United States Patent (19) 11) Patent Number: 4,895,845 Seed 45 Date of Patent: Jan. 23, 1990

(54) METHOD OF ASSISTING WEIGHT LOSS OTHER PUBLICATIONS 76) Inventor: John C. Seed, 763 Kingston Rd., Science, 198:1178-1180-Wurtman et al. Princeton, N.J. 08540 Chem. Abst. 88:130914d-Reinhard et al. The Merck Index-9th-1976-Items #396, and 3902. 21 Appl. No.: 907,837 Goodman & Gilman-The Pharmacological Basis of (22 Filed: Sep.15, 1986 Therapeutics, 6th Ed-p. 172. Primary Examiner-Douglas W. Robinson 51) Int, Cl." ...... A61K 31/50; A61K 31/495; Assistant Examiner-Raymond J. Henley, III A61K 31/44; A61K 31/135 Attorney, Agent, or Firm-Richard C. Woodbridge 52 U.S. C...... 514/252; 514/280; 514/649; 514/651; 514/910 57 ABSTRACT 58 Field of Search ...... 514/280,910, 252, 649, A method of assisting weight loss involving the con 514/651 bined administration of a rauwolfia alkaloid and at least one antidepressant, selected from the groups consisting (56) References Cited of aminoazoles, phenoxyphenylpropylamines, and U.S. PATENT DOCUMENTS aminopropiophenones, in a daily regimen with the op 4,310,524 1/1982 Wiech et al...... 514/280 tional co-administration of one or more sympathomi 4,442,113 4/1984 Lassen et al...... 424/267 metic anorexic agents. In a typical embodiment of this 4,525,359 - 6/1985 Greenway et al...... 514/280 method, reserpine and trazodone are administered in a 4,626,549 12/1986 Molloy et al...... 514/651 daily regimen with diethylpropion, fenfluramine or both diethylpropion and fenfluramine. FOREIGN PATENT DOCUMENTS 2048926 4/1972 Fed. Rep. of Germany ...... 514/280 10 Claims, No Drawings 4,895,845 1. 2 advantageously provides an antidepressant effect, it METHOD OF ASSISTING WEIGHT LOSS appears to also assist directly in weight loss and thus is distinguished from other antidepressants such as the BACKGROUND OF THE INVENTION tricyclics. The present invention pertains to a method of assist Of the aminoazole antidepressants, trazodone is pre ing weight loss in patients which involves the adminis ferred because of its availability. As a clinically co tration of a unique combination of pharmaceutically active anorexic agent, trazodone is administered in a active ingredients to suppress appetite and to a method daily amount of from about 0.1 to 6.0 mg per kg of body of maintaining that weight loss by long term, chronic weight. The effective dosage for each individual is ad administration of all or a portion of the components of O justed on the basis of clinical response. this unique combination. Typically, a combined dosage of from about 0.001 to While the causes of excess body weight and obesity 0.01 mg per kg of body weight of reserpine and 0.1 to are complex, a common denominator in the overweight 6.0 mg per kg of body weight of trazodone is adminis person's diet is a caloric intake which exceeds his body's tered daily. Conveniently, the two can be administered expenditure. A methodology which combines dietary 15 at the same time. restriction with increased physical activity will maxi The preferred phenoxyphenylpropylamine antide mize potential weight loss. However, the obese patient pressant is fluoxetine. Clinical studies indicate fluoxe has typically developed eating and activity patterns tine relieves the symptoms of major depressive illness. which are counterproductive to achieving weight re In contrast to the tricyclic antidepressants, fluoxetine duction. One efficacious treatment of obesity utilizes 20 does not inhibit the noradrenergic uptake system. This appetite suppressive drugs as adjuncts in a weight re phenoxyphenylpropylamine antidepressant should be duction program. Thus increased compliance with and administered within the range of from about 0.1 to 1.5 tolerance to a low-calorie diet will often develop when mg per kg body. However, the effective dosage should an anorexic drug is prescribed for the well-motivated be adjusted on the basis of individual clinical