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Xanax Drug Interactions

INTRODUCTION

There are currently 35 million adults aged 65 and above in the United States. By the year 2030, older adults will comprise 20% of the U.S. population; this translates into 70.1 million adults aged 65 and older (1). Researchers, clinicians, and health care providers are only beginning to recognize the pervasiveness of substance abuse problems among older adults, ages 55 and above (2). It is estimated that alcohol and prescription drug abuse affect up to 17% of older adults, with an estimated 2.5 million older adults having problems related to alcohol (3). Older adults are less likely than are younger adults to use illicit drugs; but seniors are significantly more likely to consume prescription drugs; although, they represent only 13% of the population, they account for 30% of prescription drug use and 40% of over-the-counter (OTC) drugs sold in the United States (1). Furthermore, the number of older adults who abuse alcohol and other drugs will greatly increase over the next several decades (4.5). This is due to the sheer number of Americans born during the post-World War II (WWII) baby boom who will be reaching the senior age category, as well as the increased rates of drug and alcohol abuse of this generation compared with previous generations (6).

Older adults who abuse alcohol fall into two categories: those who begin abusing alcohol in early or middle adulthood (early onset) and thorn who do not begin to abuse alcohol until after the age of 60 (late onset); those who fall into the early onset group outnumber the late onset group by 2:1 (2). Males are more likely to belong to the early-onset group; late-onset alcohol abuse is more prevalent in females and it is often associated with age-related stressors, such as retirement or loss of a spouse; and it is more likely to be undetected by health care providers (1,4).

Interactions involving prescription drugs and alcohol are especially prevalent in the senior population. Older users of medications are more likely to experience adverse effects that influence functional capacity and cognition than are younger adult (3). Columbia's National Center on Addiction and Substance Abuse (CASA) reports that almost 20% of elderly women abuse prescription drugs or alcohol (7). Research has also found that a significant number of alcoholic patients 65 years of age and older treated in an inpatient substance abuse program have drug abuse or dependence problems that arise from abuse of legally prescribed drugs (8). Interactions between alcohol and prescription drugs are a serious issue; as many as half of the 100 most common drugs prescribed to older adults react adversely with alcohol (9).

Excess alcohol consumption in older adults is associated with a host of health-related problems, such as major organ damage, gastrointestinal disturbances, heart disease, hypertension, malnutrition, accidental injuries, dementia, and depression (1). In many cases, substance abuse problems in older adults are underestimated by health care providers because the symptoms are often mistaken for dementia, depression, or other problems common to seniors. Furthermore, as compared with younger adults, older adults are less willing to self-disclose their substance abuse problems and less likely to seek help for them. For these reasons, some researchers believe that screening for alcohol and other drug abuse should become part of routine physical examinations in older adults (l).

The health care facility offers an ideal setting for screening for substance abuse in older adults. As a population, older adults tend to visit physicians more frequently than do younger adults. According to the Center for Substance Abuse (CAS), 87% of seniors see physicians regularly (3). These visits provide an excellent opportunity to screen older adults for substance abuse problems. It is important that physicians assess senior patients for substance abuse problems, and then provide or refer them to appropriate counseling and treatment as necessary. This is particularly important since it is estimated that 40% of older adults, who are at risk for substance abuse problems do not seek services for drug-related problems on their own (3). As a result, most substance abuse treatment programs have few senior clients (2). The National Drug and Alcoholism Treatment Unit Survey of 1987 found that in a population of 36,000 inpatients in drug abuse treatment, only 1.6% were age 55 or older. In this same study, only 3.3% of drug-abuse patients in detoxification units were age 55 or older, and of drug abuse inpatients, only 2.9% were age 55 or older (10).

The identification of substance abuse in the older adult is critically important (11). However, in order to identify potentially problematic drug and alcohol use, there is a need for age-validated screening tools to help identify the older substance abuser (5). This is because virtually all alcohol and drug abuse screening devices have been developed and validated with younger adults. One study looked at the validity of the Cut, Annoyed, Guilty, Eye-Opener (CAGE) as a screening instrument for alcohol and drug abuse in older adults (age 60 and above), and found that one item that was a good predictor of drug and alcohol abuse among younger adults was not a good predictor in older adults. In this study, older adults were significantly more likely than were younger adults to report that they want to cut down on alcohol and drug use. Thus, while this item on the CAGE had been found to be a good indicator of potential drug-related problems in the younger adult, in this study, it proved to be a poor predictor of drug and alcohol abuse in the older adult. As a result of this study, these researchers suggested that the CAGE be modified when screening for alcohol and drug abuse in older adults (11).

