Original Article

Clinical Studies and Practice

A comparative study of five centrally acting drugs on the pharmacological treatment of obesity

  • International Journal of Obesity volume 38, pages 10971103 (2014)
  • doi:10.1038/ijo.2013.225
  • Download Citation
Received:
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Abstract

Context:

No long-term studies have compared centrally acting drugs for treating obesity.

Objective:

To compare the efficacy and safety of diethylpropion (DEP), fenproporex (FEN), mazindol (MZD), fluoxetine (FXT) and sibutramine (SIB) in promoting weight loss.

Design and Setting:

A prospective, randomized, placebo (PCB)-controlled study conducted at a single academic institution.

Patients:

A total of 174 obese premenopausal women.

Intervention:

Participants randomly received DEP 75 mg (n=28), FEN 25 mg (n=29), MZD 2 mg (n=29), SIB 15 mg (n=30), FXT 20 mg (n=29) or PCB (n=29) daily over 52 weeks. Diet and physical activity were encouraged.

Main Outcome Measures:

The primary endpoints were changes in body weight and the proportion of women who achieved at least 5% weight loss by week 52 in the intent-to-treat population. Other measurements included anthropometry, safety, metabolic and cardiovascular parameters.

Results:

Weight loss was greater than PCB (−3.1±4.3 kg) with DEP (−10.0±6.4 kg; P<0.001), SIB (−9.5±5.9 kg; P<0.001), FEN (−7.8±6.9 kg; P<0.01) and MZD (−7.4±4.9 kg; P<0.01) but not with FXT (−2.5±4.1 kg). Ten (33.3%) women lost5% of their initial weight with PCB, compared with 20 (71.4%; P<0.001) with DEP, 20 (69%; P<0.02) with FEN, 21 (72.4%; P<0.01) with MZD, 22 (73.3%; P<0.001) with SIB and 10 (35.5%) with FXT. Each medically treated group experienced more adverse events compared with PCB (P<0.001). Compared with PCB, constipation was more prevalent with DEP, SIB and MZD (P<0.01); anxiety was more prevalent with DEP (P=0.01); and irritability occurred more frequently with DEP and FEN (P=0.02). Significant improvements in the depression and anxiety scores, binge-eating episodes and quality of life correlated with weight loss.

CONCLUSION:

The centrally acting drugs DEP, FEN, MZD and SIB were more effective than PCB in promoting weight loss in obese premenopausal women, with a satisfactory benefit–risk profile.

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References

  1. 1.

    . Medical consequences of obesity. J Clin Endocrinol Metab 2004; 89: 2583–2589.

  2. 2.

    , , , , , et al. Body-mass index and mortality among 1.46 million white adults. N Engl J Med 2010; 363: 2211–2219.

  3. 3.

    , , , , , et al. Effectiveness of lifestyle interventions for individuals with severe obesity and type 2 diabetes: results from the Look AHEAD trial. Diabetes Care 2011; 34: 2152–2157.

  4. 4.

    . Review of the key results from the Swedish Obese Subjects (SOS) trial: a prospective controlled intervention study of bariatric surgery. J Intern Med 2013; 273: 219–234.

  5. 5.

    , , , , , et al. Maintained intentional weight loss reduces cardiovascular outcomes: results from the Sibutramine Cardiovascular OUTcomes (SCOUT) trial. Diabetes Obes Metab 2012; 14: 523–530.

  6. 6.

    , , , , , et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med 2011; 365: 1597–1604.

  7. 7.

    , , , , . Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials. Int J Obes Relat Metab Disord 2002; 26: 262–273.

  8. 8.

    , , , , , et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 2005; 142: 532–546.

  9. 9.

    . Treatment strategies for obesity. Obes Rev 2007; 8 (Suppl 1): 137–144.

  10. 10.

    . Lifestyle and pharmacological approaches to weight loss: efficacy and safety. J Clin Endocrinol Metab 2008; 93 (11 Suppl 1): S81–S88.

  11. 11.

    . Anorectics on trial: a half century of federal regulation of prescription appetite suppressants. Ann Intern Med 2005; 143: 380–385.

  12. 12.

    , , , , . The roles of brain noradrenaline and dopamine in the anorectic activity of diethylpropion in rats: a comparison with d-amphetamine. Res Commun Chem Pathol Pharmacol 1979; 26: 3–11.

