pattern may be especially likely among indi viduals who have other substance use disor-
ders (e.g., alcohol, opioids, stimulants). An in itial pattern of intermit tent use socially (e.g.,
at parties) can lead to daily use and high leve ls of tolerance. Once this occurs, an increasing
level of interpersonal difficulties, as well as increasingly severe episodes of cognitive dys-
function and physiological wi thdrawal, can be expected.
The second and less frequently  observed clinical course begins with an individual who
originally obtained the medication by prescrip tion from a physician, usually for the treat-
ment of anxiety, insomnia, or somatic complain ts. As either tolerance or a need for higher
doses of the medication develops, there is a gr adual increase in the dose and frequency of


ment of anxiety, insomnia, or somatic complain ts. As either tolerance or a need for higher
doses of the medication develops, there is a gr adual increase in the dose and frequency of
self-administration. The individu al is likely to continue to justify use on the basis of his or
her original symptoms of anxiety or insomn ia, but substance-seeking behavior becomes


554 Substance-Related and Addictive Disorders
more prominent, and the individual may seek out multiple physicians to obtain sufficient
supplies of the medication. Tolerance can reach high levels, and withdrawal (including
seizures and withdrawal  delirium) may occur.
As with many substance use disorders, sedati ve, hypnotic, or anxiol ytic use disorder gen-
erally has an onset during adolescence or early adult life. There is an increased risk for misuse
and problems from many psychoactive substances  as individuals age. In particular, cognitive
impairment increases as a side effect with ag e, and the metabolism of sedatives, hypnotics, or
anxiolytics decreases with age among older indi viduals. Both acute and chronic toxic effects
of these substances, especially effects on co gnition, memory, and motor coordination, are
likely to increase with age as a consequence of pharmacodynamic and pharmacokinetic age-
related changes. Individuals with major neuroc ognitive disorder (dementia) are more likely
to develop intoxication and impaired phy siological functioning at lower doses.
Deliberate intoxication to achieve a “high” is  most likely to be observed in teenagers
and individuals in their 20s. Problems associate d with sedatives, hypnotics, or anxiolytics
are also seen in individuals in their 40s and older who escalate the dose of prescribed med-
ications. In older individuals, intoxicati on can resemble a progressive dementia.
Risk and Prognostic Factors
Temperamental. Impulsivity and novelty seeking are in dividual temperaments that re-
late to the propensity to develop a substanc e use disorder but may themselves be geneti-
cally determined.
Environmental. Since sedatives, hypnotics, or anxiolytics are all pharmaceuticals, a key


risk factor relates to availability of the substances. In the United States, the historical pat-
terns of sedative, hypn otic, or anxiolytic misuse relate to the broad prescribing patterns.
For instance, a marked decrease in prescription  of barbiturates was associated with an in-
crease in benzodiazepine pres cribing. Peer factors may rela te to genetic predisposition in
terms of how individuals select  their environment. Other individuals at heightened risk
might include those with alcohol use disorder who may receive repeated prescriptions in
response to their complaints of al cohol-related anxiety or insomnia.
Genetic and physiological. As for other substance use diso rders, the risk for sedative,
hypnotic, or anxiolytic use disorder can be re lated to individual, family, peer, social, and
environmental factors. Within these domains, genetic factors play a particularly important
role both directly and indirectly. Overall, ac ross development, genetic factors seem to play
a larger role in the onset of sedative, hypnotic,  or anxiolytic use disorder as individuals age
through puberty into adult life.
Course modifiers. Early onset of use is associated with greater likelihood for develop-
ing a sedative, hypnotic, or anxiolytic use disorder.
Culture-Related Diagnostic Issues
There are marked variations in prescription patt erns (and availability) of this class of sub-
stances in different countries, which may lead to variations in prevalence of sedative, hyp-
notic, or anxiolytic use disorders.
Gender-Related Diagnostic Issues
Females may be at higher risk than males for prescription drug mi suse of sedative, hyp-
notic, or anxiolytic substances.
Diagnostic Markers


notic, or anxiolytic substances.
Diagnostic Markers
Almost all sedative, hypnotic, or anxiolytic substances can be identified through labora-
tory evaluations of urine or blood (the latter of which can quantify the amounts of these


Sedative, Hypnotic, or Anxiolytic Use Disorder 555
agents in the body). Urine tests are likely to remain positive  for up to approximately 1 week
after the use of long-acting substa nces, such as diazepam or flurazepam.
Functional Consequences of
Sedative, Hypnotic, or Anxiolytic Use Disorder
The social and interpersonal co nsequences of sedative, hypnot ic, or anxiolytic use disorder
mimic those of alcohol in terms of the potentia l for disinhibited behavior. Accidents, interper-
sonal difficulties (such as argume nts or fights), and interference  with work or school perfor-
mance are all common outcomes. Physical examinat ion is likely to reveal evidence of a mild
decrease in most aspects of autonomic nervous system functioning, including a slower pulse,
a slightly decreased respiratory rate, and a slight  drop in blood pressure (most likely to occur
with postural changes). At high doses, sedative, hypnotic, or an xiolytic substances can be le-
thal, particularly when mixed with alcohol, al though the lethal dosage varies considerably
among the specific substances. Overdoses may be associated with a deterioration in vital signs
that signals an impending medical emergency (e .g., respiratory arrest  from barbiturates).
There may be consequences of trauma (e.g., internal bleeding or a subdural hematoma) from
accidents that occur while intoxicated. Intraven ous use of these substances can result in med-
ical complications related to the use of contaminated needles (e.g., hepatitis and HIV).
Acute intoxication can result in accidental injuries and automobile accidents. For elderly
individuals, even short-term use of these sedati ng medications at prescr ibed doses can be as-


sociated with an increased risk for cognitive problems and falls. The disinhibiting effects of
these agents, like alcohol, may potentially cont ribute to overly aggressive behavior, with sub-
sequent interpersonal and legal problems. Accide ntal or deliberate overdoses, similar to those
observed for alcohol use disorder or repeated alcohol intoxication, can occur. In contrast to
their wide margin of safety when used alone,  benzodiazepines taken in combination with al-
cohol can be particularly dangerous, and accidental overdoses are reported commonly. Acci-
dental overdoses have also been  reported in individuals who deliberately misuse barbiturates
and other nonbenzodiazepine sedatives (e.g., me thaqualone), but since these agents are much
less available than the benzodiazepines, the freq uency of overdosing is  low in most settings.
Differential Diagnosis
Other mental disorders or medical conditions. Individuals with se dative-, hypnotic-,
or anxiolytic-induced disorders may present with symptoms (e.g., anxiety) that resemble
primary mental disorders (e.g., generalized an xiety disorder vs. sedative-, hypnotic-, or
anxiolytic-induced anxiety disorder, with on set during withdrawal). The slurred speech,
incoordination, and other associa ted features characteristic of sedative, hypnotic, or anx-
iolytic intoxication could be the result of an other medical condition (e .g., multiple sclero-
sis) or of a prior head trauma (e.g., a subdural hematoma).
Alcohol use disorder. Sedative, hypnotic, or anxiolytic use disorder must be differenti-
ated from alcohol use disorder.
Clinically appropriate use of sedative, hypnotic, or anxiolytic medications. Individuals


Clinically appropriate use of sedative, hypnotic, or anxiolytic medications. Individuals
may continue to take benzodiazepine medication according to  a physician’s direction for a
legitimate medical indication over extended pe riods of time. Even if  physiological signs of
tolerance or withdrawal are manifested, many  of these individuals do not develop symp-
toms that meet the criteria for sedative, hypnotic, or anxiolytic use disorder because they
are not preoccupied with obtaining the substanc e and its use does not interfere with their
performance of usual social or occupational roles.
Comorbidity
Nonmedical use of sedative, hypnotic, or anxi olytic agents is associated with alcohol use


performance of usual social or occupational roles.
Comorbidity
Nonmedical use of sedative, hypnotic, or anxi olytic agents is associated with alcohol use
disorder, tobacco use disorder, and, generally, illicit drug use.  There may also be an over-


556 Substance-Related and Addictive Disorders
lap between sedative, hypnotic, or anxiolytic use disorder an d antisocial personality dis-
order; depressive, bipolar, and anxiety disorders; and other substance use disorders, such
as alcohol use disorder and illicit drug use disorders. Antisocial behavior and antisocial
personality disorder are especially associated with sedative, hypnotic, or anxiolytic use
disorder when the substances are obtained illegally.
Sedative, Hypnotic, or Anxiolytic Intoxication
Diagnostic Criteria
A. Recent use of a sedative, hypnotic, or anxiolytic.
B. Clinically significant maladaptive behavioral or psychological changes (e.g., inappro-
priate sexual or aggressive behavior, m ood lability, impaired judgment) that developed
during, or shortly after, sedative, hypnotic, or anxiolytic use.
C. One (or more) of the following signs or symptoms developing during, or shortly after,
sedative, hypnotic, or anxiolytic use:
1. Slurred speech.
2. Incoordination.
3. Unsteady gait.
4. Nystagmus.
5. Impairment in cognition (e.g., attention, memory).
6. Stupor or coma.
D. The signs or symptoms are not attributable to another medical condition and are not
better explained by another mental disorder, including intoxication with another sub-
stance.
Coding note:  The ICD-9-CM code is 292.89.  The ICD-10-CM code depends on whether
there is a comorbid sedative, hypnotic, or anxiolytic use disorder. If a mild sedative, hyp-


notic, or anxiolytic use disorder is comorbid, the ICD-10-CM code is F13.129,  and if a mod-
erate or severe sedative, hypnotic, or anxio lytic use disorder is comorbid, the ICD-10-CM
code is F13.229.  If there is no comorbid sedative, hypnotic, or anxiolytic use disorder, then
the ICD-10-CM code is F13.929.
Note:  For information on Developm ent and Course; Risk and Prognostic Factors; Culture-
Related Diagnostic Issues; Diagnostic Marker s; Functional Consequences of Sedative,
Hypnotic, or Anxiolytic Intoxication; and Co morbidity, see the corre sponding sections in
sedative, hypnotic, or anxiolytic use disorder.
Diagnostic Features
The essential feature of sedative, hypnotic, or anxiolytic intoxication is the presence of clini-
cally significant maladaptive behavioral or ps ychological changes (e.g ., inappropriate sexual
or aggressive behavior, mood lability, impair ed judgment, impaired social or occupational
functioning) that develo p during, or shortly after, use of a sedative, hypnotic, or anxiolytic
(Criteria A and B). As with other brain depressants, such as alcohol, these behaviors may be ac-
companied by slurred speech, incoordination (at le vels that can interfere with driving abilities
and with performing usual activities to the poin t of causing falls or automobile accidents), an
unsteady gait, nystagmus, impairment in cogn ition (e.g., attentional or memory problems),


and stupor or coma (Criterion C). Memory impa irment is a prominent feature of sedative, hyp-
notic, or anxiolytic intoxication and is most often characterized by an  anterograde amnesia that
resembles “alcoholic blackouts,” which can be  disturbing to the individual. The symptoms
must not be attributable to another medical co ndition and are not better explained by another