responses. patient. In many instances, however, the use of an ano 25 The aminopropiophenone antidepressants are thera rexic agent may produce undesired side effects or its peutically indicated for relief of depression in patients effect may diminish over a period of time. who are unresponsive or intolerant of other available DETALED DESCRIPTION antidepressants. Bupropion, the preferred aminopropi The present invention pertains to a method of assist 30 ophenone antidepressant, is not chemically related to ing weight loss in patients through the administration of other antidepressants, but is pharmacologically similar a unique combination of pharmaceutically active ingre to the tricyclic compounds; see; e.g., U.S. Pat. Nos. dients to suppress appetite. In particular, the present 3,819,706 and 3,885,046. As an effectic anorexic agent, invention involves the concomitant administration of bupropion is typically administered in a daily amount of effective amounts of a rauwolfia alkaloid and at least 35 from about 0.05 to about 7.0 mg per kg of body weight. one antidepressant selected from the group consisting of As the duration of action for these pharmaceutically aminoazoles, phenoxyphenylpropylamines, and amino active agents typically exceeds 24 hours, the frequency propiophenones in a single or multiple daily dose during of administration need not be bound to a daily dosage a weight loss regimen. While the mechanism of interac schedule. An administration regimen sufficient to sup tion between the rauwolfia alkaloid and the selected ply effective daily dosages may be satisfied by single antidepressants is not fully understood, the effectiveness daily doses, multiple daily doses, alternate day doses, of this method of assisting weight loss has been demon multiple weekly doses, or weekly doses. strated in a number of clinical studies, discussed more Since the rate of weight loss will vary from patient to fully herein. patient, and is not consistent for each patient, the effec Rauwolfia alkaloids have been used as antihyperten 45 tiveness of the treatment is best observed over a period sive therapeutic agents in the management of elevated of weeks. The patient should be carefully monitored blood pressure. Infrequently, rauwolfia alkaloid deriva with regard to other medications and to overall physi tives have been prescribed in the management of agi cal condition. Exercise naturally assists the treatment. tated psychotic states, such as schizophrenia. In the combined administration of the rauwolfia alka Typical of the known rauwolfia alkaloids are deserpi 50 dine, alperaxylon, reserpine, and rauwolfia serpentina. loid and one or more of the specified antidepressants, Of these, reserpine is preferred for the present method the administration of one or more of the sympathomi because of its availability and established clinical his metic anorexic agents has proved successful in some tory. Oral dosage of the rauwolfia alkaloid should be instances in promoting patient compliance to a calori carefully adjusted according to individual tolerance and 55 cally-restricted diet. In this embodiment the sympatho response, using the lowest possible effective dosage. mimetic anorexic agents are administered in an effective Typically, the amount of rauwolfia alkaloid adminis amount, normally its recommended dosage, over a por tered daily is from about 0.001 to about 0.01 mg per kg tion of the time during which the rauwolfia alkaloid and of body weight. one or more of the specified antidepressants are being The aminoazole antidepressants, such as etoperidone, administered. mepiprazole, and trazodone, are chemically unrelated The term sympathomimetic anorexic agents refers to to other currently available antidepressants; see; e.g., compounds pharmacologically similar to amphetamine, U.S. Pat. Nos. 3,857,845; 3,491,097; and 3,381,009. dextroamphetamine, methamphetamine, benzpheta Aminoazole antidepressants are therapeutically indi nine, phentermine, chlorphentermine, fenfluramine, cated for the relief of major depression and some clini 65 dextrofenfluramine, clortermine, mephentermine, phen cal studies have indicated the aminoazole antidepres metrazine, phendimetrazine, diethylpropion, mazindol, sants may be of value in the treatment of schizophrenic phenylpropanolamine, ephedrine, pseudoephedrine and disorders or alcohol dependency. While the aminoazole methylphenidate. 