The
Effect
of Lithium
BY MICHAEL
H. SHEARD,
AND
WAGNER,
ERNEST
on M.D.,
Impulsive
JAMES
Aggressive
L. MARINI,
PRELIMINARY REPORTS (1-4) have suggested that lithium exerts an inhibiting effect on chronic human aggressive behavior and therefore might be useful in the treatment of some forms of pathological aggressiveness in man. The previous work, however, consisted of single-blind (1-3) or nonblind (4) studies, and confirmation of these reports, as well as development of treatment criteria, requires further research using double-blind procedures. The study we will describe was a three-year double-blind evaluation of the effect of lithium on the aggressive behavior of incarcerated delinquent males with histories of chronic impulsive aggressive behavior.
Dr.
Sheard
is Associate
is Research necticut Mental
Professor
ofClinical
Psychiatry
and
Dr.
Ma-
Associate, Department of Psychiatry and ConHealth Center, Yale University School of Medicine,
34 Park
St. , New Haven, Conn. Assistant and Dr. Wagner Psychiatry when this work was
search
06508, where Ms. Bridges was Rewas Assistant Clinical Professor of done. Dr. Wagner is now in private
study was supported Administration grant
of Mental
by Alcohol, MH-21934
Drug Abuse, and Mental from the National Institute
Health.
The authors
would
tional
Institution,
their
cooperation,
like to thank the inmates Cheshire, and Mr.
Conn. , especially Josh Auerbach
and staff of the Correcfor
Mr. James statistical
Ted, for consulta-
tion. Slow-release lithium (Priadel) ries, Canterbury, England. Mich.,
provided
placebo.
I. BRIDGES,
M.A.,
METHOD Subjects The subjects were male inmates aged 16-24 at the medium security Correctional Institution at Cheshire, Conn. The criteria used for subject selection were 1) conviction for serious aggressive crimes (e.g., manslaughter, murder, rape, assault) plus a history of chronic assaultive behavior and/on a history of chronic impulsive antisocial behavior, 2) freedom from psychosis, 3) good physical health with no renal, cardiac, or organic brain disease, 4) ability to comprehend the written material used in the study, 5) sentence of sufficient duration to ensure time for completion of the study, and 6) termination ofany psychoactive medication with consent of the prescribing physician. Subjects were referred by the institution’s counseling staff, who had been given a detailed description of the study. A subject’s suitability was determined by the staffpsychiatnist (E.W.) and the senior investigator (M.H.S.). The selected subjects were then presented with a detailed oral explanation ofthe study, including purpose, risks, and possible benefits. After a 1-2 week waiting period they were asked if they were willing to participate. Those who agreed were required to sign a consent form. Identical consent forms signed by parents or guardians were required for subjects under 18. Of a total of 159 referrals, 101 subjects were judged suitable and agreed to participate. A total of 80 remained in the study long enough to receive medication. Of these, 14 dropped out of the study or were transferred, giving a sample of 66 individuals. Mean ages (±SD) were 19.4± 1.76 years for lithium subjects and 19.5± 1.49 years for placebo subjects. Procedure tion
practice. This Health
CAROLYN
in Man
M.D.
The authors conducted a double-blind, placebocontrolled study ofthe effect oflithium on aggressive behavior. The 66 subjects, who were prisoners in a medium security institution, ranged in agefrom 16 to 24 years, were physically healthy and nonpsychotic, and had histories ofchronic impulsive aggressive behavior. Subjects received lithium orplacebo daily for up to 3 months. There was a significant reduction in aggressive behavior in the lithium group as measured by a decrease in infractions involving violence. The authors suggest that lithium can have a clinically useful effect upon impulsive aggressive behavior when this behavior is not associated with psychosis.
mi
PH.D.,
Behavior
was supplied by Delandale Rowell Laboratories, Inc.,
LaboratoBaudette,
Subjects whether
were or
paid $3.75 a week not they completed
for
their participathe experiment,
and those who did finish or whose termination was beyond their control (e.g. transfer to another institution) received a bonus of $2.50 a week. Thus the total pay was $6.25 a week, for a maximum of $125.00 for 5 months, which is equivalent to the monthly remuneration for the best paying inmate jobs at the institution. Throughout the study, the subjects continued their normal routines aside from the 1-2 hours each week when they performed study tasks and evaluations. They re,
Am
J Psychiatry
133:12,
December
1976
1409
EFFECT
OF
LITHIUM
ON
AGGRESSIVE
BEHAVIOR
ceived no special privileges or amenities within the institution. Initial evaluations. All subjects received a standard
physical workup and mental status evaluation. Data on personal history were obtained, as well as information on brain damage (Memory-For-Designs Test [5]). IQ was measured by the Peabody Picture Vocabulary Test (6) and, in some cases, the Raven Progressive Matnices
Test
also
(7).
