Abstract
Background and Objectives
Gender-specific factors associated with stimulant abstinence severity were examined in a stimulant abusing or dependent residential treatment sample (N=302).
Method
Bivariate statistics tested gender differences in stimulant abstinence symptoms, measured by participant-reported experiences of early withdrawal. Multivariate linear regression examined gender and other predictors of stimulant abstinence symptom severity.
Results
Women compared to men reported greater stimulant abstinence symptom severity. Anxiety disorders and individual anxiety-related abstinence symptoms accounted for this difference. African American race/ethnicity was predictive of lower stimulant abstinence severity.
Discussion and Conclusions
Women were more sensitive to anxiety-related stimulant withdrawal symptoms.
Scientific Significance
Clinics that address anxiety-related abstinence symptoms, which more commonly occur in women, may improve treatment outcome.
Keywords: gender, stimulant abstinence severity, early withdrawal symptoms, anxiety
BACKGROUND AND OBJECTIVES
Current U.S. population surveys indicate more general drug use and higher rates of illicit drug dependence for men than women.1 However, male and female patterns of use and disorders differ by the specific drug used. Combined annual data from the most recent National Survey on Drug Use and Health showed no significant gender difference in the abuse of cocaine.2 Studies suggest that female users exceed males on the severity of dependence regardless of the stimulant used,3,4 and addiction severity at treatment entry for drug abuse has been linked to poorer outcomes in clinical samples.5
Specifically for stimulant abuse, more severe abstinence symptoms have been associated with early treatment termination and greater problems on the Addiction Severity Index drug use subscale.6,7 Stimulant abstinence symptoms are signs of early withdrawal and include sleep and eating disturbances, anxiety, and depression.7 The relationship of gender to stimulant abstinence symptoms and the specific factors associated with stimulant abstinence symptom severity are not well described. This secondary analysis examined gender characteristics among baseline participants in a multisite randomized clinical trial testing the addition of vigorous exercise compared to health education as a treatment strategy for stimulant abuse or dependence. Our central aim was to test gender differences in stimulant abstinence symptom severity, as well as the demographic, drug use, and psychiatric factors associated with more severe stimulant abstinence symptoms.
METHODS
Participants
Participants (women n = 121 and men n = 181) were from the Stimulant Reduction Intervention using Dose Exercise (STRIDE) trial, a National Institute on Drug Abuse Clinical Trials Network study (CTN-0037). Full details about the protocol are described elsewhere.8 Briefly, recruitment occurred during residential treatment in nine geographically diverse community treatment programs that had a 21- to 30-day residential length of stay and post-residential outpatient services. Eligible participants reported illicit stimulant drug use (e.g., cocaine, methamphetamine, or amphetamine) in the 30 days prior to residential treatment program (RTP) entry and received medical clearance for exercise. Individuals with an opioid dependence diagnosis, general medical conditions that contraindicated exercise, and those with psychosis or other psychiatric conditions that posed a potential safety risk were excluded. Participants provided informed consent.
Measures
All measures utilized for the STRIDE trial were described in Trivedi et al., 2011.8 Demographic variables included age, race/ethnicity, level of education, employment status, and marital status.
The Addiction Severity Index-Lite (ASI-Lite) provided lifetime measures of years of primary stimulant use (cocaine, amphetamine, or methamphetamine) and assessed problems associated with drug use in seven domains: medical, employment, alcohol, drug use, legal, family/social, and psychiatric. The Timeline Followback (TLFB) measured days of stimulant use in the 30 days prior to RTP entry.
The Composite International Diagnostic Interview (CIDI) was used to determine stimulant use disorders (categorized here as: cocaine only, cocaine and other stimulants, or other stimulants--not cocaine--only), as well as other substance use disorders using Diagnostic and Statistical Manual-IV (DSM-IV) criteria. The Fagerstrom Test for Nicotine Dependence (FTND) measured current nicotine dependence intensity.
The Mini International Neuropsychiatric Interview (MINI) measured DSM-IV psychiatric disorders, including major depression, dysthymia, mania, post-traumatic stress disorder (PTSD), panic disorder, social phobia, and obsessive compulsive disorder (OCD).
The Stimulant Selective Severity Assessment (SSSA; based on the Cocaine Selective Severity Assessment (CSSA)) measured self-reported stimulant abstinence symptom severity for the past 24 hours.7 The SSSA covered cocaine, methamphetamine, and other stimulants. Domains included carbohydrate craving, mood, appetite, sleep, energy, and pulse rate. Participants indicated the frequency or intensity of their withdrawal experiences for 16 individual symptoms on a scale of 0 to 7, including, for example, anxiety (i.e., 0 usually doesn't feel anxious; 3-4 anxious half the time; and 7 anxious all the time) and irritability (i.e., 0 most things are not irritating; 3-4 many things are irritating; and 7 mostly everything is irritating or upsetting). The CSSA stimulant craving items were not included in this SSSA measure.
