Long-Term Pharmacotherapy for Obesity in Elderly Patients

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Long-Term Pharmacotherapy forObesity in Elderly PatientsA Retrospective Evaluation of Medical Records froma Specialized Obesity Outpatient Clinic

Nıdia Celeste Horie,1 Cintia Cercato,2 Marcio C. Mancini2 and Alfredo Halpern2

1 Obesity Outpatient Clinic for the Elderly of the Department of Geriatrics, Hospital das Clinicas, Faculdade

de Medicina da Universidade de Sao Paulo (USP), Sao Paulo, Brazil

2 Group of Obesity and Metabolic Syndrome, Endocrinology & Metabolism Service, Hospital das Clinicas,

Faculdade de Medicina da USP, Sao Paulo, Brazil

Abstract Background: Obesity is a serious chronic disease and the prevalence of this

condition is increasing among the elderly. Although the benefits of weight

loss to improve control of associated diseases are well known in young adults,

they are not in older patients. The use of anti-obesity drugs to promote weight

loss is widespread in Brazil and other countries, and obesity specialists fre-

quently prescribe medicines in doses and for durations previously unreported

in the literature. Sibutramine, orlistat and amfepramone (diethylpropion)

have been evaluated in clinical trials of more than 2 years’ duration in adults,

demonstrating safety and efficacy, but long-term studies in obesity treatment

are absent for other drugs. The efficacy and safety of obesity pharmaco-

therapy among the elderly is unknown.

Objective: To describe the experience of obesity pharmacotherapy in the

elderly in a specialized obesity care setting in Brazil, with a focus on efficacy

and safety.

Methods: A retrospective evaluation was conducted on medical charts from

an outpatient clinic of a specialized tertiary centre for the treatment of

obesity. We included patients who had had at least one consultation between

January and December 2007, were aged ‡60 years at the beginning of the

treatment, had had at least 6 months of follow-up and had received a

prescription of at least one potential weight-loss drug. Diagnoses reported

on medical records were documented. Age, weight, height and body mass

index (BMI) were recorded at admission, after 6, 12, 18 and 24 months, and

at the last available visit. The medicines prescribed, together with the

dose, duration of use, adverse effects and reasons for discontinuation, were

documented.

Results: The group consisted of 44 women (86%) and 7 men (14%), with a

mean– SD age of 65.2– 4.5 years, weight of 95.3 – 12.5 kg and BMI of

ORIGINAL RESEARCH ARTICLEDrugs Aging 2010; 27 (6): 497-5061170-229X/10/0006-0497/$49.95/0

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38.5– 4.3 kg/m2. The mean – SD time of follow-up was 39.3– 26.4 months,

and the mean weight loss was 6.65 kg (p < 0.01). After the first 6 months, the

mean– SD weight loss was 5.7 – 3.8 kg (p < 0.0001). A smaller weight loss was

seen between the 6th and 12th months, with no statistically significant change

in weight thereafter. A weight loss of ‡5% was achieved by 64.71%, 63.64%,

62.16% and 69.70% in the 6th, 12th, 18th and 24thmonths, respectively, and a

weight loss of ‡10% was achieved by 17.65%, 34.09%, 32.43% and 39.39% in

the 6th, 12th, 18th and 24th months, respectively. The medicines prescribed

were sibutramine, orlistat, fluoxetine, sertraline, topiramate, fenproporex,

mazindol and amfepramone, alone or in combinations, concomitantly or

sequentially. The reasons for discontinuation were lack of response (n = 13),

loss of response (development of tolerance) [n = 11], lack of adherence (n = 14)

and adverse effects (n= 14). One episode of atrial flutter occurred in a patient

taking fenproporex. The weight-loss medications were generally well toler-

ated, and only transient adverse events were reported.

Conclusions: Long-term pharmacotherapy for obesity was effective and well

tolerated by this group of elderly patients.

