AGGRESSION/RESILIENCE
From Wondrous Words of Wisdom from World-Wise, Well-Spoken Witan, presented by the University of Wisconsin School of
Medicine and Public Health and the Madison Institute of Medicine, Inc
Educational Objectives
| The goals of this program are to help the clinician determine the etiology and treatment of aggression, and to improve his or
her recognition of the role of resilience in preventing and treating depressive disorders and posttraumatic stress disorder
(PTSD). After hearing and assimilating this program, the clinician will be better able to:
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 | 1. Determine the etiology of aggression in any given patient.
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| 2. Recognize the principal factors involved in violent behavior.
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| 3. Reduce the incidence of aggression and violence in psychiatric populations.
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| 4. Discuss the role resilience plays in the prevention and treatment of depressive disorders and PTSD.
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| 5. Increase and promote resiliency.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts
of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health
care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Citrome
is a consultant for Eli Lilly, and a speaker for Abbott Laboratories, AstraZeneca, Avanair Pharmaceuticals, and Eli Lilly. Dr.
Davidson is a speaker for Solvay, Pfizer, GlaxoSmithKline, Forest, and Merck; receives research funds and other support
from Pfizer, Eli Lilly, GlaxoSmithKline, Forest, Bristol Myers Squibb, Cephalon, AstraZeneca, Janssen, International Psychopharmacology
Algorithm Project, and CME Institute; and is an advisor to Actelion, Pfizer, GlaxoSmithKline, Forest, Eli
Lilly, Roche, MediciNova, Jazz, AstraZeneca, Wyeth, Sanofi-Aventis, Janssen, Brain Cells, Epix, Organon, Transcept,
Marinus, Synosia, ZARS, and Xenoport. The planning comittee reported nothing to disclose.
Acknowledgements
Drs. Citrome and Davidson were recorded at Wondrous Words of Wisdom from World-Wise, Well-Spoken Witan, held
March 7-8, 2008, and sponsored by the University of Wisconsin School of Medicine and Public Health and the Madison
Institute of Medicine, Inc. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation
in the production of this program.
| UNDERSTANDING AGGRESSION: FROM CAUSES TO INTERVENTIONS —Leslie L. Citrome, MD, MPH, Director,
Clinical Research and Evaluation Facility, Nathan S. Kline Institute for Psychiatric Research, New York State Office of
Mental Health; and Professor of Psychiatry, New York University School of Medicine, New York, NY
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| Introduction: Epidemiological Catchment Area (ECA) study showed probability of violent behavior 5 to 6 times higher
in those with diagnosed mental disorder than in those without diagnosed mental disorder; not all patients with schizophrenia
are aggressive, violent, or hostile, and risk increases “tremendously” in presence of co-occurring alcohol and/or
substance use; however, most aggression, violence, or hostility in today’s society attributable to people without Axis I
major mental disorder; studies show small number of patients responsible for majority of violent incidents in institutions;
staff who are in direct contact with patients are the most likely to be assaulted
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| Methods of detecting aggression: official incident reports; restraint and seclusion reports; review of patient charts;
shift-to-shift reports; staff interviews; direct observation; video monitoring shows that above methods of detection result
in under-reporting of incidents; however, video system not useful for minute-by-minute monitoring; rather, after incident
detected, video can be reviewed for several minutes before and after to analyze cause and to determine what preventive
measures can be implemented; eyewitness reliability low, and video provides more accurate record of incident
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| Etiology of aggression: multifactorial; patient factors—co-occurring substance abuse or dependence; intoxication;
withdrawal; poor impulse control; positive symptoms of psychosis; assess patient to rule out somatic conditions, substance
or alcohol dependence, antisocial personality disorder or traits, and adverse drug reactions; history of violence best
single indicator of risk for violent behavior; make sure patient does not have ready access to weapons; obtain criminal
justice records; assess content of delusions (aggression not precipitated by hallucinations, but by delusions that underlie
them); environmental factors—inpatient ward atmosphere; staff (paradoxically, too many staff can increase aggressiveness);
number of patients on ward; activities; time of day (change of shift, smoking time, and meal times especially risky)