Sedative, Hypnotic, or Anxiolytic Withdrawal 557
mental disorder (Criterion D). Intoxication ma y occur in individuals who are receiving these
substances by prescription, are borrowing the medi cation from friends or relatives, or are de-
liberately taking the substance to achieve intoxication.
Associated Features Supporting Diagnosis
Associated features include taking more medi cation than prescribed, taking multiple dif-
ferent medications, or mixing sedative, hypnotic, or anxiolytic agents with alcohol, which
can markedly increase the effects of these agents.
Prevalence
The prevalence of sedative, hypnotic, or anxi olytic intoxication in the general population
is unclear. However, it is probable that most  nonmedical users of sedatives, hypnotics, or
anxiolytics would at some time have signs or  symptoms that meet criteria for sedative,
hypnotic, or anxiolytic intoxication; if so, then the prevalence of nonmedical sedative,
hypnotic, or anxiolytic use in the general po pulation may be simila r to the prevalence of
sedative, hypnotic, or anxiolytic intoxicati on. For example, tranquilizers are used non-
medically by 2.2% of Amer icans older than 12 years.
Differential Diagnosis
Alcohol use disorders. Since the clinical presentations may be identical, distinguishing sed-
ative, hypnotic, or anxiolytic intoxication from  alcohol use disorders requires evidence for re-
cent ingestion of sedative, hypnot ic, or anxiolytic medications by  self-report, informant report,
or toxicological testing. Many individuals who misuse sedatives, hypnotics, or anxiolytics may


also misuse alcohol and other su bstances, and so multiple intoxi cation diagnoses are possible.
Alcohol intoxication. Alcohol intoxication may be distin guished from sedative, hypnotic,
or anxiolytic intoxication by the smell of al cohol on the breath. Otherwise, the features of
the two disorders may be similar.
Other sedative-, hypnotic-, or  anxiolytic-induced disorders. Sedative, hypnotic, or anx-
iolytic intoxication is distin guished from the other sedative-, hypnotic-, or anxiolytic-
induced disorders (e.g., sedative-, hypnotic-, or anxiolytic-induced anxiety disorder, with
onset during withdrawal) because the sympto ms in the latter disorders predominate in
the clinical presentation and are severe enough to warrant clinical attention.
Neurocognitive disorders. In situations of cognitive im pairment, traumatic brain in-
jury, and delirium from other causes, sedative s, hypnotics, or anxiolytics may be intoxi-
cating at quite low dosages. The differential diagnosis in these complex settings is based
on the predominant syndrome. An additional diagnosis of sedative, hypnotic, or anxio-
lytic intoxication may be appropriate even if the substance has been ingested at a low dos-
age in the setting of these other (o r similar) co-occu rring conditions.
Sedative, Hypnotic, or Anxiolytic Withdrawal
Diagnostic Criteria
A. Cessation of (or reduction in) sedative, hypnotic, or anxiolytic use that has been pro-
longed.
B. Two (or more) of the following, developing within several hours to a few days after the ces-


sation of (or reduction in) sedative, hypnotic, or anxiolytic use described in Criterion A:
1. Autonomic hyperactivity (e.g., sweating or pulse rate greater than 100 bpm).
2. Hand tremor.


558 Substance-Related and Addictive Disorders
3. Insomnia.
4. Nausea or vomiting.
5. Transient visual, tactile, or auditory hallucinations or illusions.
6. Psychomotor agitation.
7. Anxiety.
8. Grand mal seizures.
C. The signs or symptoms in Criterion B cause clinically significant distress or impairment
in social, occupational, or other important areas of functioning.
D. The signs or symptoms are not attributable to another medical condition and are not
better explained by another mental disorder, including intoxication or withdrawal from
another substance.
Specify if:
With perceptual disturbances:  This specifier may be noted when hallucinations with in-
tact reality testing or auditory, visual, or tactile illusions occur in the absence of a delirium.
Coding note:  The ICD-9-CM code is 292.0.  The ICD-10-CM code for sedative, hypnotic,
or anxiolytic withdrawal depends on whether or not there is a comorbid moderate or se-
vere sedative, hypnotic, or anxiolytic use di sorder and whether or not there are perceptual
disturbances. For sedative, hypnotic, or anxiolytic withdrawal without perceptual distur-
bances, the ICD-10-CM code is F13.239.  For sedative, hypnotic, or anxiolytic withdrawal
with perceptual disturbances, the ICD-10-CM code is F13.232.  Note that the ICD-10-CM
codes indicate the comorbid presence of a moderate or severe sedative, hypnotic, or anx-
iolytic use disorder, reflecting the fact that sedative, hypnotic, or anxiolytic withdrawal can


only occur in the presence of a moderate or severe sedative, hypnotic, or anxiolytic use
disorder. It is not permissible to code a comorbid mild sedative, hypnotic, or anxiolytic use
disorder with sedative, hypnotic, or anxiolytic withdrawal.
Note:  For information on Developm ent and Course; Risk and Prognostic Factors; Culture-
Related Diagnostic Issues; Functional Conseq uences of Sedative, Hypnotic, or Anxiolytic
Withdrawal; and Comorbidity, see the corresp onding sections in sedative, hypnotic, or
anxiolytic use disorder.
Diagnostic Features
The essential feature of sedative, hypnotic, or anxiolytic withdrawal is the presence of a char-
acteristic syndrome that develops  after a marked decrease in or cessation of intake after several
weeks or more of regular use (C riteria A and B). This withdrawal  syndrome is characterized by
two or more symptoms (similar to alcohol with drawal) that include au tonomic hyperactivity
(e.g., increases in heart rate, respiratory rate, blood pressure, or body temperature, along with
sweating); a tremor of the hands; insomnia ; nausea, sometimes accompanied by vomiting;
anxiety; and psychomotor agitation. A grand mal seizure may occur in perhaps as many as
20%–30% of individuals undergoing untreated withdrawal from these substances. In severe
withdrawal, visual, tactile, or auditory hallucinations or illus ions can occur but are usually in
the context of a delirium. If the individual’s rea lity testing is intact (i.e., he or she knows the
substance is causing the hallucinations) and the illusions occur in a clear sensorium, the spec-


ifier “with perceptual disturbances” can be note d. When hallucinations occur in the absence of
intact reality testing, a diagnosis of substanc e/medication-induced ps ychotic disorder should
be considered. The symptoms cause clinically si gnificant distress or impairment in social, oc-
cupational, or other important areas of functioning (Criterion C). The symptoms must not be
attributable to anothe r medical condition and are not bette r explained by an other mental dis-
order (e.g., alcohol withdrawal or generalized anxiety disorder) (Criterion D). Relief of with-
drawal symptoms with admini stration of any sedative-hypnotic agent would support a
diagnosis of sedative, hypnotic, or anxiolytic withdrawal.


Sedative, Hypnotic, or Anxiolytic Withdrawal 559
Associated Features Supporting Diagnosis
The timing and severity of the withdrawal sy ndrome will differ depending on the specific
substance and its pharmacokinetics and ph armacodynamics. For example, withdrawal
from shorter-acting substances that are rapidl y absorbed and that have no active metabo-
lites (e.g., triazolam) can begi n within hours after the subs tance is stopped; withdrawal
from substances with long-acting metabolites  (e.g., diazepam) may not begin for 1–2 days
or longer. The withdrawal syndrome produced by substances in this class may be charac-
terized by the development of a delirium that  can be life-threatening. There may be evi-
dence of tolerance and withdr awal in the absence of a diagnosis of a substance use
disorder in an individual who has abruptly discontinued benzodiazepines that were taken
for long periods of time at prescribed and therapeutic doses. Howe ver, ICD-10-CM codes
only allow a diagnosis of seda tive, hypnotic, or anxiolytic withdrawal in the presence of
comorbid moderate to severe sedative, hypnotic, or anxiolytic use disorder.
The time course of the withdr awal syndrome is generally predicted by the half-life of
the substance. Medications whose actions typica lly last about 10 hours or less (e.g., loraz-
epam, oxazepam, temazepam) produce withdr awal symptoms within 6–8 hours of de-
creasing blood levels that peak in intensity on the second day and improve markedly by
the fourth or fifth day. For substances with  longer half-lives (e .g., diazepam), symptoms


