Long-Term Trajectory of Substance Abuse and Psychiatric Comorbidity Rumi Kato Price, PhD, mpe

Long-Term Trajectory of Substance Abuse and Psychiatric Comorbidity*

• Rumi Kato Price, PhD, MPE

• Washington University School of Medicine

• St. Louis MO, USA

• E-mail [e-mail]

Acknowledgments*

• National Institute on Drug Abuse (K02DA00221, R01DA09281).

• Longer Life Foundations, Washington University School of Medicine and the Reinsurance Group of America.

• National Institute of Mental Health (R01MH60691).

VES Long-Term Followups. Questions to Address:

• In what ways is long-term drug use harmful?

• Why do some drug users continue to abuse drugs so long?

• What areas do we expect problems will get worse?

VES Long-Term Followups Mortality and Morbidity over 30 Years

• Mortality.

• Drug use transition patterns.

• Social and physical functioning.

• Psychiatric profiles over time.

• Drug abuse, PTSD and suicidality.

• Predictors of remission from drug abuse over time.

• Emerging drug use trends in middle age.

VES Long-Term Followups

VES Samples (N=1,227): Demographic Characteristics

Opiate Use After Vietnam by Men First Addicted in Vietnam, Compared to NARA Patients

Substance Use and Psychiatric Problems (%)

Why A 95% Remission Rate?

• Military personnel are different from civilian addicts - less psychopathology.

• Later age of onset.

• “Setting” - extinguishing conditional response was easy after coming back to U.S. (Zinberg, Archive 1972).

• Lack of availability of drugs after return to U.S.

VES Long-Term Followups: Mortality and Morbidity over 25 Years

Drugs kill.

• Drugs kill.

• A more malignant picture of the long-term impact of heroin use starting in Vietnam.

• Alcoholism and depression additional significant risk factors for premature death up to mid-40’s.

• Even a short-term intensive drug use appears to signal premature death.

VES-III. 25-Year Followup

• Drug use transition patterns.

• Social and physical functioning.

• Psychiatric profiles over time.

• Drug abuse, PTSD and suicidality.

• Patterns of remission from drug abuse over time.

Alcohol Heavy alcohol use1 Dependence2

• Alcohol Heavy alcohol use1 Dependence2

• Any illicit drug Heavy use Dependence/abuse2

• Marijuana Heavy use Dependence/abuse2

• Cocaine Heavy use

• Opiates Heavy use

• Illicit drugs other Heavy use

• than marijuana Dependence/abuse2

Landmark events (negative or positive).

• Landmark events (negative or positive).

• Employment.

• Employment.

• Married or cohabitating.

• Number of children.1

• Number of important people (max = 4).1

• Number of important people who are regular alcohol/drug users (max = 4).1

Posttraumatic stress disorder (PTSD) (based on traumatic event before or 1972 or after).1,2

• Posttraumatic stress disorder (PTSD) (based on traumatic event before or 1972 or after).1,2

• Major depression.1,2

• Adult antisocial personality (ASP).1,2

• Suicidal ideation.1

Sampling status (D+, D-, nonveteran).

• Sampling status (D+, D-, nonveteran).

• Enlistment status.

• Aptitude (military IQ test).

• Race.

• High school education.

• Age.

• Family psychopathology (depression, ASP symptoms, drinking problems, drug problems, hospitalization, life interference, suicide attempts).

Annual Prevalence Rates of Psychopathology:1972-1996

Yearly Size Social Circles: 1972-19961

VES Long-Term Followups: Mortality and Morbidity over 30 Years

Dynamics of Polydrug Abuse Over Time

• What’s the relationship between use of one drug and use of another drug over time?

• Is there evidence for switching from “harder” drug to a “softer” drug (“substitution” hypothesis)?

• Is there evidence for reducing the number of drugs abused (“unpiling” hypothesis)?

• Is there evidence for quitting all together at once (“rock-bottom” hypothesis)?

Basics of Latent Transition Analysis

Latent Transition Analysis Estimation

• For 2 classes, 2 times, 3 endorsement items to endorse:

• P(Y) = n Ln (1111211311T11112 212312

• +1111211311T12 122 222322

• +2121221321T21112 212312

• +2121221321T22 122 222322).

• P(Y) - Total log likelihood.

• i - Probability of starting in class i.

• Tij - Transition probability.

