Encyclopedia of drugs, alcohol, & addictive behavior Vol 4 (S-Z, Index)

389 Pages·2009·6.56 MB·English

by  Kranzler

VOLUME
4
Encyclopedia of
Drugs, Alcohol & Addictive Behavior
Third Edition
HENRY R. KRANZLER & PAMELA KORSMEYER
EncyclopediaofDrugs,Alcohol&AddictiveBehavior,3rdEdition,Vol4-Finals/10/18/200813:14PMPage
3
ENCYCLOPEDIA OF
DRUGS, ALCOHOL
& ADDICTIVE
BEHAVIOR
THIRD EDITION
Volume 4
S–Z; Index
Pamela Korsmeyer and Henry R. Kranzler
EDITORSINCHIEF
EncyclopediaofDrugs,Alcohol&AddictiveBehavior,3rdEdition,Vol4-Finals/10/18/200813:47PMPage1
S
signs and symptoms, but the etiologies, treatment
SADD. SeeStudentsAgainstDestructiveDecisions responsiveness,andcourseofillnessineachvary.
(SADD).
Detailed descriptions of the illness date back
to the nineteenth century. Emil Kraepelin (1856–
1926) used the term dementia praecox to describe
psychiatric states with an early onset and deterio-
SCANDINAVIAN COUNTRIES. See rating course. Eugen Bleuler (1857–1939) coined
NordicCountries(Denmark,Finland,Iceland,
thetermschizophreniafora‘‘splittingofthemind,’’
Norway,andSweden).
in his belief that the illness was a result of the
disharmony of psychological functions. The diag-
nosis of schizophrenia requires observation and
n
clinicalinterviewing.Nosignorsymptomisspecific
SCHIZOPHRENIA. Schizophrenia is a for the illness, nor do any laboratory tests exist to
psychiatric illness that can be profoundly disabling establish the diagnosis. The Diagnostic and Statis-
and is usually chronic in nature. The cause is not tical Manual of Mental Disorders, fourth edition
known, but there appears to be a genetic predis- (2000) contains the diagnostic guidelines of the
position.Theetiologyhasbeenconceptualizedina American Psychiatric Association for schizophre-
stress/diathesis (vulnerability) model: Biological nia. These include the presence of characteristic
and environmental factors (e.g., drug abuse, psy- psychotic symptoms (delusions, hallucinations, a
chosocial stresses) interact with a genetic vulner- thought disorder, inappropriate emotion); impaired
ability to precipitate the illness. Several theories abilitytowork,socialfunctioning,andself-care;and
have been proposed to explain the observed bio- continuoussignsoftheillnessforatleastsixmonths.
logical abnormalities of the disorder, including The symptoms of an affected individual can change
overactivity of the dopamine neurotransmitter sys- withtime,thereforelongitudinalfollow-upisimpor-
tems in the central nervous system, changes in tant. It should be noted that certain of these symp-
brainstructure(e.g.,enlargementofthelateralcer- tomscanbeindicativeofotherconditions(including
ebralventricles)andbrainfunction(e.g.,decreased drug abuse [cocaine, crack, PCB, amphetamines],
frontallobefunction[hypofrontality],asevidenced headinjury,braintumors,aswellasotherpsychiatric
by diminished blood flow, and deficits in attention disorders).Furthermore,itisimportanttotakeinto
and sensory filtering). Psychological and social fac- accounttheeducationallevel,intellectualability,and
torsareconsideredimportantintheexpressionand cultural affiliation of the individual when making a
courseofthedisorder.Itislikelythatschizophrenia diagnosis. The onset of illness is usually in late ado-
constitutesagroupofdisordersratherthanasingle lescenceorearlyadulthoodandisgenerallyinsidious.
entity; these disorders present with similar clinical The typical course of schizophrenia is characterized
1
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SCHIZOPHRENIA
by exacerbations and remissions. A gradual deterio- After a person has recovered from an acute epi-
rationinfunctioninggenerallyoccursthateventually sode of schizophrenia, the emphasis is on practical
reaches a plateau. However, a small proportion of aspects of management: living arrangements, self-
persons mayrecover. It is estimated that 20percent care, employment, and social relationships. Educa-
to 30 percent of affected individuals can lead some- tion of and support made available to family mem-
whatnormalliveswhereasanother20to30percent bersareimportantandcanhaveanimpactonrelapse
continuetoexperiencemoderatesymptoms. rates in the patient. Many schizophrenic patients
havetoremainonantipsychoticmedicationforpro-
Theprevalenceratesofschizophreniavarytoa
limiteddegreeworldwide,butintheUnitedStates longedperiods,sincetherateofrelapseishighafter
the lifetime prevalence is estimated to be between drug discontinuation. Side effects, primarily of a
0.5and1.5percent(aboutonein50toonein150 neurologic nature (e.g., TD), are a source of con-
people). In industrialized countries, there is a dis- cern, but in most cases the benefits of symptom
proportionate number of schizophrenic patients control outweigh the risks of pharmacotherapy.
