brian zachariah m.d. pgy4 lauren derhodge d.o. clinical … grand... · 2018-01-05 ·...
TRANSCRIPT
By:
Brian Zachariah M.D. PGY4
Lauren Derhodge D.O. Clinical Assistant Professor, Attending Physician
LEARNING OBJECTIVES
• DEFINE IMPULSIVITY
• BRIEFLY REVIEW NEUROBIOLOGY AND NEUROPATHOLOGY ASSOCIATED WITH IMPULSIVE
BEHAVIOR IN RELATION TO ADDICTION
• EXPLORE ASSOCIATION BETWEEN SUBSTANCE USE DISORDERS (SUD’S) AND IMPULSIVITY THRU
PERSONALITY INVENTORY DATA AS IT RELATES TO FOUR CLASSES OF SUBSTANCES
(STIMULANTS, ALCOHOL, OPIATES, MDMA)
• UNDERSTAND THAT IMPULSIVITY SERVES AS A PRE-EXISTING ADDICTION VULNERABILITY
MARKER BY REVIEWING:
• STUDIES OF GROUPS AT HIGH-RISK FOR DEVELOPMENT OF SUDS
• STUDIES OF PATHOLOGICAL GAMBLERS
• GENETIC ASSOCIATION STUDIES LINKING IMPULSIVITY TO GENETIC RISK FACTORS FOR ADDICTION
• BRIEFLY DIFFERENTIATE BETWEEN THE AVAILABLE CLASSES OF AGENTS AND RECOGNIZE HOW
EFFECTIVE THEY ARE FOR SPECIFIC IMPULSIVE BEHAVIORS
RELEVANCE?
• BIOLOGICAL MECHANISMS OF ADDICTION HAVE BEEN EXPLORED IN GREAT DETAIL,
UNCOVERING NEUROBIOLOGY OF DRUG USE AND EFFECTS OF CHRONIC DRUG EXPOSURE.
• HOWEVER,
• COGNITIVE ASPECTS OF ADDICTION REMAIN RELATIVELY UNEXPLORED DESPITE EVIDENCE THAT
DISRUPTION OF COGNITIVE CONTROL IS A HALLMARK OF ADDICTION
• SEVERAL STUDIES DEMONSTRATE THE IMPORTANCE OF PRE-MORBID CHARACTERISTICS IN THE
DEVELOPMENT OF LATER ADDICTION BUT THEY MAINLY HIGHLIGHT THE ROLE OF REWARD
PROCESSES, RATHER THAN PRE-MORBID IMPULSIVITY AND INHIBITORY CONTROL, AS CRITICAL
IN THE DEVELOPMENT OF SUDS
Everitt et al., 2007; Jentsch and Taylor, 1999; Robinson and Berridge, 2003
IMPULSIVITY AS A PSYCHOLOGICAL CONSTRUCT• IMPULSIVITY HAS A RANGE OF DEFINITIONS
• ACTIONS THAT ARE POORLY CONCEIVED,
• PREMATURELY EXPRESSED,
• UNDULY RISKY OR INAPPROPRIATE TO THE SITUATION THAT OFTEN RESULT IN UNDESIRABLE
CONSEQUENCES
Evenden, 1999b, de Wit, 2009
• COMPONENTS OF IMPULSIVITY INCLUDE
• ATTENTION,
• SUPPRESSING RESPONSES,
• POOR EVALUATION OF CONSEQUENCES AND/OR AN INABILITY TO FORGO IMMEDIATE SMALL REWARDS IN FAVOR OF GREATER DELAYED REWARDS.
IMPULSIVITY WITHIN EXECUTIVE FUNCTION
• AT TIMES, IMPULSIVITY IN PERSONALITY IS VALUABLE FOR RAPID DECISIONS
AT OPPORTUNE TIMES.