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| Clinical correlates of aggression: treatment noncompliance; neurologic impairment; substance abuse; lack of insight;
depression; psychosis; paranoia; anxiety; anger; target each factor for resolution or treatment; validate patient’s
feelings of anxiety, empathize with him or her, and treat
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| Principal factors in violent behavior: psychosis—study of 157 patients with psychosis showed great variation in
number of incidents per patient, ranging from zero to 27; 88 subjects had more than one aggressive incident; 354 aggressive
incidents in study were verbal (vicious cursing), 50 incidents were directed at objects, and 95 incidents involved physical
aggression against people; Positive and Negative Syndrome Score (PANSS) showed that the sicker patients were, the
more likely they were to be aggressive; study also demonstrated need for more attention to patients’ depression and anxiety;
psychopathy—“we’re kind of out of luck there, but we know what not to do”; psychopathy is not same as antisocial
personality disorder; psychopathy is construct that includes arrogant deceitful interpersonal style, deficient affective experience,
and impulsive and irresponsible behavioral style; measures of psychopathy show robust association between violence
and recidivism in offenders; psychopathy associated with “instrumental aggression” (ie, goal-directed and planned);
Psychopathy Checklist (PCL) used in forensic settings to determine degree of psychopathy, but not used in civil settings
because of stigma attached to label of “psychopath”; impulsivity—substances and conditions (eg, alcohol, attention-deficit/hyperactivity
disorder [ADHD], traumatic brain injury [TBI]) that diminish behavioral inhibition linked with increased
aggression; violent subjects make more impulsive errors on environmental tasks and score higher on self-ratings of impulsivity;
impulsive (“affective”) aggression unplanned, unprovoked or out of proportion to provocation, and results in remorse
(as opposed to psychopathy, in which there is no remorse)
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| Assault Interview Checklist: developed to identify precipitating factors of psychopathy, psychosis, and impulsivity; areas
assessed include acting on hallucinations or delusions, psychotic misinterpretation, planning, predatory gain, provocation
by victim, being ordered to do something, having request refused, remorse, amnesia, and partial denial; utility of
checklist verified in studies, but “events are impure”; particular event may be triggered by combination of psychopathy,
psychosis, and/or impulsivity; also, “people are impure,” and over time have differing degrees of control over psychosis
and impulsivity
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| Treatment directions: identify underlying causes; select appropriate treatments and/or interventions
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| Environmental interventions: clear room of all calm patients (easier to remove calm patients from room than to isolate aggressive
individual in another area); have as many staff as possible present for show of force and concern; allow patient
to talk; restraints, seclusion, and/or calming blanket may be necessary, but should be avoided if possible; immediate
goals of intervention—calm patient; decrease likelihood of harm to patient or others; encourage patient to allow diagnostic
tests or procedures; attenuate psychosis; decrease need for seclusion and/or restraint; help patient sleep (but not
during evaluation)
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| Medical interventions: immediate—early on in course of events, offer patient nonspecific sedating agents; speaker recommends
combination of 5 mg of haloperidol and 2 mg of lorazepam, administered intramuscularly, which works
faster than either agent alone, requires fewer injections, and decreases incidence of extrapyramidal symptoms (EPS),
compared to haloperidol alone; however, haloperidol as long-term antipsychotic treatment may not be desirable, due to
side effects of EPS and tardive dyskinesia (TD) and to its efficacy being limited to positive symptoms; long term—sedation
alone inadequate; treat underlying disorder; consider second-generation antipsychotic medications, mood stabilizers,
β-blockers, and selective serotonin reuptake inhibitors (SSRIs); evidence negative for efficacy of
benzodiazepines; studies show—clozapine more effective than first-generation antipsychotics in reducing aggression
in schizophrenia, and superior to risperidone and olanzapine; adjunctive valproate has few studies to support it, but
commonly used anyway; some evidence exists for carbamazepine and lamotrigine; lithium not adequately studied in
patients with schizophrenia and aggression; β-blockers well studied in patients with brain injuries, may be helpful as
adjunctive agent in schizophrenia with aggression
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| Conclusions: violence complex and multifactorial; identifying underlying cause key to optimal treatment; “low tech” interventions
