WO2001067890A2

WO2001067890A2 - Composition and method to treat weight gain and obesity attributable to psychotropic drugs

Info

Publication number: WO2001067890A2
Application number: PCT/US2001/006637
Authority: WO
Inventors: Judith J. Wurtman; Richard J. Wurtman
Original assignee: Massachusetts Institute Of Technology
Priority date: 2000-03-14
Filing date: 2001-03-02
Publication date: 2001-09-20
Also published as: WO2001067890A3; AU2001243369A1

Abstract

A composition and method of use for the prevention and/or treatment of weight problems attributed to the use of psychotropic drugs. The composition contains at least one form of carbohydrate and is substantially free of protein. In a preferred embodiment the composition is in the form of a snack food. Administration of the snack food results in an elevation of the subject's plasma Tp/Lnaa ratio, relative to the subject's pre-administration plasma Tp/Lnaa ratio. In alternative embodiments, the snack food either further contains tryptophan, 5-hydroxytryptophan, or melatonin, or is administered either after, concurrently, or before the administration of a second composition that contains either tryptophan, 5-hydroxytryptophan or melatonin.

Description

COMPOSITION AND METHOD TO TREAT WEIGHT GAIN AND OBESITY ATTRIBUTABLE TO PSYCHOTROPIC DRUGS

1. STATEMENT OF FEDERAL SUPPORT This invention was made with Government support under Grant Number NDH-

5M01-RR00088 awarded by the National Institutes of Health. The government has certain rights in the invention.

2. FIELD OF THE INVENTION The present invention relates generally to novel therapeutic compositions comprising carbohydrate blends and to methods of using the foregoing for the treatment of weight gain and obesity attributable to the use of psychotropic drugs or to combat weight gain due to the withdrawal from psychotropic drugs.

3. BACKGROUND OF THE INVENTION

There have been many treatments suggested for overcoming or reducing weight gain and/or for treating obesity. It is known that some of these weight problems are attributed to use of psychotropic drugs such as "classic" psychotropic drugs like haliperidole, thorazine, newer atypical antipsychotics like clozapine, olanzapine, risperidone; anti-depressant drugs like serotonin re-uptake inhibitors Prozac, Zoloft, and Paxil; monoamine oxidase inhibitors and trycyclics like nortryptiline and imipramine; the anti-manic drugs like lithium; anti-epileptic drugs like depakote and valproic acid; agents used to treat anxiety, panic disorder and obsessive-compulsive disorder; as well as illegal ' psychotic drugs like cocaine, heroin, marijuana and the like.

A number of studies have shown that patients with weight problems have lower serotonin levels than individuals with normal weight. One symptom of this misbalance is manifested in so-called carbohydrate craving. However, patients experiencing weight gain attributed to the use of psychotropic drugs have not been shown to manifest signs of central serotonin deficiency such as carbohydrate craving. In fact some of the psychotropic drugs such as prozac and other serotonin uptake blockers actually increase serotonin activity. Approaches aimed at changing behavior to combat this weight gain such as calorie intake restrictions, adherence to special diets or physical exercise have had limited success. Currently there is no means of treating the weight disturbances commonly experienced on a recurring basis by a large number of patients on psychotropic drugs or by those who are trying to quit such drugs. A simple treatment that does not require major behavioral changes would be of great benefit.

4. SUMMARY OF THE INVENTION

In mammals, the amino acid tryptophan is the precursor to serotonin synthesis in the brain. Certain carbohydrates when ingested can increase the ratio of tryptophan to large neutral amino acids (T.LNAA) in the blood stream. This increase of T.LNAA allows a higher level of tryptophan to enter the brain, which is necessary for increasing serotonin synthesis. While carbohydrates from normal food can shift this T:LNAA ratio to a limited extent, these normal foods also contain fats and other ingredients like fibers and protein, some of which slow down digestion and otherwise interfere with the necessary shift in the balance of amino acids in the blood.

The present invention provides novel carbohydrate compositions that are rapidly digested and reduce the incidence of weight gain and/or obesity resulting from the use of psychotropic compounds. The invention is therefore directed generally to novel therapeutic compositions comprising rapidly-digestible carbohydrate blends, and to methods of using same for the treatment, prevention, amelioration, or dietary management of weight problems. Administration of a composition according to the method of the present invention is of great benefit to those who experience disturbances of mood and/or appetite and who accordingly are treated with psychotropic drugs and consequently develop weight problems.