• EXECUTIVE FUNCTIONS IN COGNITIVE PSYCHOLOGY CONTROL ABSTRACT
THINKING, RULE ACQUISITION, PLANNING AND FLEXIBILITY IN RESPONSES
INCLUDING RULE SHIFTING, AS WELL AS INITIATING APPROPRIATE ACTIONS
AND INHIBITING INAPPROPRIATE ACTIONS.
• WITH REPETITION, DECISIONS REQUIRE LESS ATTENTION AND MAY BE RAPID,
LEARNED, BUT ARE NOT NECESSARILY IMPULSIVE.
• IMPULSIVITY LEADS TO RAPID RESPONSES WITHOUT REFLECTION.
IMPLICATED NEUROBIOLOGY AND NEUROPATHOLOGY
• THE FRONTAL LOBES ARE COMMONLY DIVIDED
INTO FIVE PARALLEL, THOUGH INTERACTING,
SUBCIRCUITS: MOTOR, OCULOMOTOR,
DORSOLATERAL, ORBITOFRONTAL CORTEX (OFC),
AND ANTERIOR CINGULATE.
• THE DORSOLATERAL PREFRONTAL CIRCUIT (DLPFC)
UNDERLIES EXECUTIVE FUNCTION, WHICH
INCLUDES THE CONTROL OF ATTENTION, AS WELL
AS THE SUSTAINED ORGANIZATION OF BEHAVIOR
TO SOLVE COMPLEX PROBLEMS
• THE DLPFC IS ESSENTIAL TO DRAW ATTENTION TO
IMPORTANT FACTORS AND TO ACTIVELY SELECT
GOALS.
Alexander et al., 1986; Cummings, 1993; Stuss and Alexander, 2000; Abe and Hanakawa, 2009; Bonelli and Cummings, 2007; Carmichael and Price, 1995a,b
The dlPFC and OFC is associated with behavioral regulation
owing to its unique capacity to maintain and integrate sensory,
affective, and associative information.
The medial prefrontal/cingulate
circuit is critical for feedback
monitoring and motivation, with
lesions producing profound
apathy.
• EXECUTIVE FUNCTIONS ARE OFTEN INVOKED
TO OVERRIDE RESPONSES THAT HAVE BEEN
AUTOMATICALLY ELICITED.
• THE FRONTAL LOBE EXECUTIVE FUNCTIONS
RECEIVE INPUT FROM ALL SENSORY
MODALITIES, INTEGRATE MEMORIES AND
USING WORKING MEMORY OF TEMPORARY
INFORMATION, ASSEMBLE REWARD AND
VALUATION INFORMATION WITH TIMING OF
EVENTS TO CARRY OUT PLANNED BEHAVIORS.
THE AMYGDALA'S (AMG) ABILITY TO DRIVE IMPULSIVE,
NON-REFLECTIVE RESPONSE SELECTION (OR DECISION-
MAKING) STEMS FROM IT’S KEY ROLE IN CONDITIONED
RESPONDING, WHEREBY APPETITIVE OR AVERSIVE STIMULI
(OR CONTEXTS) COME TO TRIGGER AUTOMATIC
RESPONDING TO THOSE STIMULI.
Balleine and Killcross, 2006
The product of such conditioning in the amygdala (AMG) is
thought to underlie the craving triggered by people, places, and
things associated with drug use.
• EXECUTIVE FUNCTION CAN BE ALTERED BY ENVIRONMENTAL FACTORS THAT CHANGE DIRECTED
GOALS.
• FOR EXAMPLE, SMELLING POPCORN WILL DISTRACT INDIVIDUALS, DRAW THEM TO THE SOURCE, INDUCE
HUNGER AND AUTOMATICALLY STIMULATE EATING.
• THIS IS NORMAL; HOWEVER, NOT ALL WILL BE DISTRACTED.
• PEOPLE, WHO ARE DIETING, ACTIVATE EXECUTIVE FUNCTIONS DRAWING ATTENTION TO THE
DISTRACTING SMELL AND BLOCK EATING, OFTEN THROUGH A STRATEGY OF LEAVING THE AREA AND
AVOIDING FURTHER DISTRACTION.