may not develop for more than 1 week, peak in  intensity during the second week, and de-
crease markedly during the third or fourth week. There may be additional longer-term
symptoms at a much lower level of inte nsity that persist for several months.
The longer the substance has been taken and the higher the dosages used, the more likely
it is that there will be severe withdrawal. However, withdrawal has been reported with as little
as 15 mg of diazepam (or its eq uivalent in other benzodiazepines) when taken daily for several
months. Doses of approximately 40 mg of diazepa m (or its equivalent) daily are more likely to
produce clinically relevant withdrawal symptoms, and even higher doses (e.g., 100 mg of di-
azepam) are more likely to be followed by withdrawal seizures or delirium. Sedative, hyp-
notic, or anxiolytic withdrawal delirium is ch aracterized by disturbances in consciousness and
cognition, with visual, tactile, or auditory ha llucinations. When present, sedative, hypnotic, or
anxiolytic withdrawal delirium should be diagnosed instead of withdrawal.
Prevalence
The prevalence of sedative, hypnotic, or anxiolytic withdrawal is unclear.
Diagnostic Markers
Seizures and autonomic instability in the setting of a history of prolonged exposure to sed-
ative, hypnotic, or anxiolytic medications su ggest a high likelihood of sedative, hypnotic,
or anxiolytic withdrawal.
Differential Diagnosis
Other medical disorders. The symptoms of sedative, hypnotic, or anxiolytic with-
drawal may be mimicked by other medical cond itions (e.g., hypoglyc emia, diabetic keto-


acidosis). If seizures are a feature of the seda tive, hypnotic, or anxi olytic withdrawal, the
differential diagnosis includes the various causes  of seizures (e.g., infections, head injury,
poisonings).
Essential tremor. Essential tremor, a disorder that frequently runs in families, may
erroneously suggest the tremulousness associat ed with sedative, hypnotic, or anxiolytic
withdrawal.
Alcohol withdrawal. Alcohol withdrawal produces a sy ndrome very similar to that of
sedative, hypnotic, or anxiolytic withdrawal.


560 Substance-Related and Addictive Disorders
Other sedative-, hypnotic-, or  anxiolytic-induced disorders. Sedative, hypnotic, or anx-
iolytic withdrawal is distingu ished from the other sedative-, hypnotic-, or anxiolytic-
induced disorders (e.g., sedative-, hypnotic-, or anxiolytic-induced anxiety disorder, with
onset during withdrawal) beca use the symptoms in the latter disorders predominate in
the clinical presentation and are severe enough to warrant clinical attention.
Anxiety disorders. Recurrence or worsening of an underlying anxiety disorder pro-
duces a syndrome similar to sedative, hypnotic, or anxiolytic withdrawal. Withdrawal
would be suspected with an abrupt reduction in the dosage of a sedative, hypnotic, or anx-
iolytic medication. When a taper is under wa y, distinguishing the withdrawal syndrome
from the underlying anxiety disorder can be difficult. As with alco hol, lingering with-
drawal symptoms (e.g., anxiety, moodiness, and trouble sleeping) can be mistaken for
non-substance/medication-induc ed anxiety or depr essive disorders (e.g., generalized
anxiety disorder).
Other Sedative-, Hypnotic-,
or Anxiolytic-Induced Disorders
The following sedative-, hypnotic-, or anxiolyt ic-induced disorders are described in other
chapters of the manual with disorders with  which they share phenomenology (see the sub-
stance/medication-induced mental disorders in  these chapters): sedative-, hypnotic-, or
anxiolytic-induced psychotic disorder (“Schizophrenia Spectrum and Other Psychotic
Disorders”); sedative-, hypnotic-, or anxiolytic -induced bipolar disord er (“Bipolar and Re-


lated Disorders”); sedative-, hypnotic-, or anxiolytic-induced depressive disorder (“De-
pressive Disorders”); sedative-, hypnotic-,  or anxiolytic-induced anxiety disorder
(“Anxiety Disorders”); sedative-, hypnotic-, or  anxiolytic-induced sleep disorder (“Sleep-
Wake Disorders”); sedative-, hypnotic-, or anxiolytic-induc ed sexual dysfunction (“Sex-
ual Dysfunctions”); and sedative-, hypnotic-, or anxiolytic-induced major or mild neuro-
cognitive disorder (“Neurocog nitive Disorders”). For seda tive, hypnotic, or anxiolytic
intoxication delirium and sedative, hypnotic, or anxiolytic withdrawal delirium, see the
criteria and discussion of delirium in the chapter “Neurocognitive Disorders.” These sed-
ative-, hypnotic-, or anxiolytic-induced disorders are diagnosed inst ead of sedative, hyp-
notic, or anxiolytic intoxication or sedative, hypnotic, or anxiolytic withdrawal only when
the symptoms are sufficiently severe to  warrant independent clinical attention.
Unspecified Sedative-, Hypnotic-,
or Anxiolytic-Related Disorder
292.9 (F13.99)
This category applies to presentations in which symptoms characteristic of a sedative-,
hypnotic-, or anxiolytic-related disorder that cause clinically significant distress or impair-
ment in social, occupational, or other impor tant areas of functioning predominate but do
not meet the full criteria for any specific s edative-, hypnotic-, or anxiolytic-related disorder
or any of the disorders in the substance-related and addictive disorders diagnostic class.


Stimulant Use Disorder 561
Stimulant-Related Disorders
Stimulant Use Disorder
Stimulant Intoxication
Stimulant Withdrawal
Other Stimulant-Induced Disorders
Unspecified Stimulant-Related Disorder
Stimulant Use Disorder
Diagnostic Criteria
A. A pattern of amphetamine-type substance, cocaine, or other stimulant use leading to
clinically significant impairment or distress, as manifested by at least two of the follow-
ing, occurring within a 12-month period:
1. The stimulant is often taken in larger amounts or over a longer period than was in-
tended.
2. There is a persistent desire or unsuccessful efforts to cut down or control stimulant use.
3. A great deal of time is spent in activities necessary to obtain the stimulant, use the
stimulant, or recover from its effects.
4. Craving, or a strong desire or urge to use the stimulant.
5. Recurrent stimulant use resulting in a failure to fulfill major role obligations at work,
school, or home.
6. Continued stimulant use despite having persi stent or recurrent social or interper-
sonal problems caused or exacerbated by the effects of the stimulant.
7. Important social, occupational, or recreat ional activities are given up or reduced be-
cause of stimulant use.
8. Recurrent stimulant use in situations in which it is physically hazardous.
9. Stimulant use is continued despite knowledge of having a persistent or recurrent
physical or psychological problem that is  likely to have been caused or exacerbated
by the stimulant.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of the stimulant to achieve intoxication
or desired effect.
b. A markedly diminished effect with continued use of the same amount of the


b. A markedly diminished effect with continued use of the same amount of the
stimulant.
Note:  This criterion is not considered to be met for those taking stimulant medica-
tions solely under appropriate medical supervision, such as medications for atten-
tion-deficit/hyperactivity disorder or narcolepsy.
11. Withdrawal, as manifested by either of the following:
a. The characteristic withdrawal syndrome fo r the stimulant (refer to Criteria A and
B of the criteria set for stimulant withdrawal, p. 569).
b. The stimulant (or a closely related substance) is taken to relieve or avoid with-
drawal symptoms.


562 Substance-Related and Addictive Disorders
Note:  This criterion is not considered to be met for those taking stimulant medica-
tions solely under appropriate medical supervision, such as medications for atten-
tion-deficit/hyperactivity disorder or narcolepsy.
Specify if:
In early remission:  After full criteria for stimulant use disorder were previously met,
none of the criteria for stimulant use disorder have been met for at least 3 months but
for less than 12 months (with the exception that Criterion A4, “Craving, or a strong de-
sire or urge to use the stimulant,” may be met).
In sustained remission:  After full criteria for stimulant use disorder were previously
met, none of the criteria for stimulant use disorder have been met at any time during a
period of 12 months or longer (with the exception that Criterion A4, “Craving, or a
strong desire or urge to use the stimulant,” may be met).
Specify if:
In a controlled environment:  This additional specifier is used if the individual is in an
environment where access to stimulants is restricted.
Coding based on current severity:  Note for ICD-10-CM codes: If an amphetamine in-
toxication, amphetamine withdrawal, or anot her amphetamine-induced mental disorder is
also present, do not use the codes below for amphetamine use disorder. Instead, the co-
morbid amphetamine use disorder is indicat ed in the 4th character of the amphetamine-
induced disorder code (see the coding note for amphetamine intoxication, amphetamine
withdrawal, or a specific amphetamine-induced m ental disorder). For example, if there is
comorbid amphetamine-type or other stimulant-induced depressive disorder and amphet-


comorbid amphetamine-type or other stimulant-induced depressive disorder and amphet-
amine-type or other stimulant use disorder, only the amphetamine-type or other stimulant-
induced depressive disorder code is given, with the 4th character indicating whether the
comorbid amphetamine-type or other stimulant use disorder is mild, moderate, or severe:
F15.14 for mild amphetamine-type or other st imulant use disorder with amphetamine-type
or other stimulant-induced depressive disorder or F15.24 for a moderate or severe am-
phetamine-type or other stimulant use disorder  with amphetamine-type or other stimulant-
induced depressive disorder. Similarly, if there is comorbid cocaine-induced depressive
disorder and cocaine use disorder, only the cocaine-induced depressive disorder code is
given, with the 4th character indicating whether the comorbid cocaine use disorder is mild,
moderate, or severe: F14.14 for mild cocaine use disorder with cocaine-induced depressive
disorder or F14.24 for a moderate or severe cocaine use disorder with cocaine-induced
depressive disorder.
Specify current severity:
Mild:  Presence of 2–3 symptoms.
305.70 (F15.10)  Amphetamine-type substance
305.60 (F14.10)  Cocaine
305.70 (F15.10)  Other or unspecified stimulant
Moderate: Presence of 4–5 symptoms.
304.40 (F15.20)  Amphetamine-type substance
304.20 (F14.20)  Cocaine
304.40 (F15.20)  Other or unspecified stimulant
Severe:  Presence of 6 or more symptoms.
304.40 (F15.20)  Amphetamine-type substance
304.20 (F14.20)  Cocaine