in the lower socioeconomic classes. Some experts Making sure that the patient complies with medica-
think this is due to the schizophrenic’s loss of tionuseisoftenaproblem.
education and social opportunity, while others
maintain this is more a direct result of the stresses SeealsoAmphetamine;CannabisSativa;Complications:
MentalDisorders.
of poverty.
The management of affected individualsinvolves
BIBLIOGRAPHY
hospitalization when there is an exacerbation of the
illness, plus the use of medication. The mainstay of Andreasen,N.C.(1986).Schizophrenia.InA.J.Frances&
R. E. Hales (Eds.), Psychiatry update: The American
pharmacologic treatment is the class of drugs known
Psychiatric Association annual review (Vol. 5). Wash-
as antipsychotics. Many antipsychotics are available
ington,D.C.:AmericanPsychiatricPress.
andtheyacttocontrolthepsychoticsymptoms;most
of them do so by blocking the actions of the neuro- Apgar, B. (1999). Antipsychotic drugs for treatment of
schizophrenia.AmericanFamilyPhysician,60,1220.
transmitter dopamine. About 75 percent of patients
respondtothesedrugs;however,therearesideeffects, Berkow, R., Ed. (1997). The Merck manual of medical
including muscle stiffness, tremors, and weight gain. information—home edition. Whitehouse Station, NJ:
The drugs may also cause tardive dyskinesia (TD), a MerckResearchLaboratories.(2004,2nd.Ed.)
disorderthatcausesinvoluntaryrepetitivemovements
Green,M.F.(2003).Schizophreniarevealed:Fromneurons
ofthebody,mouth,andtongue. to social interactions. New York: W. W. Norton &
Company.
Someofthemorecommonlyprescribedantipsy-
chotics include: chlorpromazine, fluphenazine, hal- Karno,M.,etal.(1989).Schizophrenia.InH.I.Kaplan&
operidol, olanzapine, and risperidone. The atypical B. J. Sadock (Eds.). Comprehensive textbook of psychia-
try, 5th ed. Baltimore, MD: Lippincott Williams &
antipsychotic clozapine has been identified as the
Wilkins.(2004,8thed.)
best choice for managing resistant schizophrenia;
however,upto73percentofpatientstreatedwith Kilian,J.G.,etal.(1999).Myocarditisandcardiomyopathy
clozapine report clinically relevant side effects. associatedwithclozapine.TheLancet,354,1841.
These can be quite severe, and include potentially Nasrallah, H. A., & Smeltzer, D. J. (2003). Contemporary
fatal neuroleptic malignant syndrome (NMS), diagnosis and management of the patient with schizo-
myocarditis, cardiomyopathy, and dangerous low- phrenia. Newton, PA: Handbooks in Health Care
ering of the white blood cell count (for the latter, Company.
regularandfrequentbloodtestingisrequireddur- Oldham,J.M.(1995).Schizophreniaandpsychosis.InG.
ing the treatment period). In a study following J. Subak-Sharpe (Ed.),The Columbiauniversity college
8,000 patients in Australia who started clozapine of physicians & surgeons complete home medical guide,
3rded.NewYork:CrownPublishers,Inc.
treatmentbetweenJanuary1993andMarch1999,
fifteendevelopedmyocarditis,andeightdeveloped
MYROSLAVAROMACH
cardiomyopathy; a total of six patients died within KARENPARKER
the six years. REVISEDBYPUBLISHER(2001)
2 ENCYCLOPEDIA OF DRUGS, ALCOHOL & ADDICTIVE BEHAVIOR, 3RD EDITION
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SECOBARBITAL
n n
SCOPOLAMINE AND ATROPINE. SECOBARBITAL. Secobarbital, prescribed
Scopolamine(d-hyoscine)andatropine(dl-hyoscy- and sold as Seconal, is a short-acting barbiturate
amine)isatropanealkaloidfoundintheleavesand used principally as a sedative-hypnotic drug but
seeds of several plant species of the family Solana- occasionally as a preanesthetic agent. It is a non-
ceae, including deadly nightshade (Atropa bella- specific central nervous system (CNS) depressant
donna)andhenbane(Hyoscyamusniger).Atropine, and greatly impairs the mental and/or physical
amajoralkaloidindeadlynightshade,isalsofound abilitiesnecessaryforthesafeoperationofautomo-
in jimsonweed (Datura stramonium). In Europe, biles and complex machinery.