• IMPULSIVITY CAN INCLUDE WEAK INHIBITORY CONTROL, LACK OF ATTENTION, OR BAD DECISIONS.
• THUS, EXECUTIVE FUNCTIONS OPPOSE IMPULSIVITY.
• SIMILAR FACTORS MAY BE INVOLVED IN SUBSTANCE CRAVING CUES PROMOTING USE AND/OR
CAUSING RELAPSE.
• AMYGDALA ACTIVATION HAS BEEN SUGGESTED TO CAUSE THE
NEGATIVE MOTIVATIONAL STATE THAT DRIVES ADDICTION
• SUPPORTED BY HUMAN NEUROIMAGING DATA SHOWING
AMYGDALA HYPERACTIVATION IN RESPONSE TO STIMULI THAT
INDUCE CRAVING.
• THUS, A WEAKNESS IN EXECUTIVE FUNCTION TIPS THE
DECISIONAL BALANCE FROM DLPFC-OFC-ACC CONTROLLED
RESPONSES, PARTICULARLY IF AMG TO DRIVE CREATES URGENCY
THAT PROMOTES IMPULSIVE, AUTOMATIC RESPONDING TO
DOMINATE BEHAVIOR
Koob, 2009; Breiter et al., 1997; Childress et al., 1999; Kilts et al., 2001;
IMPULSIVITY – STIMULANT (COCAINE/METHAMPHETAMINE) USE DISORDER
• ELEVATED IMPULSIVITY SCORES ON SELF-REPORT MEASURES (TYPICALLY THE BIS) HAVE BEEN
DEMONSTRATED IN COCAINE-DEPENDENT OUTPATIENTS AND YOUNG STIMULANT USERS
• ELEVATED BIS SCORES WERE CORRELATED NEGATIVELY WITH AGE OF FIRST COCAINE USE,
CONSISTENT WITH A VULNERABILITY PATHWAY WHERE HIGH IMPULSIVITY PREDISPOSE EARLY
RECREATIONAL DRUG-TAKING.
Coffeet al., 2003; Moeller et al., 2004; Leland and Paulus, 2005; Moeller et al., 2002
IMPULSIVITY – OPIATE (HEROIN) USE DISORDER
• ON SELF-REPORT MEASURES, HEROIN USERS HAVE SHOWN INCREASED IMPULSIVITY SCORES
ON THE BIS AND EYSENCK SCALE.
• HEROIN USERS ALSO SCORE LOWER ON PERSONALITY MEASURES OF FUTURE TIME
PERSPECTIVE, SUGGESTING DECREASED ABILITY TO PLAN AHEAD OR A HIGHER FOCUS ON
IMMEDIATE AS COMPARED TO DELAYED EVENTS .
Ersche et al., 2006; Verdejo-Garcia and Perez-Garcia, 2007; Kirby et al., 1999; Madden et al., 1997; Petry et al., 1998
IMPULSIVITY – ALCOHOL USE DISORDER
• ALCOHOL USE IS CONSISTENTLY ASSOCIATED WITH ELEVATED TRAIT IMPULSIVITY.
• RECENT STUDIES HAVE REPORTED THAT ALCOHOL DEPENDENT SUBJECTS HAVE HIGHER SCORES
ON THE UPPS SUBSCALE OF URGENCY, I.E. THE TENDENCY TO ACT IMPULSIVELY IN RESPONSE
TO NEGATIVE EVENTS, SENSATION SEEKING, AND MORE TRADITIONAL MEASURES SUCH AS
THE BIS.
Whiteside and Lynam, 2003; Bjork et al., 2004a; Mitchell et al., 2005
IMPULSIVITY – MDMA “ECSTASY” USE DISORDER
• MULTIPLE STUDIES HAVE SHOWN INCREASED TRAIT IMPULSIVITY IN ECSTASY USERS AS
MEASURED BY SEVERAL SELF-REPORT INVENTORIES.