It is therefore an object of the present invention to provide therapeutic compositions useful for the treatment, prevention or dietary management of obesity.

It is a further object of the present invention to provide therapeutic compositions comprising novel blends of carbohydrates, such as, but not limited to, dextrose, galactose, pre-gelatinized starch, mannose, sucrose, maltose, lactose, dextrin, maltodextrin, and mixtures thereof, wherein they contain no more than 1-2 grams of fat, and preferably are essentially fat free.

It is a further object of the present invention to provide therapeutic compositions including carbohydrate blends comprising about 20-200 g of a rapidly-digestible carbohydrate blend in a solution essentially free of protein, wherein the solution comprises a ratio of about 3-12 mL water to about 1 gram carbohydrate' blend and an acidulant selected from the group consisting of adipic acid, citric acid, fumaric acid, lactic acid, succinic acid, tartaric acid, ascorbic acid, acetic acid, and malic acid, to maintain a therapeutically effective pH at less than 6 and wherein the carbohydrate blend comprises about 60-100% dextrose, dextrin, maltodextrin, or a mixture thereof, and 0 to 40% starch or pre-gelatinized starch, or a mixture thereof. It is a further object of the present invention to provide carbohydrate blends comprising novel mixtures of dextrose and starch, particularly in ratios of about 80% to 100% dextrose to 0 to 20% starch, wherein the total amount of carbohydrate in said blend comprises about 40-80 grams. Still more preferred are compositions comprising carbohydrate blends of dextrose and starch in ratios of about 80% to 85% dextrose to 15 to 20% starch. Specifically preferred is a composition comprising a carbohydrate blend of 45 g dextrose and 3 g starch.

It is a further object of the present invention to provide carbohydrate blends in the form of a solution comprising dextrose, starch and water. Preferably, the solution comprises about 2-10 mL of water to 1 gram of carbohydrate blend. More preferably, the solution comprises about 5-6 mL water to 1 gram of carbohydrate blend.

It is a further object of the present invention to provide compositions wherein the solution further comprises an acidulant to maintain a therapeutically effective pH at less than 6. Such acidulants include, but are not limited to, adipic acid, citric acid, fumaric acid, lactic acid, succinic acid, tartaric acid, ascorbic acid, acetic acid, and malic acid. Preferred are solutions with a pH between about 2 and 5. More preferred is a solution comprising 60 g dextrose and 10 g galactose, 280 mL water and malic acid to maintain the solution at a pH of 2. It is a further object of the present invention to provide a composition further comprising prodrugs of serotonin, or intermediates in the biosynthesis of serotonin such as tryptophan or 5-hydroxytryptophan, or their salts.

It is a further object of the present invention to provide a composition further comprising melatonin.

It is a further object of the present invention to provide therapeutic compositions for treating, preventing, ameliorating, or managing weight problems, wherein such weight problems result from the use of psychotropic drugs. Such methods comprise administering a therapeutically effective amount of said novel compositions to subjects in need of such treatment. Without limiting the invention, and by way of theoretical hypothesis only, it is believed that such therapeutic compositions are effective by increasing the ratio of T:LNAA in the blood stream thereby increasing the level of serotonin production in the brain. Such increase is believed to relieve those conditions related to serotonin and brain functioning by supplying the nutrients necessary for serotonin synthesis.

It is a further object of the present invention to provide a method of treating, ameliorating, preventing or managing obesity resulting from the use of psychotropic drugs, comprising administering a combination of novel carbohydrate blend compositions of the present invention together with other useful agents, such as but not limited to vitamins; tryptophan, 5-hydroxytryptophan, tyrosine, and other amino acids; ovarian hormones; detoxifying agents and/or diuretics.

5. DETAILED DESCRIPTION OF THE INVENTION The present invention is directed to compositions and methods for effecting weight loss and/or preventing weight gain associated with the use of psychotropic drugs such as those affecting serotonin mediated neurotransmission, including drugs that act directly upon the receptors, as well as drugs that reduce the rate of firing of the serotonin neurons. More specifically, the invention is applicable in situations when drugs affecting serotonin-mediated neurological networking and transmission are involved. The present invention is directed towards assisting individuals that are taking, or are planning on taking psychotropic drugs, wherein the psychotropic drugs result in the individual's having lower-than-normal serotonin-mediated neurotransmission, thus encompassing either lower than normal amounts of serotonin inside the synapses, or a decreased ability of that serotonin to combine with its receptors.