in centuries past, henbane was a component of Before the introduction of the benzodiaze-
socalled witches’ brews or was applied as an oint- pines, secobarbital was the drug most commonly
ment to mucous membranes. According to some used to treatinsomnia.Prolonged orinappropriate
folk tales, the idea that witches fly on broomsticks useofsecobarbitalcanproducetoleranceandphys-
was derived from the sensation of a flying experi- ical dependence. If high doses have been used,
ence after the use of such ointments. abrupt cessation can result in severe withdrawal
symptoms that include convulsions. Secobarbital
Scopolamine and atropine have very similar
is more likely to be abused than benzodiazepines
actions. They act as competitive antagonists at both
and appears to produce greater euphoria in certain
peripheral and central muscarinic cholinergic recep-
individuals than would a comparable sedative dose
tors.Scopolamineisstillsometimesusedclinicallyfor
of a benzodiazepine. Consequently, it is classified
thetreatmentofmotionsickness.Thecompoundalso
as a Schedule II class drug in the Controlled Sub-
causes central nervous system depression, leading to
stances Act, which indicates that although it is
drowsiness, amnesia, and fatigue. It also has some
acceptable for clinical use, it is considered to have a
euphoric effects and abuse liability, but these are not
high abuse potential. As with other barbiturates,
consideredtobeofsuchmagnitudetorequirecontrol
secobarbitalshouldneverbecombinedwithanother
of the drug under the Controlled Substances Act.
CNS depressant because respiratory depression can
Atropine has fewer actions on the central nervous
occur.
systemthanscopolamine.Itisusedtoreduceactions
at peripheral cholinergic structures—it produces
decreased gastric and intestinal secretions as well as
O
CHCH CH
spasmsandalsoresultsinpupillarydilation.Itblocks 2 2
theactionofthevagusnervethatresultsinslowingof HN
theheart.Itisoftenusedbeforeoperationstoprevent CHCHCHCH
2 2 3
unwantedreflexslowingoftheheartbeat. O N O CH
H 3
High doses of either of these tropane alkaloids
can cause confusion and delirium accompanied by
Figure1.Chemicalstructureofsecobarbital.ILLUSTRATIONBY
decreased sweating, dry mouth, and dilated pupils.
GGSINFORMATIONSERVICES.GALE,CENGAGELEARNING
SeealsoAlkaloids;Jimsonweed.
SeealsoAbuseLiabilityofDrugs:TestinginHumans;
BIBLIOGRAPHY DrugInteractionandtheBrain;DrugInteractions
Brown, J. H., & Taylor, P. (1996). Muscarinic receptor andAlcohol.
agonists and antagonists. In A. G. Gilman et al.
(Eds.), The pharmacological basis of therapeutics, 9th
BIBLIOGRAPHY
ed.NewYork:McGraw-HillMedical.(2005,11thed.)
Hobbs, W. R., Rall, T. W., & Verdoorn, T. A. (1996).
Hesse, M. (2002). Alkaloids. Weinheim, Germany: Wiley- Hypnoticsandsedatives.InA.G.Gilmanetal.(Eds.),
VCH. Thepharmacologicalbasisoftherapeutics,9thed.(361–
396).NewYork:McGraw-HillMedical.(2005,11thed.
Houghton,P.J.,&Bisset,N.G.(1985).Drugsofethno-
origin.InD.C.Howell(Ed.),Drugsincentralnervous Karch, S. B. (2006). Drug abuse handbook, 2nd ed. Boca
systemdisorders.NewYork:MarcelDekker. Raton,FL:CRCPress.
ROBERTZACZEK SCOTTE.LUKAS
ENCYCLOPEDIA OF DRUGS, ALCOHOL & ADDICTIVE BEHAVIOR, 3RD EDITION 3
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SECULAR ORGANIZATIONS FOR SOBRIETY (SOS)
n Abuse/Dependence;Treatment:AnOverviewof
SECULAR ORGANIZATIONS FOR DrugAbuse/Dependence.