• IN THESE STUDIES, BOTH RECREATIONAL AND HEAVY USERS SHOWED HIGHER SCORES ON
IMPULSIVENESS, VENTURESOME DESIRE AND SENSATION SEEKING.
Butler and Montgomery, 2004; Morgan, 1998; Parrott et al., 2000
IMPULSIVITY=PREEXISTING?
• THERE IS NO CONSISTENT ASSOCIATION BETWEEN THE DURATION OF DRUG USE AND
IMPULSIVITY, AND STUDIES OF ABSTINENT DRUG USERS TYPICALLY DETECT COMPARABLE
EFFECTS TO CURRENT USERS, AND MINIMAL CORRELATIONS BETWEEN IMPULSIVITY AND THE
DURATION OF ABSTINENCE.
• THIS IS CONSISTENT WITH THE HYPOTHESIS THAT IMPULSIVITY IS A PRE-EXISTING
CHARACTERISTIC IN DRUG USERS, WHICH DOES NOT CHANGE RADICALLY WITH THE
DEVELOPMENT OF THE ADDICTION OR WITH LONG-TERM ABSTINENCE.
IMPULSIVITY - ADOLESCENCE• ADOLESCENCE IS A CRITICAL PERIOD FOR THE DEVELOPMENT OF SUDS.
• RETROSPECTIVE STUDIES IN ADULT SUD GROUPS REPORT THAT THE INITIATION OF USE OF THE
SUBSTANCE OF LATER DEPENDENCE INVARIABLY STARTS BEFORE AGE 18.
• NEURODEVELOPMENTAL TRAJECTORIES DURING THE ADOLESCENT PERIOD MAY CONVEY
VULNERABILITY TO HIGH-RISK BEHAVIORS LIKE DRUG-TAKING, DUE TO
• RELATIVE IMMATURITY OF FRONTAL CORTICAL CONTROL SYSTEMS
• RELATIVE MATURITY OF STRIATAL SYSTEMS RESPONSIBLE FOR REWARD PROCESSING AND
MOTIVATION
• THIS IMBALANCE MAKES ADOLESCENCE A PERIOD DURING WHICH THE ACTIVITY OF THE
REWARD SYSTEM PREVAILS OVER THAT OF THE SYSTEMS GOVERNING AVOIDANCE OR SELF-
CONTROL.
(Helzer et al., 1991; Wagner and Anthony, 2002; Chambers et al., 2003; Ernst et al., 2006a
• CROSS-SECTIONAL STUDIES IN ADOLESCENT SAMPLES HAVE SHOWN THAT ELEVATED TRAIT
IMPULSIVITY (E.G. SENSATION SEEKING) AND HIGHER RATES OF DELAY-DISCOUNTING WERE
ASSOCIATED WITH EARLIER AGE OF ALCOHOL AND DRUG EXPERIMENTATION.
Kollins, 2003; Martin et al., 2002, 2004
• WONG ET AL. (2006) ASSESSED A SAMPLE OF 514 CHILDREN OF ALCOHOLICS AND MATCHED
CONTROLS TO ANALYZE THE IMPACT OF NEURODEVELOPMENTAL PATTERNS OF IMPULSIVITY
(AS MEASURED BY CLINICIANS’ RATINGS OF BEHAVIORAL SELF-CONTROL) AND RESILIENCY ON
SUBSEQUENT EXPERIMENTATION WITH DRUG USE AND SUD.
• IMPULSIVITY AND RESILIENCY WERE ASSESSED AT 3 YEARS INTERVALS USING FIVE WAVES OF
CHILDREN FROM 2- TO 14-YEAR OLD. THEIR RESULTS ELEGANTLY SHOW THAT SLOWER RATES
OF DEVELOPMENT OF BEHAVIORAL SELF-CONTROL STRONGLY AND SPECIFICALLY PREDICT
EARLY INITIATION OF DRUG USE AT AGE 14 AND HIGHER NUMBER OF DRUG-RELATED
PROBLEMS AT AGE 17.