The neurotransmitter serotonin (5-hydroxytryptamine or 5-HT) is 3-(beta- aminoethyl)-5-hydroxyindole. It stimulates or inhibits a variety of smooth muscles and nerves and, among others, has effects on secretion by both exocrine and endocrine glands and on functioning of the respiratory, cardiovascular and central nervous systems. Within the central nervous system (CNS), serotonin serves as a neurotransmitter in the brain and spinal cord, where it is the chemical transmitter of neurons referred to as tryptaminergic or serotoninergic neurons. These neurons are involved in control of sleep, appetite, nutrient selection, blood pressure, mood, endocrine secretion, aggressivity and numerous other sensitivities to external stimuli. When serotonin either directly or indirectly is dysfunctional or levels of it are aberrant, various clinical symptoms occur. These may be manifest in a patient as a stress, anxiety, changes in mood or personality, irritation, insomnia and the like. The drugs for such indications are discussed in Goodman and Gilman's Pharmacological Basis of Therapeutics, Seventh Edition, 1985, Alfred G. Gilman et al., editors, pages 192-201 "Drags Used in the Treatment of Disorders of Mood", incorporated by reference. Additional discussion of these drug compounds and their analogs' pharmacologic action in inhibiting 5-HT and in treating neurological disorders is found in the Physician's Desk Reference (PDR), 47th Ed., 1993, published by Medical Economics Co., Inc., Montvale, N.J., indexed by generic compound name and incorporated by reference herein.

In its broad embodiment, the present invention comprises the treatment, inhibition, and/or amelioration of weight gain resulting from the administration of psychotropic drugs such as "classic" psychotropic drugs, including but not limited to haliperidole, thorazine and the like, or newer "atypical" antipsychotics including but not limited to clozapine, olanzapine, or risperidone; anti-depressant drugs including but not limited to serotonin re-uptake inhibitors such as Prozac, Zoloft, and Paxil; monoamine oxidase inhibitors and tricyclics such as nortryptiline and imipramine; anti-manic drugs such as lithium; anti-epileptic drugs such as depakote and valproic acid; agents used to treat anxiety, panic disorder and obsessive-compulsive disorder; as well as illegal psychotic drugs such as cocaine, heroin, marijuana and the like.

In its preferred embodiment, the present invention comprises the treatment or inhibition of weight gain resulting from the administration of antipsychotics including but not limited to atypical antipsychotics, anti-epileptic medications, and medications for the treatment of bipolar manic depressive diseases. Atypical antipsychotics include but are not limited to clozapine, olanzapine, loxapine, molindone, resperidone, and thiothixine. Anti-epileptic, bi-polar and related medications include but are not limited to lithium, valproic acid, divalproex sodium, gabapentin, felbamate, and carbamazepine.

Therefore, various classes of psychotropic drugs exist that are taken by patients in need thereof and in the course of such therapy or as result of a drug withdrawal, these patients experience weight gain. Accordingly this invention preferably benefits patients in need of weight loss whose weight gain is attributed the use of psychotropic drugs.

For the purposes of this disclosure, the terms "subject", "individual", and "patient" may be used interchangeably to refer to a human exhibiting weight problems.

Preferably, the composition is a snack food that is comprised of complex and/or simple carbohydrates, and is substantially free of protein. As used herein, the term

"carbohydrate" encompasses both complex carbohydrates and simple sugars. Preferably, the carbohydrate is of a high glycemic index, such as maltodextrin, polycose (a synthetic polyglucose), dextrose, sucrose, maltose, to name a few. Other sources of carbohydrate include but are not limited to, galactose, pre-gelatinized starch, mannose, lactose, dextrin, and mixtures of the above. Rapidly digestible blends of carbohydrate can likewise be used.

As used herein, the term "protein" includes any high quality protein derived from an animal or plant source, and does not include basic amino acids, amino acid derivatives, or small peptides. Proteins derived from animal foods such as dairy products or eggs are suitable, including, but not limited to, whey, casein, or albumin. The snack food can be further comprised of additional ingredients including, but not limited to, sources of fat, fiber, calcium, and other vitamins and minerals. The composition provided is preferably low in fat, however, with preferably less than 20% of the calories provided in the composition deriving from fat. The amount of fiber, such as methylcellulose, can also be adjusted, but preferably provides between about 20-25 grams of fiber per day.