SOBRIETY (SOS). Secular Organizations
for Sobriety is a self-help organization for alcohol BIBLIOGRAPHY
and drug users, founded as an alternative to Alco-
Humphreys,K.(2004).Self-helporganizations foralcohol
holicsAnonymous(AA)andothergroupsbasedon and drug problems: Toward evidence-based practice
AA.Itwasintendedtoofferhelptopeoplewhoare and policy. Journal of Substance Abuse Treatment, 26,
uncomfortable with the emphasis on spirituality 3,151–158.
that is a central tenet of the AA Twelve-Step Pro- Secular Organizations for Sobriety (SOS). Available from
grams.FoundedbyJamesChristopher,SOSbegan http://www.secularsobriety.org.
with a 1985 article. ‘‘Sobriety without Supersti-
JEROMEH.JAFFE
tion,’’ describing Christopher’s own path to sobri-
ety. SOS claimed in 1991 to have an international
membershipof20,000,makingitthelargestofthe
n
alternative groups. In 1987, it was recognized by
the State of California as an alternative to AA in SEDATIVE. Sedativeisageneraltermusedto
sentencing offenders to mandatory participation in describe a number of drugs that decrease activity,
drug rehabilitation. Members of SOS are not nec- moderate excitement, and have a calming effect.
essarilynonreligious;however,manydonotbelieve The primary use for these drugs is to reduce anxi-
in an intervening higher power who takes respon- ety, but higher doses will usually cause sleep (a
sibility for their individual problems. drug used primarily to cause sleep is called a hyp-
notic). Although the term sedative is still used, the
Unlike AA—whichemphasizesthat the individ-
drugs usually prescribed to produce this calming
ual is powerless over alcoholism and must look to a
effect are benzodiazepines, which are more com-
‘‘higher power’’ for help in achieving and maintain-
monly known as antianxiety agents or minor
ing sobriety—SOS and other alternative organiza-
tranquilizers.
tionsassertthecapacityofindividualstocontroltheir
ownbehavior.SOSstressestotalabstinence,personal SeealsoBarbiturates;DrugTypes;Sedative-Hypnotic.
responsibility, and self-reliance as the means to
achieve and maintain sobriety (recovery), but the
BIBLIOGRAPHY
organization recognizes the importance of partici-
Hobbs, W. R., Rall, T. W., & Verdoorn, T. A. (1996).
pating in a mutually supportive group as an adjunct
Hypnotics and sedatives. In A. G. Gilman et al.
to recovery. Members learn that open and honest
(Eds.), The pharmacological basis of therapeutics, 9th
communication aids in making the appropriate life ed. (361–396). New York: McGraw-Hill Medical.
choices that are essential to recovery. SOS shares (2005,11thed.)
with other self-help groups the importance of ano-
Meyer,J.S.,&amp:Quenzer,L.F.(2004).Psychopharma-
nymity and the abstention from all drugs and cology:Drugs,thebrainandbehavior.Sunderland,MA:
alcohol. SinauerAssociates.
SOS consists of a nonprofit network of auton- SCOTTE.LUKAS
omous nonprofessional local groups dedicated
solelytohelpingindividualswithalcoholandother
drug addictions. It encourages and is supportive of
n
continued scientific inquiry into the understanding
SEDATIVE-HYPNOTIC. Sedative-hypnotic
of alcoholism and drug addiction.
drugs are used to reduce motor activity and pro-
Among other self-help organizations that see mote relaxation, drowsiness, and sleep. The term
themselvesasalternativestoAAareRationalRecov- is hyphenated because by adjusting the dose, the
ery(RR)andWomenforSobriety(WFS). same group of drugs can be used to produce
mild sedation (calming, relaxation) or sleepiness.
SeealsoCoercedTreatmentforSubstanceOffenders;
Thus the distinction between a sedative and a
ModelsofAlcoholismandDrugAbuse;Treatment:
AnOverview;Treatment:AnOverviewofAlcohol hypnotic (sleeping pill) is often a matter of
4 ENCYCLOPEDIA OF DRUGS, ALCOHOL & ADDICTIVE BEHAVIOR, 3RD EDITION
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SEDATIVES: ADVERSE CONSEQUENCES OF CHRONIC USE
dose—lower doses act as sedatives and higher SeealsoAbuseLiabilityofDrugs:TestinginHumans;
doses promote sleep. DrugInteractionsandAlcohol;DrugTypes;Sui-
cideandSubstanceAbuse.