4,895,845 3 4. A representative sympathomimetic anorexic agent is The following examples typify the mode of applica diethylpropion. The usual adult dosage of diethylpro tion for the method of assisting weight loss. pion is typically from about 0.15 to about 4.0 mg per kg of body weight but again the dosage should be individu EXAMPLE alized to obtain the most desirable effect. Diethylpro 5 Patient A, a 61 year old male, was diagnosed as both pion is a known stimulant of the central nervous system hypertensive and diabetic. He was observed to be 23 and this medication generally is administered early in lbs. over his ideal weight of 185 lbs. The combined the normal waking hours of the patient to prevent possi administration of reserpine and trazodone during a 40 ble insomnia. Surprisingly, however, the stimulating week regimen resulted in a weight loss of 17.2 lbs. Sub effects of diethylpropion are partially surpressed in 10 sequently, fenfluramine and then both fenfluramine and many patients in the practice of the present invention so diethylpropion were administered in conjunction with that, in such cases, it can be administered later in the the reserpine and trazodone as adjuncts to weight re day. duction. The following table enumerates the dosage and Alternatively, the sympathomimetic anorexic can be weight changes observed during the 75 week therapy. fenfluramine. This can be administered in the aforemen 15 tioned regimen of the rauwolfia alkaloid and one or more of the specified antidepressants as a useful adjunct Daily Dosages (ng) Period of Weight to weight reduction. The preferred dosage of fenflura Trazo-, Fenflur- Diethyl- Treatment Change mine is typically from about 0.2 to about 1.8 mg per kg Reserpine done amine propion (weeks) (lbs.) of body weight but should be individualized to obtain 25 100 - 1. --5.5 25 200 - m 8 - 7.0 the most therapeutic response at the lowest effective SO 200 31 -- 15.7 dose. Fenfluramine and dextrofenfluramine are pharma SO 200 20 4 - 1.3 cologically distinct from other sympathomimetic ano SO 200 40 8 - 1.0 rexics in that their mode of action results in the depres 50 200 60 5 --2.7 sion of the central nervous system. Thus, fenfluramine 25 50 200 60 75 9 - 1.2 and dextrofenfluramine can be administered later in the 50 200 80 75 9 -2.0 day than is the case with many other sympathomimetic agents. This differentiating characteristic of fenflura mine and dextrofenfluramine also can be utilized to EXAMPLE 2 permit co-administration of these anorexic agents with 30 Patient B, a 56 year old female, was diagnosed as other sympathomimetic compounds, such as diethyl hypertensive. She was observed to be 75 lbs. over her propion, without exacerbating potential side effects, ideal weight of 117 lbs. The combined administration of such as insomnia, restlessness, or irritability. reserpine and trazodone during a 62 week regimen re An alternate embodiment of weight loss involves the sulted in a weight loss of 26.5 lbs. The following table co-administration of at least one or more of the specified 35 enumerates the dosage and weight changes observed antidepressants with one or more sympathomimetic during the 120 week therapy. anorexic agents. While the appetite suppressant drugs are known to be useful adjuncts to a weight loss pro Period of Weight gram, the usual duration of their efficacy is brief. After Daily Dosages (ng) Treatment Change about six to twelve weeks of administration, tolerance to some