Background

Obesity is a chronic disease associated withseveral metabolic alterations such as hyper-tension, diabetes mellitus and dyslipidaemia,[1]

and increasing rates of morbidity and mortal-ity due to heart disease and cancer.[2] In theelderly, obesity enhances disabilities and therisk of frailty syndrome,[3] and impairs qualityof life.[4]

Overweight and obesity have been increasingin the general population, including in the el-derly.[5,6] In Brazil, the prevalence of obesity inadults increased from 2.8% (1974–5) to 8.8%(2002–3) among men and from 7.8% (1974–5) to12.7% (2002–3) among women. The prevalence ofobesity increases with age, reaching 21% inwomen and 11% in men between the age of 55and 64 years. Prevalence decreases for those aged‡65 years to 17.1% of women and 10.2% of menbetween the ages of 65 and 74 years and 14.3% ofwomen and 5.6% of men aged ‡75 years.[7]

However, these observations can be affected bysurvival bias due to higher mortality rates atyounger ages in the obese.[8] Therefore, pre-mature mortality of the obese would tend to re-duce the mean bodyweight and body mass index(BMI) in surviving older adults.

Aging is associated with several harmful chan-ges in body composition. After 20–30 years of age,fat-free mass progressively decreases, whereasfat mass increases.[9,10] There is a redistributionof body fat, with a greater increase in intra-abdominal fat than in subcutaneous or total bodyfat.[11] Obesity is also associated with a greaterintramuscular and intrahepatic fat content, whichis associated with insulin resistance.[12]

However, the treatment of obesity in old agestill remains controversial, especially regardingthe use of anti-obesity medication. Most ran-domized controlled trials that evaluated the useof pharmacotherapy for obesity excluded olderpeople, and others included only a small numberof older subjects.[13,14]

The anti-obesity drugs can be classified[15,16] as(i) fat absorption altering, such as orlistat, whichis a lipase inhibitor; (ii) thermogenesis increasing,such as ephedrine, which increases the basal meta-bolic rate; and (iii) appetite altering, which canbe classified by chemical characteristics or path-way of action. All of the centrally acting anorecticagents except mazindol are derivatives of b-phenylethylamine, which is structurally similar todopamine, noradrenaline (norepinephrine) andadrenaline (epinephrine). Some agents, suchas phentermine, amfepramone (diethylpropion),

498 Horie et al.

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fenproporex and phendimetrazine, are similar toamphetamines and stimulate the release of nor-adrenaline, whereas other agents, such as dex-fenfluramine and fenfluramine, affect serotoninrelease and reuptake. Mazindol is structurallyrelated to the tricyclic antidepressants, and in-hibits noradrenaline reuptake. The aforemen-tioned drugs are also called sympathomimetics.Sibutramine inhibits the reuptake of nor-adrenaline and serotonin. The active metabolitesof sibutramine also cause noradrenaline andserotonin reuptake inhibition. These neuro-transmitters are responsible for satiety and re-duce caloric intake. Fluoxetine and sertraline areselective serotonin reuptake inhibitors (SSRIs),which are usually indicated to treat depression,bulimia and binge eating disorder, but have beenassociated with weight loss in some studies. Someantiepileptic agents, such as topiramate anddrugs acting as antagonists in the endogenousendocannabinoid system, also reduce appetite ordecrease binge eating.

Data from a recent meta-analysis that eval-uated the pharmacotherapy of obesity (meanage of subjects 34–54 years) demonstrated thatsibutramine, orlistat, phentermine and probablyamfepramone, fluoxetine, bupropion and topir-amate promote weight loss for at least 6 monthswhen given with diet recommendations.[17] Sibu-tramine and orlistat are approved for use for>2 years, but the length of time they should beused after that remains an unanswered question,even for young adults.

One study[18] demonstrated that sibutraminepharmacokinetics in the elderly are similar tothose in the young. The SCOUT (SibutramineCardiovascular OUTcomes) trial[19] includedpatients aged ‡55 years with an increased risk ofcardiovascular disease who were randomly se-lected to take sibutramine or placebo. In the first6-week phase, the mean age of patients exceeded60 years and sibutramine appeared to be effica-cious, tolerable and safe.

Two randomized placebo-controlled trials ofamfepramone demonstrated the efficacy andsafety of the drug at 2 years (n = 3688)[20] and1 year (n = 69).[21] However, both trials excludedelderly patients.