In some people, sedative-hypnotics can pro-
duce a paradoxical state of excitement and confu-
BIBLIOGRAPHY
sion. This response tends to occur more frequently
Hobbs,W.R.,Rall,T.W.,&Verdoorn,T.A.(1996).Hyp-
in the very young and older populations. Some of
notics and sedatives. In A. G. Gilman et al. (Eds.), The
these drugs have the potential to be abused. Very pharmacologicalbasisoftherapeutics,9thed.(361–396).
high doses of most sedative-hypnotic drugs will NewYork:McGraw-HillMedical.(2005,11thed.)
produce general anesthesia and can depress respi-
Katzung,B.G.(2006).Basic&clinicalpharmacology.New
ration so much that breathing must be maintained York:McGraw-HillMedical.
artificiallyordeathwilloccur.Thebenzodiazepines
Nemeroff, C. B. & Schatsberg, A. F. (Eds.) (1998). The
are an exception to this general rule in that higher American psychiatric press textbook of psychopharmacol-
doses typically produce sleep and are far less likely ogy.Washington,D.C.:AmericanPsychiatricPress.
to severely depress respiration.
Parker, J.N., &Parker,P. M.(2002).Theofficial patient’
sourcebook on prescription CNS depressants dependence.
Oneofthefirstagentstobeaddedtothelistof
Boulder,CO:NetLibrary.
the classic sedatives (alcohol and opiates) was bro-
mide, introduced in 1857 as a treatment for epi- SCOTTE.LUKAS
REVISEDBYNICHOLASDEMARTINIS(2001)
lepsy. Chloral hydrate was introduced in 1869 and
paraldehyde was first used in 1882. The barbitu-
rates were introduced in the early 1900s and
n
remained the dominant drugs for inducing sleep
SEDATIVES: ADVERSE CONSE-
and sedation until the bezodiazepines were devel-
QUENCES OF CHRONIC USE. Seda-
oped in the late 1950s and early 1960s. A number
tive drugs are also called hypnotics or sedative-
of miscellaneous non-barbiturate sedatives (eth-
hypnotics.Theyaresometimesreferredtoasminor
chlorvynol,glutethimide,carbromal,methylparafy-
tranquilizers or anxiolytics (antianxiety medica-
nol, methyprylon, methaqualone) were introduced
tions). Technically, a sedative decreases activity
in the 1940s and 1950s, and for a brief period
and has a calming effect whereas a hypnotic produ-
rivaled the barbiturates in popularity, but their
ces drowsiness, allowing for the onset and mainte-
used declined rapidly along with the use of barbi-
nance of sleep. Ideally, a hypnotic produces a state
turates. The bromides were recognized to have
ofsleepsimilartonaturalsleepandfromwhichthe
toxic properties, but they were still in use until
sleeper may be easily awakened. The same drug
the mid-twentieth century; chloral hydrate and
usedforsedation,pharmacologicallyinducedsleep,
paraldehyde were used well into the late 1970s
and general systemic anesthesia may be seen to
and are still used in some places. Some drugs with
induce a continuum of central nervous system
other medical uses are prescribed as hypnotics, but
(CNS) depression. Such drugs are usually referred
the effectiveness of these substances remains to be
to, therefore, as sedative-hypnotics, and they are
proven in well-controlled clinical trials.
widely prescribed in the treatment of insomnia
(sleepproblems).Althoughsomepeopletakethese
An advance in the development of sedative-
drugs only occasionally and for specific sleep prob-
hypnotics occurred with the discovery of non-
lems (e.g., secondary to grief, time-limited stress,
benzodiazepine drugs that also act on the benso-
long-distance flights), many more take them over
diazepine receptor. Zolpidem and zaleplon are
prolonged periods (months, and even years) as a
short-acting hypnotics that demonstrate fewer
presumedaidtonightlysleep.Theydothisdespite
side-effects and less tendency for rebound insom-
medical advice that restricts the use of such drugs
nia when they are discontinued, a common prob-
to approximately two weeks.
lem with the benzodiazepines. These drugs also
demonstrate less abuse potential than many of All thesedativesareavailableintabletsorcap-
the other sedative-hypnotics and little respiratory sules for oral dosage, and some are also available
depression. for intravenous or intramuscular administration.
