The Reinforcing Mechanisms of Smoking in Adult ADHD

• Sponsor: University of California, Irvine (Other)
• Overall Status: Completed
• CT.gov ID: NCT00573859
• Collaborator: (none)
• Enrollment: 27
• Location: 1
• Arm: 1
• Duration (Months): 45
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Whereas the smoking prevalence rates in the general population are declining, rates among people diagnosed with attention-deficit hyperactivity disorder (ADHD) continue to be elevated. Smoking may be a form of self-medication in people with ADHD, which has specific reinforcing mechanisms such as improvement of ADHD core symptoms, enhancement of moods and arousal, or a combination of both. In addition, the reinforcing effects of smoking may be potentiated by stimulant medication.

The study examined the reinforcing effects of ad libitum smoking with and without ADHD medication in adult smokers with clinically diagnosed ADHD. Participants were adults with ADHD. The effects of two day of ADHD medication compared to two days on placebo for were studied on nicotine intake (i.e., cotinine levels). In addition, task performance on the Continuous Performance Task and nicotine withdrawal symptoms were examined in response to ADHD medication + smoking a cigarette versus ADHD medication + abstinence versus placebo medication + smoking versus placebo medication + abstinence.

The study identified the reinforcing mechanisms of smoking in interaction with ADHD medication. The findings will contribute to a better understanding of nicotine addiction and facilitate the development of targeted smoking cessation and prevention programs for individuals with ADHD and other people with deficiencies in impulse control and excessive risk taking.

Condition or Disease	Intervention/Treatment	Phase
ADHD	Drug: ADHD medication; Drug: Placebo	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: The Reinforcing Mechanisms of Smoking in Adult ADHD
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ADHD medication versus placebo For the ADHD medication condition, participants received their usual dosage of their usual ADHD medication (e.g., Dextroamphetamine; Amphetamine mixed salts; Atomoxetine; O-Methylphenidate; Lisdexamfetamine). For the placebo condition, a placebo pill was administered.	Drug: ADHD medication; For the ADHD medication condition, participants received their usual dosage of their usual ADHD medication for two consecutive days.; Other Names: Dextroamphetamine Amphetamine mixed salts Atomoxetine O-Methylphenidate Lisdexamfetamine ; Drug: Placebo; For the placebo condition, participants received placebo pills for two consecutive days.

Outcome Measures

Primary Outcome Measures

1. The Effects of ADHD Medication Versus Placebo on Cotinine Levels [4 days]

   Salivary cotinine was measured across two days on ADHD medication versus two days on placebo.

Secondary Outcome Measures

1. The Interacting Effects of Smoking and Overnight Abstinence With ADHD Medication and Placebo on Continuous Performance Task (CPT) Errors of Omission. [4 days]

   In the morning of each monitoring day, approximately 60 minutes after medication or placebo pill administration, participants were asked to either abstain from smoking or smoke their first cigarette of the day 5 minutes prior to starting the CPT.

2. The Interacting Effects of Smoking and Abstinence With ADHD Medication and Placebo on Nicotine Withdrawal Measured by the Shiffman-Jarvik Withdrawal Questionnaire. [4 days]

   The Shiffman-Jarvik withdrawal questionnaire measures nicotine withdrawal and was completed after each CPT assessment. The questionnaire consists of 25 items using 8-point scales. Total scores range from 0 to 200 and higher scores reflect higher levels of nicotine withdrawal.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• An age of 18 to 45 years

• A history of ADHD

• Current diagnosis of ADHD according to clinical criteria

• Current treatment with stimulant medication

• Smoking of 10 cigarettes or more per day

Exclusion Criteria:

• Treatment for any major medical illness such as cancer, heart disease, diabetes, skin diseases, current major depressive episode, and schizophrenia even if currently controlled by medication

• Current pregnancy, as measured by a pregnancy test (Clear Blue Easy, Unipath, Bedford, UK), or planning to become pregnant within the next 6 months. These individuals will not be included because smoking may cause harm to the unborn fetus

• Nursing mothers

• Non-English speaking people, because the majority of measurements used in the study have not been validated in languages other than English

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Pediatrics	Irvine	California	United States	92612

Sponsors and Collaborators

• University of California, Irvine

Investigators

• Principal Investigator: Jean G Gehricke, Ph.D., University of California, Irvine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of California, Irvine
• ClinicalTrials.gov Identifier: NCT00573859
• Other Study ID Numbers: 2006-5156; NIH grant# DA018752
• First Posted: Dec 14, 2007
• Last Update Posted: Nov 6, 2011
• Last Verified: Sep 1, 2011

• Keywords provided by University of California, Irvine: Smoking; ADHD; Stimulant medication
• Additional relevant MeSH terms: Methylphenidate; Amphetamine; Lisdexamfetamine Dimesylate; Dextroamphetamine; Atomoxetine Hydrochloride