CURRENT STUDY

The purpose of the current study was to examine possible differences in responses of older adults (ages 55 to 86) and younger adults (ages 18 to 54) to the Drug Abuse Problem Assessment for Primary Care (DAPA-PC), a computerized screening instrument for alcohol and drug use and abuse. The current study is unique in that it is the first to look at possible differences in older and younger adults' responses on a computerized drug and alcohol screening instrument. Because older adults tend to view substance abuse as a moral failing rather than a medical problem (1), they may be more reluctant to disclose information about alcohol and drug use during conventional, face-to-face interview types of assessments commonly used in health care settings. Thus, a computerized screening instrument may be particularly well-suited for use with older adults who tend to exhibit more shame and lowered self-esteem regarding alcohol and drug use (2).

THE DRUG ABUSE PROBLEM ASSESSMENT FOR PRIMARY CARE

Recognizing the need for increased screening of patients for risk of substance abuse problems, Danya International, Inc, in Silver Spring, MD, developed the Drug Abuse Problem Assessment for Primary Care (DAPAPC) under a contract from the National Institute on Drug Abuse. The DAPA-PC system is an easily implemented, computerized, comprehensive resource for drug abuse .screening in a primary care setting. The DAPA-PC is a self-administered, Internet-based screening instrument that features automatic scoring, generation of a patient profile for medical reference, and presentation of unique motivational messages and advice to the patient. A detailed description of the development of the DAPA-PC can be found in Ref. (12).

The DAPA-PC system is designed as a two-level screening instrument. All users of the DAPA-PC system begin by answering a very brief risk and trauma assessment called The Health and Safety Screen. Extensive research has indicated that asking about trauma is a predictive yet non-threatening way to determine a patient's level of drug and alcohol use or abuse (13). The types of questions asked on The Health and Safety Screen can be easily integrated into medical screening and are likely to be answered more honestly because they do not overtly address substance abuse. In addition, this type of screen allows the provider to explore drug and alcohol related issues such as depression or physical/emotional abuse. The time frame for responses to questions on The Health and Safety Screen is five years; a patient's score on this screen determines whether the patient will be moved into the second level of the system, The Drug and Alcohol Problem Screen.

The second screen, The Drug and Alcohol Problem Screen, focuses on drugs and alcohol problems directly. During the development of this screen, specific questions were evaluated from 10 widely used drug screening instruments, such as the Cage Questions Adapted to Include Drugs (CAGE-AID), T-ACE, TWEAK, Short Michigan Alcoholism Screening Test (S-MAST), Brief Michigan Alcohol Screening Test (B-MAST), Alcohol Use Disorders Identification Test (AUDIT), NEW, Substance Abuse Subtle Screening Inventory (SASSI), Drug Abuse Screening Test (DAST) and a Simple Screening Instrument developed by the Treatment Improvement Protocol (TIP #11). It was determined that the AOD Simple Screening Instrument, a composite of many of the instruments previously listed, should form the foundation of the DAPA-PC tool. The questions that compose the DAPA-PC are presented in Fig. 1.

In the past six months:

l) Have you felt that you use too much alcohol and/or other drugs?

2) Have you tried to quit. control, or reduce your drinking and/or
other drug use?

3) Have you experienced sickness, shakiness, nervousness, or depression
when you stopped using alcohol and/or other drugs?

4) Has anyone mentioned things you said or did while drinking and/or
using drugs that you didn't remember saying or doing?

5) Has your drinking and/or drug use caused problems with
relationships, school, or work?

6) Have you been arrested or had other legal problems related to your
drinking and/or drug use?

7) Have you spent a lot of time thinking about or trying to get alcohol
and/or other drugs?

8) Has a friend, employer, doctor, or relative ever expressed concern
about your drinking and/or drug use?

9) What substance do you use the most?

--Alcohol

--Marijuana/Hashish

--Cocaine or crack cocaine

--Opiates and opiate-like drugs such as heroin, Dilauded, Percodan,
Percocet

--Sedatives such as Valium, Xanax, and other sleeping pills

--Inhalants such as glue, paint, or aerosols

--Other

10) In the last 30 days, how often have you used this substance?