ENCYCLOPEDIA OF DRUGS, ALCOHOL & ADDICTIVE BEHAVIOR, 3RD EDITION 5
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SEDATIVES: ADVERSE CONSEQUENCES OF CHRONIC USE
Almost all sedatives have the same behavioral brain.Thenewestsedative,ramelteon(Rozerem),isa
effects as alcohol (ethanol). Many individuals melatoninagonist.Itdiffersbothchemicallyandphar-
who abuse sedatives, are, or have been, problem macologicallyfromthebenzodiazepines.Other,older
drinkers.Accordingtoguidelinespublishedbythe hypnoticsarechloralhydrate(Noctec),achloralderiv-
American Psychiatric Association (1990), patients ative,andhydroxyzine(Vistaril),anantihistamine.
with a history of alcoholism or other drug abuse
problems should not be treated with benzodiaze-
BENZODIAZEPINES
pinesedativesonachronicbasisbecausetheyareat
Although the use of benzodiazepines as sedative-
a high risk of developing benzodiazepine abuse.
hypnoticdrugsisdecreasinginfavorofneweragents,
This, however, remains a controversial issue (Cir-
theyarestillprescribedwithgreatfrequency.Thekey
aulo & Nace, 2000).
concernsintheuseofthebenzodiazepinesasahyp-
noticare:
USE OFHYPNOTICS
Sleep problems in adults are of three main types: 1. Adverse effects experienced while the patient is
taking the drug;
1. Problems of falling asleep (sleep initiation);
2. Possiblephysicalandpsychologicaldependence;
2. Problems staying asleep (sleep maintenance);
3. Rebound insomnia and withdrawal symptoms
3. Early-morning wakening.
when the patient stops taking the drug.
Sleep-onsetproblemsvarylittlewithage;early-
Classification. Benzodiazepines can be classified
morning wakening is often secondary to depres-
on pharmacokinetic grounds into three groups:
sion, and sleep-maintenance problems show a clear
long-acting (e.g., flurazepam [Dalmane], diaze-
and marked increase with aging. Whereas approx-
pam, chlordiazepoxide [Librium]), medium-acting
imately 10 percent of young adults complain of
(temazepam), and short-acting (triazolam, oxaze-
serious sleep problems, this increases to 30 to 50
pam [Serax], lorazepam) sedative-hypnotics. Their
percentofthoseaged70orolder(Morgan,1990).
efficacy, at least in short-term use, has been well
Thisage-relatedpatternforcomplaintsofinsomnia
documented. The pattern of improvement in sleep
is reflected in the pattern of use of sedative-hyp-
corresponds fairly closely withthe pharmacokinetic
notic drugs. The results of one survey indicate that
properties of each drug, providing that factors of
4 percent of people older than 65 used a hypnotic
absorption and elimination are taken into account.
agent continuously for more than a decade (Mor-
For example, temazepam is absorbed relatively
gan et al., 1988). According to a 2002 poll con-
slowly and has little effect on sleep-initiation time
ducted by the National Sleep Foundation, 15 per- whereas triazolam is absorbed relatively rapidly,
cent of the subjects polled reported using a sleep which brings sleep on more quickly.
aid (either prescription or over-the-counter) at
Each sedative-hypnotic has a minimally effec-
leastafewnightspermonth.Acrossallagegroups,
tive dose but the dose that is usually effective may
roughly twice as many women as men take seda-
betwiceashighastheminimum.Furtherincreases
tive-hypnotic drugs.
may, however, cause side effects and rebound
insomnia without substantially improving sleep.
COMMONLYUSED HYPNOTICS
In sleep-laboratory studies many benzodiazepines
The most commonly prescribed hypnotics include
lose their efficacy after about two weeks of nightly
thebenzodiazepinestemazepam(Restoril)andtriazo-
use. Subjectively, however, patients often feel that
lam (Halcion). Some sedative benzodiazepines are
theirsleepisimprovedforlongerperiodsthanthis.
also used to induce sleep including alprazolam
(Xanax),lorazepam(Ativan),anddiazepam(Valium).
Adverse Effects. Benzodiazepine sedatives have
Neweragentsincludethenon-benzodiazepineszolpi-
three major adverse effects:
dem (Ambien), zaleplon (Sonata), and eszopiclone
(Lunesta). Although these drugs differ chemically 1. Cumulative effects with repeated dosage, par-
from the benzodiazepines, their mode of action is ticularly if the patient has not yet metabolized
similar in that they target the same receptors in the the previous dose;
6 ENCYCLOPEDIA OF DRUGS, ALCOHOL & ADDICTIVE BEHAVIOR, 3RD EDITION
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SEDATIVES: ADVERSE CONSEQUENCES OF CHRONIC USE
2. Additive effects when given with other classes deterioration or dementia, use of a benzodiazepine
of sedatives or with alcohol; mayintensifythesesymptoms.