The compositions of the present invention can be provided in any convenient form, including but not limited to powders, liquids, soups, food bars, pudding, and milk shakes. Natural and/or artificial flavorings can also be added, including the following flavors: chocolate, vanilla, strawberry, apple, ram, banana, orange, mocha, etc. As stated, in its preferred embodiment, the composition is a snack food.

Preferably the snack food should elevate the Tp/Lnaa ratio relative to the pre- consumption levels. Preferably, the post-consumption plasma Tp/Lnaa ratio is elevated relative to the pre-consumption plasma Tp/Lnaa ratio by about 10% or more, more preferably by 15% or more, most preferably by about 20% to about 30% or more.

Higher levels of tryptophan in the brain after the snack is consumed, in turn, enhance the synthesis of serotonin in the brain which provides an enhanced feeling of satisfaction, well being and ability to control further food intake. The present invention, thus, provides broadly, food compositions for consumption in connection with a weight loss diet plan. Preferably, the snack food comprises at least one form of carbohydrate and is substantially free of protein. The snack food can include complex carbohydrates, simple sugars or both.

In a particular embodiment of the invention, the snack food has a caloric content ranging from about 50 to about 500 calories, preferably, from about 175 to about 225 calories, and most preferably, from about 200 to about 225 calories. Its protein content is preferably substantially zero. Its carbohydrate content can range from about 20 to about

200 grams, preferably about 40 to about 60 grams, most preferably about 45 grams. In addition, the snack food of the present invention can also provide about 0 to about 5 grams of fat, preferably, about 0 to about 3 grams, most preferably, about 1-2 grams, and about 0 to about 20 grams of fiber, preferably, about 1 to about 15, and most preferably, about 5 to about 10 grams. The carbohydrates used in the present invention should preferably have a glycemic index higher than fructose. Suitable carbohydrates (CHO) include, but are not limited to, dextrose, sucrose, maltose, maltodextrin or polycose.

A number of compounds stimulate or enhance serotonin-mediated neurotransmission, sometimes referred to as serotoninergic drugs, and are thus useful in extending the beneficial effect obtained through the administration of the carbohydrate containing composition; e.g. the snack food. The compounds can be added to the carbohydrate composition, or can be administered as a second composition. This second composition can be administered either prior to, concurrently or after the carbohydrate composition. Preferably the second composition is administered within one hour after administration of the carbohydrate composition. In a preferred embodiment, these compounds include D,L-fenfluramine, dexfenfluramine, tryptophan, melatonin and pharmaceutically acceptable salts thereof. Suitable salts can be formed from the above compounds, for example, as addition salts using the following acids: inorganic acids such as hydrochloric acid, sulfuric acid, and phosphoric acid or organic acids such as acetic acid, maleic acid, valeric acid, caproic acid, benzoic acid and nicotinic acid.

"Fenfluramines" is used in the present application as meaning a racemic mixture of D,L-fenfluramine, which is also called N-ethyl-α-methyl-3-(trifluoro- methyl)benzeneethanamine; the dextrorotatory isomer known as dexfenfluramine and also as D-fenfluramine; or the pharmaceutically acceptable salts of these compounds. Suitable salts can be formed from dexfenfluramine or D-L-fenfluramine, for example, as addition salts using the following acids: inorganic acids such as hydrochloric acid, sulfuric acid, and phosphoric acid or organic acids such as acetic acid, maleic acid, valeric acid, caproic acid, benzoic acid and nicotinic acid.

The serotoninergic drags MK-212, DOI, m-CPP, Ro 60-0175/ORG 35030, Ro 60-0332/ORG 35035, Ro 60-0175, Org 12962, Ro 60-0332, (S)-2-(chloro-5-fluoro-indol- l-yl)-l-methylethylamine 1:1 C4H4O4, (S)-2-(4,4,7-trimethyl-l,4-dihydro-indeno(l, 2- b)pyrrol-l-yl)-l-methylethylamine 1:1 C4H4O4, and SB 206553 fall into the class of drags which activate postsynaptic receptors. These are agonist drags which bombard the serotonin receptors of postsynaptic cells and mimic the effect of large amounts of serotonin reacting with the postsynaptic cells' serotonin receptors.