304.20 (F14.20)  Cocaine
304.40 (F15.20)  Other or unspecified stimulant


Stimulant Use Disorder 563
Specifiers
“In a controlled environment” app lies as a further specifier of remission if the individual is
both in remission and in a controlled environm ent (i.e., in early remission in a controlled
environment or in sustained remission in a controlled environment). Examples of these
environments are closely supe rvised and substanc e-free jails, therapeutic communities,
and locked hospital units.
Diagnostic Features
The amphetamine and amphetamine-type stimul ants include substances with a substi-
tuted-phenylethylamine struct ure, such as amphetamine, dextroamphetamine, and meth-
amphetamine. Also included are those substanc es that are structura lly different but have
similar effects, such as methylphenidate. These substances are usually taken orally or in-
travenously, although methamphetamine is also  taken by the nasal route. In addition to
the synthetic amphetamine-type compounds, th ere are naturally occurring, plant-derived
stimulants such as khât.  Amphetamines and other stimulants  may be obtained by prescrip-
tion for the treatment of obesity, attention-deficit/hyperactivity disorder, and narcolepsy.
Consequently, prescribed stimul ants may be diverted into the illegal market. The effects of
amphetamines and amphetamine-like drugs are sim ilar to those of cocaine, such that the
criteria for stimulant use disord er are presented here as a sing le disorder with the ability to
specify the particular stimulant used by the individual. Cocaine may be consumed in sev-
eral preparations (e.g., coca leaves, coca pa ste, cocaine hydrochloride, and cocaine alka-
loids such as freebase and crack) that differ in  potency because of varying levels of purity


and speed of onset. However, in all forms of the substance, cocaine is the active ingredient.
Cocaine hydrochloride powder is usually “snorted” through the nostrils or dissolved in
water and injected intravenously.
Individuals exposed to amphetamine-type stimulants or cocaine can develop stimu-
lant use disorder as rapidly as  1 week, although the onset is  not always th is rapid. Re-
gardless of the route of administration, tole rance occurs with repeated use. Withdrawal
symptoms, particularly hypersomnia, increa sed appetite, and dysphoria, can occur and
can enhance craving. Most individuals with stimulant use disorder have experienced tol-
erance or withdrawal.
Use patterns and course are similar for di sorders involving amphetamine-type stimu-
lants and cocaine, as both substances are po tent central nervous system stimulants with
similar psychoactive and sympathomimetic effects. Amphetamine-type stimulants are
longer acting than cocaine and thus are used fewer times per day. Usage may be chronic or
episodic, with binges punctuated by brief no n-use periods. Aggressive or violent behavior
is common when high doses are smoked, ingested, or administered intravenously. Intense
temporary anxiety resembling panic disorder or generalized anxiety disorder, as well as
paranoid ideation and psychotic episodes that resemble schizophrenia, is seen with high-
dose use.
Withdrawal states are associated with temporary but intense depressive symptoms that
can resemble a major depressive episode; the depressive symptoms usually resolve within
1 week. Tolerance to amphetamine -type stimulants develops and leads to escalation of the
dose. Conversely, some users of amphetami ne-type stimulants develop sensitization,
characterized by enhanced effects.
Associated Features Supporting Diagnosis


characterized by enhanced effects.
Associated Features Supporting Diagnosis
When injected or smoked, stimulants typica lly produce an instant feeling of well-being,
confidence, and euphoria. Dramatic behavior al changes can rapidly develop with stimu-
lant use disorder. Chaotic behavior, social is olation, aggressive behavior, and sexual dys-
function can result from long -term stimulant use disorder.


564 Substance-Related and Addictive Disorders
Individuals with acute intoxication may pr esent with rambling speech, headache, tran-
sient ideas of reference, and tinnitus. There may be paranoid ideati on, auditory halluci-
nations in a clear sensorium, and tactile hallucinations, which the individual usually
recognizes as drug effects. Thre ats or acting out of aggressive  behavior may occur. Depres-
sion, suicidal ideation, irritability, anhedonia,  emotional lability, or disturbances in atten-
tion and concentration commonly occur during withdrawal. Mental disturbances associated
with cocaine use usually resolve hours to days  after cessation of use but can persist for
1 month. Physiological changes during stimulant withdrawal ar e opposite to those of the
intoxication phase, sometimes including bradycardia. Temporary depressive symptoms
may meet symptomatic and duration criteria for major depressive episode. Histories con-
sistent with repeated panic attacks, social an xiety disorder (social phobia)–like behavior,
and generalized anxiety–like syndromes are co mmon, as are eating disorders. One ex-
treme instance of stimulant toxicity is st imulant-induced psychotic disorder, a disorder
that resembles schizophrenia, with delusions and hallucinations.
Individuals with stimulant use disorder of ten develop conditioned responses to drug-
related stimuli (e.g., craving on seeing an y white powderlike substance). These responses
contribute to relapse, are difficult to extinguish, and persist after detoxification.
Depressive symptoms with su icidal ideation or behavior  can occur and are generally
the most serious problems seen during stimulant withdrawal.
Prevalence
Stimulant use disorder: amphetamine-type stimulants. Estimated 12-month prevalence


Stimulant use disorder: amphetamine-type stimulants. Estimated 12-month prevalence
of amphetamine-type stimulant use disorder in the United States is 0.2% among 12- to 17-
year-olds and 0.2% among individuals 18 year s and older. Rates are similar among adult
males and females (0.2%), but among 12- to 17- year-olds, the rate for females (0.3%) is
greater than that for males (0.1%). Intravenou s stimulant use has a male-to-female ratio of
3:1 or 4:1, but rates are more balanced amon g non-injecting users, with males representing
54% of primary treatment admissions. Twelve -month prevalence is greater among 18- to
29-year-olds (0.4%) compared with 45- to 64-ye ar-olds (0.1%). For 12- to 17-year-olds, rates
are highest among whites and African Americans (0.3%) compared with Hispanics (0.1%)
and Asian Americans and Pacific Islanders (0.01%), with amphetamine-type stimulant use
disorder virtually absent among Native Americans. Among adults, rates are highest among
Native Americans and Alaska Natives (0.6%) compared with whites (0.2%) and Hispanics
(0.2%), with amphetamine-type stimulant use disorder virtually absent among African
Americans and Asian Americans and Pacific Islanders. Past-year nonprescribed use of
prescription stimulants occu rred among 5%–9% of children  through high school, with
5%–35% of college-age persons reporting past-year use.
Stimulant use disorder: cocaine. Estimated 12-month prevalence of cocaine use disorder


Stimulant use disorder: cocaine. Estimated 12-month prevalence of cocaine use disorder
in the United States is 0.2% among 12- to 17- year-olds and 0.3% amon g individuals 18 years
and older. Rates are higher among males (0 .4%) than among females (0.1%). Rates are
highest among 18- to 29-year-olds (0.6%) and lo west among 45- to 64-year-olds (0.1%). Among
adults, rates are greater among Native Amer icans (0.8%) compared with African Ameri-
cans (0.4%), Hispanics (0.3%), whites (0.2%) , and Asian Americans and Pacific Islanders
(0.1%). In contrast, for 12- to 17-year-olds, rates are similar among Hispanics (0.2%), whites
(0.2%), and Asian Americans and Pacific Islanders (0.2%); and lower among African Amer-
icans (0.02%); with cocaine use disorder vi rtually absent among Native Americans and
Alaska Natives.
Development and Course
Stimulant use disorders occur throughout all levels of society and are more common among


Alaska Natives.
Development and Course
Stimulant use disorders occur throughout all levels of society and are more common among
individuals ages 12–25 years compared with indi viduals 26 years and olde r. First regular use


Stimulant Use Disorder 565
among individuals in treatment occurs, on average, at approximately age 23 years. For pri-
mary methamphetamine–primary treatment admissions, the average age is 31 years.
Some individuals begin stimulant use to control weight or to improve performance in
school, work, or athlet ics. This includes obtaining medications such as methylphenidate or
amphetamine salts prescribed to others for the treatment of attention-deficit/hyperac-
tivity disorder. Stimulant use disorder can develop rapidly with intravenous or smoked
administration; among primary admissions fo r amphetamine-type stimulant use, 66% re-
ported smoking, 18% reported inje cting, and 10% reported snorting.
Patterns of stimulant administration include episodic or daily (or almost daily) use.
Episodic use tends to be separated by 2 or more days of non-use (e.g., intense use over a
weekend or on one or more weekdays). “Bin ges” involve continuous high-dose use over
hours or days and are often associated with  physical dependence. Binges usually termi-
nate only when stimulant supplies are deplet ed or exhaustion ensues. Chronic daily use
may involve high or low doses, often with an increase in dose over time.
Stimulant smoking and intravenous use are a ssociated with rapid progression to se-
vere-level stimulant use disorder, often occu rring over weeks to months. Intranasal use of
cocaine and oral use of amphetamine-type stim ulants result in more  gradual progression
occurring over months to years. With continui ng use, there is a diminution of pleasurable
effects due to tolerance and an increase in dysphoric effects.
Risk and Prognostic Factors


Risk and Prognostic Factors
Temperamental. Comorbid bipolar disorder, schizophrenia, antisocial personality disor-
der, and other substance use disorders are risk  factors for developing stimulant use disorder
and for relapse to cocaine use in treatment samp les. Also, impulsivity and similar personality
traits may affect treatment outcomes. Childhood  conduct disorder and adult antisocial per-
sonality disorder are associated with the la ter development of stim ulant-related disorders.
Environmental. Predictors of cocaine use among teenagers include prenatal cocaine ex-
posure, postnatal cocaine use by parents, and exposure to  community violence during
childhood. For youths, especially females, risk  factors include living in an unstable home
environment, having a psychiatric conditio n, and associating with dealers and users.
Culture-Related Diagnostic Issues
Stimulant use–attendant disorders affect all ra cial/ethnic, socioeconomic, age, and gender
groups. Diagnostic issues may be  related to societal consequenc es (e.g., arrest, school sus-
pensions, employment suspension). Despite sm all variations, cocaine and other stimulant
use disorder diagnostic criteria perform eq ually across gender and race/ethnicity groups.
Chronic use of cocaine impairs cardiac left ventricular function in African Americans.
Approximately 66% of individuals admitt ed for primary methamphetamine/amphet-
amine-related disorders are non-Hispanic whit e, followed by 21% of Hispanic origin, 3%
Asian and Pacific Islander, and 3% non-Hispanic black.
Diagnostic Markers
Benzoylecgonine, a metabolite of cocaine, typi cally remains in the urine for 1–3 days after
a single dose and may be present for 7–12 days in individuals using repeated high doses.