3. Residual effects after the medication is dis-
Abuse, Dependence, and Withdrawal. Some
continued.
argue thatrebound insomniaisitself a signofphys-
Patientstakingbenzodiazepinesmayfeeldrowsy, iological dependence on benzodiazepine hypnotics
havereducedpsychomotorspeed,andimpairedcon-
(e.g.,Morgan,1990).Othersinsistthatdependence
centration. These in turn can adversely affect their isshownonlywhenwithdrawalfromadrugleadsto
abilitytofunction,sotheyshouldbecautionedabout symptomsotherthanareboundoftheoriginalprob-
driving and operating machinery while taking these
lems. In general, psychological dependence onben-
drugs. The longer-acting the drug, the more pro- zodiazepinescandevelopratherrapidly.Afteronlya
nounced these effects. Tolerance to these sedative
few weeks, patients who attempt to discontinue the
effects builds up to some extent with repeated use medication may experience restlessness, disturbing
ofthedrug.
dreams, paranoid ideas and delusions, and feelings
Allbenzodiazepinescanimpairtheuser’sability of tension or anxiety in the early morning. With-
tolearnandremembernewinformation.Thismem- drawal following the use of a moderate dose of a
oryimpairmentismostpronouncedafewhoursafter benzodiazepine may include dizziness, increased
taking the drug, so when taken as a sleep aid such sensitivity to light and sound, and muscle cramps.
effectsmaybemuchreducedbythetimetheperson Abrupt withdrawal following high-dose usage may
wakes the next morning. As with other adverse resultinseizuresanddelirium.
effects, higher doses cause greater problems. Rarer
The syndrome of withdrawal from benzodia-
adverse effects include disinhibition and aggressive
zepines may be slow in onset because these drugs
behavior. These effects have been reported for
remain in the body for relatively long periods.
some benzodiazepines (e.g., triazolam, flunitraze-
Withdrawal appears to be most severe in patients
pam[Rohypnol,notmarketedintheUnitedStates])
who used benzodiazepines that are absorbed rap-
morethanothers.
idly and have a rapid decline in blood serum levels
Rebound insomnia refers to the heightened (e.g., alprazolam, lorazepam, and triazolam). In
insomnia that may occur when the patient stops patients who abuse both benzodiazepines and
taking the drug, such that the sleep pattern is alcohol,adelayedbenzodiazepinewithdrawalsyn-
actually worse than it was before the medication. drome may complicate withdrawal from alcohol.
Studies have established that rebound insomnia is Patients who are high-dose abusers of benzodia-
generally at its worst following the use of shorter- zepines usually require inpatient detoxification.
acting benzodiazepines and at its least following
the use of longer-acting benzodiazepines (Roehrs Abuse. Animal studies indicate that benzodiaze-
et al., 1986). Rebound is clearly dose-related, and pines, like cocaine and opioids, activate a reward
the patient should be prescribed the lowest effec- pathwayinthebrainsofmostmammals.Inhumans
tive dose, with rebound effects described to warn the benzodiazepines have reinforcing effects that
the patient about overdosing for faster or better appear to be more pronounced in frequent users
drug-induced sleep. ofotherrecreationaldrugs.Forexample,alcoholics
andheroinaddictswillattimesusebenzodiazepines
Age-related changes in the way that drugs are
to extend the supply of their most-preferred drug
metabolized and excreted mean that benzodiaze-
becausealcoholandheroinarealsodepressants.
pines accumulate more in older patients and, there-
fore, adverse effects are more pronounced in the Abuse of benzodiazepines by themselves is rel-
elderly,whoareparticularlysusceptibletotheeffects atively unusual but sometimes occurs among users
of these drugs on their psychomotor performance who seek a high from massive amounts of these
(e.g.,balanceandgait).Consequently,olderpatients drugs. Street drug dealers sell benzodiazepines at a
takingbenzodiazepinesedativesareespeciallyatrisk relativelylowcostinmostmajorcities.Someabus-
of falls resulting in hip or femur fractures and are ers combine benzodiazepines with other drugs to
at an increased risk of being involved in a motor enhance the effects; for example, some believe that
vehicle accident. In elderly patients with cognitive taking diazepam half an hour after an oral dose of
ENCYCLOPEDIA OF DRUGS, ALCOHOL & ADDICTIVE BEHAVIOR, 3RD EDITION 7
EncyclopediaofDrugs,Alcohol&AddictiveBehavior,3rdEdition,Vol4-Finals/10/18/200813:47PMPage8
SEDATIVES: ADVERSE CONSEQUENCES OF CHRONIC USE
methadonewillproduceahighthatismoreintense elderly patients because they are less likely to cause
than can be obtained from taking either drug by restlessness in confused or demented patients.