6-Chloro-2-(l-piperazinyl)pyrazine (MK-212), can be obtained from Merck & Co., Inc. Whitehouse Station, NJ. (S)-2-(4, 4, 7-trimethyl-l, 4-dihydro-indeno (1, 2-B) pyrrol- l-yl-)-l-methyl-ethylamine (Ro 60-175/ORG 35030) can be obtained from F. Hoffmann-LaRoche Ltd., Basel, Switzerland. (S)-2-(Chloro-5-fluoro-indol-l-yl)-l- methylethylamine (Ro 60-0332/ORG 35035) is obtained from F. Hoffmann LaRoche Ltd., Basel, Switzerland. l-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) can be obtained from Research Biochemical International, Natick, MA. l-(3- Chlorophenyl)piperazine (m-CPP) can be obtained from Research Biochemical

International, Natick, MA.

Because serotonin present in the bloodstream is excluded by the blood-brain barrier from entry into the brain, the administration of precursors such as L-tryptophan (L-TP) or L-5-hydroxytryptophan (L-5-HTP) is used to increase brain concentrations of serotonin. The supplementation of precursors for serotonin comprises administering, for an effective period, an effective amount of L-tryptophan or preferably L-5- hydroxytryptophan as the intermediate precursors for serotonin (5-hydroxytryptamine). It is understood that any of its L, D or racemic forms are suitable, but preferably precursors are in L form. Furthermore, one skilled in the art will know to make tryptophan from 3- indolacetic acid or 3-indolpyruvic acid or use these acids as alternative to tryptophan and thus avoid the hepatic degradation by tryptophan pyrrolase. Other precursors or intermediates thereof are equally suitable with or without further modification, including but not limited to diethyl N-benzyloxycarbonyl-5-benzyloxycarbonyloxy-L-tryptophyl-L- aspartate, dibenzyl N-benzyloxycarbonyl-5-hydroxy-L-tryptophanylasρartate, 5- Hydroxy-L-tryptophyl-L-aspartic acid trihydrate, diethyl N-benzyloxycarbonyl-5- hydroxy-L-tryptophyl-L-glutamate, diethyl 5-hydroxy-L-tryptoρhyl-L-glutamate hydrochloride, dibenzyl L-benzyloxycarbonyl-5-hydroxytryptophyl-L-glutamate, 5- hydroxy-L-tryptophyl-L-glutamic acid, pentachlorophenyl ester of N-benzyloxycarbonyl- 5-hydroxy-L-tryptophan, methyl ester of N-benzyloxycarbonyl-5-hydroxy-L-tryptophyl- L-tyrosine, N-Acetyl-5-hydroxy-L-tryptophan, methyl ester of N-acetyl-5-hydroxy-L- tryptophyl-L-tyrosine, methyl ester of n-acetyl-5-hydroxy-L-tryptophyl-5-hydroxy-L- tryptophan, 5-hydroxy-L-tryptophyl-L-alanine hydrate, 5-hydroxy-L-tryptophan-L-valine, 5-hydroxy-L-tryptophyl-L-leucine, 5-hydroxy-L-tryptoρhyl-L-proline, 5-hydroxy-L- tryptophyl-L-phenylalanine, 5-hydroxy-L-tryptophyl-5-hydroxy-L-tryptophan, 5- hydroxy-L-tryptophyl-L-tryptophan, 1-5-hydroxytryptophyl-L-serine, 5-hydroxy-L- tryptophyl-L-arginine, 5-hydroxy-L-tryptophylglycine, 5-hydroxy 1-tryptophyl-gamma- aminobutyric acid, 5-hydroxy-L-tryptophanamide hydrate, methyl ester of 5-hydroxy-L- tryptophyl-L-histidine, benzyl ester of L-5-hydroxytryptophan, benzyl ester of N- benzyloxycarbonyl-5-hydroxy-L-tryptophyl-5-hydroxy-L-tryptophan, 5-Hydroxy-L- tryptophyl-5-hydroxy-L-tryptophan hemihydrate, 5-hydroxytryptophan inosinate, theophylline salt of (DL) 5-hydroxytryptophan, and the like.