can be effective
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| RESILIENCE AND THE EFFECTS OF ANTIDEPRESSANTS —Jonathan Davidson, MD, Professor, Department of Psychiatry
and Behavioral Sciences, Duke University School of Medicine, Durham, NC
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| Introduction: resilience defined as ability to cope successfully with adversity
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| Why bother with it? “it may be a form of preventive psychiatry”; evidence shows that degree of resilience correlates
closely with chance of making full remission when treated with antidepressants; reduces incidence of coronary heart disease;
requires patient’s active participation; prosocial; altruistic; not just absence of depression or poor function, but offers
“added value”
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| Trauma and posttraumatic stress disorder (PTSD): most survivors of trauma do not develop PTSD (survey
shows that >50% of general population experiences trauma, but <20% develops PTSD), suggesting that some degree of
resilience is norm
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| Characteristics of resilience: within the individual—optimism; faith; humor; self-efficacy; self-confidence; resourcefulness;
adaptability; ability to bounce back; hardiness; environmental—ability to establish social support; connectedness;
altruism
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| Measures relating to resilience: many exist, including Kobasa’s Hardiness Scale and Antonovsky’s Sense of Coherence
Scale; Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Defensive Function
Scale
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| Connor Davidson Resilience Scale (CD-RISC): developed by speaker and colleague specifically to measure resilience;
25 items in which patient rates self over past month; each item rated from zero (not at all true) to 4 (true nearly all the
time); higher scores equal greater resilience; US population as whole averages score of ≈80, family practice patients
average 71, and patients with depression average 58; lowest scores (average of 50) found in patients with PTSD and patients
with substance abuse in remission with history of suicide attempts (average 49; without suicide attempts, 60)
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| Is resilience just the inverse of related constructs? studies find resilience is not inverse of conditions such as neuroticism,
disability, depression, or anxiety; one study found resilience higher in people who are extroverted, conscientious,
or use active coping skills to deal with problems; also found resilience moderates relationship between early
childhood trauma and current levels of psychiatric symptoms; study concluded that individuals with higher resilience
have fewer psychiatric symptoms, no matter how much trauma they have experienced; another study found that having
sense of humor when things are not going well is predictive of doing well in treatment for PTSD
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| Neurobiology of resilience: for central nervous system to respond well under adversity, individual must be able to—
maintain reward expectations in unrewarding environment; regulate fear conditioning and extinction in presence of uncontrollable
stress or adversity; preserve ability to encode, consolidate, and retrieve memory at times of hyperarousal;
act effectively when afraid; maintain effective bonding and attachments following interpersonal abuse or loss; neuropeptide
Y (NPY)—produces anxiolytic effects; associated with improvements in performance and behavior under extreme
stress; studies of members of Special Forces found that when exposed to stress, their NPY goes up rapidly, then drops to
baseline within 24 hr; in control group, NPY peaked at lower level, then dropped to below baseline within 24 hr; these
results raise question of whether NPY-like compounds could help therapeutically; serotonin transporter gene—has
short (S) and long (L) alleles; presence of 1 or 2 S alleles results in less efficient system of reuptake of serotonin; found
that in individuals with early childhood trauma, presence of 2 L alleles does not increase likelihood of having adult depression,
but, in presence of 2 S alleles, the worse the childhood trauma, the greater the likelihood of developing adult
depression; norepinephrine transporter (NET)—rats deficient in NET showed initially greater autonomic response to
stress, followed by sustained lowering of blood pressure and heart rate and increased heart-rate variability, compared to
rats with adequate NET; in forced swim test, NET-deficient rats had reduced immobility time (increased immobility time
considered to be marker of depression)
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| Environmental factors: study found that to extent boys and girls able to elicit positive responses from their caregiving