--once a month--2-3 times a month--weekly--2-3 times a week--daily

--Amphetamines or other stimulants

--LSD, PCP, Ecstasy or other Hallucinoganics

--Inhalants, such as glue, paint or aerosols

--Other

--None

10) In the last 30 days, how often have you use this substance?

--once a month

--2-3 times a month

--weekly

--2-3 times a week

--weekly

--daily

--no use

11) What other substance do you use the most, if any?

--Alcohol

--Marijuana/Hashish

--Cocaine or crack cocaine

--Opiates and opiate-like drugs such as heroin, Dilauded, Pereodan,
Pereocet

--Sedatives such as Valium, Xanax and other sleeping pills

--Amphetamines or other stimulants

--LSD, PCP, Ecstasy or other Hallucinogenics

12) In the last 30 days, how often have you use this substance?
once a month

--inhalants, such as glue, paint, or aerosols

--Other

--None

10) In the last 30 days, how often have you use this substance?

--once a month

--2-3 times a month

--weekly

--2-3 times a week

--weekly

--daily

--no use

Once the patient completes the Drug and Alcohol Problem Screen. information is posted indicating whether the respondent's health is at risk from drinking alcohol or using drugs. If a health risk is indicated, advice and options on how to minimize this risk, including information about health links for the patient to explore, are displayed. After the patient completes the instrument, the provider can access a summary of the patient's results, along with useful links of interest to the health care professional.

The DAPA-PC has proven to be a reliable and valid instrument for screening adults who may be at risk for drug problems in a primary care setting (14-16). This instrument could have important public health implications and cost savings. First, it can be easily implemented on a wide-scale basis in primary health care facilities. Second, it can cut the cost of drug screening and assessment because it is computer generated, and does not need a trained professional for administration. Third, because it is completed in privacy, it may increase the likelihood that patients will respond openly and honestly to sensitive questions about their use of alcohol and drugs.

METHOD

Sample Description

Participants were recruited from a diverse population presenting for care at the George Washington University Medical Faculty Associates clinic in downtown Washington, DC. Recruitment literature was made available through signs and flyers posted and distributed in the waiting room of the health-care facility. Those interested in participating in the study approached a research assistant stationed in the waiting room; thus, the sample was self-selected. The George Washington Institutional Review Board did not allow for active recruiting of patients visiting the health-care facility, indicating that this might be coercive and may cause people to feel pressure to participate in the study. Therefore, it is not possible to determine how many people read the recruitment literature and decided not to participate in the study.

Participants

Data were collected from 327 participants. The average age of the sample was 41 years (range=18-86 years). Slightly more than half the participants were female (56%). Approximately half of the participants were white (48%); the next most represented ethnic group was African American (42%). The majority of participants were not married (79%), the average highest educational level was close to 15 years. The demographics of the sample represent the community served by the George Washington clinic, which is diverse in both socioeconomic status and racial/ ethnic composition.

The total sample was subdivided into two groups: younger adults (age 18 to 541 and older adults (age 55 to 86). Table 1 presents the subject characteristics of the two groups.

As shown in Table 1, when the demographic characteristics of the two groups were compared, two significant differences were found. First, there were significantly more males in the older adult group (57%) than in the younger group (41%) (p<0.05). Second, there were significantly more Caucasian older participants than younger participants (67% and 43%, respectively; p<0.05), and significantly fewer African American older respondents than younger respondents (27% and 46%, respectively, p< 0.05). There were no significant differences between the two groups in marital status or in highest educational level attained.

MEASURES

As part of a comprehensive psychometric study of the DAPA-PC, the following measures were used to collect data from participants.

Urine and Hair Specimens

Urine and hair specimens were used to identify the physiological presence of drugs or alcohol. The urinalysis was used as the external criteria for recent or short-term use of drugs or alcohol (i.e., one to two days). Urine analysis was completed using the OnTrak TesTcup5 from Roche Diagnostic System, which can identify exposure of all major drug classes in the past 2-3 days. Hair analysis, conducted by Psychemedics Corporation, was used to identify long-term exposure to drugs (i.e., within 90 days prior to the visit).

Diagnostic Interview Schedule--Alcohol Dependence/Abuse Module and Drug Dependence/Abuse Module

This Diagnostic Interview Schedule (DIS) was designed by a group of researchers at Washington University (Robins, et al,) for administration by trained lay interviewers. This instrument elicits data for the DSM-IV adult diagnoses. Only the alcohol and drug modules of the DIS were used in the current study.