IMPULSIVITY - ADHD AND EXTERNALIZING BEHAVIORAL PROBLEM ADOLESCENTS
• THERE IS A HIGHER PREVALENCE OF SUDS IN ADOLESCENTS AND ADULTS WHO WERE
PREVIOUSLY DIAGNOSED WITH ADHD AND OTHER EXTERNALIZING BEHAVIORAL PROBLEMS
DURING THEIR CHILDHOOD.
• ERNST ET AL., (2006A) CONDUCTED A PROSPECTIVE STUDY EXAMINING BEHAVIORAL
PREDICTORS OF DRUG-TAKING IN ADOLESCENTS WITH (N = 50) AND WITHOUT (N =28)
ADHD DIAGNOSES AGED 12–14, THE PARTICIPANTS COMPLETED THE BIS AND AN
AGGRESSION RATING SCALE, AND AT 4-YEAR FOLLOW-UP WERE SCREENED FOR THE
INITIATION OF SUBSTANCE USE.
• IN THIS STUDY, ADHD DIAGNOSIS DID NOT SIGNIFICANTLY PREDICT LATER USE OF ALCOHOL,
TOBACCO OR MARIJUANA BUT ELEVATED BIS IMPULSIVITY WAS A SIGNIFICANT PREDICTOR OF
ALCOHOL USE, AND AGGRESSION RATINGS WERE ASSOCIATED WITH TOBACCO AND MARIJUANA
USE.
Biederman et al., 1997; Molina et al., 2007; Wilens et al., 1997
• ELKINS ET AL. (2007) ASSESSED A LARGE SAMPLE OF 11-YEAR-OLD TWINS (760 FEMALE AND
752 MALE TWINS) FOR CATEGORICAL ADHD DIAGNOSIS, AS WELL AS DIMENSIONAL
MEASURES OF INATTENTION VS. IMPULSIVE/HYPERACTIVE SYMPTOMS. THEY USED THESE
ASSESSMENTS TO PROSPECTIVELY PREDICT DRUG USE INITIATION AND SUD.
• FOLLOW-UP ASSESSMENT OF OUTCOME VARIABLES AT AGES 14 AND 18 SHOWED THAT
DIMENSIONAL SYMPTOMS OF IMPULSIVITY/HYPERACTIVITY WERE STRONGER PREDICTORS THAN
INATTENTION OR ADHD DIAGNOSIS FOR INITIATION OF TOBACCO, ALCOHOL AND ILLICIT DRUGS
USE AT 14.
IMPULSIVITY IN ADOLESCENT OFFSPRING OF SUD PARENTS
• MORE CONSISTENT EVIDENCE IN FAVOR OF IMPULSIVITY AS A VULNERABILITY MARKER FOR
SUD COMES FROM CROSS-SECTIONAL AND LONGITUDINAL STUDIES OF CHILDREN WITH SUD
PARENTS.
• THESE STUDIES HAVE ELEGANTLY DEMONSTRATED THAT
• CHILDREN OF SUD PARENTS HAVE ELEVATED IMPULSIVITY BEFORE DRUG EXPOSURE AND
• IMPULSIVITY INDICES ARE STRONG RELIABLE PREDICTORS OF LATER DRUG INITIATION AND
DRUG/ALCOHOL PROBLEMS.
IMPULSIVITY – PROBLEM GAMBLER’S (PG’S)
• RATIONALE FOR STUDYING PG’S INCLUDE THAT VULNERABILITY MECHANISMS OVERLAP WITH
THAT OF THOSE WITH SUD’S BUT WITHOUT EXOGENOUS SUBSTANCE USE.
• CASE-CONTROL STUDIES COMPARING SELF-REPORTED IMPULSIVITY IN PG AND NON-GAMBLING
CONTROLS HAVE DEMONSTRATED ELEVATED SCORES ON THE BIS, THE EYSENCK IMPULSIVITY
QUESTIONNAIRE, THE CALIFORNIA PERSONALITY INVENTORY, EGO CONTROL SCALE, AND THE
ZUCKERMAN SSS.
