Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Addiction potential of phentermine prescribed during long-term treatment of obesity

Abstract

Objective:

To investigate if phentermine treatment induces phentermine abuse, psychological dependence (addiction) or phentermine drug craving in overweight, obese and weight loss maintenance patients. To investigate whether amphetamine-like withdrawal occurs after abrupt cessation of long-term phentermine treatment.

Design:

Clinical intervention trial with interruption of phentermine treatment in long-term patients.

Subjects:

269 obese, overweight or formerly obese subjects (age: 20–88 years, BMI: 21–74 kg m−2) treated with phentermine long-term (LTP, N=117), 1.1–21.1 years, or short-term (ATP, N=152), 4–22 days, with phentermine doses of 18.75–112.5 (LTP) and 15–93.75 (ATP) mg per day.

Measurements:

Module K of the Mini International Neuropsychiatric Interview modified for phentermine (MINI-SUD), Severity of Dependence Scale (SDS), 45-item Cocaine Craving Questionnaire-NOW (CCQ-NOW) modified for phentermine (PCQ-NOW), and Amphetamine Withdrawal Questionnaire (AWQ) modified for phentermine (PWQ).

Results:

MINI-SUD interviews were negative for phentermine abuse or psychological dependence in all LTP patients. SDS examination scores were low for all LTP and ATP patients, indicating they were not psychologically dependent upon phentermine. PCQ-NOW scores were low for all LTP and ATP patients, indicating neither short-term nor long-term phentermine treatment had induced phentermine craving. Other than an increase in hunger or eating, amphetamine-like withdrawal symptoms did not occur upon abrupt phentermine cessation as measured by sequential PWQ scores.

Conclusions:

Phentermine abuse or psychological dependence (addiction) does not occur in patients treated with phentermine for obesity. Phentermine treatment does not induce phentermine drug craving, a hallmark sign of addiction. Amphetamine-like withdrawal does not occur upon abrupt treatment cessation even at doses much higher than commonly recommended and after treatment durations of up to 21 years.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Samaranayake NR, Ong KL, Leung RY, Cheung BM . Management of obesity in the National Health and Nutrition Examination Survey (NHANES), 2007-2008. Ann Epidemiol 2012; 22: 349–353.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  3. Glazer G . Long-term pharmacotherapy of obesity 2000: a review of efficacy and safety. Arch Intern Med 2001; 161: 1814–1824.

    Article  CAS  PubMed  Google Scholar 

  4. Ioannides-Demos LL, Piccenna L, McNeil JJ . Pharmacotherapies for obesity: past, current, and future therapies. J Obes 2011; 2011: 179674.

    Article  PubMed  Google Scholar 

  5. Kang JG, Park CY, Kang JH, Park YW, Park SW . Randomized controlled trial to investigate the effects of a newly developed formulation of phentermine diffuse-controlled release for obesity. Diabetes Obes Metab 2010; 12: 876–882.

    Article  CAS  PubMed  Google Scholar 

  6. Kim KK, Cho HJ, Kang HC, Youn BB, Lee KR . Effects on weight reduction and safety of short-term phentermine administration in korean obese people. Yonsei Med J 2006; 47: 614–625.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Frank A . The long-term management of obesity with continuing pharmacotherapy. Obes Res 2004; 12: 1821–1827.

    Article  PubMed  Google Scholar 

  8. Hendricks EJ, Greenway FL, Westman EC, Gupta AK . Blood pressure and heart rate effects, weight loss and maintenance during long-term phentermine pharmacotherapy for obesity. Obesity (Silver Spring) 2011; 19: 2351–2360.

    Article  CAS  Google Scholar 

  9. Rothman RB . Treatment of obesity with ‘combination’ pharmacotherapy. Am J Ther 2010; 17: 596–603.

    Article  PubMed  Google Scholar 

  10. Hendricks EJ, Rothman RB, Greenway FL . How physician obesity specialists use drugs to treat obesity. Obesity (Silver Spring) 2009; 17: 1730–1735.

    Article  Google Scholar 

  11. Hendricks EJ, Greenway FL . A study of abrupt phentermine cessation in patients in a weight management program. Am J Ther 2011; 18: 292–299.