Brazil is one of the largest consumers andproducers of anorectics. Data from the Interna-tional Narcotics Control Board[22] show that thiscountry was responsible for legal production of81% of amfepramone, 61% of fenproporex and39% of mazindol in the world in 2007.

A recent article reporting a survey that wasgiven to members of the American Society ofBariatric Physicians[23] reported that almost allphysicians prescribed anti-obesity medicationsand all recommended phentermine (usually indoses above the National Institutes of Health[NIH] Obesity Treatment Guidelines). Phendi-metrazine, metformin and phentermine plus L-5-hydroxytryptophan [oxitriptan] with carbidopawere all used for obesity treatment more fre-quently than either orlistat or sibutramine. Thisstudy verified that combination drugs that havenot been studied in randomized clinical trials arefrequently used to treat obesity.

There are no published articles describingtrials of obesity treatment in the elderly usingpotential anti-obesity drugs,[16] i.e. fluoxetine,sertraline, mazindol, amfepramone, fenproporex,orlistat, topiramate or phentermine. Therefore,the available data are insufficient to determinethe efficacy and safety of most anti-obesity drugsin older people.[24]

Given the widespread use of anti-obesity drugsin real-life settings and the lack of controlledstudies to support such use, the aim of this studywas to describe retrospectively the experienceof use of anti-obesity medications in older adultsattending a specialized obesity centre. The eval-uation focused on the prescription profile,reported adverse effects and efficiency of anti-obesity drugs in promoting weight loss.

Methods

Study approval was obtained from the EthicsCommittee of Hospital das Clınicas, Sao Paulo,Brazil, for a retrospective medical record reviewof patients who had had at least one consultationbetween January and December 2007. Thesetting was a public outpatient clinic of the En-docrinology & Metabology Service at Hospitaldas Clınicas, School of Medicine, Universidade

Long-Term Obesity Pharmacotherapy in the Elderly 499


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de Sao Paulo, which is a specialized tertiary cen-tre for the treatment of obesity. Inclusion criteriawere age ‡60 years[5] at the beginning of treat-ment, follow-up ‡6 months and use of pharma-cotherapy for obesity. Patients with insufficientdata in the medical charts were excluded.

The following medications were considered tohave potential to promote weight loss: fluoxetine,sertraline, mazindol, fenproporex, amfepramone,sibutramine, orlistat and topiramate. Phenter-mine is not available in Brazil. The followingaspects of drug use were recorded: dose, durationof use, adverse effects and reasons for stoppingthe drug.

Pharmacotherapy for each patient was de-termined by criteria established by the attendingphysician. Although there was no official gui-dance as to when to initiate drug therapy, usuallythe anti-obesity drug was prescribed after thefailure of a lifestyle approach. The choice ofmedicine was based on characteristics of the pa-tient such as co-morbidities, eating behaviourand response to or adverse effects of previoustreatment. The availability and cost of the medi-cines were also considered.

Fluoxetine and sertraline were provided by thehospital for over 10 years. Since 2005, sibu-tramine, orlistat, amfepramone, mazindol andfenproporex have been available most of thetime.

The drugs were usually introduced one at atime, in low doses, and the response and adverseeffects were evaluated in subsequent consulta-tions. If there was a response (weight loss) withno or few adverse effects, the drug was continued.If there was no response, the dose was increasedor the drug was changed. If a patient who showedan initial response regained weight, the dose wasincreased until it promoted weight loss again, andwas then maintained at that dose if it continuedto be tolerated. If a patient stopped responding toone drug, after assessment of other causes of fail-ure, the drug was discontinued and substitutedor combined with another drug. There was notime limit for maintaining the prescription: thedrug was continued if it was promoting weight lossor preventing regain, and discontinued if therewere major adverse effects or loss of response.

All diagnoses reported in the medical recordswere documented. Age, weight, height and BMIwere recorded at admission, after 6, 12, 18 and24 months and at the last available visit. Patientswere classified according to their BMI (kg/m2) asoverweight (25–29), obesity class I (30–34), obe-sity class II (35–39) and obesity class III (‡40).[25]To measure the efficacy of obesity treatment,patients were classified according to the percen-tage of weight loss, i.e. ‡5% or ‡10% of their in-itial bodyweight.