  13. 13.

    , . Neurochemical and behavioral effects elicited by bupropion and diethylpropion in rats. Behav Brain Res 2010; 211: 132–139.

  14. 14.

    , , , , et al. A randomized double-blind placebo-controlled study of the long-term efficacy and safety of diethylpropion in the treatment of obese subjects. Int J Obes (Lond) 2009; 33: 857–865.

  15. 15.

    , , . Amphetamine and fenproporex levels following multidose administration of fenproporex. J Anal Toxicol 1999; 23: 187–194.

  16. 16.

    , . Treatment of obesity: an update on anti-obesity medications. Obes Rev 2003; 4: 25–42.

  17. 17.

    . Clinical studies with mazindol. Obes Res 1995; 3 (Suppl 4): 549S–552S.

  18. 18.

    . Systemic mazindol reduces food intake in rats via suppression of meal size and meal number. J Psychopharmacol 2008; 22: 532–535.

  19. 19.

    , . Sibutramine effects on central mechanisms regulating energy homeostasis. Curr Neuropharmacol 2012; 10: 49–52.

  20. 20.

    , , , , , et al. Sibutramine produces dose-related weight loss. Obes Res 1999; 7: 189–198.

  21. 21.

    , , , , WFSBP Task Force on Eating Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of eating disorders. World J Biol Psychiatry 2011; 12: 400–443.

  22. 22.

    , , , , , . Fluoxetine: a randomized clinical trial in the treatment of obesity. Int J Obes Relat Metab Disord 1994; 18: 129–135.

  23. 23.

    , . Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry 2010; 71: 1259–1272.

  24. 24.

    , , , , , et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med 2010; 363: 905–917.

  25. 25.

    , , , . Comparison of Beck Depression Inventories-IA and -II in psychiatric outpatients. J Pers Assess 1996; 67: 588–597.

  26. 26.

    , , , . An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol 1988; 56: 893–897.

  27. 27.

    , , , . Translation and adaptation into Portuguese of the Binge-Eating Scale. Rev Bras Psiquiatr 2001; 23: 215–220.

  28. 28.

    , . The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30: 473–483.

  29. 29.

    WHOQOL Group. The World Health Organization Quality of Life assessment (WHOQOL): position paper from the World Health Organization. Soc Sci Med 1995; 41: 1403–1409.

  30. 30.

    , , , . Assessing impact of weight on quality of life. Obes Res 1995; 3: 49–56.

  31. 31.

    , , , , , . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

  32. 32.

    . Statistical considerations in the intent-to-treat principle. Control Clin Trials 2000; 21: 167–189.

  33. 33.

    . The first decade of sibutramine and orlistat: a reappraisal of their expanding roles in the treatment of obesity and associated conditions. Arq Bras Endocrinol Metabol 2009; 53: 262–270.

  34. 34.

    , , , , , et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet 2011; 377: 1341–1352.

  35. 35.

    , , , . A randomized double-blind clinical trial of fluoxetine in obese diabetics. Int J Obes Relat Metab Disord 1992; 16 (Suppl 4): S67–S72.

  36. 36.

    . Clinical studies with fluoxetine in obesity. Am J Clin Nutr 1992; 55 (Suppl 1): 181S–184S.

  37. 37.

    , , , , , et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 2010; 363: 245–256.

  38. 38.

    , , , , , et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2010; 376: 595–605.

  39. 39.

    , , , . Effect of sibutramine on weight loss and blood pressure: a meta-analysis of controlled trials. Obes Res 2003; 11: 1116–1123.

  40. 40.

    , , . Pharmacotherapies for obesity: past, current, and future therapies. J Obes 2011; 2011: 179674.

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Acknowledgements

SIB and FXT were generously provided by Medley Pharmaceuticals. FEN and DEP were generously provided by Aché Pharmaceuticals. MZD and PCB were prepared by Apparenza Drugstore, which was also responsible for packing all medications in identical bottles.

Author information

Affiliations

  1. Endocrine Division (SEMPR), Department of Internal Medicine, Parana Federal University, Curitiba, Brazil

    • H Suplicy
    • , C L Boguszewski
    • , C M C dos Santos
    • , M do Desterro de Figueiredo
    • , D R Cunha
    •  & R Radominski

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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to H Suplicy.