ObesityPC-IINCT01402674
Long-term Phentermine Pharmacotherapy: An Investigation for Symptoms of Dependence, Cravings, or Withdrawal
A study testing Abrupt cessation of phentermine pharmacotherapy in people with Obesity and Phentermine Withdrawal, run by Center for Weight Management, California at 2 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Obesity, Phentermine Withdrawal
- What is being tested?
- Abrupt cessation of phentermine pharmacotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 269 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2011to Nov 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 years or older.
- Duration of phentermine treatment
- For LPT patients, on phentermine pharmacotherapy consecutively for 2 years or more and willing to take a drug holiday for 48 to 72 hours.
- 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.
- For APT patients, on phentermine pharmacotherapy for 7 to 14 days at 37.5 mg/day or less.
Who cannot join
- 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.
- Patients who were taking phentermine in combination with any other anti-obesity drug.
- Patients who are taking medications such as beta-blockers, which may modulate the stimulant effect of phentermine.
- Pregnant patients, nursing mothers, patients with uncontrolled hypertension, hyperthyroidism, severe cardiovascular disease, glaucoma, and known hypersensitivity to phentermine -
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Center for Weight Management
Roseville, California, 95661
Center for Weight Management
Sacramento, California, 95816
About this study
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.
Read more
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
- Long-term phentermine-treated (LPT) patients do not develop phentermine dependence or cravings.
- LPT patients who cease taking phentermine abruptly do not experience amphetamine-like withdrawal symptoms.
Specific Aims
- To compare the severity of phentermine dependence and craving between LPT patients and acute phentermine-treated (APT) patients
- To compare the severity of stimulant withdrawal symptoms before and after phentermine cessation in LPT patients.
- To examine the prevalence of phentermine dependence in LPT patients
- Conditions
- Obesity, Phentermine Withdrawal
- Being tested
- Abrupt cessation of phentermine pharmacotherapy
- Keywords
- Obesity treatment, Phentermine, Withholding treatment, Phentermine dependence
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abrupt cessation of phentermine pharmacotherapyDrug
Also called Phentermine-HCL, generic
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.
| Study group | Role | What they receive |
|---|---|---|
| LPT | Active comparator | Subjects treated with phentermine for 2 years or more. Receives: Drug: Abrupt cessation of phentermine pharmacotherapy |
| APT | No intervention | Patients treated with phentermine for 7 to 14 days. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Signs or symptoms of phentermine dependence (addiction)
Psychometric scales will be used for assessment of signs or symptoms of phentermine dependence, phentermine withdrawal, or phentermine cravings
Measured: Long-term cohort subjects on phentermine 2 years or more.
Signs or symptoms of phentermine dependence (addiction)
Psychometric scales will be used for assessment of signs or symptoms of phentermine dependence, or phentermine cravings.
Measured: Short-term cohort subjects on phentermine (APT) for 7 to 14 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2011 (estimated)
- Study startAug 2011
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 269 participants (actual)
Sponsor and investigators
- Lead sponsor
- Center for Weight Management, California
- Sponsor type
- University, hospital or other
- Collaborators
- American Society of Bariatric Physicians
- Responsible party
- Principal investigator, Ed J. Hendricks, M.D., Center for Weight Management, California
- Investigators
- Ed J Hendricks, MD, Principal investigator, Center for Weight Management
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01402674
- Sponsor's protocol ID
- 11061-01
- Acronym
- PC-II
- Status last verified
- Jan 2013
- First submitted
- 23 Jul 2011
- Last updated
- 28 Jan 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Hendricks EJ, Greenway FL. A study of abrupt phentermine cessation in patients in a weight management program. Am J Ther. 2011 Jul;18(4):292-9. doi: 10.1097/MJT.0b013e3181d070d7.
PubMed 20592662Hendricks 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 Dec;19(12):2351-60. doi: 10.1038/oby.2011.94. Epub 2011 Apr 28.
PubMed 21527891Hendricks EJ, Rothman RB, Greenway FL. How physician obesity specialists use drugs to treat obesity. Obesity (Silver Spring). 2009 Sep;17(9):1730-5. doi: 10.1038/oby.2009.69. Epub 2009 Mar 19.
PubMed 19300434Kampman KM, Volpicelli JR, McGinnis DE, Alterman AI, Weinrieb RM, D'Angelo L, Epperson LE. Reliability and validity of the Cocaine Selective Severity Assessment. Addict Behav. 1998 Jul-Aug;23(4):449-61. doi: 10.1016/s0306-4603(98)00011-2.
PubMed 9698974McGregor C, Srisurapanont M, Jittiwutikarn J, Laobhripatr S, Wongtan T, White JM. The nature, time course and severity of methamphetamine withdrawal. Addiction. 2005 Sep;100(9):1320-9. doi: 10.1111/j.1360-0443.2005.01160.x.
PubMed 16128721McGregor C, Srisurapanont M, Mitchell A, Longo MC, Cahill S, White JM. Psychometric evaluation of the Amphetamine Cessation Symptom Assessment. J Subst Abuse Treat. 2008 Jun;34(4):443-9. doi: 10.1016/j.jsat.2007.05.007. Epub 2007 Jul 13.