Mildly elevated liver function tests can be pr esent in cocaine injectors or users with con-
comitant alcohol use. There are no neurobiological markers of diagnostic utility. Discon-
tinuation of chronic cocaine use may be asso ciated with electroencephalographic changes,
suggesting persistent abnormalit ies; alterations in secretion patterns of prolactin; and
downregulation of dopamine receptors.
Short-half-life amphetamine-type stim ulants (MDMA [3,4-methylenedioxy- N-methyl-
amphetamine], methamphetamine) can be detected  for 1–3 days, and possibly up to 4 days


566 Substance-Related and Addictive Disorders
depending on dosage and metabolism. Hair sampl es can be used to detect presence of am-
phetamine-type stimulants for up to 90 days. Other laboratory findings, as well as physical
findings and other medical conditions (e.g., weight loss, malnutrition; poor hygiene), are
similar for both cocaine and amphet amine-type stimulant use disorder.
Functional Consequences of  Stimulant Use Disorder
Various medical conditions may occur dependin g on the route of administration. Intrana-
sal users often develop sinusitis, irritation, bl eeding of the nasal mucosa, and a perforated
nasal septum. Individuals who smoke the drugs are at increased risk for respiratory prob-
lems (e.g., coughing, bronchitis, and pneumonitis). Injectors have puncture marks and
“tracks,” most commonly on their forearms. Ri sk of HIV infection increases with frequent
intravenous injections and unsafe sexual acti vity. Other sexually transmitted diseases,
hepatitis, and tuberculosis and other lung infections are also seen . Weight loss and mal-
nutrition are common.
Chest pain may be a common symptom during stimulant intoxication. Myocardial in-
farction, palpitations and arrhythmias, sudden  death from respiratory or cardiac arrest,
and stroke have been associated with stimulant use among young and otherwise healthy
individuals. Seizures can occur with stimulant use. Pneumothorax can result from per-
forming Valsalva-like maneuvers done to better absorb inhaled smoke. Traumatic injuries
due to violent behavior are common among in dividuals trafficking drugs. Cocaine use is
associated with irregularities in placental bl ood flow, abruptio placentae, premature labor
and delivery, and an increased prevalence of infants with very low birth weights.


and delivery, and an increased prevalence of infants with very low birth weights.
Individuals with stimulant use disorder may become involved in theft, prostitution, or
drug dealing in order to acquire drugs or money for drugs.
Neurocognitive impairment is common am ong methamphetamine users. Oral health
problems include “meth mouth” with gum dise ase, tooth decay, and mouth sores related
to the toxic effects of smoking the drug and to bruxism while intoxicated. Adverse pulmo-
nary effects appear to be le ss common for amphetamine-type  stimulants because they are
smoked fewer times per day. Emergency department visits are common for stimulant-re-
lated mental disorder symptoms, injury, skin infections, and dental pathology.
Differential Diagnosis
Primary mental disorders. Stimulant-induced disorders may resemble primary mental
disorders (e.g., major depressive disorder) (for discussion of th is differential diagnosis, see
“Stimulant Withdrawal”). The mental disturbanc es resulting from the effects of stimulants
should be distinguished from  the symptoms of schizophrenia; depressive and bipolar dis-
orders; generalized anxiety disorder; and panic disorder.
Phencyclidine intoxication. Intoxication with phencyclidine (“PCP” or “angel dust”) or
synthetic “designer drugs” such as mephedrone (known by different names, including
“bath salts”) may cause a similar clinical pict ure and can only be di stinguished from stim-
ulant intoxication by the presence of coca ine or amphetamine-type substance metabolites
in a urine or plasma sample.
Stimulant intoxication and withdrawal. Stimulant intoxication and withdrawal are dis-
tinguished from the other stimulant-induced di sorders (e.g., anxiety disorder, with onset


during intoxication) because the symptoms in the latter disorders predominate the clinical
presentation and are severe enough to warrant independent clinical attention.
Comorbidity
Stimulant-related disorders often co-occur wi th other substance use disorders, especially
those involving substances with  sedative properties, which are often taken to reduce in-


Stimulant Intoxication 567
somnia, nervousness, and other unpleasant side effects. Cocaine users often use alcohol,
while amphetamine-type stimulant users ofte n use cannabis. Stimulant use disorder may
be associated with posttraumatic stress diso rder, antisocial personality disorder, atten-
tion-deficit/hyperacti vity disorder, and gambling di sorder. Cardiopulmonary problems
are often present in individuals seeking treatm ent for cocaine-related problems, with chest
pain being the most common. Medical problems occur in response to adulterants used as
“cutting” agents. Cocaine users who ingest co caine cut with levamisole, an antimicrobial
and veterinary medication, may experience agranulocytosis and febrile neutropenia.
Stimulant Intoxication
Diagnostic Criteria
A. Recent use of an amphetamine-type substance, cocaine, or other stimulant.
B. Clinically significant problematic behavioral or psychological changes (e.g., euphoria
or affective blunting; changes in sociability; hypervigilance; interpersonal sensitivity;
anxiety, tension, or anger; stereotyped behaviors; impaired judgment) that developed
during, or shortly after, use of a stimulant.
C. Two (or more) of the following signs or symptoms, developing during, or shortly after,
stimulant use:
1. Tachycardia or bradycardia.
2. Pupillary dilation.
3. Elevated or lowered blood pressure.
4. Perspiration or chills.
5. Nausea or vomiting.
6. Evidence of weight loss.
7. Psychomotor agitation or retardation.
8. Muscular weakness, respiratory depression , chest pain, or cardiac arrhythmias.


8. Muscular weakness, respiratory depression , chest pain, or cardiac arrhythmias.
9. Confusion, seizures, dyskinesias, dystonias, or coma.
D. The signs or symptoms are not attributable to another medical condition and are not
better explained by another mental disorder, including intoxication with another sub-
stance.
Specify the specific intoxicant (i.e., amphetamine-type substance, cocaine, or other
stimulant).
Specify if:
With perceptual disturbances:  This specifier may be noted when hallucinations with
intact reality testing or auditory, visual, or tactile illusions occur in the absence of a de-
lirium.
Coding note:  The ICD-9-CM code is 292.89.  The ICD-10-CM code depends on whether
the stimulant is an amphetamine, cocaine, or other stimulant; whether there is a comorbid
amphetamine, cocaine, or other stimulant use disorder; and whether or not there are per-
ceptual disturbances.
For amphetamine, cocaine, or other stimulant intoxication, without perceptual dis-
turbances:  If a mild amphetamine or other stimulant use disorder is comorbid, the ICD-
10-CM code is F15.129, and if a moderate or severe amphetamine or other stimulant use
disorder is comorbid, the ICD-10-CM code is F15.229.  If there is no comorbid amphet-
amine or other stimulant use disorder, then the ICD-10-CM code is F15.929. Similarly, if
a mild cocaine use disorder is comorbid, the ICD-10-CM code is F14.129,  and if a mod-


erate or severe cocaine use disorder is comorbid, the ICD-10-CM code is F14.229. If
there is no comorbid cocaine use disorder, then the ICD-10-CM code is F14.929.