of the sympathomimetic anorexic agents devel Reserpine Trazodone (weeks) (lbs.) .25 O 7 -- 0 ops and they are no longer dependable aids in control .25 150 39 -21.0 ling appetite. Significant increases in the efficacy of 25 200 23 -5.5 appetite suppression drugs is observed in a method 25 46 -- 2.2 which utilizes at least one antidepressant selected from 45 25 150 5 -3.2 the groups consisting of aminoazoles, phenoxyphenyl propylamines and aminopropiophenones, during the co-administration of sympathomimetic anorexic agents. EXAMPLE 3 Clinical studies thus demonstrate potentiation in the Patient C, a 60 year old male, was diagnosed as hy duration of action of the sympathomimetic anorexics, SO pertensive. He was observed to be 38 lbs. over his ideal such as diethylpropion and fenfluramine, when adminis weight of 165 lbs. The combined administration of re tered in a daily regimen with at least one or more of the serpine and trazodone during a 41 week regimen re specified antidepressants. sulted in a weight loss of 25.3 lbs. The following table The preferred dosage of the antidepressant trazodone enumerates the dosage and weight changes observed in this embodiment is from about 0.1 to 6.0 mg per kg of 55 during the 41 week therapy. body weight during the co-administration of the sympa thomimetic anorexic agent. In this embodiment, dieth ylpropion is administered at a dosage of about 0.15 to Period of Weight about 4.0 mg per kg of body weight whereas fenflura Daily Dosages (ng) Treatment Change mine is administered in a regimen with the selected Reserpine Trazodone (weeks) (bs.) antidepressant in the range of from about 0.2 to about 25 100 2 -- 7.5 1.8 mg per kg of body weight. The most effective dos 25 200 35 -32.8 ages for the combined administration of the diethylpro pion and the fenfluramine during the co-administration of one or more of the specified antidepressants should 65 EXAMPLE 4 be within the ranges previously recited. However, the Patient D, a 62 year old male, was diagnosed as hy preferred dosages should be adjusted on the basis of the pertensive. He was observed to be 62 lbs. over his ideal individual clinical response of each patient. weight of 158 lbs. The combined administration of re 4,895,845 5 6 serpine and trazodone during a 26 week regimen re sulted in a weight loss of 16 lbs. Subsequently, diethyl Period of Weight propion and then both diethylpropion and fenfluramine Daily Dosages (ng) Treatment Change were administered in conjunction with the reserpine Reserpine Trazodone Diethylpropion (weeks) (bs.) and trazodone as adjuncts to weight reduction. The 25 50 --0.3 following table enumerates the dosage and weight 25 50 75 7 - 15.8 changes observed during the 68 week therapy. 25 100 75 3 +3.2 25 100 25a 5 - 10.4 2S 150 25 5 -6.0 - Daily Dosages (ng) - Period of Weight O .12 200 25 2 -5.3 Trazo- Fenflur- Diethyl- Treatment Change .12 200 75a 2 -7.5 Reserpine done amine propion (weeks) (lbs.) .12 200 75 6 -3.0 Alternate day administration. 2S 200 X --0.8 50 200 m 16 - 2.0 50 300 5 -2.0 15 EXAMPLE 7 - 300 O are- 3 -0.5 50 300 pre- - 1.5 Patient G, a 45 year old female, was diagnosed as 50 300 75 1. -- 1.0 50 300 6 --4.5 hypertensive. She was observed to be 84 lbs. over her 50 300 WO 75 2 -3.7 ideal weight of 145 lbs. The combined administration of SO 300 20 75 2 -3.3 20 reserpine and trazodone was augmented with both di 50 300 75 2 -0.7 ethylpropion and fenfluramine during a five week regi .50 300 40 O 3 -0.8 men which resulted in a weight loss of 14.6 lbs. The SO 300 -- 75 2 -3.5 50 300 20 75 4. -2.5 following table enumerates the dosage and weight 50 300 40 75 4. - 4.8 changes observed during the 26 week therapy. 50 300 ar -0.2 25 .75 300 m 3 --0.5 .75 300 40b 75b 5 -- 6.5 Daily Dosages (ng) Period of Weight .75 300 20 75 3 -2.8 Trazo- Fenflur- Diethyl- Treatment Change .75 300 40 75 2 -2.7 Reserpine done amine propion (weeks) (lbs.) .75 300 80 75 2 -3.0 75 2 -- 1.5 Patient onission. 