    Article  PubMed  Google Scholar 

  12. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998; 59 (Suppl 20): 22–33 quiz 34-57.

    PubMed  Google Scholar 

  13. Gossop M, Darke S, Griffiths P, Hando J, Powis B, Hall W et al. The Severity of Dependence Scale (SDS): psychometric properties of the SDS in English and Australian samples of heroin, cocaine and amphetamine users. Addiction 1995; 90: 607–614.

    Article  CAS  PubMed  Google Scholar 

  14. Tiffany ST, Singleton E, Haertzen CA, Henningfield JE . The development of a cocaine craving questionnaire. Drug Alcohol Depend 1993; 34: 19–28.

    Article  CAS  PubMed  Google Scholar 

  15. McGregor C Amphetamine withdrawal:nature, time course, and treatment. PhD Thesis. Department of Clinical and Experimental Pharmacology, University of Adelaide, Adelaide, 2005, 224pp.

  16. Srisurapanont M, Jarusuraisin N, Jittiwutikan J . Amphetamine withdrawal: I. Reliability, validity and factor structure of a measure. Aust N Z J Psychiatry 1999; 33: 89–93.

    Article  CAS  PubMed  Google Scholar 

  17. Heinz AJ, Epstein DH, Schroeder JR, Singleton EG, Heishman SJ, Preston KL . Heroin and cocaine craving and use during treatment: measurement validation and potential relationships. J Subst Abuse Treat 2006; 31: 355–364.

    Article  PubMed  Google Scholar 

  18. Bruno R, Matthews AJ, Topp L, Degenhardt L, Gomez R, Dunn M . Can the severity of dependence scale be usefully applied to ‘ecstasy’? Neuropsychobiology 2009; 60: 137–147.

    Article  CAS  PubMed  Google Scholar 

  19. Topp L, Mattick RP . Choosing a cut-off on the Severity of Dependence Scale (SDS) for amphetamine users. Addiction 1997; 92: 839–845.

    Article  CAS  PubMed  Google Scholar 

  20. Kaye S, Darke S . Determining a diagnostic cut-off on the Severity of Dependence Scale (SDS) for cocaine dependence. Addiction 2002; 97: 727–731.

    Article  PubMed  Google Scholar 

  21. Martin G, Copeland J, Gates P, Gilmour S . The Severity of Dependence Scale (SDS) in an adolescent population of cannabis users: reliability, validity and diagnostic cut-off. Drug Alcohol Depend 2006; 83: 90–93.

    Article  PubMed  Google Scholar 

  22. Tiffany ST, Wray JM . The clinical significance of drug craving. Ann N Y Acad Sci 2012; 1248: 1–17.

    Article  CAS  PubMed  Google Scholar 

  23. Newton TF, De La Garza R 2nd, Kalechstein AD, Tziortzis D, Jacobsen CA . Theories of addiction: methamphetamine users' explanations for continuing drug use and relapse. Am J Addict 2009; 18: 294–300.

    Article  PubMed  PubMed Central  Google Scholar 

  24. McGregor C, Srisurapanont M, Jittiwutikarn J, Laobhripatr S, Wongtan T, White JM . The nature, time course and severity of methamphetamine withdrawal. Addiction 2005; 100: 1320–1329.

    Article  PubMed  Google Scholar 

  25. van Rossum JM, Simons F . Locomotor activity and anorexogenic action. Psychopharmacologia 1969; 14: 248–254.

    Article  CAS  PubMed  Google Scholar 

  26. Srisurapanont M, Arunpongpaisal S, Wada K, Marsden J, Ali R, Kongsakon R . Comparisons of methamphetamine psychotic and schizophrenic symptoms: a differential item functioning analysis. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 959–964.

