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

This study has been completed.
Sponsor:
Collaborator:
American Society of Bariatric Physicians
Information provided by (Responsible Party):
Ed J. Hendricks, M.D., Center for Weight Management, California
ClinicalTrials.gov Identifier:
NCT01402674
First received: July 23, 2011
Last updated: January 25, 2013
Last verified: January 2013
  Purpose

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

Condition Intervention
Obesity
Phentermine Withdrawal
Drug: Abrupt cessation of phentermine pharmacotherapy

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Long-term Phentermine Pharmacotherapy: An Investigation for Symptoms of Dependence, Cravings, or Withdrawal

Resource links provided by NLM:


Further study details as provided by Center for Weight Management, California:

Primary Outcome Measures:
  • Signs or symptoms of phentermine dependence (addiction) [ Time Frame: Long-term cohort subjects on phentermine 2 years or more. ] [ Designated as safety issue: No ]
    Psychometric scales will be used for assessment of signs or symptoms of phentermine dependence, phentermine withdrawal, or phentermine cravings

  • Signs or symptoms of phentermine dependence (addiction) [ Time Frame: Short-term cohort subjects on phentermine (APT) for 7 to 14 days. ] [ Designated as safety issue: No ]
    Psychometric scales will be used for assessment of signs or symptoms of phentermine dependence, or phentermine cravings.


Enrollment: 269
Study Start Date: August 2011
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Phentermine-HCL, generic
No Intervention: APT
Patients treated with phentermine for 7 to 14 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 -
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01402674

Locations
United States, California
Center for Weight Management
Roseville, California, United States, 95661
Center for Weight Management
Sacramento, California, United States, 95816
Sponsors and Collaborators
Center for Weight Management, California
American Society of Bariatric Physicians
Investigators
Principal Investigator: Ed J Hendricks, MD Center for Weight Management
  More Information

Publications:
Responsible Party: Ed J. Hendricks, M.D., Medical Director, Center for Weight Management, California
ClinicalTrials.gov Identifier: NCT01402674     History of Changes
Other Study ID Numbers: 11061-01
Study First Received: July 23, 2011
Last Updated: January 25, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Center for Weight Management, California:
Obesity treatment
Phentermine
Withholding treatment
Phentermine dependence

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Phentermine
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Appetite Depressants
Anti-Obesity Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014