30 25 50 75 -3.0 Patient varied administration to alternate weeks. 2S 100 75 -0.2 25 300 75 -2.6 50a 300 20 75 5 - 14.6 EXAMPLE 5 20 75 16 -20.2 Patient E, a 73 year old female, was diagnosed as Patient reported drowsiness; discontinued reserpine and trazodone. hypertensive. She was observed to be 10 lbs. over her 35 ideal weight of 127 lbs. The combined administration of EXAMPLE 8 reserpine and trazodone during a 25 week regimen re Patient H, a 64 year old female, was diagnosed as sulted in a weight gain of 2 lbs. Subsequently, diethyl both neuropathic and obese. She was observed to be 60 propion was administered in conjunction with the reser lbs. over her ideal weight of 140 lbs. Patient reported pine and trazodone as an adjunct to weight reduction. intolerance to either diethylpropion or fenfluramine The following table enumerates the dosage and weight when administered in conjunction with the reserpine changes observed during the 68 week therapy. and trazodone. The following table enumerates the dosage and weight changes observed during the 46 Period of Weight 45 week therapy. Daily Dosages (ng) Treatment Change Reserpine Trazodone Diethylpropion (weeks) (bs.) Daily Dosages (ng) Period of Weight .0 O O 4 --2.0 Trazo- Fenflur- Diethyl- Treatment Change 10 200 4. -2.3 Reserpine done amine propion (weeks) (lbs.) 10 m 4. 4.0 50 .10 150 4. - 1.2 25 400 O 4 - 1.3 25 150 8 -- 4.0 2S 400 75 -3.7 50 150 3 - 1.2 25 400 O O 2 -3.3 50 200 m 8 -0.7 25 400 75 2 --0.7 50 200 75 6 - 11.0 25 100 1 --2.8 50 200 m 2 -3.5 55 2S 100 75 1 -2.8 50 200 75 10 -8.8 2S 100 o m 1 --3.0 50 200 11 -4.4 200 16 --2.3 25 100 6 0.0 O 12 -2.7 20 2 -3.0 O O 75 2 -6.3 25 2 --3.5 EXAMPLE 6 60 Patient F, a 23 year old male, was diagnosed as obese. He was observed to be 55 lbs. over his ideal weight of EXAMPLE 9 190 lbs. Diethylpropion administration was in conjunc Patient I, a 68 year old male, was diagnosed as both tion with the reserpine and trazodone and resulted in a 65 diabetic and obese. He was observed to be 200 lbs. over weight loss of 45 lbs. during the 30 week regimen. The his ideal weight of 120 lbs. The combined administra following table enumerates the dosage and weight tion of reserpine and trazodone during a 7 week regi changes observed during the 31 week therapy. men resulted in a weight loss of 9 lbs. The following 4,895,845 7 8 table enumerates the dosage and weight changes ob served during the 15 week therapy. - Daily Dosages (ing) Period of Weight Trazo- Fenflur- Diethyl- Treatment Change Period of Weight 5 Reserpine done amine propion (weeks) (lbs.) Daily Dosages (ng) Treatment Change 25 50 --5.3 Reserpine Trazodone (weeks) (bs.) 25 100 o o 1 -- 0.7 25 pre- 8 -- 4.5 25 100 20 2 -0.6 .25 200 2 - 1.5 25 100 40 WOO 2 -- 1.4 50 200 5 -7.8 50 100 80 Wr 2 -1.7 10 00 80 75 4 -2.7 O 200 80 75 -5.3 25 200 80 75 13 -29.0 EXAMPLE 10 Patient J, a 62 year old male, was diagnosed as both hypertensive and diabetic. He was observed to be 50 15 EXAMPLE 13 lbs. over his ideal weight of 160 lbs. The combined Patient M, a 35 year old male, was diagnosed as administration of reserpine and trazodone in conjunc obese. He was observed to be 47 lbs. over his ideal tion with fenfluramine resulted in a weight loss of 30 lbs. weight of 140/1bs. The combined therapy of reserpine during a 25 week regimen. The following table enumer and trazodone was augmented with diethylpropion and ates the dosage and weight changes observed during the 20 then both diethylpropion and fenfluramine as adjuncts 28 week therapy. to weight reduction. The following table enumerates the dosage and weight changes observed during the 20 Period of Weight week therapy. Daily Dosages (ng) Treatment Change 25 Reserpine Trazodone Fenfluramine (weeks) (bs.) m 0.0 Daily Dosages (ng) Period of Weight re- Ma 40 --3.0 Trazo- Fenflur. Diethyl- Treatment Change 25 50 40 26 -30.5 Reserpine done amine propion (weeks) (lbs.) 3O 50 m 75 1 -- 1.6 25 50 75 2 -3.2 EXAMPLE 1. 