• kit - Endorsement probability for item k if the observation is in class i at time t.

• n - Number of observations with the given pattern of endorsement.

• The EM algorithm to select parameters that maximize P(Y).

Latent Transition Model of Polydrug Abuse*

LTA Endorsement Patterns: Alcohol + Nicotine - 4 classes, Unconstrained

Polydrug use is certainly common; however, substance abusers appear to have their “choice” of substance.

• Polydrug use is certainly common; however, substance abusers appear to have their “choice” of substance.

• Gradually increasing abstinence applies to most substances, except for cocaine.

• Switching of the main substance use is asymmetrical (MJ to ALC, OP to COC).

• “Narrowing of repertoire” occurs gradually over time.

VES Long-Term Followups Consequences of Drug Abuse over 30 Years

VES Long-Term Followups Consequences of Drug Abuse over 30 Years

PTSD most stable over time; drug dependence declines, but suicidal behavior increases over time to midlife.

• PTSD most stable over time; drug dependence declines, but suicidal behavior increases over time to midlife.

• Associations become stronger over time.

• Alcohol dependence and antisocial personality not as strong as predictors of suicidal ideation over time.

• Drug dependence exacerbates PTSD and suicidal ideation; once the course is set, self-medication kicks in.

VES Long-Term Followups: Mortality and Morbidity over 30 years

Patterns and Predictors of Remission

• Are the remission patterns stable over time?

• Are the remission patterns different across classes of substances?

• How common is spontaneous remission?

• Are the predictors of remission the same as covariates of long-term abuse?

A reasonable range of inclusion criteria beyond any use.

• A reasonable range of inclusion criteria beyond any use.

• Alcohol - 7+ drinks/day, daily drinking 2+ weeks, 6+ drinks/day/per week for several weeks.
• Nicotine - 20 cigarettes/day at least year.
• Marijuana and other illicit drugs - 5+ times use.

• Abuse to remission threshold higher than occasional use, but lower than DSM level.

• Alcohol: on - 7+ drinks/day when drinking most; off - quit attempt 3+ months.
• Nicotine: on - 20 cigarettes/day usually; off - quit attempt 3+ months.
• Marijuana other illicit drugs - “Most frequent” use;
• off - not “most frequent use.”

“Spontaneous” Remission from Licit and Illicit Substance Abuse

VES Long-Term Followups: Mortality and Morbidity over 30 years

• Predictors of remission - Can we detect a symptom pattern that is likely to lead to remission?

Flow of the ANN: A Multilayer Perceptron (MLP) Model

VES Long-Term Followups Symptom Patterns Predicting Remission

• Predictive power was in a good range when socio-environmental measures were included; better than DSM symptoms alone.

• Unique ANN weights capturing subtle changes? e.g., Hazardous use accompanied remission from cocaine heavy use and operated differently from severity symptoms (potentially a “make or break”role).

• Time-dependent logistic regression and on ANN weight structure analyses were inconsistent.

VES-IV: “Suicide” Study

• Quasi case-control design to take advantage of the existence of a large number of suicidals.

• Episode-based interview to capture protective factors mitigating suicide risk.

• Quantitative-qualitative integration to examine the patterns of interactions between risk and protective factors.

VES Long-Term Followups: Mortality and Morbidity over 30 years

VES Limitations

• Special population: disadvantaged Vietnam veterans with high levels of trauma and opiate exposure.

• Cohort and gender specific population.

• Impact of censoring by death unknown.

• Yearly-assessed measures not available for some behaviors.

• Most yearly measured retrospective self-report since 1972.

• Measures since 1996 still tentative.

VES Followups Over 30 Years Summary (1)

VES Followups Over 30 Years Summary (2)

VES Followups over 30 Years Summary (3)

VES-III & IV Collaborators

• WU Medicine Rumi Kato Price, Lee Robins,

• Edward Spitznagel, George Murphy,

• Collins Lewis

• WU Social Work Enola Proctor, Sally Haywood

• St. Louis VA Katherine Virgo, Seth Eisen

• Readjustment Counseling Services (Vet Center)

• Gary Collins, Rodney Haug, Robert

• Mathes

• St. Louis Crisis Services Center

• G. Lee Judy

• Consultants Bruce Goldberger, Gery Ryan

• Contract Work Research Triangle Institute,

• Psychemedics