ANALYSES

Responses of older participants were compared to those of the younger adults for the DAPA-PC, DIS, and hair and urine analyses. Bivariate analyses including chi-square tests to compare categorical variables and t-tests to compare continuous variables were used.

RESULTS

Rates of drug use were found to be similar in the older adult and younger adult groups. According to the DIS, approximately one-quarter of the seniors and one-third of the nonseniors were diagnosed with substance abuse or dependence (the difference between older and younger responders was not significant). Based on responses to the DAPA-PC, approximately half of both groups reported having used alcohol in the previous six months. The only difference that was found in self-reported and objectively measured drug use was in rates of recent (previous 2-3 days) marijuana use. Of the younger adults, 7% were found to have used marijuana recently, as evidenced by urinalysis; but there was no recent marijuana use among older adults (p<0.05). No significant between-group differences were found in marijuana use according to hair analysis (20% for older adults and 19% for younger adults). Findings by specific measures are described in the following section.

Hair and Urine Test Results

Results for older participants were similar to those found for younger participants. As compared with 24% of younger adults, 20% of older adults tested positive for drug use on hair or urine analyses. Based on the hair analyses, marijuana was the most used substance (20% of older adults testing positive), followed by cocaine/crack use (9% testing positive). Urine test results did not show any drug use for older adults in the previous three days. As described previously, younger adult participants had significantly more traces of marijuana in their urine samples (7% vs. 0% of older adults; p<0.05), but this finding was not supported by hair analyses. No other differences were found between the two groups in hair or urine analyses.

Diagnostic Interview Schedule Diagnoses

More younger adults than older adults received a diagnosis of drug abuse on the DIS. Twenty-five percent of older adults compared with 37% of younger adults were diagnosed with substance abuse or dependence according to the DIS. but this between-group difference was not significant.

DAPA-PC Results

Older adults were significantly less likely than were younger adults to respond positively to two questions on the DAPA-PC. These questions were: 1) "In the past six months, have you felt that you use too much alcohol and/or other drugs?" (8% older adults and 19% younger adults responded in the affirmative; p<0.05); and; 2) "In the past six months. have you tried to quit, control, or reduce your drinking and/or other drug use?" (15% seniors and 27% nonseniors responded in the affirmative; p<0.05). Responses were similar for both groups on the remaining questions on the DATA-PC. Table 2 presents the responses of older and younger adults to the questions on the DAPA-PC.

DISCUSSION

Similar rates of drug use were found among older and younger adults in the current study. According to the Diagnostic Interview Schedule (DIS), one fourth of the older adults in this study were diagnosed with substance abuse or dependence. This finding supports previous estimates from the literature that find that a significant number of older adults abuse or are dependent on drugs (3). The fact that 25% of the older adults who participated in the current study were at risk for drug abuse and dependence is important, given that adults, age 55 and above, constitute the fastest growing segment of the American population (1). Moreover, in keeping with findings from the literature, alcohol was by far the substance reported as most used by the older adult population in this study (3).

The current study found significant differences between older and younger adults in responses to the DAPA-PC screening instrument. Although drug use between these two groups was found to be similar as measured by the DAPA-PC, DIS, and objective measures, it appears that older adults perceive their risk for drug abuse and dependence as lower than do younger adults. This was evidenced by older adults' responses to specific DAPA-PC questions that assessed their perceptions about their use of drugs and alcohol. Despite similar amounts of overall drug use, older adults were less likely to report that they felt their use of alcohol and/or drugs was excessive. Older adults, as compared with younger respondents, were also less likely to report that they tried to quit, control, or reduce their drinking and/or other drug use in the past six months. These findings support existing literature suggesting that, as compared with their younger counterparts, older adults often do not report their substance-related problems, and are less likely to seek help for them (1). This reluctance to acknowledge substance abuse may also be related to the low numbers of seniors that seek treatment for drug- and alcohol-related problems.

One potential problem with using a computerized screening device such as the DAPA-PC with older adults may have to do with this population's lack of familiarity with computers, as compared with younger adults. However, in the present study, on average, older adults did not demonstrate any difficulties with completing the DAPA-PC. Moreover, there is support in the literature that older adults are able to utilize computerized screening devices. In one study that evaluated the feasibility of a computerized alcohol screening devise with adults aged 60 and over, nearly all of the 106 participants were able to independently complete the computerized screening instrument used in the study while in the waiting room of their health care facility (18).