Analysis
Bivariate tests for gender comparisons on sample characteristics were conducted using chi-square and t tests, for categorical and continuous variables, respectively. A multivariate linear regression model tested the relationship of gender to stimulant abstinence symptom severity while controlling for other variables. Gender and variables found to be significant (p < .05) on bivariate tests were entered into the regression model simultaneously. ASI subscales were not included because of the overlap with other more informative variables (e.g., the psychiatric problems subscale versus specific psychiatric diagnoses). For the modelled days of cocaine and methamphetamine use variables, we set days of use for non-users to zero. Non-users were participants who responded ‘no’ to screening questions for any past-30 day cocaine or methamphetamine use. Diagnostics showed that normality and other standard assumptions for linear regression were met.
To further characterize the relationship between gender and stimulant abstinence symptom severity, two post hoc analyses were conducted. First, one variable at a time was removed from the linear regression model to examine the change in the relationship between gender and abstinence symptom severity. We removed comorbid psychiatric diagnosis variables with the smallest p-values. Additionally, t tests were conducted for gender and each individual abstinence symptom item.
RESULTS
Gender characteristics
On demographic variables, women were younger than men, M=35.67 (SD=9.9) versus M=41.17 (SD=10.8) years, and more likely to be Hispanic, 17.36% versus 5.52%, p-values < .001. Men were more likely to have a high school degree or more education (86.19% versus 74.38%, p=.023) and to be employed (39.23% versus 19.83%) and African American (51.93% versus 29.75%), p-values < .001.
Table 1 shows gender comparisons on measures of stimulant drug use, drug use problems, and comorbid drug use and psychiatric disorders. Men reported more years using stimulants as their primary drug. Women reported higher median cocaine and methamphetamine use days prior to RTP entry, and were more likely to report dual stimulant use disorders (cocaine use disorder plus another non-cocaine stimulant use disorder). Most men met the diagnosis for a cocaine use disorder only. Women had higher ASI subscale scores on employment, family/social, and psychiatric problems, while men had higher scores for alcohol problems. Men were also more likely to be diagnosed with alcohol dependence as well as marijuana dependence, and had greater nicotine dependence intensity. Women had a higher prevalence of current manic episode, panic disorder, and OCD diagnoses.
Table 1.
Sample Characteristics and Stimulant Abstinence Symptom Severity by Gender
| Baseline variables | Total M (SD) or % N = 302 | Male M (SD) or % n = 181 | Female M (SD) or % n = 121 | p |
|---|---|---|---|---|
| Drug Use Characteristics | ||||
| Years of Primary Stimulant Use | 11.14 (9.3) | 13.42 (10.9) | 9.14 (7.1) | 0.012 |
| Days of Cocaine Use (TLFB)a | 9.00 | 8.00 | 11.00 | 0.002 |
| Days of Methamphetamine Use (TLFB)b | 12.00 | 9.50 | 20.00 | 0.006 |
| Drug Use Diagnoses (CIDI) | ||||
| Stimulant Use Disorders (%) | 0.001 | |||
| Cocaine only | 58.80 | 65.75 | 48.33 | |
| Cocaine and other stimulant | 30.56 | 28.18 | 34.17 | |
| Other stimulant (not cocaine) | 10.63 | 6.08 | 17.50 | |
| Alcohol Dependence (%) | 50.33 | 57.46 | 39.67 | 0.002 |
| Marijuana Dependence (%) | 31.89 | 36.46 | 25.00 | 0.037 |
| Drug Use Problems (ASI-Lite) | ||||
| Alcohol | 0.21 (0.2) | 0.26 (0.3) | 0.13 (0.2) | < 0.001 |
| Drugs | 0.17 (0.1) | 0.16 (0.1) | 0.17 (0.1) | 0.454 |
| Employment | 0.71 (0.3) | 0.67 (0.3) | 0.76 (0.3) | 0.006 |
| Family/Social | 0.22 (0.2) | 0.20 (0.2) | 0.25 (0.2) | 0.046 |
| Legal | 0.14 (0.2) | 0.13 (0.2) | 0.15 (0.2) | 0.441 |
| Medical | 0.16 (0.3) | 0.15 (0.3) | 0.18 (0.3) | 0.373 |
| Psychiatric | 0.27 (0.2) | 0.22 (0.2) | 0.34 (0.2) | < 0.001 |
| Nicotine Dependence Intensity (FTND) | ||||
| 3.45 (2.1) | 3.76 (2.2) | 3.02 (1.8) | 0.011 | |
| Comorbid Psychiatric Diagnoses (MINI) | ||||
| Major Depressive Episode (%) | 22.85 | 19.34 | 28.10 | 0.076 |
| Dysthymia (%) | 9.44 | 11.64 | 5.75 | 0.137 |
| Manic Episode (%) | 4.97 | 2.76 | 8.26 | 0.031 |
| Post-traumatic Stress Disorder (%) | 9.60 | 8.29 | 11.57 | 0.343 |
| Panic Disorder (%) | 6.02 | 3.31 | 10.17 | 0.015 |
| Social Phobia (%) | 10.93 | 10.50 | 11.57 | 0.770 |
| Obsessive Compulsive Disorder (%) | 5.96 | 3.31 | 9.92 | 0.018 |
| Stimulant Abstinence Severity | ||||
| SSSA Score | 11.77 (11.5) | 10.44 (11.1) | 13.78 (11.9) | 0.013 |
Notes: TLFB = Timeline Followback; CIDI = Composite International Diagnostic Interview; ASI = Addiction Severity Index; FTND = Fagerstrom Test for Nicotine Dependence; MINI = Mini International Neuropsychiatric Interview; SSSA = Stimulant Selective Severity Assessment;
Median days of use computed for those who used cocaine in the 30 days prior to residential treatment program (RTP) entry (Men n = 157 and Women n = 82); and
Median days of use computed for those who used methamphetamine in the 30 days prior to RTP entry (Men n = 38 and Women n = 43).