The
Lykken
administered.
In addition,
initial evaluation battery Multiphasic Personality
Scale (10), the The Buss-Dunkee tive
Check
Form
Sociopathy
List
(13),
all subjects
consisting Inventory
Eysenck Hostility
Scale
and
the
received
of the (9), the
Personality Inventory
(8) was
an
Minnesota Rotter I-E
Inventory (12), the
Personality
(Ii), Adjec-
Research
(14). The 5-month experimental began with I medication-free month that as a control period. During the next 3 months
Experimental
protocol served subjects
design.
were
given
once-daily
doses
of
either
al privileges. in two
2.
A test
tune
groups
not differ in number by more than 3 subjects at any given time. The study staff-a psychopharmacologist (J L. M a psychologist (C.I. B.), and a psychiatrist (E.W.)-were blind to medication assignment, as were all of the personnel at the institution. Lithium and placebo were packed in identical capsules, and each subject received 5 capsules once a day. Serum lithium 1ev.
els
.),
were
assayed
by altering Thus,
weekly
the amount
placebo
subjects
and
adjusted
oflithium took
when
within 5 capsules
containing
pla-
tion
frequently,
time
in the
“hole”
(segregation unit). Minor infractions are less serious offenses such as possession of contraband or being out of place and usually are punished by loss of recreation1410
Am
J Psychiatry
133:12,
December
Affect
ComPic-
administered
each
chi-squane and linear
tests, analyses of discriminant func-
analysis.
RESU
LTS
66 subjects, 34 received lithium for periods of (N=20), 2 months (N=8) or 1 month (N=6),
32
received
Personality,
or
for
1 month
were
and
significantly
than p
Effect
of Lithium
BY MICHAEL
H. SHEARD,
AND
WAGNER,
ERNEST
on M.D.,
Impulsive
JAMES
Aggressive
L. MARINI,
PRELIMINARY REPORTS (1-4) have suggested that lithium exerts an inhibiting effect on chronic human aggressive behavior and therefore might be useful in the treatment of some forms of pathological aggressiveness in man. The previous work, however, consisted of single-blind (1-3) or nonblind (4) studies, and confirmation of these reports, as well as development of treatment criteria, requires further research using double-blind procedures. The study we will describe was a three-year double-blind evaluation of the effect of lithium on the aggressive behavior of incarcerated delinquent males with histories of chronic impulsive aggressive behavior.
Dr.
Sheard
is Associate
is Research necticut Mental
Professor
ofClinical
Psychiatry
and
Dr.
Ma-
Associate, Department of Psychiatry and ConHealth Center, Yale University School of Medicine,
34 Park
St. , New Haven, Conn. Assistant and Dr. Wagner Psychiatry when this work was
search
06508, where Ms. Bridges was Rewas Assistant Clinical Professor of done. Dr. Wagner is now in private
study was supported Administration grant
of Mental
by Alcohol, MH-21934
Drug Abuse, and Mental from the National Institute
Health.
The authors
would
tional
Institution,
their
cooperation,
like to thank the inmates Cheshire, and Mr.
Conn. , especially Josh Auerbach
and staff of the Correcfor
Mr. James statistical
Ted, for consulta-
tion. Slow-release lithium (Priadel) ries, Canterbury, England. Mich.,
provided
placebo.
