group consisting of aminoazoles, phenoxyphenylpropylamines,
and aminopropiophenones in a single or multiple daily dose during
a weight loss regimen. While the mechanism of interaction between
the rauwolfia alkaloid and the selected antidepressants is not fully
understood, the effectiveness of this method of assisting weight
loss has been demonstrated in a number of clinical studies, discussed
more fully herein.
Rauwolfia alkaloids have been used as antihypertensive therapeutic
agents in the management of elevated blood pressure. Infrequently,
rauwolfia alkaloid derivatives have been prescribed in the management
of agitated psychotic states, such as schizophrenia.
Typical of the known rauwolfia alkaloids are deserpidine, alperaxylon,
reserpine, and rauwolfia serpentina. Of these, reserpine is preferred
for the present method because of its availability and established
clinical history. Oral dosage of the rauwolfia alkaloid should be
carefully adjusted according to individual tolerance and response,
using the lowest possible effective dosage. Typically, the amount
of rauwolfia alkaloid administered daily is from about 0.001 to
about 0.01 mg per kg of body weight.
The aminoazole antidepressants, such as etoperidone, mepiprazole,
and trazodone, are chemically unrelated to other currently available
antidepressants; see; e.g., U.S. Pat. Nos. 3,857,845; 3,491,097;
and 3,381,009. Aminoazole antidepressants are therapeutically indicated
for the relief of major depression and some clinical studies have
indicated the aminoazole antidepressants may be of value in the
treatment of schizophrenic disorders or alcohol dependency. While
the aminoazole advantageously provides an antidepressant effect,
it appears to also assist directly in weight loss and thus is distinguished
from other antidepressants such as the tricyclics.
Of the aminoazole antidepressants, trazodone is preferred because
of its availability. As a clinically co-active anorexic agent, trazodone
is administered in a daily amount of from about 0.1 to 6.0 mg per
kg of body weight. The effective dosage for each individual is adjusted
on the basis of clinical response.
Typically, a combined dosage of from about 0.001 to 0.01 mg per
kg of body weight of reserpine and 0.1 to 6.0 mg per kg of body
weight of trazodone is administered daily. Conveniently, the two
can be administered at the same time.
The preferred phenoxyphenylpropylamine antidepressant is fluoxetine.
Clinical studies indicate fluoxetine relieves the symptoms of major
depressive illness. In contrast to the tricyclic antidepressants,
fluoxetine does not inhibit the noradrenergic uptake system. This
phenoxyphenylpropylamine antidepressant should be administered within
the range of from about 0.1 to 1.5 mg per kg body. However, the
effective dosage should be adjusted on the basis of individual clinical
responses.
The aminopropiophenone antidepressants are therapeutically indicated
for relief of depression in patients who are unresponsive or intolerant
of other available antidepressants. Bupropion, the preferred aminopropiophenone
antidepressant, is not chemically related to other antidepressants,
but is pharmacologically similar to the tricyclic compounds; see;
e.g., U.S. Pat. Nos. 3,819,706 and 3,885,046. As an effectic anorexic
agent, bupropion is typically administered in a daily amount of
from about 0.05 to about 7.0 mg per kg of body weight.
As the duration of action for these pharmaceutically active agents
typically exceeds 24 hours, the frequency of administration need
not be bound to a daily dosage schedule. An administration regimen
sufficient to supply effective daily dosages may be satisfied by
single daily doses, multiple daily doses, alternate day doses, multiple
weekly doses, or weekly doses.
Since the rate of weight loss will vary from patient to patient,
and is not consistent for each patient, the effectiveness of the
treatment is best observed over a period of weeks. The patient should
be carefully monitored with regard to other medications and to overall
physical condition. Exercise naturally assists the treatment.
In the combined administration of the rauwolfia alkaloid and one
or more of the specified antidepressants, the administration of
one or more of the sympathomimetic anorexic agents has proved successful
in some instances in promoting patient compliance to a calorically-restricted
diet. In this embodiment the sympathomimetic anorexic agents are
administered in an effective amount, normally its recommended dosage,
over a portion of the time during which the rauwolfia alkaloid and
one or more of the specified antidepressants are being administered.
The term sympathomimetic anorexic agents refers to compounds pharmacologically
similar to amphetamine, dextroamphetamine, methamphetamine, benzphetamine,
phentermine, chlorphentermine, fenfluramine, dextrofenfluramine,
clortermine, mephentermine, phenmetrazine, phendimetrazine, diethylpropion,
mazindol, phenylpropanolamine, ephedrine, pseudoephedrine and methylphenidate.
A representative sympathomimetic anorexic agent is diethylpropion.
The usual adult dosage of diethylpropion is typically from about
0.15 to about 4.0 mg per kg of body weight but again the dosage
should be individualized to obtain the most desirable effect. Diethylpropion
is a known stimulant of the central nervous system and this medication
generally is administered early in the normal waking hours of the
patient to prevent possible insomnia. Surprisingly, however, the
stimulating effects of diethylpropion are partially surpressed in
many patients in the practice of the present invention so that,
in such cases, it can be administered later in the day.
Alternatively, the sympathomimetic anorexic can be fenfluramine.
This can be administered in the aforementioned regimen of the rauwolfia
alkaloid and one or more of the specified antidepressants as a useful
adjunct to weight reduction. The preferred dosage of fenfluramine
is typically from about 0.2 to about 1.8 mg per kg of body weight
but should be individualized to obtain the most therapeutic response
at the lowest effective dose. Fenfluramine and dextrofenfluramine
are pharmacologically distinct from other sympathomimetic anorexics
in that their mode of action results in the depression of the central
nervous system. Thus, fenfluramine and dextrofenfluramine can be
administered later in the day than is the case with many other sympathomimetic
agents. This differentiating characteristic of fenfluramine and
dextrofenfluramine also can be utilized to permit co-administration
of these anorexic agents with other sympathomimetic compounds, such
as diethylpropion, without exacerbating potential side effects,
such as insomnia, restlessness, or irritability.
An alternate embodiment of weight loss involves the co-administration
of at least one or more of the specified antidepressants with one
or more sympathomimetic anorexic agents. While the appetite suppressant
drugs are known to be useful adjuncts to a weight loss program,
the usual duration of their efficacy is brief. After about six to
twelve weeks of administration, tolerance to some of the sympathomimetic
anorexic agents develops and they are no longer dependable aids
in controlling appetite. Significant increases in the efficacy of
appetite suppression drugs is observed in a method which utilizes
at least one antidepressant selected from the groups consisting
of aminoazoles, phenoxyphenylpropylamines and aminopropiophenones,
during the co-administration of sympathomimetic anorexic agents.
Clinical studies thus demonstrate potentiation in the duration of
action of the sympathomimetic anorexics, such as diethylpropion
and fenfluramine, when administered in a daily regimen with at least
one or more of the specified antidepressants.
The preferred dosage of the antidepressant trazodone in this embodiment
is from about 0.1 to 6.0 mg per kg of body weight during the co-administration
of the sympathomimetic anorexic agent. In this embodiment, diethylpropion
is administered at a dosage of about 0.15 to about 4.0 mg per kg
of body weight whereas fenfluramine is administered in a regimen
with the selected antidepressant in the range of from about 0.2
to about 1.8 mg per kg of body weight. The most effective dosages
for the combined administration of the diethylpropion and the fenfluramine
during the co-administration of one or more of the specified antidepressants
should be within the ranges previously recited. However, the preferred
dosages should be adjusted on the basis of the individual clinical
response of each patient.
The following examples typify the mode of application for the method
of assisting weight loss.
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