Study Results

Participant Flow

Arm/Group Title	ADHD Medication Versus Placebo
Arm/Group Description	Smokers with ADHD participated in two consecutive days under ADHD medication versus 2 consecutive days on placebo. For the ADHD medication condition, participants received their usual dosage of their usual medication in the morning of each monitoring day. For the placebo condition, a placebo pill was provided in the morning of each day. The smoking period assessed the effects of the first cigarette of the day on secondary outcome measures. The abstinence period assessed the effects of overnight abstinence on the secondary outcome measures.
Period Title: Medication Versus Placebo
STARTED	27
COMPLETED	15
NOT COMPLETED	12
Period Title: Medication Versus Placebo
STARTED	27
COMPLETED	15
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	ADHD Medication Versus Placebo
Arm/Group Description	Smokers with ADHD participated in two consecutive days under ADHD medication versus 2 consecutive days on placebo. For the ADHD medication condition, participants received their usual dosage of their usual medication in the morning of each monitoring day. For the placebo condition, a placebo pill was provided in the morning of each day. The smoking period assessed the effects of the first cigarette of the day on secondary outcome measures. The abstinence period assessed the effects of overnight abstinence on the secondary outcome measures.
Overall Participants	27
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	27 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27.2 (8.9)
Sex: Female, Male (Count of Participants)
Female	4 14.8%
Male	23 85.2%
Region of Enrollment (participants) [Number]
United States	27 100%

Outcome Measures

1. Primary Outcome

Title	The Effects of ADHD Medication Versus Placebo on Cotinine Levels
Description	Salivary cotinine was measured across two days on ADHD medication versus two days on placebo.
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

Smokers with ADHD

Arm/Group Title	ADHD Medication Versus Placebo
Arm/Group Description	Smokers with ADHD participated in two consecutive days under ADHD medication versus 2 consecutive days on placebo. For the ADHD medication condition, participants received their usual dosage of their usual medication in the morning of each monitoring day. For the placebo condition, a placebo pill was provided in the morning of each day. The smoking period assessed the effects of the first cigarette of the day on secondary outcome measures. The abstinence period assessed the effects of overnight abstinence on the secondary outcome measures.
Measure Participants	15
ADHD medication	180.7 (33.3)
Placebo	274.0 (70.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADHD Medication Versus Placebo
	Comments	A 2 (ADHD medication versus Placebo) repeated measure ANOVA
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

2. Secondary Outcome

Title	The Interacting Effects of Smoking and Overnight Abstinence With ADHD Medication and Placebo on Continuous Performance Task (CPT) Errors of Omission.
Description	In the morning of each monitoring day, approximately 60 minutes after medication or placebo pill administration, participants were asked to either abstain from smoking or smoke their first cigarette of the day 5 minutes prior to starting the CPT.
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADHD Medication Versus Placebo
Arm/Group Description	Smokers with ADHD participated in two consecutive days under ADHD medication versus 2 consecutive days on placebo. For the ADHD medication condition, participants received their usual dosage of their usual medication in the morning of each monitoring day. For the placebo condition, a placebo pill was provided in the morning of each day. The smoking period assessed the effects of the first cigarette of the day on secondary outcome measures. The abstinence period assessed the effects of overnight abstinence on the secondary outcome measures.
Measure Participants	15
ADHD medication + Smoking	0.40 (0.1)
ADHD medication + Abstinence	1.08 (0.3)
Placebo + Smoking	1.00 (0.4)
Placebo + Abstinence	2.8 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADHD Medication Versus Placebo
	Comments	Four-way repeated measure ANOVA
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

3. Secondary Outcome

Title	The Interacting Effects of Smoking and Abstinence With ADHD Medication and Placebo on Nicotine Withdrawal Measured by the Shiffman-Jarvik Withdrawal Questionnaire.
Description	The Shiffman-Jarvik withdrawal questionnaire measures nicotine withdrawal and was completed after each CPT assessment. The questionnaire consists of 25 items using 8-point scales. Total scores range from 0 to 200 and higher scores reflect higher levels of nicotine withdrawal.
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADHD Medication Versus Placebo
Arm/Group Description	Smokers with ADHD participated in two consecutive days under ADHD medication versus 2 consecutive days on placebo. For the ADHD medication condition, participants received their usual dosage of their usual medication in the morning of each monitoring day. For the placebo condition, a placebo pill was provided in the morning of each day. The smoking period assessed the effects of the first cigarette of the day on secondary outcome measures. The abstinence period assessed the effects of overnight abstinence on the secondary outcome measures.
Measure Participants	15
ADHD medication + Smoking	92.7 (2.9)
ADHD medication + Abstinence	91.3 (3.5)
Placebo + Smoking	97.0 (4.8)
Placebo + Abstinence	102.0 (4.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADHD Medication Versus Placebo
	Comments	Friedman's two-way analysis of variance by ranks.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Friedman's two analysis of ranks
	Comments

Adverse Events

Arm/Group Title	ADHD Medication Versus Placebo
Arm/Group Description	Smokers with ADHD participated in two consecutive days under ADHD medication versus 2 consecutive days on placebo. For the ADHD medication condition, participants received their usual dosage of their usual medication in the morning of each monitoring day. For the placebo condition, a placebo pill was provided in the morning of each day. The smoking period assessed the effects of the first cigarette of the day on secondary outcome measures. The abstinence period assessed the effects of overnight abstinence on the secondary outcome measures.
All Cause Mortality
	ADHD Medication Versus Placebo
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	ADHD Medication Versus Placebo
	Affected / at Risk (%)	# Events
Total	0/27 (0%)
Other (Not Including Serious) Adverse Events
	ADHD Medication Versus Placebo
	Affected / at Risk (%)	# Events
Total	0/27 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.