Stimulant abstinence symptom severity
On the SSSA, women reported greater stimulant abstinence symptom severity compared to men (Table 1). In the multivariate model, gender was no longer associated with abstinence symptom severity, p-value > .05. Model results are presented in Table 2. African American race/ethnicity was associated with lower abstinence symptom severity than non-African Americans after controlling for other variables in the model. Other modelled variables were non-significant; however, after two variables were removed from the model, i.e., 1) panic disorder and 2) OCD diagnoses, gender was associated with a higher stimulant abstinence severity score compared to men. Post hoc tests also identified higher scores for women on four individual abstinence symptoms, including anxiety (men: M=1.02, SD=1.7; women: M=1.74, SD=2.1, p=.001), tension (men: M=0.72, SD=1.5; women: M=1.09, SD=1.8, p=.047), attention (men: M=0.62, SD=1.4; women: M=1.12, SD=1.9, p=.008), and irritability (men: M=0.80, SD=1.4; women: M=1.55, SD=2.1, p<.001).
Table 2.
Regression Analysis for Gender and other Variables Predicting Stimulant Abstinence Symptom Severity
| B | SE | p | |
|---|---|---|---|
| Gender | 2.710 | 1.5 | 0.071 |
| Age | 0.014 | 0.1 | 0.847 |
| High School or more Education | 0.101 | 0.3 | 0.766 |
| Employed | 0.682 | 1.5 | 0.642 |
| African American | −4.651 | 1.6 | 0.005 |
| Hispanic | −2.994 | 2.3 | 0.202 |
| Years of Primary Stimulant Use | −0.020 | 0.1 | 0.820 |
| Days of Cocaine Use | −0.047 | 0.1 | 0.553 |
| Days of Methamphetamine Use | −0.046 | 0.1 | 0.647 |
| Alcohol Dependence | 2.155 | 1.4 | 0.119 |
| Marijuana Dependence | 1.015 | 1.5 | 0.485 |
| Nicotine Dependence Intensity | 0.519 | 1.5 | 0.722 |
| Manic Episode | 3.450 | 3.2 | 0.288 |
| Panic Disorder | 5.636 | 3.2 | 0.076 |
| Obsessive Compulsive Disorder (OCD) | 4.545 | 2.9 | 0.119 |
Notes. A follow-up analysis, showed that gender (B=3.23, SE=1.5, p=.031) was associated with abstinence symptom severity after two variables were removed from the model, i.e., 1) panic disorder and 2) OCD.
DISCUSSION AND CONCLUSIONS
We identified differences between men and women on measures of stimulant use and associated disorders. Women were more likely to report dual stimulant use disorders (i.e., cocaine and other stimulant use disorders), while most men met diagnosis for a cocaine use disorder only. These dual stimulant diagnoses corresponded with both more methamphetamine use days and more cocaine use days for women than men. Preclinical and clinical studies provide some evidence to indicate that women, via increased estrogen levels, are more vulnerable to the reinforcing effects of stimulant drugs.9
Women reported greater drug use problems in employment, family/social, and psychiatric domains compared to men. Men reported greater problems related to alcohol and were more likely to have an alcohol dependence diagnosis. This is consistent with other studies involving stimulant abusers, with women reporting more employment and economic issues and men more alcohol problems.10,11 Women in treatment also report significantly greater depressive symptomatology and a history of abuse and violence in their lives,10,5 although in the current study, major depression, dysthymia, and PTSD were not significantly different in men and women.