These serotonin precursors can be administered alone or in combination with the stimulants of serotonin synthesis including but not limited to vitamin Bl, vitamin B3, vitamin B6, biotin, S-adenosylmethionine, folic acid, ascorbic acid, magnesium, coenzyme Q10, and piracetam. Alternatively and additionally one skilled in the art will know to include serotoninergic drags that act as serotonin agonists including but not limited to ergolide mesylate, pergolide mesylate, buspirone, (3beta)-2,3-dihydrolysergine, (3beta)-2,3- dihydroisolysergine, (3beta)-2,3-dihydrolysergol, (3beta)-2,3-dihydrolysergene, (3beta, 5beta, 8beta)-9,10-didehydro-2,3-dihydro-6-methyl-8-(methylthiomethyl) ergoline, (3beta, 5beta, 8beta)-9,10-didehydro-2,3-dihydro-6-methylergoline-8-ac etonitrile, (3beta, 5beta, 8beta)-9, 10-didehydiO-2,3-dihydro-6-methyl-8-(phenylthiomethyl) ergoline, (3beta, 5beta, 8beta)-9,10-didehydro-2,3-dihydro-6-methyl-8-(2-pyridyl thiomethyl) ergoline, (3beta)-2,3-dihydro-methyllysergate, (3beta, 5beta, 8beta)-9,10-didehydro-2,3- dihydro-8-methyl-6-propylergoline. For practicing the invention, the active serotonin-mediated neurotransmission stimulating compound can be administered to a patient as a pharmaceutical composition comprising the active compound admixed with a pharmaceutically acceptable carrier, including one or more excipients. For example, the compound or precursor can be administered to a patient as a pharmaceutical composition comprising in a preferred embodiment either L-tryptophan or L-5-hydroxytryptophan admixed with a pharmaceutically acceptable carrier, including one or more excipients.

It is to be understood that according to the teachings of the invention, the invention can be practiced by administering serotonin-mediated neurotransmission stimulating compounds, for example, tryptophan or 5-hydroxytryptophan, to a subject as a single unit dose one or more times per day, or as a plurality of unit doses once or more times per day without deviating from the teachings of the invention.

It is to be further understood that the present invention as disclosed herein, also includes a method of making a medicament for treating and/or inhibiting weight gain resulting from the use of psychotropic drugs, wherein the method comprises a step of mixing a serotonin precursor such as tryptophan or 5-hydroxytryptophan with a pharmaceutically acceptable inert ingredient.

The pharmaceutically acceptable carrier, excipient, and/or inert ingredient of choice utilized for a formulation used in accordance with the invention depends on the mode of administration to a subject. The compositions of this invention are suitable for oral, parenteral, buccal, sublingual or rectal administration. The resulting pharmaceutical compositions are, for example, tablets, coated tablets, capsules, soft gelatin capsules, drinkable emulsions, suspensions or solutions for oral or injectable administration, sublingual tablets or suppositories. They can also be formulated into a sustained release form. Among the various excipients which can be used for these purposes include talc, magnesium phosphate, lactose or silica or the like. To the solid forms can be added a filler, a diluent, a binder such as ethyl-cellulose, dihydroxypropyl cellulose, carboxymethyl cellulose, microcrystalline cellulose, gum arabic, gum tragacanth or gelatin. The compositions of this invention can also be flavored, colored or coated with a wax or a plasticizer.

The compositions of this invention can also be administered through sachets to which the subject adds water, or as a food based preparation, functional food, dietary supplement or nutraceutical. For the purposes of this application, "functional food" is defined as a food engineered or supplemented to give improved nutritional value, "dietary supplement" is defined as a substance produced by isolation, or microbial culture purification that gives health benefits, and "nutraceutical" is defined as a food, or parts of a food, that provide medical or health benefits, including prevention and treatment of clinical conditions and/or symptoms related thereto. The compositions of this invention can also be isolated from varying plants or components thereof including but not limited to root, tuber, rind/peel, bark, seed, fruit, bulb, flower, rhizome, leaf, stem, oil, shell, capsule, twig, resin, extract, and bean. In addition, the aforementioned components can be consumed by the subject, thereby providing the subject with the active ingredient(s) of the invention disclosed herein.

Where either tryptophan or 5-hydroxytryptophan or a pharmaceutically acceptable salt thereof is administered, an effective dose ranges from about 20 mg to about 4 g/day, preferably from about 50 mg to about 1 g/day, more preferably about 50 mg to about 400 mg/day, and most preferably about 100 mg/day. As stated, this administration can be concurrent with, or subsequent to, administration of the carbohydrate blend composition. The following examples are further provided. 6. EXAMPLES

5.1 COMPOSITIONAL INFORMATION

The composition is a carbohydrate blend of the present invention. The composition ingredients are all generally recognized as safe (GRAS) without limitations; the compositions themselves are therefore also GRAS; and the compositions are formulated in full compliance with all good manufacturing practice. regulations of the Food and Drag Administration (FDA).