itself. Chloral derivatives are also relatively safe to give to
children for sedation before or after surgery. They
Overdose. Benzodiazepine overdose is a serious can,however,causegastricirritationandrashes.
though rarely fatal event unless accompanied by the
concomitant ingestion of alcohol or other CNS Antihistamines. Antihistamines, commonly used
depressants. Symptoms of benzodiazepine overdose for the treatment of allergies, often cause drowsiness,
include sleepiness, incoordination, and diminished leading to their use as sedatives. Diphenhydramine
mental facilities. In more serious cases, low blood (Benadryl,Nytol,Sominex)andhydroxyzine(Atarax,
pressure,respiratorydepression,andcomacanoccur. Vistaril) are two antihistamines often prescribed for
Inaconsciouspatient,treatmentusuallybeginswith patientswhoneed onlya mild sedative. Theyaresafe
the inducement of emesis (vomiting). In an uncon- and do not produce dependency. They should not,
scious patient, the contents of the stomach are however, be used together with alcohol. The most
removed by gastric lavage (stomach pumping). In commonsideeffectofthesemedicationsisdrymouth.
additiontosupportivecare,abenzodiazepineantag-
onist, flumazenil (Romazicon) can be used to Buspirone. Buspirone (BuSpar) is the only anti-
improve the level of consciousness. anxietymedicationthatisnotasedative.Becauseit
does not produce depressant effects or depen-
dence, it is used in the treatment of depression as
NON-BENZODIAZEPINE HYPNOTICS
Newer compounds include such non-benzodiaze- well as anxiety. Unlike the sedatives, buspirone
pine hypnotics as eszopiclone (Lunesta), zolpidem does not affect the patient’s alertness or motor
(Ambien), and zaleplon (Sonata), which act either skills, it does not intensify the effects of alcohol,
atypically or selectively on benzodiazepine recep- and it does not produce a withdrawal syndrome.
tors.Theyarealsoknownasbenzodiazepinerecep- Because it has no potential to be abused or to
tor agonists though they are chemically distinct produce dependence in patients with a history of
frombenzodiazepines(andfromeachother).They drugoralcoholdependence,buspironemaybethe
are short-acting drugs and at normal clinical doses anxiolytic of choice for these patients.
causelittleresidualsedation(hangover).Theriskof
rebound insomnia or dependence with these com- Melatonin Agonists. Melatonin is a natural
pounds is much lower than with benzodiazepines, sleep-inducing hormone produced by the pineal
but not absent (Lader, 1992). Memory problems glandinthebrain.Naturalmelatoninhasbeenused
have been reported with these agents. A phenom- toinducesleep.Ramelteon,aprescriptiondrugthat
enon called sleep driving in which an individual works on melatonin receptors in the brain, is the
operates a motor vehicle without memory of the most recently approved sedative and is believed to
event has been associated with zolpidem. Retro- lackthepotentialtocausedependenceorabuse.
grade amnesia, a condition in which the patient
SeealsoAccidentsandInjuriesfromDrugs;Addiction:
cannot recall events immediately prior to taking ConceptsandDefinitions;Aging,Drugs,and
the drug, has been reported in patients who have Alcohol;Barbiturates;Barbiturates:Complications;
taken zalepon. Benzodiazepines:Complications;DrugInteraction
andtheBrain;DrugInteractionsandAlcohol;
Memory,EffectsofDrugson.
OTHER SEDATIVE/HYPNOTIC DRUGS
Barbiturates. Barbiturates were used until the
BIBLIOGRAPHY
1950s as sleeping pills but were superseded by the
American Psychiatric Association. (1990). Benzodiazepine
benzodiazepines.Withtheexceptionofphenobarbital dependence, toxicity, and abuse: A task force report of
(Luminal), which is still used as a sedative and as an the American Psychiatric Association. Arlington, VA:
anticonvulsant,thebarbituratesarerarelyprescribed. AmericanPsychiatricPublishing.
Beers, M. H., & Berkow, R. (Eds.). (1999). The Merck
Chloral Derivatives. These compounds, which manual of diagnosis and therapy (17th ed.). White-
include chloral hydrate, are sometimes used with houseStation,NJ:MerckResearchLaboratories.
8 ENCYCLOPEDIA OF DRUGS, ALCOHOL & ADDICTIVE BEHAVIOR, 3RD EDITION