All patients also consulted a nutritionist andreceived conventional guidance on a hypocaloricdiet.

Statistical Analysis

The normality of variables was assessed by useof graphs of normal probability distributions.Weapplied the Student’s t-test and Pearson correla-tion for normally distributed variables. For uni-variate analysis of predictors of weight loss ‡5%at 6 months and final follow-up, a two-samplet-test and a chi-squared (w2) test were carried out.All statistical tests were considered to be signif-icant at p-value < 0.05.

Results

Fifty-one patients met the inclusion criteria.This group consisted of 44 (86%) womenand 7 (14%) men, with a mean –SD age of65.2– 4.5 years (maximum79.3 years), amean– SDweight of 95.3 – 12.5 kg (range 73.8–128.9 kg),and a mean – SD BMI of 38.5 – 4.3 kg/m2

(range 28.4–52.6 kg/m2).Six (11.8%) patients were classified as obesity

class I, 32 (62.8%) as obesity class II and 12(23.5%) as obesity class III. One patient (1.96%)was overweight. The mean – SD period of follow-up was 39.3 – 26.4 months and the mean weightloss was 6.65 kg until the last evaluation(p < 0.01). The patients’ anthropometric dataand systolic and diastolic blood pressure at thebeginning of the follow-up period and every6 months thereafter are shown in table I.

The patients had a median of seven diagnoses(minimum three, maximum 13) described on their

500 Horie et al.


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medical records. Hypertension was diagnosed in84.3% of patients, 70.6% had dyslipidaemia and45.1% had diabetes. The main diagnoses are dis-played in table II in order of frequency.

Mean weight loss over time in the treatedpatients is shown in figure 1. During the first6 months, the mean – SD weight loss was5.7 – 3.8 kg (p < 0.0001). For the 44 patients withfollow-up ‡12 months, the mean –SD weight lossbetween the 6th and the 12th month was1.4 – 3.6 kg (p = 0.011). After 12 months, weightloss was maintained.

In terms of treatment efficacy, 66.7% and33.3% of patients had lost ‡5% and ‡10%, re-spectively, of their initial weight at the last visitrecorded on their medical records. Figure 2shows the proportion of patients who had lost‡5% and ‡10% of their initial weight after each6-month treatment period.

In univariate analysis, gender, initial age, in-itial weight and BMI did not correlate withachieving a weight loss of ‡5%.

Most patients (n = 39) received a prescriptionof more than one medication at different timesduring follow-up. There was a maximum of threedrugs at a time in a prescription. Combinationsof medications, such as an SSRI with sibu-tramine, an SSRI with a sympathomimetic drug(mazindol, fenproporex or amfepramone), sibu-tramine with topiramate, and orlistat with sibu-tramine, were also used. Table III shows thefrequency of prescriptions of each drug, as wellas their mean doses, their mean and maximumdurations of use, the mean and maximum weightloss associated with use of each drug, and themean weight loss per year with each drug.

Table IV shows the frequency of use of drugcombinations.

Data obtained from the medical recordsshowed that the reasons for stopping and/or re-placing medications were lack of therapeuticresponse (n = 13), development of tolerance(n = 11), lack of adherence to treatment (n = 14)and adverse effects (n = 14). There were no re-cords of patients discontinuing or replacingmedicines for more than one reason.

Among those patients who stopped or chan-ged medication because of adverse effects, ninewho did so were taking sympathomimetic drugs,two were taking sibutramine, two were takingfluoxetine and one was taking sertraline. Theadverse events reported – as well as the time whenthe event occurred after starting the medication –

are shown in table V.

Table I. Patients’ weight, body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP) during the follow-up perioda,b

Parameter Time of measurement

Baseline 6 months 12 months 18 months 24 months

Weight (kg) 95.3 – 12.5 89.6 – 13.3**** 88.7 – 14.0** 88.6 – 13.7 87.5 – 14.1

BMI (kg/m2) 38.5 – 4.3 36.2 – 4.5**** 35.4 – 4.3*** 35.7 – 4.0 35.3 – 4.1

SBP (mmHg) 138.4 – 19.8 135.3 – 27.3 133.8 – 13.0 131.9 – 15.4 128.6 – 14.5

DBP (mmHg) 85.0 – 13.3 84.0 – 13.0 80.9 – 7.1 82.7 – 13.0 78.2 – 9.8*

a Data are given as mean – SD.

b All p-values represent comparisons between the current value and those obtained 6 months previously (Student’s t-test).

