This document summarizes a prospective clinical trial investigating withdrawal symptoms in patients who had been taking phentermine for weight loss treatment for over 1 year. 72 patients ceased taking phentermine and were examined at 0, 24, and 48 hours after cessation using a phentermine withdrawal questionnaire based on measures of amphetamine withdrawal. Scores on the questionnaire were low and similar to control groups, suggesting that abrupt discontinuation of phentermine did not produce significant amphetamine-like withdrawal symptoms. The study concludes that fear of inducing addiction is not a medically sound reason to withhold phentermine treatment for obesity.

1. Long-term Phentermine
Pharmacotherapy – An
Investigation for Amphetaminelike Withdrawal
Ed J. Hendricks, MD, FASBP
ECO 2013
May 15, 2013
Liverpool, U.K.

2. Phenethylamine

3. Phenethylamine Derivatives

4. Phentermine
• Phentermine is presumed addicting
• No human evidence of addiction
• Obesity treatment specialists have seen neither
addiction nor withdrawal
• Patients taking phentermine can cease abruptly
without symptoms other than hunger
• Some patients experience lower energy levels

5. Withdrawal Study Rationale
• Amphetamine addiction, abuse and withdrawal
syndromes now well described.
• If phentermine is addicting, abrupt cessation
should induce amphetamine-like withdrawal.
• Use addiction metrics to assess symptoms in
phentermine-treated patients.

6. Research Setting
• Private, Fee-for-service, Obesity Medicine
specialty practice
• Metropolitan Sacramento, California, USA
• In operation, with same MD 24 years
• Treatment modalities:
– Low carbohydrate, optimum protein: 100%
– Behavior, Lifestyle modification: 100%
– Pharmacotherapy: 95%
– Phentermine: 90%

7. Research Plan
•
•
•
•
Prospective Interventional Clinical trial
Patients phentermine-treated for > 1 year.
Consent to cease phentermine ~ 48 hours
Examine for signs of Abuse, Addiction,
Phentermine cravings.
• Examine for withdrawal symptoms while on
drug (D0) and at ~ 24 hours (D1) and
~ 48 hours (D2) after abrupt cessation.

8. Study Demographics
Subjects
Male
Female
W/H/B/A
Age, Years
Age Range, Years
Rx Duration, Years
Time Range, Years
Dose mg/d
Dose Range, mg/day
72
7 (9.7%)
65 (90.3%)
63/7/2/0
50.9 (19.4)
29 – 86
8.3 (5.0)
1.1 – 21.5
53.6 (21.3)
18.75 – 112.5

9. PWQ
• Phentermine Withdrawal Questionnaire
• from Amphetamine Withdrawal Questionnaire
• Assessment of major 10 symptoms occurring
in Amphetamine-addicted subjects after abrupt
amphetamine cessation
• Likert scale scoring 0 – 4, total range 0 – 40

11. AWQ Total Scores
McGregor, Addiction 2005; 100(9): 1320-9.

12. AWQ Item Scores
McGregor, Addiction 2005; 100(9): 1320-9.

13. AWQ Item Scores
McGregor, Addiction 2005; 100(9): 1320-9.

14. AWQ Item Scores
McGregor, Addiction 2005; 100(9): 1320-9.

15. AWQ vs PWQ 10-item Scores
20
15
McGregor AA
McG. Controls
Study Subjects
10
5
0
0
1
2
Day of Abstinence

16. Hunger Scores
2.5
2
1.5
McGregor AA
Study Subjects
1
0.5
0
0
1
Day of Abstinence
2

17. 9-Item Scores
16
14
12
10
8
6
4
2
0
McGregor AA
Study Subjects
0
1
Day of Abstinence
2

18. PWQ Data
Measure
10-Item
Hunger
9-Item
D0
D1
D2
Friedman
Test, df=2
3.39 (3.5) 3.55 (3.1) 2.99 (2.7) p = 0.046
0.77 (0.97) 1.02 (1.0) 1.03 (1.1) p = 0.027
2.65 (3.0) 2.35 (2.6) 1.95 (2.4) p = 0.084

19. Conclusions
• Abrupt cessation of phentermine treatment
does not produce amphetamine-like
withdrawal.
• Fear of inducing addiction is an inappropriate
justification for withholding phentermine
treatment for obesity.

20. WITH THANKS TO:
Frank Greenway, MD
Pennington Biomedical Research Center
Baton rouge, Louisiana, USA
Manit Srisurapanont, MD, PhD
Chang Mai University
Chang Mai, Thailand
Richard Atkinson, MD
Editor, International Journal of Obesity

21. Phentermine Rx Weight Loss
1 Year
Mean Wt. Loss = 18.7 %
Mean Wt. Loss = 17.7 Kg
Hendricks, Obesity 2011; 19(12):2351-60.

22. Phentermine & Weight Loss
No phentermine Rx
Phentermine Rx
Treatment duration YEARS
Hendricks, Obesity 2011; 19(12):2351-60.