By: Brian Zachariah M.D. PGY4 Lauren Derhodge D.O. Clinical Assistant Professor, Attending Physician

Size: px

Start display at page:

Download "By: Brian Zachariah M.D. PGY4 Lauren Derhodge D.O. Clinical Assistant Professor, Attending Physician"

Phyllis Porter
5 years ago
Views:

1 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

2 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.

3 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

4 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 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. Evenden, 1999b, de Wit, 2009

INCLUDING RULE SHIFTING, AS WELL AS INITIATING APPROPRIATE ACTIONS AND INHIBITING INAPPROPRIATE ACTIONS.

5 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

6 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

7 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.

8 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

9 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. 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. Balleine and Killcross, 2006

THIS IS NORMAL; HOWEVER, NOT ALL WILL BE DISTRACTED.

10 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

11 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

12 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

13 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

URGENCY, I.E. THE TENDENCY TO ACT IMPULSIVELY IN RESPONSE TO NEGATIVE EVENTS, SENSATION SEEKING, AND MORE

14 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

15 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

16 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.

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

17 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

18 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

19 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.

20 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

21 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

FROM CROSS-SECTIONAL AND LONGITUDINAL STUDIES OF CHILDREN WITH SUD

THESE STUDIES HAVE ELEGANTLY DEMONSTRATED THAT CHILDREN OF SUD PARENTS

22 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.

25 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

26 GENETIC ASSOCIATION STUDIES OF IMPULSIVITY WITH RISK FACTORS FOR ADDICTION

27 PRACTICAL IMPLICATION? PERSISTENCE OF DEPENDENCE AND MOTIVATION TO CONTROL ADDICTIVE BEHAVIOR RELY ON THE DECISIONAL BALANCE BETWEEN REFLECTIVE AND IMPULSIVE SYSTEMS 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 neurobiology of behavioral change needed in recovery from addiction requires frontal-cortical involvement Hettema et al., 2005; Clay et al., 2008

PSYCHOPHARMACOLOGICAL OPTIONS FOR IMPULSIVITY SSRI S: LOW LEVELS OF THE SEROTONIN METABOLITE 5-HYDROXYINDOLEACETIC ACID AND BLUNTED SEROTONERGIC RESPONSE WITHIN THE VENTROMEDIAL PREFRONTAL CORTEX ARE

28 PSYCHOPHARMACOLOGICAL OPTIONS FOR IMPULSIVITY 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:

29 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 placebocontrolled trial. J Clin Psychiatry. 2007;68:

30 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: Grant JE, Schreiber LR, Odlaug BL. Phenomenology and treatment of behavioural addictions. Can J Psychiatry. 2013;58: 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

ATYPICALS HAVE MIXED REPORTS OLANZAPINE TRICHOTILLOMANIA BUT NOT IN GAMBLING DISORDER RISPERIDONE AND QUETIAPINE IN CONDUCT DISORDER LITHIUM MOST STUDIES ON

Van Ameringen M, Mancini C, Patterson B, et al. A randomized, double-blind, placebo-controlled trial of olanzapine in the treatment of trichotillomania.

31 ATYPICALS HAVE MIXED REPORTS OLANZAPINE TRICHOTILLOMANIA BUT NOT IN GAMBLING DISORDER RISPERIDONE AND QUETIAPINE IN CONDUCT DISORDER LITHIUM MOST STUDIES ON BIPOLAR MANIA AND EFFICACY IN REDUCING IMPULSIVITY ASSOCIATED WITH GRANDIOSITY 7 STUDIES DEMONSTRATING EFFICACY IN ADOLESCENTS WITH 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: Grant JE, Leppink EW. Choosing a treatment for disruptive, impulse-control, and conduct disorders. Curr Psychiatry. 2015;14:29-

32 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

33 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) , 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:

Evidence-Based Treatment Approaches for Gambling Disorder

Evidence-Based Treatment Approaches for Gambling Disorder Jon E. Grant, JD, MD, MPH Professor University of Chicago Pritzker School of Medicine Chicago, IL 6/8/2016 Disclosure Information My research is