*p = 0.013, **p = 0.011, ***p = 0.007, ****p < 0.0001.

Table II. Baseline diagnosis of the 51 elderly patients receiving

pharmacological anti-obesity treatment

Diagnosis % (n)

Hypertension 84.3 (43)

Dyslipidaemia 70.6 (36)

Diabetes mellitus 45.1 (23)

Symptomatic osteoarthritis 45.1 (23)

Glucose intolerance or fasting glucose >100 mg/dL 41.2 (21)

Hypothyroidism 29.4 (15)

Sleep apnoea syndrome 21.6 (11)

Osteopenia or osteoporosis 21.6 (11)

Cancer (past history) 19.6 (10)

Coronary artery disease 17.7 (9)

Major depression 15.7 (8)

Gastro-oesophageal reflux disease 15.7 (8)

Cholelithiasis 13.7 (7)

Bipolar mood disorder 5.9 (3)



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Discussion

This study describes the experience ofpharmacotherapy for obesity in elderly patientsin a specialized clinic in Brazil. The prescribedtreatment was in accordance with practice by theclinic experts. Therefore, the results are indicative

of actual practice, unlike the results of clinicalstudies that often do not assess elderly patientsbecause such patients do not meet strict inclusionand exclusion criteria. Given that there are in-sufficient published data to determine the efficacyand safety of long-term anti-obesity pharmaco-therapy in the elderly,[23] the report of the ex-perience of a specialized centre is of great value.

The high number of concomitant diagnosesdocumented in these elderly patients suggeststhat management of this age group will be morecomplicated. The main pathologies reported wereclosely correlated with being overweight.[25,26]

Several studies have shown that weight loss, evenwhen relatively low (5% of initial weight), cansignificantly improve some conditions such ashypertension, diabetes, dyslipidaemia, sleep ap-noea and gastro-oesophageal reflux.[25] Thus, el-derly individuals who have many obesity-relatedcomplications must be treated in an effectivemanner to improve these conditions. However,there are few studies of intentional weight loss

Wei

ght (

kg)

85.0

87.5

90.0

92.5

95.0

97.5

0 6 12(n = 51) (n = 51) (n = 44)

Time (months)

(n = 37) (n = 33)18 24

89.688.7 88.6

87.5

95.3

Fig. 1. Mean (– standard error of the mean) bodyweight of patientsreceiving obesity pharmacotherapy from baseline to 24 months.

06

(n = 51)12

(n = 44)

Time (months)

18(n = 37)

24(n = 33)

10

20 17.65

34.09

62.16

32.43

69.70

39.39

63.6464.71

30

40

Per

cent

age

of p

atie

nts

50

60

70

80

≥5% weight loss≥10% weight loss

Fig. 2. Percentage of patients achieving a loss of ‡5% and ‡10% of initial weight from baseline to 24 months. Data are cumulative, such thatthe percentages of patients who lost ‡5% include those who lost ‡10%.

502 Horie et al.


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aimed at treating weight-related health problemsin the elderly. The evidence suggests thatintentional weight loss may be of benefit in con-trolling cardiovascular risk factors,[27,28] reducingmedications for weight-related health condi-tions,[29] and improving pulmonary disease[30]

and osteoarthritis.[31] Even in the elderly, mod-erate weight loss may significantly improve theconsequences of obesity.[32] However, there havebeen no large clinical trials on the effects ofweight loss on health outcomes in old age. In thisstudy, we could not analyse the improvement indiseases associated with the treatment of obesitybecause the patients were treated with specificpharmacotherapy for these conditions.