We found greater stimulant abstinence symptom severity in women compared to men. More severe early withdrawal symptoms appeared to be positively associated with anxiety-related symptoms (e.g., anxiety, tension, difficulty concentrating, and irritability), and panic disorder and OCD diagnoses appeared to account for the association between gender and stimulant abstinence symptom severity. Being African American was negatively associated with stimulant abstinence symptom severity. African Americans in the STRIDE sample, relative to other racial/ethnic groups, were majority male, reported better mental health status, and had low psychiatric comorbidity,12 which may help describe our findings here. Women may be more sensitive to the anxiety-related stimulant withdrawal symptoms. STRIDE women compared to men reported higher rates of anxiety-related disorders (i.e., panic disorder and obsessive compulsive disorder). Greater psychological severity in women is associated with poorer treatment retention and outcomes.5 Individuals who remain anxious during treatment may be at greater risk for using substances to reduce anxiety symptoms.13
There were some limitations to this study, including the retrospective assessment of drug use, drug use problems, and drug and psychiatric disorders. Self-report measures may be subject to recall bias (e.g., years of primary stimulant use), although most time periods assessed were relatively short (e.g., 24 hours and past 30 days for the SSSA and TLFB, respectively). The generalizability of our findings may be limited by the trial's sampling criteria. In particular, eligible participants agreed to participate in a clinical trial and were medically cleared and willing to exercise.
SCIENTIFIC SIGNIFICANCE
Addiction severity at treatment entry is associated with treatment retention and abstinence outcomes. The CSSA is one measure of stimulant abstinence severity that has been shown to predict attrition from treatment,6 and could be used by clinic staff during the admissions process to identify and target stimulant abusing patients with greater risk for poor treatment outcomes. It is a brief self-administered measure, which potentially makes it well adaptable to a clinical setting. It could also be an effective tool for identifying specific symptoms (e.g., anxiety, tension, and irritability) to discuss with patients in treatment sessions. This study emphasized anxiety-related withdrawal experiences as salient topics for clinicians to address in treatment to reduce stimulant abstinence symptoms and potentially the risk for relapse to substance use. Mood and anxiety disorders are more prevalent in women and non-Hispanic whites.14 There are mixed findings related to gender and treatment retention,5 but women who complete stimulant treatment are reported to have similar or better outcomes than men.15 Future prospective studies could help clarify the relationships we identified between gender, race/ethnicity, stimulant abstinence symptom severity, and associated anxiety-related factors.
Acknowledgements
The research reported in this publication was supported by the National Institute on Drug Abuse, Rockville, MD of the National Institutes of Health under award number U10DA020024 (PI: Trivedi). The content and writing are solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This paper was originally presented as a poster at the 2014 Society for Social Work and Research annual meeting.
Footnotes
Declaration of Interest
Dr. Chartier has received research support from the National Institute on Alcohol Abuse and Alcoholism. Dr. Sanchez has received funding from the U.S. DHHS Office of Minority Health. Dr. Killeen has received consulting fees from Rosewood Institute of Eating Disorders and the Research Foundation of the City University of New York. She has received funding from the National Institute of Drug Abuse, National Institute of Nursing Research, and the South Carolina Department of Alcohol and other Drug Abuse Services. Dr. Greer has received research funding from NARSAD and consulting fees from H Lundbeck A/S and Takeda Pharmaceuticals International, Inc. Dr. Trivedi is or has been an advisor/consultant to: Abbott Laboratories, Inc., Abdi Ibrahim, Akzo (Organon Pharmaceuticals Inc.), Alkermes, AstraZeneca, Axon Advisors, Bristol-Myers Squibb Company, Cephalon, Inc., Cerecor, Concert Pharmaceuticals, Inc., Eli Lilly & Company, Evotec, Fabre Kramer Pharmaceuticals, Inc., Forest Pharmaceuticals, GlaxoSmithKline, Janssen Global Services, LLC, Janssen Pharmaceutica Products, LP, Johnson & Johnson PRD, Libby, Lundbeck, Meade Johnson, MedAvante, Medscape, Medtronic, Merck, Mitsubishi Tanabe Pharma Development America, Inc., Naurex, Neuronetics, Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals, Inc., Pfizer Inc., PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products Ltd., Sepracor, SHIRE Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Transcept, VantagePoint, Vivus, and Wyeth-Ayerst Laboratories. In addition, he has received research support from: Agency for Healthcare Research and Quality, Corcept Therapeutics, Inc., Cyberonics, Inc., National Alliance for Research in Schizophrenia and Depression, National Institute of Mental Health, National Institute on Drug Abuse, Novartis, Pharmacia & Upjohn, Predix Pharmaceuticals (Epix), and Solvay Pharmaceuticals, Inc. Our other authors report no conflicts of interest.
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