568 Substance-Related and Addictive Disorders
For amphetamine, cocaine, or other stimulant intoxication, with perceptual distur-
bances:  If a mild amphetamine or other stimulant use disorder is comorbid, the ICD-10-
CM code is F15.122, and if a moderate or severe amphetamine or other stimulant use
disorder is comorbid, the ICD-10-CM code is F15.222.  If there is no comorbid amphet-
amine or other stimulant use disorder, then the ICD-10-CM code is F15.922. Similarly, if
a mild cocaine use disorder is comorbid, the ICD-10-CM code is F14.122,  and if a mod-
erate or severe cocaine use disorder is comorbid, the ICD-10-CM code is F14.222. If
there is no comorbid cocaine use disorder, then the ICD-10-CM code is F14.922.
Diagnostic Features
The essential feature of stimulant intoxicati on, related to amphetamine-type stimulants
and cocaine, is the presence of clinically significant behavioral or psychological changes
that develop during, or shortly after, use of stimulants (Criteria A and B). Auditory hallu-
cinations may be prominent, as may paranoid  ideation, and these symptoms must be dis-
tinguished from an independent psychotic disorder such as schizophrenia. Stimulant
intoxication usually begins with a “high” f eeling and includes one or more of the follow-
ing: euphoria with enhanced vigor, gregarious ness, hyperactivity, restlessness, hypervig-
ilance, interpersonal sensitivity, talkativenes s, anxiety, tension, alertness, grandiosity,


stereotyped and repetitive behavior, anger, impaired judgment, and, in the case of chronic
intoxication, affective blunting with fatigue or sadness and social withdrawal. These be-
havioral and psychological changes are acco mpanied by two or more of the following
signs and symptoms that develop during or sh ortly after stimulant us e: tachycardia or bra-
dycardia; pupillary dilation; el evated or lowered blood pressu re; perspiration or chills;
nausea or vomiting; evidence of weight loss ; psychomotor agitation or retardation; mus-
cular weakness, respiratory depression, chest pain, or card iac arrhythmias; and confu-
sion, seizures, dyskinesias, dystonias, or coma  (Criterion C). Intoxi cation, either acute or
chronic, is often associated with impaired so cial or occupational functioning. Severe in-
toxication can lead to convulsions, cardiac arrhythmias, hyperpyrexia, and death. For the
diagnosis of stimulant intoxica tion to be made, the symptoms must not be attributable
to another medical condition and not better explained by anot her mental disorder (Crite-
rion D). While stimulant intoxica tion occurs in individuals with stimulant use disorders, in-
toxication is not a criterion for stimulant us e disorder, which is confirmed by the presence
of two of the 11 diagnostic criteria for use disorder.
Associated Features Supporting Diagnosis
The magnitude and direction of the behavioral  and physiological changes depend on many
variables, including the dose used and the ch aracteristics of the individual using the sub-
stance or the context (e.g., tolerance, rate of absorption, chronicity of use, context in which


it is taken). Stimulant effects such as eupho ria, increased pulse an d blood pressure, and
psychomotor activity are most commonly seen . Depressant effects such as sadness, brady-
cardia, decreased blood pressure, and decr eased psychomotor activity are less common
and generally emerge only wi th chronic high-dose use.
Differential Diagnosis
Stimulant-induced disorders. Stimulant intoxication is distinguished from the other
stimulant-induced disorders (e.g., stimulant- induced depressive di sorder, bipolar disor-
der, psychotic disorder, anxiety disorder) because the severity of the intoxication symp-
toms exceeds that associated with the stim ulant-induced disorders, and the symptoms
warrant independent clinical attention. Stimulant intoxication delirium would be distin-
guished by a disturbance in level of  awareness and change in cognition.


Stimulant Withdrawal 569
Other mental disorders. Salient mental disturbances associated with stimulant intoxi-
cation should be distinguished from the symptoms of schizophrenia, paranoid type; bi-
polar and depressive disorders; generalized  anxiety disorder; and panic disorder as
described in DSM-5.
Stimulant Withdrawal
Diagnostic Criteria
A. Cessation of (or reduction in) prolonged amphetamine-type substance, cocaine, or
other stimulant use.
B. Dysphoric mood and two (or more) of the following physiological changes, developing
within a few hours to several days after Criterion A:
1. Fatigue.
2. Vivid, unpleasant dreams.
3. Insomnia or hypersomnia.
4. Increased appetite.
5. Psychomotor retardation or agitation.
C. The signs or symptoms in Criterion B cause clinically significant distress or impairment
in social, occupational, or other important areas of functioning.
D. The signs or symptoms are not attributable to another medical condition and are not
better explained by another mental disorder, including intoxication or withdrawal from
another substance.
Specify the specific substance that causes the withdrawal syndrome  (i.e., amphet-
amine-type substance, cocaine, or other stimulant).
Coding note: The ICD-9-CM code is 292.0. The ICD-10-CM code depends on whether
the stimulant is an amphetamine, cocaine, or other stimulant. The ICD-10-CM code for
amphetamine or an other stimulant withdrawal is F15.23, and the ICD-10-CM for cocaine
withdrawal is F14.23. Note that the ICD-10-CM code indicates the comorbid presence of
a moderate or severe amphetamine, cocaine, or other stimulant use disorder, reflecting


a moderate or severe amphetamine, cocaine, or other stimulant use disorder, reflecting
the fact that amphetamine, cocaine, or other stimulant withdrawal can only occur in the
presence of a moderate or severe amphetamine, cocaine, or other stimulant use disorder.
It is not permissible to code a comorbid mild amphetamine, cocaine, or other stimulant use
disorder with amphetamine, cocaine, or other stimulant withdrawal.
Diagnostic Features
The essential feature of stimulant withdrawal is the presence of a characteristic with-
drawal syndrome that develops within a few hours to several days after the cessation of
(or marked reduction in) stimulant use (genera lly high dose) that has been prolonged (Cri-
terion A). The withdrawal syndrome is char acterized by the development of dysphoric
mood accompanied by two or more of the fo llowing physiological changes: fatigue, vivid
and unpleasant dreams, insomnia or hypers omnia, increased appetite, and psychomotor
retardation or agitation (Crite rion B). Bradycardia is often present and is a reliable mea-
sure of stimulant withdrawal.
Anhedonia and drug craving can often be pres ent but are not part of the diagnostic cri-
teria. These symptoms cause clinically signif icant distress or impairment in social, occu-
pational, or other important areas of functioning (Criterion C). The symptoms must not be
attributable to another medica l condition and are not better explained by another mental
disorder (Criterion D).


570 Substance-Related and Addictive Disorders
Associated Features Supporting Diagnosis
Acute withdrawal symptoms (“a crash”) are ofte n seen after periods of repetitive high-dose
use (“runs” or “binges”). These periods are char acterized by intense and unpleasant feelings of
lassitude and depression and increased appetite, generally requiring several days of rest and
recuperation. Depressive symptoms with suicidal  ideation or behavior can occur and are gen-
erally the most serious problems seen during “crashing” or other forms of stimulant with-
drawal. The majority of individuals with st imulant use disorder experience a withdrawal
syndrome at some point, and virtually all in dividuals with the diso rder report tolerance.
Differential Diagnosis
Stimulant use disorder and other stimulant-induced disorders. Stimulant withdrawal
is distinguished from stimulan t use disorder and from the other stimulant-induced disor-
ders (e.g., stimulant-induced intoxication delirium, depressi ve disorder, bipolar disorder,
psychotic disorder, anxiety disorder, sexual  dysfunction, sleep disorder) because the
symptoms of withdrawal predominate the clin ical presentation and are severe enough to
warrant independent clinical attention.
Other Stimulant-Induced Disorders
The following stimulant-induced disorders (w hich include amphetamine-, cocaine-, and
other stimulant–induced disorder s) are described in other chapters of the manual with dis-
orders with which they share phenomenol ogy (see the substance/medication-induced
mental disorders in these chapters): stimulan t-induced psychotic disorder (“Schizophrenia
Spectrum and Other Psychotic Disorders”); st imulant-induced bipolar disorder (“Bipolar
and Related Disorders”); stimulant-induced de pressive disorder (“De pressive Disorders”);


and Related Disorders”); stimulant-induced de pressive disorder (“De pressive Disorders”);
stimulant-induced anxiety disorder (“Anxiet y Disorders”); stimulant-induced obsessive-
compulsive disorder (“Obsessive-Compulsive and Related Disorders”); stimulant-induced
sleep disorder (“Sleep-Wake Disorders”); and stimulant-induced sexual dysfunction (“Sex-
ual Dysfunctions”). For stimulant intoxication  delirium, see the criteria and discussion of
delirium in the chapter “Neurocognitive Disorders.” These stimulant-induced disorders
are diagnosed instead of stimulant intoxication or stimulant withdrawal only when the
symptoms are sufficiently severe to wa rrant independent clinical attention.
Unspecified Stimulant-Related Disorder
This category applies to presentations in which symptoms characteristic of a stimulant-
related disorder that cause clinically significant distress or impairment in social, occupa-
tional, or other important areas of functioning predominate but do not meet the full criteria
for any specific stimulant-related disorder or any of the disorders in the substance-related
and addictive disorders diagnostic class.
Coding note: The ICD-9-CM code is 292.9. The ICD-10-CM code depends on whether
the stimulant is an amphetamine, cocaine, or another stimulant. The ICD-10-CM code for
an unspecified amphetamine- or other stimulant-related disorder is F15.99.  The ICD-10-
CM code for an unspecified cocaine-related disorder is F14.99.


Tobacco Use Disorder 571
Tobacco-Related Disorders
Tobacco Use Disorder
Tobacco Withdrawal
Other Tobacco-Ind uced Disorders
Unspecified Tobacco-Related Disorder
Tobacco Use Disorder
Diagnostic Criteria
A. A problematic pattern of tobacco use leading to clinically significant impairment or dis-
tress, as manifested by at least two of the following, occurring within a 12-month period:
1. Tobacco is often taken in larger amounts or over a longer period than was intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control tobacco use.
3. A great deal of time is spent in activities necessary to obtain or use tobacco.
4. Craving, or a strong desire or urge to use tobacco.
5. Recurrent tobacco use resulting in a failure to fulfill major role obligations at work,
school, or home (e.g., interference with work).
6. Continued tobacco use despite having persistent or recurrent social or interper-
sonal problems caused or exacerbated by the effects of tobacco (e.g., arguments
with others about tobacco use).
7. Important social, occupational, or recreat ional activities are given up or reduced be-
cause of tobacco use.
8. Recurrent tobacco use in situations in which it is physically hazardous (e.g., smok-
ing in bed).
9. Tobacco use is continued despite knowledge of having a persistent or recurrent
physical or psychological problem that is  likely to have been caused or exacerbated
by tobacco.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of tobacco to achieve the desired effect.
b. A markedly diminished effect with conti nued use of the same amount of tobacco.
11. Withdrawal, as manifested by either of the following:


11. Withdrawal, as manifested by either of the following:
a. The characteristic withdraw al syndrome for tobacco (refer to Criteria A and B of
the criteria set for tobacco withdrawal).
b. Tobacco (or a closely related substance, such as nicotine) is taken to relieve or
avoid withdrawal symptoms.
Specify if:
In early remission:  After full criteria for tobacco use disorder were previously met,
none of the criteria for tobacco use disorder have been met for at least 3 months but
for less than 12 months (with the exception that Criterion A4, “Craving, or a strong de-
sire or urge to use tobacco,” may be met).
In sustained remission:  After full criteria for tobacco use disorder were previously
met, none of the criteria for tobacco use disorder have been met at any time during a
period of 12 months or longer (with the exception that Criterion A4, “Craving, or a
strong desire or urge to use tobacco,” may be met).