In regard to weight loss caused by pharmaco-logical treatment, the clinical benefit observed inthis study was similar to that reported in the lit-erature, with a higher rate of weight loss duringthe first 6 months of treatment;[13,14] however,this finding was observed despite the fact that,unlike some other studies, there was no intensivelifestyle intervention at the beginning of thetreatment. As the greatest challenge in treatingobesity is weight loss maintenance, it is interest-ing to consider that during follow-up the patientsdid not show a tendency to regain weight over a2-year period. A possible reason for maintenanceof this successful outcome was that most patientscontinued being treated with pharmacotherapyand, in this study, the attending physician wasfree to change or add medications. The patho-physiology of obesity is complex, and a combi-nation of medications may enhance the result byacting via different pharmacological mechan-isms. In addition, substitution of therapy canbe useful in cases of tolerance or emergence ofpreviously non-existent contraindications.

As shown in table III, the most frequently usedmedications were SSRIs, which were often usedin combination with sibutramine or with a sym-pathomimetic. In addition, eight patients werediagnosed with major depression during treat-ment and they received sertraline or fluoxetine,which could also support weight loss. In previousstudies, SSRIs did not demonstrate a sustainedeffect on weight loss; however, as these medicineswere widely used by physicians at the clinic,T

ab

leII

I.T

ype,

frequency,dose,dura

tion

and

eff

ects

on

weig

htofanti-o

besity

medic

ines

pre

scribed

Medic

ation

nM

ean

dose

[mg

(–S

D)]

Mean

dura

tion

ofth

era

py

[month

s(–

SD

)]

Maxim

um

dura

tion

ofth

era

py

(y)

Mean

weig

ht

at

pre

scription

[kg

(–S

D)]

Mean

weig

htlo

ss

[kg

(–S

D)]

Mean

weig

ht

loss

per

year

(kg)

Maxim

um

weig

htlo

ss

(kg)

Flu

oxetine

36

47.7

–17.0

28.9

–20.0

7.2

93.6

7–

14.1

03.5

5–

4.4

21.9

014.6

Sib

utr

am

ine

29

11.3

–2.2

12.4

–11.9

3.9

92.9

9–

11.8

82.4

6–

6.2

02.3

818.1

Fenpro

pore

x12

45.6

–12.1

35.5

–27.4

7.1

94.5

2–

13.8

91.4

1–

3.5

20.4

89.6

Orlis

tat

11

330.0

–55.6

8.7

–5.0

1.4

96.1

8–

15.7

83.3

0–

5.8

64.5

812.8

Sert

ralin

e10

116.7

–25.8

20.0

–15.0

4.8

89.1

3–

10.9

81.8

3–

3.8

61.1

07.2

Am

fepra

mone

9100.0

–50.0

11.8

–14.9

3.1

96.3

8–

15.8

30.8

4–

4.6

90.8

69.7

Mazin

dol

83.2

–1.3

7.4

–10.6

2.5

92.6

0–

12.0

00.4

1–

2.2

50.6

72.6

Topiram

ate

4156.3

–59.1

24.7

–18.6

4.0

99.9

8–

20.2

40.1

5–

3.9

70.0

74.2



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possibly they perceived some possible benefitsnot just in weight loss, but also with respect toimprovement in mood or eating behaviour. Thethree patients who were diagnosed with bipolarmood disorder were treated with topiramate,since this drug can be used as a mood stabilizerwhile also enhancing weight loss. Of the 11patients who received orlistat, all had hyperten-

sion, nine had dyslipidaemia, four had diabetesand five had glucose intolerance or abnormalfasting glucose. The use of medications that treatmore than one condition at the same time is acurrently recommended strategy, e.g. whenchoosing antihypertensive medications to treatassociated conditions such as heart failure orheart disease, and it is a particularly useful strat-egy in patients with multiple co-morbidities.[33]

In the cases mentioned above in which patientswere treated with SSRIs, topiramate and orlistat,the medication chosen had the potential topromote weight loss and effectively treat con-comitant disorders.

Since the medications were used for non-standardized durations, at different doses, inseveral different combinations and in a relativelysmall number of patients, we could not comparethe effect of each drug. However, it was possibleto determine the profile of prescription.