Examples of carbohydrate compositions include but are not limited to: (1) 44.5 g of dextrose, 3 g starch, 1.4 g malic acid, pH 2, 270 mL water, orange flavoring; (2) 60 g dextrose, pH 5, 180 mL water; (3) 60g dextrose, pH 2, 360 mL water; and (4) 30g dextrose, pH 2, 360 mL water.

5.2 APPETITE

Blood samples are obtained from subjects at various times before and after consumption of carbohydrate blends of the present invention to determine the ratio of T:LNAA. Subjects administered with carbohydrate blends of the present invention, have a T:LNAA ratio of 0.217±0.025 after ingestion compared with a 0.168±0.016 pre- ingestion measurements and compared with carbohydrate blends containing proteins and other constituents. Further, there is an earlier onset and greater increase of T:LNAA using blends of the present invention over normal carbohydrates (bagel, juice, or potato).

5.3 HUMAN TESTS Carbohydrate blends of present invention or a placebo solution are tested in subjects suffering from weight gain due to psychotropic drug use.

A 42 year old female gained 35 pounds on Zoloft and attributed the weight gain uncontrollable carbohydrate craving. She was not obese prior to Zoloft treatment. She begins loosing weight after treatment with a carbohydrate-rich, protein and fat poor beverage that elevates brain tryptophan uptake even though she continues on Zoloft.

A 35 year old woman gained about 70 pounds from treatment with depakote for bipolar disease (mania and depression). She initiates instant weight reducing diet therapy with carbohydrate beverage and successfully looses weight. Reduction of carbohydrate craving, is a significant effect by the instant composition.

A woman of 73 gained about 60 pounds from long term treatment with Prozac. After about nine months on the instant diet she looses approximately 40 pounds while still being on anti-depressant therapy. Due to orthopedic problems she is immobile and weight loss cannot be attributed to any physical exercise or any other activities or treatments. The eating habits are now under control and craving for carbohydrates is ceased.

A 32 years old man experiencing cocaine withdrawal gains about 25 pounds, which appears to be attributable to carbohydrate craving. Therapy with the instant compositions quickly results in weight loss of about 15 pounds. Man is lost to follow-up and no further information is available to verify further progression. A woman in her thirties with a long history of depression treatment failure is presented requesting new treatment. She had, at various times, been bulimic, self- mutilating, alcoholic, and subject to obsessive thoughts. She had recurrent major depressive episodes which included characteristic vegetative signs of disturbed sleep, decreased appetite, energy, ability to concentrate and remember as well as the affective symptoms of sadness, irritability, and intense anxiety. A withdrawal from antidepressants caused weight gain. While on new therapy with clomipramine hydrochloride (Anafranil) she became able to sleep but within a few months gained 50 pounds. The carbohydrate composition however causes her to lose weight by about 30 pounds.

An obese woman in her forties is hospitalized for recurrent major depressive symptoms. She is treated with large doses of amitriptyline (Elavil), fluoxetine hydrochloride (Prozac) and eventually sertraline hydrochloride (Zoloft) with marginal effects. She then took a lethal overdose of amitriptyline from which she surprisingly survived. During her hospital stay, a stimulant, Ritalin, is added in doses up to 160 mg daily because of her lifelong distractibility and school difficulties consistent with Attention Deficit Disorder. She feels markedly better on Ritalin plus Zoloft 150 mg in the morning but still complains of craving for sweets, which in her case resulted in 100 lb plus weight gain. She begins carbohydrate therapy along with substantial doses of alprazalom (Xanax). The combination allows her to be out of a hospital and within a reasonable period of time she looses about 60 pounds. A 37 year old librarian with a bipolar depression which resisted tricyclics, a- typical antidepressants, and lithium, is presented. In addition she complained of weight problems which made her even more depressed. She started taking 600 mg Tegretal with 50 mg of Trexan in combination with a carbohydrate diet. She then reports that the medicine combined with diet improves her mood and reduces her weight considerably.

A 45 year old woman, enters the clinic weighing 279 pounds, she is 5 '5" in hight. She has been on medications for years for bipolar illness. At presentation she is on Risperidone (Risperdal), an antipsychotic medication, Venlaxfaxine (Effexor) an antidepressant that prevents norepinephrine and serotonic reuptake, and gabapentine

(Neurontin), and anticonvulsant. Each of the three drags are known to cause weight gain. After having been in the program for seven weeks her current weight is 256 pounds. She states in group and individual sessions that the carbohydrate composition is the first and only thing that she has taken that has terminated her nightly binges.