572 Substance-Related and Addictive Disorders
Specify if:
On maintenance therapy: The individual is taking a long-term maintenance medica-
tion, such as nicotine replacement medication, and no criteria for tobacco use disorder
have been met for that class of medication (except tolerance to, or withdrawal from,
the nicotine replacement medication).
In a controlled environment:  This additional specifier is used if the individual is in an
environment where access to tobacco is restricted.
Coding based on current severity:  Note for ICD-10-CM codes: If a tobacco withdrawal or
tobacco-induced sleep disorder is also present, do not use the codes below for tobacco use
disorder. Instead, the comorbid tobacco use disorder is indicated in the 4th character of the
tobacco-induced disorder code (see the coding note for tobacco withdrawal or tobacco-
induced sleep disorder). For example, if ther e is comorbid tobacco-induced sleep disorder and
tobacco use disorder, only the tobacco-induced sleep disorder code is given, with the 4th char-
acter indicating whether the comorbid tobacco use disorder is moderate or severe: F17.208
for moderate or severe tobacco use disorder with tobacco-induced sleep disorder. It is not per-
missible to code a comorbid mild tobacco use disorder with a tobacco-induced sleep disorder.
Specify current severity:
305.1 (Z72.0) Mild:  Presence of 2–3 symptoms.
305.1 (F17.200) Moderate: Presence of 4–5 symptoms.
305.1 (F17.200) Severe:  Presence of 6 or more symptoms.
Specifiers
“On maintenance therapy” applies as a further specifier to individuals being maintained on
other tobacco cessation me dication (e.g., bupropio n, varenicline) and as  a further specifier of


remission if the individual is both in remissi on and on maintenance therapy. “In a controlled
environment” applies as a further specifier of re mission if the individual is both in remission
and in a controlled environment (i.e., in early remission in a controlled environment or in sus-
tained remission in a controlled environment). Examples of these environments are closely su-
pervised and substance-free jails, therapeutic communities, and locked hospital units.
Diagnostic Features
Tobacco use disorder is common among individu als who use cigarettes and smokeless to-
bacco daily and is uncommon among individuals who do not use tobacco daily or who use
nicotine medications. Tolerance to tobacco is exemplified by the disappearance of nausea
and dizziness after repeated intake and with a more intense effect of tobacco the first time
it is used during the day. Cessation of to bacco use can produce a well-defined withdrawal
syndrome. Many individuals with tobacco use disorder use tobacco to relieve or to avoid
withdrawal symptoms (e.g., after being in a sit uation where use is restricted). Many indi-
viduals who use tobacco have tobacco-relat ed physical symptoms or diseases and con-
tinue to smoke. The large majority report crav ing when they do not smoke for several hours.
Spending excessive time usin g tobacco can be exemplified by chain-smoking (i.e., smok-
ing one cigarette after another with no time between cigarettes). Because tobacco sources
are readily and legally available, and because nicotine intoxication is very rare, spending a
great deal of time attempting to procure toba cco or recovering from its effects is uncom-
mon. Giving up important social, occupational , or recreational acti vities can occur when
an individual forgoes an activity because it occurs in tobacco use–restricted areas. Use of


an individual forgoes an activity because it occurs in tobacco use–restricted areas. Use of
tobacco rarely results in failu re to fulfill major role obligat ions (e.g., in terference with
work, interference with home obligations), bu t persistent social or interpersonal problems
(e.g., having arguments with others about to bacco use, avoiding social situations because
of others’ disapproval of tobacco use) or use that is physically hazardous (e.g., smoking in


Tobacco Use Disorder 573
bed, smoking around flammable chemicals) oc cur at an intermediate prevalence. Although
these criteria are less often endorsed by toba cco users, if endorsed, they can indicate a
more severe disorder.
Associated Features Supporting Diagnosis
Smoking within 30 minutes of waking, smoking daily, smoking more cigarettes per day,
and waking at night to smoke are associated with tobacco use di sorder. Environmental
cues can evoke craving and withdrawal. Serious medical conditions, such as lung and
other cancers, cardiac and pulmonary disease , perinatal problems, cough, shortness of
breath, and accelerated skin aging, often occur.
Prevalence
Cigarettes are the most commonly used toba cco product, representing over 90% of to-
bacco/nicotine use. In the United States, 57% of adults have never been smokers, 22% are
former smokers, and 21% are current smokers.  Approximately 20% of current U.S. smok-
ers are nondaily smokers. The prevalence of sm okeless tobacco use is less than 5%, and the
prevalence of tobacco use in pipes and cigars is less than 1%.
DSM-IV nicotine dependence criteria can be used to estimate the prevalence of tobacco
use disorder, but since they are a subset of to bacco use disorder criteria, the prevalence of
tobacco use disorder will be somewhat greater. The 12-month prevalence of DSM-IV nic-
otine dependence in the United States is 13% among adults age 18 years and older. Rates
are similar among adult males (14%) and fe males (12%) and decline in age from 17%
among 18- to 29-year-old s to 4% among individuals age 65 years and older. The prevalence


of current nicotine dependence is greate r among Native American and Alaska Natives
(23%) than among whites (14%) but is less am ong African Americans (10%), Asian Amer-
icans and Pacific Islanders (6%), and Hispan ics (6%). The prevalence among current daily
smokers is approximately 50%.
In many developing nations, the prevalence  of smoking is much greater in males than
in females, but this is not the case in develope d nations. However, ther e often is a lag in the
demographic transition such that smoking increases in females at a later time.
Development and Course
The majority of U.S. adolescents experiment with tobacco use, and by age 18 years, about
20% smoke at least monthly. Most of these in dividuals become daily tobacco users. Initi-
ation of smoking after age 21 years is rare. In general, some of the to bacco use disorder cri-
teria symptoms occur soon after beginning to bacco use, and many individuals’ pattern of
use meets current tobacco use diso rder criteria by late adolescence. More than 80% of in-
dividuals who use tobacco atte mpt to quit at some time, but 60% relapse within 1 week
and less than 5% remain abstinent for life . However, most indivi duals who use tobacco
make multiple attempts such that one-half of  tobacco users eventually abstain. Individuals
who use tobacco who do quit usually do not do  so until after age 30 years. Although non-
daily smoking in the United States was previ ously rare, it has beco me more prevalent in
the last decade, especially among younger individuals who use tobacco.
Risk and Prognostic Factors
Temperamental. Individuals with externalizing pers onality traits are more likely to


Temperamental. Individuals with externalizing pers onality traits are more likely to
initiate tobacco use. Children with attentio n-deficit/hyperactivity disorder or conduct
disorder, and adults with depr essive, bipolar, anxiety, pers onality, psychotic, or other
substance use disorders, are at higher risk of starting and continuing tobacco use and of to-
bacco use disorder.


574 Substance-Related and Addictive Disorders
Environmental. Individuals with low incomes and low educational levels are more likely
to initiate tobacco use an d are less likely to stop.
Genetic and physiological. Genetic factors contribute to the onset of tobacco use, the
continuation of tobacco use, and the developm ent of tobacco use disorder, with a degree of
heritability equivalent to that observed with other substance use disorders (i.e., about
50%). Some of this risk is specific to toba cco, and some is common with the vulnerability to
developing any substance use disorder.
Culture-Related Diagnostic Issues
Cultures and subcultures vary widely in their acceptance of the use of tobacco. The prev-
alence of tobacco use declined in the United  States from the 1960s through the 1990s, but
this decrease has been less evident in Africa n American and Hispanic populations. Also,
smoking in developing countries is more prev alent than in developed nations. The degree
to which these cultural differences are due to  income, education, and tobacco control ac-
tivities in a country is unclear. Non-Hispan ic white smokers appear to be more likely to
develop tobacco use disorder than are smoker s. Some ethnic differences may be biologi-
cally based. African American males tend to have higher nicotine blood levels for a given
number of cigarettes, and this might contribute  to greater difficulty in quitting. Also, the
speed of nicotine metabolism is significantly different for whites compared with African
Americans and can vary by genotypes associated with ethnicities.
Diagnostic Markers
Carbon monoxide in the breath, and nicotine and its metabolite cotinine in blood, saliva, or
urine, can be used to measure the extent of cu rrent tobacco or nicotine use; however, these
are only weakly related to tobacco use disorder.


are only weakly related to tobacco use disorder.
Functional Consequences of Tobacco Use Disorder
Medical consequences of tobacco use often be gin when tobacco users are in their 40s and
usually become progressively more debilitat ing over time. One-half of smokers who do
not stop using tobacco will die early from a tobacco-related illness, and smoking-related
morbidity occurs in more than one-half of tobacco users. Most medical conditions result
from exposure to carbon monoxide, tars, an d other non-nicotine components of tobacco.
The major predictor of reversibility is duration of smoking. Secondhand smoke increases
the risk of heart disease and cancer by 30%. Long-term use of nicotine medications does
not appear to cause medical harm.
Comorbidity
The most common medical diseases from smoking are cardiovascular illnesses, chronic
obstructive pulmonary disease, and cancers. Smoking also increases perinatal problems,
such as low birth weight and miscarriage. Th e most common psychiat ric comorbidities are
alcohol/substance, depressive, bipolar, anxiet y, personality, and attention-deficit/hyper-
activity disorders. In individuals with curren t tobacco use disorder, the prevalence of cur-
rent alcohol, drug, anxiety, depressive, bi polar, and personality disorders ranges from
22% to 32%. Nicotine-dependent smokers are 2.7–8.1 times more likely to have these dis-
orders than nondependent smokers, never-smokers, or ex-smokers.