environment, they were stress resistant despite parental alcoholism and long-term poverty; also found link between infant’s
having “easy” temperament and being able to access sources of support; another study found greatest risk factor for
developing PTSD is decreased social support
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| Increasing resiliency: in study of treatment of PTSD, speaker found fluoxetine helped patients to cope with daily stress
better than placebo; this finding was so intriguing that his group went on to study effect of antidepressants on resilience in
PTSD and found selective norepinephrine reuptake inhibitor (SNRI) had significant advantage over placebo in enhancing
resilience; another study found mindfulness meditation enhanced resilience in business managers; factors that promote
resiliency—active coping style; physical exercise; positive outlook; moral compass; social support; cognitive flexibility;
study of Hawaiian children found that interests and hobbies provided solace in hard times, and taking on socially desirable
tasks and having supportive relationships increased resiliency; speaker’s study found having sense of humor predicts
remission in PTSD
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| Does resilience protect against PTSD? speaker’s group studied resilience, spiritual beliefs, forgiveness of perpetrator,
continued feelings of revenge, and continued feelings of anger toward perpetrator, and found the more resilient the individual,
the fewer PTSD symptoms he or she had; moreover, anger was strong correlate of continued PTSD
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| How can resilience be promoted? antidepressants, cognitive behavioral therapy, and mindfulness meditation may
help; treatment that reduces symptoms may increase resilience; employ >1 approach to promoting resilience; requires active
participation by patient; address individual and societal components
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| Conclusions: shift focus to increasing positive rather than decreasing negative; resilience not a proxy for other related
constructs; resilience involves genetic, biologic, and environmental factors; resilience measurable and modifiable individually
and culturally
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Suggested Reading
Campbell-Sills L, Stein MB: Psychometric analysis and refinement of the Connor-Davidson Resilience Scale (CD-
RISC): Validation of a 10-item measure of resilience. J Trauma Stress 20:1019, 2007; Chaichan W: Evaluation of the
use of the positive and negative syndrome scale-excited component as a criterion for administration of p.r.n. medication. J
Psychiatr Pract 14:105, 2008; Charney DS: Psychobiological mechanisms of resilience and vulnerability: implications
for successful adaptation to extreme stress. Am J Psychiatry 161:195, 2004; Citrome L et al: Risperidone alone versus
risperidone plus valproate in the treatment of patients with schizophrenia and hostility. Int Clin Psychopharmacol 22:356,
2007; Citrome L: Comparison of intramuscular ziprasidone, olanzapine, or aripiprazole for agitation: a quantitative review
of efficacy and safety. J Clin Psychiatry 68:1876, 2007; Citrome L: The psychopharmacology of violence with emphasis
on schizophrenia, part 2: long-term treatment. J Clin Psychiatry 68:331, 2007; Citrome L: The
psychopharmacology of violence with emphasis on schizophrenia, part 1: acute treatment. J Clin Psychiatry 68:163, 2007;
Connor KM et al: Spirituality, resilience, and anger in survivors of violent trauma: a community survey. J Trauma
Stress 16:487, 2003; Connor KM, Davidson JR: Development of a new resilience scale: the Connor-Davidson Resilience
Scale (CD-RISC). Depress Anxiety 18:76, 2003; Connor KM: Assessment of resilience in the aftermath of trauma.
J Clin Psychiatry 67(Suppl 2):46, 2006; Davidson J et al: Treatment of posttraumatic stress disorder with venlafaxine
extended release: a 6-month randomized controlled trial. Arch Gen Psychiatry 63:1158, 2006; Dunn SG, Alholm SE:
Safe strategies for potentially violent patients, Part 1. J Med Pract Manage 23:86, 2007; Hodgins S et al: Aggressive behaviour,
victimization and crime among severely mentally ill patients requiring hospitalisation. Br J Psychiatry 191:343,
2007; Nickel MK, Loew TH: Treatment of aggression with topiramate in male borderline patients, part II: 18-month
follow-up. Eur Psychiatry 23:115, 2008; Nolan KA, Citrome L: Reducing inpatient aggression: does paying attention
pay off? Psychiatr Q 79:91, 2008; Richardson GE: The metatheory of resilience and resiliency. J Clin Psychol 58:307,
2002; Roy A et al: Low resilience in suicide attempters. Arch Suicide Res, 11:265, 2007; Vaillant GE: Mental health.
Am J Psychiatry 160:1373, 2003; Vaishnavi S et al: An abbreviated version of the Connor-Davidson Resilience Scale
(CD-RISC), the CD-RISC2: psychometric properties and applications in psychopharmacological trials. Psychiatry Res
152:293, 2007.
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