The experimental results show compositions of the present invention comprising novel carbohydrate blends inhibit weight gain and promote weight loss. Various modifications of the invention in addition to those shown and described herein will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims.

Claims

What is claimed is:

1. A method of inhibiting or treating weight gain in a subject, wherein the weight gain is associated with the subject's use of psychotropic drugs, comprising: administering an effective amount of a composition comprising at least one form of carbohydrate and being substantially free of protein.

2. The method of claim 1, wherein the carbohydrate is dextrose, galactose, pre-gelatinized starch, mannose, sucrose, maltose, lactose, dextrin, maltodextrin, or mixtures thereof.

3. The method of claim 1, wherein the carbohydrate is 0 to 40% starch, pre- gelatinized starch, or a mixture thereof.

4. The method of claim 1, wherein the carbohydrate comprises a mixture of dextrose and starch.

5. The method of claim 1, wherein the carbohydrate comprises a mixture of dextrose, starch, and water.

6. The method of claim 1 , wherein the composition further comprises an acidulant.

7. The method of claim 6, wherein the acidulant maintains a pH of less than 6.

8. The method of claim 7, wherein the acidulant is adipic acid, citric acid, fumaric acid, lactic acid, succinic acid, tartaric acid, ascorbic acid, acetic acid, or malic acid.

9. The method of claim 1, wherein administration of the composition results in an elevation of the subject's plasma Tp/Lnaa ratio, relative to the subject's pre- ^• administration plasma Tp/Lnaa ratio.

10. The method of claim 1, wherein the composition provides about 0 to about 5 grams of fat, and about 0 to about 20 grams of fiber

11. The method of claim 1 , further comprising administering a second composition, wherein the second composition comprises an agent selected from the group consisting of prodrugs of serotonin, intermediates in the biosynthesis of serotonin, salts thereof, melatonin, vitamins, amino acids, ovarian hormones, detoxifying agents, diuretics, and combinations thereof, and wherein the second composition is administered before, concurrent, or after administration of said first composition.

12. The method of claim 1, further comprising administering a second composition, wherein the second composition comprises tryptophan or 5- hydroxytryptophan, and wherein the second composition is administered before, concurrent, or after administration of said first composition.

13. The method of claim 12, wherein the second composition is administered within one hour of the first composition.

14. The method of claim 1, the composition further comprising an agent selected from the group consisting of prodrugs of serotonin, intermediates in the biosynthesis of serotonin, salts thereof, melatonin, vitamins; tryptophan, 5- hydroxytryptophan, amino acids, ovarian hormones; detoxifying agents, diuretics, and combinations thereof.

15. A snack food for inhibiting or treating weight gain in a subject, wherein the weight gain is associated with the use of psychotropic drugs, comprising: about 20 to about 200 grams of a rapidly-digestible carbohydrate blend in a solution essentially free of protein, wherein the solution comprises a ratio of about 3 to about 12 mL water to about 1 gram carbohydrate blend; and an acidulant selected from the group consisting of adipic acid, citric acid, fumaric acid, lactic acid, succinic acid, tartaric acid, ascorbic acid, acetic acid, and malic acid, to maintain a therapeutically effective pH at less than 6, wherein the carbohydrate blend comprises about 60 to about 100% dextrose, dextrin, maltodextrin, or a mixture thereof, and about 0 to about 40% starch or pre-gelatinized starch, or a mixture thereof, wherein the composition provides about 0 to about 5 grams of fat, and about 0 to about 20 grams of fiber, and wherein the snack food has a caloric content ranging from about 50 to about 500 calories.

16. The snack food of claim 15, further comprising at least one vitamin, amino acid, ovarian hormone, detoxifying agent or diuretic.

17. The snack food of claim 15, further comprising at least one prodrug of serotonin, intermediate in the biosynthesis of serotonin, or salt thereof.

18. The snack food of claim 15 , further comprising tryptophan or 5-

hydroxytryptophan.

19. The snack food of claim 15, further comprising melatonin.

20. The snack food of claim 15, wherein ingestion of the snack food by a subject results in an elevation of the subject's plasma Tp/Lnaa ratio, relative to the subject's pre-administration plasma Tp/Lnaa ratio.