Long-term Phentermine Pharmacotherapy – An

Investigation for Amphetamine-like Withdrawal

Ed J. Hendricks, MD, FASBP ECO 2013

May 15, 2013 Liverpool, U.K.

Phenethylamine

Phenethylamine Derivatives

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

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.

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%

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.

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

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

AWQ Total Scores

McGregor, Addiction 2005; 100(9): 1320-9.

AWQ Item Scores

McGregor, Addiction 2005; 100(9): 1320-9.

AWQ Item Scores

McGregor, Addiction 2005; 100(9): 1320-9.

AWQ Item Scores

McGregor, Addiction 2005; 100(9): 1320-9.

AWQ vs PWQ 10-item Scores

0

5

10

15

20

0 1 2

McGregor AA McG. Controls Study Subjects

Day of Abstinence

Hunger Scores

0

0.5

1

1.5

2

2.5

0 1 2

McGregor AA Study Subjects

Day of Abstinence

9-Item Scores

0 2 4 6 8

10 12 14 16

0 1 2

McGregor AA Study Subjects

Day of Abstinence

PWQ Data

Measure D0 D1 D2 FriedmanTest, df=2

10-Item 3.39 (3.5) 3.55 (3.1) 2.99 (2.7) p = 0.046 Hunger 0.77 (0.97) 1.02 (1.0) 1.03 (1.1) p = 0.027 9-Item 2.65 (3.0) 2.35 (2.6) 1.95 (2.4) p = 0.084

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.

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

Phentermine Rx Weight Loss 1 Year

Mean Wt. Loss = 18.7 % Mean Wt. Loss = 17.7 Kg

Hendricks, Obesity 2011; 19(12):2351-60.

Phentermine & Weight Loss

Hendricks, Obesity 2011; 19(12):2351-60.

No phentermine Rx

Phentermine Rx