PubMed 17629443Srisurapanont M, Jarusuraisin N, Jittiwutikan J. Amphetamine withdrawal: I. Reliability, validity and factor structure of a measure. Aust N Z J Psychiatry. 1999 Feb;33(1):89-93. doi: 10.1046/j.1440-1614.1999.00517.x.
PubMed 10197890Tiffany ST, Singleton E, Haertzen CA, Henningfield JE. The development of a cocaine craving questionnaire. Drug Alcohol Depend. 1993 Dec;34(1):19-28. doi: 10.1016/0376-8716(93)90042-o.
PubMed 8174499
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long-term Phentermine Pharmacotherapy: An Investigation for Symptoms of Dependence, Cravings, or Withdrawal
- ClinicalTrials.gov ID
- NCT01402674
- Acronym / sponsor ID
- PC-II / 11061-01
- Conditions
- Obesity, Phentermine Withdrawal
- Keywords
- Obesity treatment, Phentermine, Withholding treatment, Phentermine dependence
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 269 participants (actual)
- Lead sponsor
- Center for Weight Management, CaliforniaUniversity, hospital or other
- Collaborators
- American Society of Bariatric Physicians
- Study start
- Aug 2011
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 26 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Long-term phentermine-treated (LPT) patients do not develop phentermine dependence or cravings.
- LPT patients who cease taking phentermine abruptly do not experience amphetamine-like withdrawal symptoms.
Specific Aims
- To compare the severity of phentermine dependence and craving between LPT patients and acute phentermine-treated (APT) patients
- To compare the severity of stimulant withdrawal symptoms before and after phentermine cessation in LPT patients.
- To examine the prevalence of phentermine dependence in LPT patients
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LPT | Active comparator | Drug: Abrupt cessation of phentermine pharmacotherapySubjects treated with phentermine for 2 years or more. |
| APT | No intervention | –Patients treated with phentermine for 7 to 14 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Aged 18 years or older.
- Duration of phentermine treatment
Key exclusion criteria (4 listed)
- 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.
- Patients who were taking phentermine in combination with any other anti-obesity drug.
- Patients who are taking medications such as beta-blockers, which may modulate the stimulant effect of phentermine.
- Pregnant patients, nursing mothers, patients with uncontrolled hypertension, hyperthyroidism, severe cardiovascular disease, glaucoma, and known hypersensitivity to phentermine -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Abrupt cessation of phentermine pharmacotherapyAlso: Phentermine-HCL, genericPatients 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. | Drug | LPT |
Primary outcome
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
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2013.
- Background: PubMed 20592662Hendricks EJ, Greenway FL. A study of abrupt phentermine cessation in patients in a weight management program. Am J Ther. 2011 Jul;18(4):292-9. doi: 10.1097/MJT.0b013e3181d070d7.
- Background: PubMed 21527891Hendricks 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 Dec;19(12):2351-60. doi: 10.1038/oby.2011.94. Epub 2011 Apr 28.
- Background: PubMed 19300434Hendricks EJ, Rothman RB, Greenway FL. How physician obesity specialists use drugs to treat obesity. Obesity (Silver Spring). 2009 Sep;17(9):1730-5. doi: 10.1038/oby.2009.69. Epub 2009 Mar 19.
- Background: PubMed 9698974Kampman KM, Volpicelli JR, McGinnis DE, Alterman AI, Weinrieb RM, D'Angelo L, Epperson LE. Reliability and validity of the Cocaine Selective Severity Assessment. Addict Behav. 1998 Jul-Aug;23(4):449-61. doi: 10.1016/s0306-4603(98)00011-2.
- Background: PubMed 16128721McGregor C, Srisurapanont M, Jittiwutikarn J, Laobhripatr S, Wongtan T, White JM. The nature, time course and severity of methamphetamine withdrawal. Addiction. 2005 Sep;100(9):1320-9. doi: 10.1111/j.1360-0443.2005.01160.x.
- Background: PubMed 17629443McGregor C, Srisurapanont M, Mitchell A, Longo MC, Cahill S, White JM. Psychometric evaluation of the Amphetamine Cessation Symptom Assessment. J Subst Abuse Treat. 2008 Jun;34(4):443-9. doi: 10.1016/j.jsat.2007.05.007. Epub 2007 Jul 13.
- Background: PubMed 10197890Srisurapanont M, Jarusuraisin N, Jittiwutikan J. Amphetamine withdrawal: I. Reliability, validity and factor structure of a measure. Aust N Z J Psychiatry. 1999 Feb;33(1):89-93. doi: 10.1046/j.1440-1614.1999.00517.x.
- Background: PubMed 8174499Tiffany ST, Singleton E, Haertzen CA, Henningfield JE. The development of a cocaine craving questionnaire. Drug Alcohol Depend. 1993 Dec;34(1):19-28. doi: 10.1016/0376-8716(93)90042-o.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ed J Hendricks, MD principal investigator
Center for Weight Management
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Abrupt cessation of phentermine pharmacotherapy in people with Obesity and Phentermine Withdrawal, run by Center for Weight Management, California at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Signs or symptoms of phentermine dependence (addiction) (time frame: Long-term cohort subjects on phentermine 2 years or more.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01402674, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2013.