Sympathomimetic drugs are approved forshort-term use (12 weeks). However, in the lit-erature, there is a report on the use of phenter-mine for >40 years by the same patient.[34] In2000, a technical opinion of the Advisory Groupfor Research on Anorexigenic Drugs, released byANVISA (National Health Surveillance Agency,Brazil),[35] concluded that amfepramone, fenpro-porex and mazindol were effective, inexpensive

Table IV. Frequency of combinations of anti-obesity medicines

prescribed

Combination N

Fluoxetine + sibutramine 14

Fluoxetine + fenproporex 8

Fluoxetine + amfepramone 7

Fluoxetine + mazindol 4

Fluoxetine + topiramate 2

Fluoxetine + fenproporex + orlistat 2

Fluoxetine + topiramate + orlistat 1

Fluoxetine + sibutramine + orlistat 1

Sertraline + fenproporex 3

Sertraline + sibutramine 2

Sertraline + mazindol 1

Sertraline + topiramate 1

Sertraline + topiramate + orlistat 1

Orlistat + sibutramine 2

Orlistat + topiramate 1

Orlistat + fenproporex 1

Table V. Medication, adverse event related to discontinuation of medication and time of the adverse event

Medication Adverse event Time after starting

therapy (days)

Amfepramone Depression 291

Amfepramone Insomnia 833

Amfepramone Insomnia 316

Fenproporex Anxiety 76

Fenproporex Atrial flutter 441

Fenproporex Insomnia 351

Mazindol Constipation 4

Mazindol Dry mouth 3

Mazindol Dry mouth 47

Fluoxetine Nonspecific thoracic sensation 28

Fluoxetine Gastro-oesophageal reflux 898

Sertraline Bipolar mood disorder 269

Sibutramine Insomnia 76

Sibutramine Ecchymosis 15

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is prohibited.

and represented an alternative valid therapy withinfrequent serious adverse effects. In the presentstudy, the mean duration of use of fenproporexwas nearly 3 years, with a mean weight lossof 1.41 kg. The mean duration of use ofamfepramone was almost 1 year, with a meanweight loss of 0.84 kg. The mild weight lossobserved and the use of these drugs over longperiods indicate that they were used for weightmaintenance.

Despite the fact that medications were takenfor long periods of time, the frequency of dis-continuations due to adverse effects was low.There was only one report of atrial flutter duringuse of fenproporex, and the patient had beentaking the medication for >1 year. Therefore,a cause-consequence relation could not beestablished. No patients needed to discontinueany medication because of an increase in bloodpressure. However, during clinical follow-up,physicians were able to adjust antihypertensivemedications. Only four patients stopped theirmedication because of insomnia: three were tak-ing sympathomimetic drugs and one was takingsibutramine. No patients received prescriptionsfor hypnotic drugs during this study.

An important limitation of the present studyrelates to its design, which is retrospectiveand based on patients’ medical records. Theoccurrence of adverse effects leading to discon-tinuation of medications might have beenunderestimated because of record failures or be-cause the patients did not report adverse effects.There may also have been a patient selection bias,as it is possible that patients who did not re-spond well to treatment or who experiencedadverse effects did not return for follow-up visitsin the first 6 months and were not included in thestudy.

Another limitation is that we did not use acontrol group treated with only diet and physicalactivity for comparison. Studies reveal that ad-dition of medication typically improves short-and long-term weight loss compared with lifestylemodification alone.[32,36] The best results, how-ever, were obtained when medications werecombined with an intensive programme of life-style modification.

Conclusion

Our study showed that long-term pharma-cotherapy for obesity of older adults in a real-world setting was effective and well tolerated.There is a need for prospective controlled studiesof anti-obesity pharmacotherapy in the elderly.

Acknowledgements

No external funding was required to conduct of this study.The authors have no conflicts of interest that are directlyrelevant to the content of this study.

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Correspondence: Dr Nıdia Celeste Horie, NADI - Nucleo deAssistencia Domiciliar Interdisciplinar, 4o. andar, Av. Dr.Eneas de Carvalho Aguiar, 255. CEP:05403-000-Sao Paulo,Brazil.E-mail: [email protected]

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Long-Term Pharmacotherapy for Obesity in Elderly Patients