• DEFICIENT PERFORMANCE ON NEUROCOGNITIVE MEASURES OF INHIBITORY CONTROL,
INCLUDING TESTS OF RESPONSE INHIBITION, DELAY-DISCOUNTING AND RISKY DECISION-
MAKING CAN BE NOTED AS WELL
Carlton and Manowitz, 1994; Fuentes et al., 2006; Petry, 2001c; Rodriguez-Jimenez et al., 2006a, Blaszczynski et al., 1997, McCormick et al., 1987, Potenza et al., 2003
GENETIC ASSOCIATION STUDIES OF IMPULSIVITY WITH RISK FACTORS FOR ADDICTION
PRACTICAL IMPLICATION?
• PERSISTENCE OF DEPENDENCE AND MOTIVATION TO CONTROL ADDICTIVE BEHAVIOR RELY ON
THE DECISIONAL BALANCE BETWEEN REFLECTIVE AND IMPULSIVE SYSTEMS
• neurobiology of
behavioral change
needed in recovery
from addiction requires
frontal-cortical
involvement
Hettema et al., 2005; Clay et al., 2008
• motivation interview
therapy and cognitive
behavioral therapy
activate frontal-cortical
executive functions that
through use promotes
maintenance of controlled
behavior.
• This activation of executive
functions increases
attention and frontal lobe
function reducing
impulsivity and preventing
relapse
SSRI’S:
• LOW LEVELS OF THE SEROTONIN METABOLITE 5-HYDROXYINDOLEACETIC ACID AND
BLUNTED SEROTONERGIC RESPONSE WITHIN THE VENTROMEDIAL PREFRONTAL CORTEX
ARE ASSOCIATED WITH IMPULSIVE BEHAVIORS, ESPECIALLY AGGRESSION.
• MOST BENEFIT NOTED IN PERSON’S WITH DEPRESSION OR ANXIETY WITH IMPULSIVE
BEHAVIORS AS A MEANS OF COPING
Coccaro EF, Lee RJ, Kavoussi RJ. A double-blind, randomized, placebo-controlled trial of fluoxetine in patients with intermittent explosive disorder. J Clin Psychiatry. 2009;70:653-662.
PSYCHOPHARMACOLOGICAL OPTIONS FOR IMPULSIVITY
SNRI’S
• ANIMAL RESEARCH SUPPORTS AN EMERGING ROLE FOR THE NORADRENALINE SYSTEM IN
IMPULSE CONTROL
• NO PLACEBO-CONTROLLED TRIALS OF A NORADRENERGIC AGENT IN THE TREATMENT OF
MOST IMPULSE CONTROL DISORDERS
• ONE STUDY WITH ATOMOXETINE AND BINGE EATNG DISORDER
McElroy SL, Guerdjikova A, Kotwal R, et al. Atomoxetine in the treatment of binge-eating disorder: a randomized placebo-
controlled trial. J Clin Psychiatry. 2007;68:390-398.
• OPIOID ANTAGONISTS
• NALTREXONE PHARMACOTHERAPY FOR ALCOHOL DEPENDENCE INCREASES OFC ACTIVATION AND
APPEARS PROMISING FOR CERTAIN TYPES OF IMPULSIVE BEHAVIOR
• MOST NOTABLY ALCOHOL USE DISORDERS, GAMBLING DISORDER, AND KLEPTOMANIA
• GLUTAMERGIC AGENTS
• IMPROVING GLUTAMATERGIC TONE IN THE NUCLEUS ACCUMBENS HAS BEEN IMPLICATED IN
REDUCING THE REWARD-SEEKING BEHAVIOR IN SUBSTANCE ADDICTIONS
• THESE AGENTS MAY IMPROVE IMPULSIVITY BY DECREASING DRIVE
• N-ACETYLCYSTEINE (AVAILABLE OVER-THE-COUNTER), HAS SHOWN SOME BENEFIT IN TREATING
MARIJUANA DEPENDENCE, GAMBLING DISORDER, AND TRICHOTILLOMANIA
• MEMANTINE, AN N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST, HAS SHOWN EARLY PROMISE IN
TREATING ALCOHOL USE DISORDERS, GAMBLING DISORDER, KLEPTOMANIA, AND COMPULSIVE
BUYING
Boettiger et al., 2009
Deepmala, Slattery J, Kumar N, et al. Clinical trials of N-acetylcysteine in psychiatry and neurology: a systematic
review. Neurosci Biobehav Rev. 2015;55:294-321.