I. BRIDGES,
M.A.,
METHOD Subjects The subjects were male inmates aged 16-24 at the medium security Correctional Institution at Cheshire, Conn. The criteria used for subject selection were 1) conviction for serious aggressive crimes (e.g., manslaughter, murder, rape, assault) plus a history of chronic assaultive behavior and/on a history of chronic impulsive antisocial behavior, 2) freedom from psychosis, 3) good physical health with no renal, cardiac, or organic brain disease, 4) ability to comprehend the written material used in the study, 5) sentence of sufficient duration to ensure time for completion of the study, and 6) termination ofany psychoactive medication with consent of the prescribing physician. Subjects were referred by the institution’s counseling staff, who had been given a detailed description of the study. A subject’s suitability was determined by the staffpsychiatnist (E.W.) and the senior investigator (M.H.S.). The selected subjects were then presented with a detailed oral explanation ofthe study, including purpose, risks, and possible benefits. After a 1-2 week waiting period they were asked if they were willing to participate. Those who agreed were required to sign a consent form. Identical consent forms signed by parents or guardians were required for subjects under 18. Of a total of 159 referrals, 101 subjects were judged suitable and agreed to participate. A total of 80 remained in the study long enough to receive medication. Of these, 14 dropped out of the study or were transferred, giving a sample of 66 individuals. Mean ages (±SD) were 19.4± 1.76 years for lithium subjects and 19.5± 1.49 years for placebo subjects. Procedure tion
practice. This Health
CAROLYN
in Man
M.D.
The authors conducted a double-blind, placebocontrolled study ofthe effect oflithium on aggressive behavior. The 66 subjects, who were prisoners in a medium security institution, ranged in agefrom 16 to 24 years, were physically healthy and nonpsychotic, and had histories ofchronic impulsive aggressive behavior. Subjects received lithium orplacebo daily for up to 3 months. There was a significant reduction in aggressive behavior in the lithium group as measured by a decrease in infractions involving violence. The authors suggest that lithium can have a clinically useful effect upon impulsive aggressive behavior when this behavior is not associated with psychosis.
mi
PH.D.,
Behavior
was supplied by Delandale Rowell Laboratories, Inc.,
LaboratoBaudette,
Subjects whether
were or
paid $3.75 a week not they completed
for
their participathe experiment,
and those who did finish or whose termination was beyond their control (e.g. transfer to another institution) received a bonus of $2.50 a week. Thus the total pay was $6.25 a week, for a maximum of $125.00 for 5 months, which is equivalent to the monthly remuneration for the best paying inmate jobs at the institution. Throughout the study, the subjects continued their normal routines aside from the 1-2 hours each week when they performed study tasks and evaluations. They re,
Am
J Psychiatry
133:12,
December
1976
1409
EFFECT
OF
LITHIUM
ON
AGGRESSIVE
BEHAVIOR
ceived no special privileges or amenities within the institution. Initial evaluations. All subjects received a standard
physical workup and mental status evaluation. Data on personal history were obtained, as well as information on brain damage (Memory-For-Designs Test [5]). IQ was measured by the Peabody Picture Vocabulary Test (6) and, in some cases, the Raven Progressive Matnices
Test
also
(7).
The
Lykken
administered.
In addition,
initial evaluation battery Multiphasic Personality
Scale (10), the The Buss-Dunkee tive
Check
Form
Sociopathy
List
(13),
all subjects
consisting Inventory
Eysenck Hostility
Scale
and
the
received
of the (9), the
Personality Inventory
(8) was
an
Minnesota Rotter I-E
Inventory (12), the
Personality
(Ii), Adjec-
Research
(14). The 5-month experimental began with I medication-free month that as a control period. During the next 3 months
Experimental
protocol served subjects
design.
were
given
once-daily
doses
of
either
al privileges. in two
2.
A test
tune
groups
not differ in number by more than 3 subjects at any given time. The study staff-a psychopharmacologist (J L. M a psychologist (C.I. B.), and a psychiatrist (E.W.)-were blind to medication assignment, as were all of the personnel at the institution. Lithium and placebo were packed in identical capsules, and each subject received 5 capsules once a day. Serum lithium 1ev.
els
.),
were
assayed
by altering Thus,
weekly
the amount
placebo
subjects
and
adjusted
oflithium took
when
within 5 capsules
containing
pla-
tion
frequently,
time
in the
“hole”
(segregation unit). Minor infractions are less serious offenses such as possession of contraband or being out of place and usually are punished by loss of recreation1410
Am
J Psychiatry
133:12,
December
Affect
ComPic-
administered
each
chi-squane and linear
tests, analyses of discriminant func-
analysis.
RESU
LTS
66 subjects, 34 received lithium for periods of (N=20), 2 months (N=8) or 1 month (N=6),
32
received
Personality,
or
for
1 month
were
and
significantly
than p