Thus, computerized screening instruments for drug and alcohol use and abuse can assist health care providers in determining whether observed symptoms in their older patients may be due in part or whole to substance abuse rather than a physical or psychological condition. This is an important distinction due to the fact that the symptoms of substance abuse can mimic those of many disorders common to seniors, including diabetes, dementia, and depression (3).

Fingerhood writes that older adults are particularly susceptible to adverse medical outcomes from substance abuse. Research indicates that brief interventions by primary care providers can have a major impact on preventing medical morbidity due to substance abuse (2). Thus, another way in which the DAPA-PC can be helpful to older adults is to serve as a brief intervention by providing personalized motivational messages and recommendations to the patient who may be in need of treatment or of further assessment. The motivational messages provided by the DAPA-PC can be particularly useful when the patient chooses not to disclose the results of the screening to the primary health care professional.

The usefulness of the DAPA-PC might be increased by adapting the Health and Safety Screen to include some of the risk factors associated with substance abuse in older adults. Suggested risk factors include loss of a spouse or other family members or friends through death or separation (3,19), feelings of uselessness or feelings of dependency (20), and reactions to alienation, poverty and feelings of low status in society (21). Questions about symptoms that may indicate prescription drug abuse would also be helpful in screening older patients. Symptoms of drug abuse may include loss of motivation, memory loss, family or marital discord, difficulty with activities of daily life, trouble sleeping, drug seeking behavior, and doctor shopping (2). Including questions on the DAPA-PC that better address these issues may help in determining whether substance abuse is a problem in an older adult's life.

The findings of the current study emphasize the feasibility and importance of screening older adults for potential drug and alcohol use and abuse. Health care professionals in primary care facilities are in a unique position to identify older adults at risk for alcohol and drug abuse and dependence. Given the fact that older adults tend to make frequent visits to health care facilities, primary health care providers could play a key role in increasing awareness of the drug and alcohol-related health risks to older adults. The Drug Abuse Problem Assessment for Primary Care (DAPA-PC) may be particularly well-suited to screen for substance abuse in older adults. The use of a computerized screening instrument can serve as an efficient use of the health care clinician's time by allowing patients to be screened while in the waiting room, resulting in the need for the clinician to follow up with a patient only when prompted by the results of the screening. A screening system such as the DAPA-PC that includes assessment of factors related to substance abuse, while not directly asking about substance abuse, may he especially useful for screening populations of adults, age 55 and over, a group where drug and alcohol use is often perceived as a moral failing, and thus kept hidden from the outside world.

Table 1. Subject characteristics by group.

                Younger adults (age 18-54)   Older adults (age 55-86)

N                        266                       61
Males (a)                 41%                      57%
Females (a)               59%                      43%
White (a)                 67%                      43%
Black (a)                 27%                      46%

(a) p < 0.05.

Table 2. Responses to drug and alcohol problem (DAP) screen by
age group on DAPA questions.

                                 Percentage of    Percentage of
                                 older adults     younger adults
Question                           (n=61)           (n=238)

1. Felt used too much                8 (a)            19 (a)
   alcohol/drugs
2. Tried to quit                    15 (a)            27 (a)
3. Had withdrawal symptoms           3                 9
4. Did not remember things          13                18
5. Drugs led to problems             8                11
   at school/work
6. Arrested/legal problems           3                 5
7. Lot of time thinking/trying       3                 8
   to get drugs
8. Others concerned about           10                13
   your drug use

                                 Most     Other     Most     Other
Substance used
None                              36       75        30       76
Alcohol                           51        8        57        7
Other (marijuana. cocaine,        13       16        13       17
 opiates, etc.)
Use in past 30 days
None                              44       78        39       83
Some (once a month                56       21        60       17
 to daily)

(a) p < 0.05.

ACKNOWLEDGMENTS

The DAPA-PC screening instrument was developed with funding from a Small Business Innovative Research Grant, Phases I and II, from the National Institute on Drug Abuse, contract number N44DA86505.

REFERENCES

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(2.) Fingerhood M. Substance abuse in older people. J Am Geriatr Soc 2000: 48(8):985-995.

(3.) Center for Substance Abuse Treatment (CSAT). Substance Abuse Among Older Adults. Treatment Improvement Protocol Series. DHHS Pub No (SMA:98-3179). Washington, DC: US Government Printing Office. 1998:26.

(4.) Barrick C, Conners GJ. Relapse prevention and maintaining abstinence in older adults with alcohol-use disorders. Drugs Aging 2002: 19(8):583-594.