    Article  CAS  PubMed  Google Scholar 

  27. Kish SJ . Pharmacologic mechanisms of crystal meth. CMAJ 2008; 178: 1679–1682.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Zorick T, Nestor L, Miotto K, Sugar C, Hellemann G, Scanlon G et al. Withdrawal symptoms in abstinent methamphetamine-dependent subjects. Addiction 2010; 105: 1809–1818.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Brauer LH, Johanson CE, Schuster CR, Rothman RB, de Wit H . Evaluation of phentermine and fenfluramine, alone and in combination, in normal, healthy volunteers. Neuropsychopharmacology 1996; 14: 233–241.

    Article  CAS  PubMed  Google Scholar 

  30. Jasinski DR, Faries DE, Moore RJ, Schuh LM, Allen AJ . Abuse liability assessment of atomoxetine in a drug-abusing population. Drug Alcohol Depend 2008; 95: 140–146.

    Article  CAS  PubMed  Google Scholar 

  31. Schoedel KA, Addy C, Chakraborty B, Rosko K, Dunbar S, Maes A et al. Human abuse potential and cognitive effects of taranabant, a cannabinoid 1 receptor inverse agonist: a randomized, double-blind, placebo- and active-controlled, crossover study in recreational polydrug users. J Clin Psychopharmacol 2012; 32: 492–502.

    Article  CAS  PubMed  Google Scholar 

  32. Couper FJ, Pemberton M, Jarvis A, Hughes M, Logan BK . Prevalence of drug use in commercial tractor-trailer drivers. J Forensic Sci 2002; 47: 562–567.

    PubMed  Google Scholar 

  33. Lee S, Kim J, In S, Choi H, Chung H, Chung KH . Detection of phentermine in hair samples from drug suspects. Forensic Sci Int 2011; 207: e5–e7.

    Article  CAS  PubMed  Google Scholar 

  34. Jain NC, Budd RD, Sneath TC . Frequency of use or abuse of amphetamine-related drugs. Am J Drug Alcohol Abuse 1979; 6: 53–57.

    Article  CAS  PubMed  Google Scholar 

  35. Greene WM, Sylvester M, Abraham J . Addiction liability of pharmacotherapeutic interventions in obesity. Curr Pharm Des 2011; 17: 1188–1192.

    Article  CAS  PubMed  Google Scholar 

  36. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4th edn American Psychiatric Association: Washington, DC, USA, 2000.

  37. O'Brien CP, Volkow N, Li TK . What's in a word? Addiction versus dependence in DSM-V. Am J Psychiatry 2006; 163: 764–765.

    Article  PubMed  Google Scholar 

  38. Kampman KM, Volpicelli JR, McGinnis DE, Alterman AI, Weinrieb RM, D'Angelo L et al. Reliability and validity of the Cocaine Selective Severity Assessment. Addict Behav 1998; 23: 449–461.

    Article  CAS  PubMed  Google Scholar 

  39. Shoptaw SJ, Kao U, Heinzerling K, Ling W . Treatment for amphetamine withdrawal. Cochrane Database Syst Rev 2009; CD003021 doi: 10.1002/14651858.

  40. Ahmadi J, Kampman K, Dackis C . Outcome predictors in cocaine dependence treatment trials. Am J Addict 2006; 15: 434–439.

    Article  PubMed  Google Scholar 

  41. Ahmadi J, Kampman KM, Oslin DM, Pettinati HM, Dackis C, Sparkman T . Predictors of treatment outcome in outpatient cocaine and alcohol dependence treatment. Am J Addict 2009; 18: 81–86.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E J Hendricks.

Ethics declarations

Competing interests

Dr Hendricks has received honoraria from Akramax Pharmaceuticals, Eurodrug Laboratories, Citius Pharmaceuticals and Vivus pharmaceuticals. Dr Greenway has received honoraria from Baronova, Basic Research, Citius, Diabetic Living, Eisai, GNC, Jenny Craig, Lithera, Merck, Naturalpha, Nume Health, Orexigen, Plensat, Takeda, Thetis, Unigene and Zafgen. The remaining authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hendricks, E., Srisurapanont, M., Schmidt, S. et al. Addiction potential of phentermine prescribed during long-term treatment of obesity. Int J Obes 38, 292–298 (2014). https://doi.org/10.1038/ijo.2013.74

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2013.74

Keywords

This article is cited by

Search

Quick links