Grant JE, Schreiber LR, Odlaug BL. Phenomenology and treatment of behavioural addictions. Can J Psychiatry. 2013;58:252-
259.
• ATYPICALS HAVE MIXED REPORTS
• OLANZAPINE – TRICHOTILLOMANIA BUT NOT
IN GAMBLING DISORDER
• RISPERIDONE AND QUETIAPINE IN CONDUCT
DISORDER
. Van Ameringen M, Mancini C, Patterson B, et al. A randomized, double-blind, placebo-controlled trial of olanzapine in the
treatment of trichotillomania. J Clin Psychiatry. 2010;71:1336-1343.
Grant JE, Leppink EW. Choosing a treatment for disruptive, impulse-control, and conduct disorders. Curr Psychiatry.
2015;14:29-
• LITHIUM
• MOST STUDIES ON BIPOLAR
MANIA AND EFFICACY IN
REDUCING IMPULSIVITY
ASSOCIATED WITH GRANDIOSITY
• 7 STUDIES DEMONSTRATING
EFFICACY IN ADOLESCENTS WITH
CONDUCT DISORDER
FUTURE CLINICAL IMPLICATIONS?
• CHARACTERIZATION OF VULNERABILITY MARKERS FOR ADDICTION IS ESSENTIAL FOR
• DETECTING AT-RISK INDIVIDUALS
• IMPLEMENT EARLY DETECTION AND TREATMENT INTERVENTION, THEREBY AVERTING THE DEVASTATING
EFFECTS OF LONG-TERM USE.
• STANDARDIZING PREDICTIVE CONSTRUCTS WHICH HIGHLIGHTS SPECIFIC RISK CATEGORIES
THAT MAY BE THE BASIS FOR SUD TREATMENT RECOMMENDATIONS
• TREATMENT IMPLICATIONS FOR COMORBID CONDITIONS WITH IMPULSE DISORDER AND SUD
REFERENCES
• FULTON TIMM CREWS, CHARLOTTE ANN BOETTIGER, IMPULSIVITY, FRONTAL LOBES AND RISK
FOR ADDICTION, PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR – ELSEVIER; SEPTEMBER
2009
• ANTONIO VERDEJO-GARCIA, ANDREW J. LAWRENCE, LUKE CLARK, IMPULSIVITY AS A
VULNERABILITY MARKER FOR SUBSTANCE-USE DISORDERS: REVIEW OF FINDINGS FROM HIGH-
RISK RESEARCH, PROBLEM GAMBLERS AND GENETIC ASSOCIATION STUDIES; NEUROSCIENCE
AND BIOBEHAVIORAL REVIEWS 32 (2008) 777–810, NOVEMBER 2007
• JON E. GRANT, JD, MD, MPH AND SAMUEL R. CHAMBERLAIN, MD, PHD,
PSYCHOPHARMACOLOGICAL OPTIONS FOR TREATING IMPULSIVITY, PSYCHIATRIC TIMES
• BLANCO C, POTENZA MN, KIM SW, ET AL. A PILOT STUDY OF IMPULSIVITY AND COMPULSIVITY
IN PATHOLOGICAL GAMBLING. PSYCHIATRY RES. 2009;167:161-168.