Long-term Phentermine Pharmacotherapy: An Investigation for Symptoms of Dependence, Cravings, or Withdrawal (PC-II)

January 25, 2013 updated by: Ed J. Hendricks, M.D., Center for Weight Management, California

Phentermine, an amphetamine congener, is the most widely used anti-obesity drug in the U.S. Although phentermine is the agent-of-choice among physicians specializing in obesity treatment, the use of this drug for obesity treatment by other physicians has long been curtailed because misapprehensions regarding phentermine safety. Concerns of phentermine-induced adverse cardiovascular reactions and of phentermine-induced addiction are two fears that have had a profound negative impact on phentermine prescribing. Although warnings of high incidence rates of adverse cardiovascular and psychiatric effects are included in FDA labeling and are often repeated in published reviews, the few clinical reports in the peer-reviewed medical literature of such adverse effects are anecdotal. Fear of phentermine adverse effects does not inhibit the use of phentermine by obesity treatment specialists. A 2008 survey of prescribing practices found that 98% of bariatric medicine specialists used pharmacotherapy in treating obesity and that 97% of those prescribed phentermine as their first choice.

The fear that phentermine has addiction potential appears to be a factor influencing curtailment of use. At the time that phentermine was approved in 1959 the expectations were that it would prove to be addicting, although perhaps less so than amphetamine. These expectations were based on the chemical structural similarities between phentermine and amphetamine and on evidence in rats that phentermine stimulated spontaneous activity. No evidence suggesting the drug had human addiction potential appeared in clinical trials conducted prior to approval.

After 52 years of use there is no evidence in the peer-reviewed medical literature to support the hypothesis that phentermine has significant human addiction potential. Research in addiction medicine has undergone significant development in the last 50 years. Concepts of addiction have shifted from an early focus on tolerance and withdrawal to a current emphasis on the psychological components of dependence. Drug addiction has been redefined as drug dependence and standardized diagnostic criteria have been adopted for drug abuse, dependence and withdrawal. Psychometric testing methods have been developed, validated, and applied clinically for measurements of dependence, drug craving, and withdrawal for a wide variety of substances of abuse including cocaine, heroin, and amphetamine.

Until recently, none of these addiction medicine metrics had been used to study the addiction potential of phentermine. Presumably, since phentermine is an amphetamine congener, any clinical characteristics of dependence or withdrawal should mimic those of amphetamine dependence or withdrawal. One recent retrospective study investigated symptoms occurring when patients treated with long-term phentermine in a weight management program abruptly ceased taking phentermine. The study found that patients on long-term phentermine who ceased phentermine abruptly by their choice did not have an amphetamine-like withdrawal symptom complex. Significantly there was no evidence of phentermine cravings. Further investigation is warranted.

The addiction potential of a drug may be investigated by measuring the drug's propensity to induce dependence, to induce cravings for the drug, and for cessation of the drug to induce characteristic withdrawal symptoms. In the case of amphetamine withdrawal symptoms appear very quickly reaching a maximum at 48 hours after drug cessation.

In this prospective study the addiction potential of phentermine will be assessed with validated psychometric scales to examine patients who have taken phentermine long-term for two years or more. Patients who have taken phentermine for 7 to 14 days will also be assessed. Participating patients who have taken phentermine long-term in this study will be asked to interrupt phentermine therapy for 48 hours to participate in the study. Scale examinations will be conducted at 24 and at 48 hours after drug cessation.

Hypotheses

  1. Long-term phentermine-treated (LPT) patients do not develop phentermine dependence or cravings.
  2. LPT patients who cease taking phentermine abruptly do not experience amphetamine-like withdrawal symptoms.

Specific Aims

  1. To compare the severity of phentermine dependence and craving between LPT patients and acute phentermine-treated (APT) patients
  2. To compare the severity of stimulant withdrawal symptoms before and after phentermine cessation in LPT patients.
  3. To examine the prevalence of phentermine dependence in LPT patients

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

269

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Roseville, California, United States, 95661
        • Center for Weight Management
      • Sacramento, California, United States, 95816
        • Center for Weight Management

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Aged 18 years or older.

  2. Duration of phentermine treatment

    1. For LPT patients, on phentermine pharmacotherapy consecutively for 2 years or more and willing to take a drug holiday for 48 to 72 hours.
    2. LPT Patients who have taken drug holidays on their own during the most recent 2 years may be included provided there has not been a holiday in the 90 days prior to matriculation in this study.
    3. For APT patients, on phentermine pharmacotherapy for 7 to 14 days at 37.5 mg/day or less.

Exclusion Criteria:

  1. Patients with confirmed Axis I psychiatric conditions including depression, ADHD, SAD, bipolar disorder, substance abuse disorders (except caffeine and nicotine) and patients taking drugs for any of these conditions, including anti-depressant drugs, drugs for ADHD and lithium.
  2. Patients who were taking phentermine in combination with any other anti-obesity drug.
  3. Patients who are taking medications such as beta-blockers, which may modulate the stimulant effect of phentermine.
  4. Pregnant patients, nursing mothers, patients with uncontrolled hypertension, hyperthyroidism, severe cardiovascular disease, glaucoma, and known hypersensitivity to phentermine -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: LPT
Subjects treated with phentermine for 2 years or more.
Drug: Abrupt cessation of phentermine pharmacotherapy
Patients will be asked to cease taking phentermine, then to complete psychometric scales 24 and 48 hours later. Patients will be examined at 48 hours by physician who will determine if phentermine should be continued or discontinued.
Other Names:
  • Phentermine-HCL, generic
No Intervention: APT
Patients treated with phentermine for 7 to 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Signs or symptoms of phentermine dependence (addiction)
Time Frame: Long-term cohort subjects on phentermine 2 years or more.
Psychometric scales will be used for assessment of signs or symptoms of phentermine dependence, phentermine withdrawal, or phentermine cravings
Long-term cohort subjects on phentermine 2 years or more.
Signs or symptoms of phentermine dependence (addiction)
Time Frame: Short-term cohort subjects on phentermine (APT) for 7 to 14 days.
Psychometric scales will be used for assessment of signs or symptoms of phentermine dependence, or phentermine cravings.
Short-term cohort subjects on phentermine (APT) for 7 to 14 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Center for Weight Management, California

Collaborators

American Society of Bariatric Physicians

Investigators

  • Principal Investigator: Ed J Hendricks, MD, Center for Weight Management

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2011

Primary Completion (Actual)

November 1, 2012

Study Completion (Actual)

November 1, 2012

Study Registration Dates

First Submitted

July 23, 2011

First Submitted That Met QC Criteria

July 25, 2011

First Posted (Estimate)

July 26, 2011

Study Record Updates

Last Update Posted (Estimate)

January 28, 2013

Last Update Submitted That Met QC Criteria

January 25, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11061-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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