50 50 20 75 2 -0.2 50 50 40 75 2 -2.3 Patient K, a 30 year old female, was diagnosed as SO 50 20 75 3 -0.3 obese. She was observed to be 54 lbs. over her ideal 50 50 40 75 4. -0.8 weight of 127 lbs. The combined administration of re- 35 25 50 60 OO 6 - 1.8 serpine and trazodone was augmented by fenfluramine as an adjunct to weight reduction. During this 12 week regimen, a weight loss of 7 lbs. was recorded. The fol- EXAMPLE 14 lowing table enumerates the dosage and weight changes Patient N, a 60 year old female, was diagnosed as observed during the 20 week therapy. '' obese. She was observed to be 110 lbs. over her ideal weight of 135 lbs. The administration of reserpine was Daily Dosages (ng) Period of Weight augmented with diethylpropion and then both diethyl Trazo. Fenflur. Diethyl- Treatment Change propion and fenfluramine as adjuncts to weight reduc Reserpine done amine propion (weeks) (Ibs.) 45 tion. When this regimen was supplemented with trazo as as done for 17 weeks, a weight loss of 15 lbs. was recorded. 25 50 m 1. -3.4 The following table enumerates the dosage and weight 25 50 O- 25 2 0.7 changes observed during the 21 week therapy. 25 50 20 - 1.0 2S 50 40 W 1. --0 50 : 8 - 2 - g aily Dosages (ng) Period of Weight 50 100 60 3 - 1.3 Trazo- Fenflur- Diethyl- Treatment Change 50 100 40 o 4 - E.O Reserpine done amine propion (weeks) (lbs.) MO 3a - 1.3 .25 75 1 - 1.6 Patient pregnant; discontinued medication. 55 25 20 75 1. -- 1.6 50 40 75 1 -2.0 50 20 75 1. -0.6 EXAMPLE 12 50 50 20 75 1 --2.8 Patient L, a 39 year old male, was diagnosed as hy- : . -: pertensive. He was observed to be 76 lbs. over his ideal 60 50 100 40 75 3 -2.4 weight of 166 lbs. The combined administration of re- 50 50 40 75 1. 0.0 serpine and trazodone was augmented by fenfluramine 50 50 80 75 3 - 1.6 and then both fenfluramine and diethylpropion as ad- : so : -: juncts to weight reduction. During a 13 week regimen 50 100 80 75 2 –03 this combination of pharmaceutically-active agents re- 65 .50 100 90 100 1. -2.0 sulted in a weight loss of 29 lbs. The following table 50 100 80 00 1. -2.0 enumerates the dosage and weight changes observed 50 125 80 100 1 -0.2 during the 26 week therapy. 4,895,845 9 10 EXAMPLE 15 EXAMPLE 18 Patient O, a 40 year old male, was diagnosed as obese. Patient R, a 36 year old male, was diagnosed as hy He was observed to be 60 lbs. over his ideal weight of pertensive. He was observed to be 83 lbs. over his ideal 186 lbs. The combined administration of reserpine and 5 weight of 161 lbs. During a 22 week regimen of trazo trazodone was augmented with diethylpropion and then done, diethylpropion and fenfluramine, a weight loss of both diethylpropion and fenfluramine. The following 24.3 lbs. was recorded. The following table enumerates table enumerates the dosage and weight changes ob the dosage and weight changes observed during the 28 week therapy. served during the 13 week therapy. O

Daily Dosages (ing) Period of Weight Daily Dosages (ng) Period of Weight Trazo- Fenflur- Diethyl- Treatinent Change Fen- Treatment Change Reserpine done amine propion (weeks) (lbs.) Trazodone fluramine Diethylpropion (weeks) (lbs.) 00 O -3.7 25 75 32 15 100 75 5 -- 1.0 25 50 75 0.0 100 20 75 7 - 11.0 25 SO 00 1a -- 4.0 100 40 75 9 -5.8 2S 50 wa 00 4. -7.0 100 80 75 6 - 4.8 25 50 20 OO - 1.5 25 -- 20 00 5 -6.7 20 Patient took medication intermittently EXAMPLE 19 Patient S, a 52 year old female, was diagnosed as EXAMPLE 16 hypertensive. She was observed to be 12 lbs. over her Patient P, a 60 year old female, was diagnosed as 25 ideal weight of 115 lbs. The following table enumerates diabetic. She was observed to be 63 lbs. over her ideal the dosage and weight changes observed during the 13 weight of 120 lbs. The combined administration of re week therapy. serpine and trazodone during a 7 week regimen resulted in no net weight loss. Subsequently, diethylpropion and Period of Weight then both diethylpropion and fenfluramine were admin- 30 Daily Dosages (mg) Treatment Change istered in conjunction with reserpine as adjuncts to Reserpine Trazodone Fenfluramine (weeks) (lbs.) weight reduction. The following table enumerates the 200 DX 3 -- 1.0 200 20 2 -2.8 dosage and weight changes observed during the 65 200 40 2 -2.6 week therapy. 