(5.) Johnson I. Alcohol problems in old age: a review of recent epidemiological research, Int J Geriatr Psychiatry 2000: 15(7):575-581.

(6.) Patterson TL, Jeste DV. The potential impact of the baby-boom generation on substance abuse among elderly persons. Psychiatr Serv 1999; 50(9):1184-1188.

(7.) Columbia's National Center on Addiction and Substance Abuse. Under the Rug: Substance Abuse and The Mature Woman. 1998. Available online at http://www.casacolumbia.orglpublications1456/publications_show.htm?doc_id = 5882.

(8.) Moos RH, Mertens JR, Brennan PL. Patterns of diagnosis and treatment among late-middle-aged and older substance abuse patients. J Stud Alcohol 1993; 54(4):479-487.

(9.) Carroll L. AMA focuses on alcoholism in the elderly. Med Trib Family Phys 1995; 36(19):1-7.

(10.) National Institute on Drug Abuse & National Institute on Alcohol Abuse and Alcoholism. National Drug and Alcoholism Treatment Unit Survey (NDATUS), 1987 Final Report, DHHS Publication No. (ADM) 89-1626; Alcohol, Drug Abuse, and Mental Health Administration, Rockville, MD, 1989.

(11.) Hinkin CH, Castellon SA, Dickson-Fuhrman E, Danm G, Jaffe J. Jarvik L. Screening for drug and alcohol abuse among older adults using a modified version of the CAGE. Am J Addict 2001; 10:319-326.

(12.) Holtz K, Landis RD, Nemes S, Hoffman J. DAPA-PC: development of a computerized screening system to identify substance abuse in primary care. J Health Qual 2001; 23(3):34-37.

(13.) Israel Y, Hollander O, Sanchez-Craig M, Booker S, Miller V, Ginguck R, Rankin JG. Screening for problem drinking and counseling by the primary care physician-nurse team. Alcohol Clin Exper Res 1996: 20(8):1443-1450.

(14.) Nemes S, Zeiler C, Hoffman J, Holtz K, Landis RD. Poster Presentation: Psychometric Properties of Online Drug Problem Screen. Los Angeles, CA: American Society of Addiction Medicine; April 2001.

(15.) Nemes S, Rao PA, Hoffman J, Holtz K, Zeiler C. A role for an online drug and alcohol screening instrument in primary health care settings. J Am Board Fam Pract (under review).

(16.) Zeiler CA, Nemes S, Holtz KD, Landis RD, Hoffman J. Responses to a drug and alcohol problem assessment for primary care by ethnicity. Am J Drug Alcohol Abuse 2002; 28(3):513-524.

(17.) Gerbert B, Bronstone A, Pantilat S, McPhee S, Allerton M, Moe J. When asked, patients tell. Med Care 1999; 37:104-111.

(18.) Nguyen K, link A, Beck JC, Higa J. Feasibility of using an alcohol-screening and health education system with older primary care patients. J Am Board of Faro Pract 2001; 14(1):7-15.

(19.) Bucholz KK, Sheline Y, Helzer JE. The epidemiology of alcohol use, problems, and dependence in elders: a review. In: Beresford TP, Gomberg E, eds. Alcohol and Aging. New York: Oxford University Press, 1995; 19-41.

(20.) Bergman S, Amir M. Crime and delinquency among the aged in Israel. Geriatrics 1973; 28(1):149-157.

(21.) Pascarelli EF, Fischer W. Drug dependence in the elderly. Int J Aging Hum Der 1974; 5(4):347-356.

(22.) Robins LN, Helzer JE, Croghan JL, Ratcliff KS. National Institue of Mental Health Diagnostic Interview Schedule: Its history, characteristics and validity. Archives of General Psychiatry 38:381-389.

Susanna Nemes, Ph.D., (1), * Patricia A. Rao, Ph.D., (1) Christine Zeiler, M.S., (2) Kelly Munly, M.A., (1) Kristine D. Holtz, Ph.D., (1) and Jeffrey Hoffman, Ph.D. (1)

(1) Danya International, Inc., Silver Spring, Maryland, USA

(2) Department of Energy

* Correspondence: Susanna Nemes, Ph.D., Vice President of Tobacco, Drug and Alcohol Research, Danya International, Inc., 8737 Colesville Road, Suite 1200, Silver Spring, MD 20910, USA; E-mail: snemes@danya.com.

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