200 60 2 - 1.0 35 25 200 40 2 -2.6 2S 200 60 2 -1.2 Daily Dosages (mg) Period of Weight Trazo- Fenflur- Diethyl- Treatment Change Reserpine done amine propion (weeks) (lbs.) EXAMPLE 2.0 25 200 2 -0.6 40 25 100 - 2 -0.2 Patient T, a 29 year old male, was diagnosed as hy 2S 50 3 - 1.0 pertensive. He was observed to be 36 lbs. over his ideal 25 100a 9 - i.2 weight of 155 lbs. The following table enumerates the 25 O- O 50 7 -0.6 dosage and weight changes observed during the 26 25 40 res --0.3 25 18 -3.3 45 week therapy. 25 40 37.5 6 -5.6 25 18 --6.2 Daily Dosages (ng) Period of Weight Patient experienced insomnia on this dosage. Fen- Treatment Change Trazodone fluramine Diethylpropion (weeks) (bs.) 50 200 75 5 0.0 EXAMPLE 17 200 20 75 2 -1.7 Patient Q, a 65 year old female, was diagnosed as 200 DO is 19 -3.7 hypertensive. She was observed to be 30 lbs. over her ideal weight of 132 lbs. The combined administration of What is claimed is: reserpine and trazodone was augmented with fenflura- 55 1. A method of assisting weight loss in a human in mine for three weeks during which time the patient need thereof which comprises administering to said reported a variety of side effects. The following table human, over a sustained period of time, both a rauwolfia enumerates the dosage and weight changes observed alkaloid in the form of reserpine, and at least one antide during the 7 week therapy, pressant selected from the group consisting of trazo 60 done, bupropion and fluoxetine in an administration regimen sufficient to supply effective daily dosages Period of Weight thereof for assisting weight loss. - Daily Dosages (ing) Treatment Change 2. The method of claim 1 wherein said antidepressant Reserpine Trazodone Fenfluramine (weeks) (bs.) is trazodone and both reserpine and trazodone are ad 25 50 w 2 --2.5 65 ministered concomitantly. 25 50 20 3 -1.7 3. The method of claim 1 wherein the daily dosage of 2S 50 2 -3.6 reserpine is between about 0.001 and about 0.01 milli gram per kilogram of human body weight. 4,895,845 11 12 4. The method of claim 1 wherein said antidepressant administered, said reserpine, trazodone, and fluoxetine is trazodone and the daily dosage of trazodone is be being administered in a regimen sufficient to supply tween about 0.1 and about 6.0 milligram per kilogram of effective daily dosages thereof for assisting weight loss. human body weight. 9. The method of claim 1 wherein the rauwolfia alka 5. The method of claim 1 wherein said antidepressant 5 loid is reserpine, and trazodone, bupropion, and fluoxe is fluoxetine and both reserpine and fluoxetine are ad tine are administered, said reserpine, trazodone, bupro ministered concomitantly. pion and fluoxetine being administered in a regimen 6. The method of claim 1 wherein the daily dosage of sufficient to supply effective daily dosages thereof for reserpine is between about 0.001 and about 0.01 milli assisting weight loss. gram per kilogram of human body weight. O 10. The method of claim 1 wherein the rauwolfia 7. The method of claim 1 wherein said antidepressant alkaloid is reserpine, and both trazodone and bupropion is fluoxetine and the daily dosage of fluoxetine is be are administered, said reserpine, trazodone, and bupro tween about 0.1 and about 1.5 milligram per kilogram of pion being administered in a regimen sufficient to sup human body weight. ply effective daily dosages thereof for assisting weight 8. The method of claim 1 wherein the rauwolfia alka- 15 loss. loid is reserpine, and both trazodone and fluoxetine are k

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