Tobacco Withdrawal 575
Tobacco Withdrawal
Diagnostic Criteria 292.0 (F17.203)
A. Daily use of tobacco for at least several weeks.
B. Abrupt cessation of tobacco use, or reduction in the amount of tobacco used, followed
within 24 hours by four (or more) of the following signs or symptoms:
1. Irritability, frustration, or anger.
2. Anxiety.
3. Difficulty concentrating.
4. Increased appetite.
5. Restlessness.
6. Depressed mood.
7. Insomnia.
C. The signs or symptoms in Criterion B cause clinically significant distress or impairment
in social, occupational, or other important areas of functioning.
D. The signs or symptoms are not attributed to another medical condition and are not bet-
ter explained by another mental disorder, including intoxication or withdrawal from an-
other substance.
Coding note:  The ICD-9-CM code is 292.0. The ICD-10-CM code for tobacco withdrawal
is F17.203. Note that the ICD-10-CM code indicates the comorbid presence of a moderate
or severe tobacco use disorder, reflecting the fact that tobacco withdrawal can only occur
in the presence of a moderate or severe toba cco use disorder. It is not permissible to code
a comorbid mild tobacco use disorder with tobacco withdrawal.
Diagnostic Features
Withdrawal symptoms impair the ability to st op tobacco use. The symptoms after absti-
nence from tobacco are in large part due to nicotine deprivation. Symptoms are much
more intense among individuals who smoke cigarettes or use smokeless tobacco than
among those who use nicotine medications. This difference in symptom intensity is likely
due to the more rapid onset and higher levels of nicotine with cigarette smoking. Tobacco


due to the more rapid onset and higher levels of nicotine with cigarette smoking. Tobacco
withdrawal is common among daily tobacco users who stop or reduce but can also occur
among nondaily users. Typically, heart rate decreases by 5–12 beats per minute in the first
few days after stopping smoking, and weight increases an average of 4–7 lb (2–3 kg) over
the first year after stopping smoking. Tobacco withdrawal can produce clinically signifi-
cant mood changes and functional impairment.
Associated Features Supporting Diagnosis
Craving for sweet or sugary foods and impaired performance on tasks requiring vigilance
are associated with tobacco withdrawal. Abstinence can increase constipation, coughing,
dizziness, dreaming/nightmare s, nausea, and sore throat. Smoking increases the metab-
olism of many medications used to treat mental disorders; thus, cessation of smoking can
increase the blood levels of these medications, and this can produce clinically significant
outcomes. This effect appears to be due not to nicotine but rather  to other compounds in
tobacco.


576 Substance-Related and Addictive Disorders
Prevalence
Approximately 50% of tobacco users who quit for 2 or more days will have symptoms that
meet criteria for tobacco withdrawal. The most commonly endorsed signs and symptoms
are anxiety, irritability, and difficulty concentrating. The least commonly endorsed symp-
toms are depression and insomnia.
Development and Course
Tobacco withdrawal usually begins within 24 hours of stopping or cutting down on to-
bacco use, peaks at 2–3 days after abstinence, and lasts 2–3 weeks. Tobacco withdrawal
symptoms can occur among adolescent tobacco users, even prior to daily tobacco use. Pro-
longed symptoms beyond 1 month are uncommon.
Risk and Prognostic Factors
Temperamental. Smokers with depressive disorders,  bipolar disorders, anxiety disor-
ders, attention-deficit/hypera ctivity disorder, and other substance use disorders have
more severe withdrawal.
Genetic and physiological. Genotype can influence the probability of withdrawal upon
abstinence.
Diagnostic Markers
Carbon monoxide in the breath, and nicotine and its metabolite cotinine in blood, saliva, or
urine, can be used to measure the extent of tobacco or nicotine use but are only weakly re-
lated to tobacco withdrawal.
Functional Consequences  of Tobacco Withdrawal
Abstinence from cigarettes can cause clinically significant distress. Withdrawal impairs
the ability to stop or control tobacco use. Whether tobacco withdraw al can prompt a new
mental disorder or recurrence of  a mental disorder is debatable,  but if this occurs, it would
be in a small minority of tobacco users.
Differential Diagnosis
The symptoms of tobacco with drawal overlap with those of other substance withdrawal


Differential Diagnosis
The symptoms of tobacco with drawal overlap with those of other substance withdrawal
syndromes (e.g., alcohol withdrawal; sedative, hypnotic, or anxiolytic withdrawal; stim-
ulant withdrawal; caffeine withdrawal; opioid withdrawal); caffeine intoxication; anxiety,
depressive, bipolar, and sleep disorders; an d medication-induced akathisia. Admission to
smoke-free inpatient units or voluntary smoking cessation ca n induce withdrawal symp-
toms that mimic, intensify, or disguise othe r disorders or adverse effects of medications
used to treat mental disorders (e.g., irritabi lity thought to be du e to alcohol withdrawal
could be due to tobacco with drawal). Reduction in sympto ms with the use of nicotine
medications confirms the diagnosis.
Other Tobacco-Induced Disorders
Tobacco-induced sleep disorder is discussed in the chapter “Sleep -Wake Disorders” (see
“Substance/Medication-In duced Sleep Disorder”).


Unspecified Tobacco-Related Disorder 577
Unspecified Tobacco-Related Disorder
292.9 (F17.209)
This category applies to presentations in which symptoms characteristic of a tobacco-
related disorder that cause clinically significant distress or impairment in social, occupa-
tional, or other important areas of functioning predominate but do not meet the full criteria
for any specific tobacco-related disorder or any of the disorders in the substance-related
and addictive disorders diagnostic class.
Other (or Unknown)
Substance–Related Disorders
Other (or Unknown) Su bstance Use Disorder
Other (or Unknown) Substance Intoxication
Other (or Unknown) Substance Withdrawal
Other (or Unknown) Subs tance–Induced Disorders
Unspecified Other (or Unknown)  Substance–Related Disorder
Other (or Unknown) Substance Use Disorder
Diagnostic Criteria
A. A problematic pattern of use of an intoxicating substance not able to be classified
within the alcohol; caffeine; cannabis; hallucinogen (phencyclidine and others); inhal-
ant; opioid; sedative, hypnotic, or anxiolytic; stimulant; or tobacco categories and lead-
ing to clinically significant impairment or distress, as manifested by at least two of the
following, occurring within a 12-month period:
1. The substance is often taken in larger amounts or over a longer period than was
intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control use of the
substance.
3. A great deal of time is spent in activities necessary to obtain the substance, use the
substance, or recover from its effects.
4. Craving, or a strong desire or urge to use the substance.
5. Recurrent use of the substance resulting in a failure to fulfill major role obligations
at work, school, or home.


at work, school, or home.
6. Continued use of the substance despite having persistent or recurrent social or in-
terpersonal problems caused or exacerbated by the effects of its use.
7. Important social, occupational, or recreat ional activities are given up or reduced be-
cause of use of the substance.
8. Recurrent use of the substance in situations in which it is physically hazardous.
9. Use of the substance is continued despite knowledge of having a persistent or re-
current physical or psychological problem that is likely to have been caused or ex-
acerbated by the substance.


578 Substance-Related and Addictive Disorders
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of the substance to achieve intoxication
or desired effect.
b. A markedly diminished effect with continued use of the same amount of the sub-
stance.
11. Withdrawal, as manifested by either of the following:
a. The characteristic withdrawal syndrome fo r other (or unknown) substance (refer to
Criteria A and B of the criteria sets fo r other [or unknown] substance withdrawal,
p. 583).
b. The substance (or a closely related substance) is taken to relieve or avoid with-
drawal symptoms.
Specify if:
In early remission:  After full criteria for other (or unknown) substance use disorder were
previously met, none of the criteria for other (or unknown) substance use disorder have
been met for at least 3 months but for less than 12 months (with the exception that Cri-
terion A4, “Craving, or a strong desire or urge to use the substance,” may be met).
In sustained remission:  After full criteria for other (or unknown) substance use disor-
der were previously met, none of the criteria  for other (or unknown) substance use dis-
order have been met at any time during a period of 12 months or longer (with the
exception that Criterion A4, “Craving, or a strong desire or urge to use the substance,”
may be met).
Specify if:
In a controlled environment:  This additional specifier is used if the individual is in an
environment where access to the substance is restricted.
Coding based on current severity:  Note for ICD-10-CM codes: If an other (or unknown) sub-


stance intoxication, other (or unknown) substance withdrawal, or another other (or unknown)
substance–induced mental disorder is present, do not use the codes below for other (or un-
known) substance use disorder. Instead, the comorbid other (or unknown) substance use dis-
order is indicated in the 4th character of the other (or unknown) substance–induced disorder
code (see the coding note for other (or unknown) substance intoxication, other (or unknown)
substance withdrawal, or specific other (or unknown) substance–induced mental disorder).
For example, if there is comorbid other (or unknown) substance–induced depressive disorder
and other (or unknown) substance use disorder, only the other (or unknown) substance–
induced depressive disorder code is given, with the 4th character indicating whether the co-
morbid other (or unknown) substance use disorder  is mild, moderate, or severe: F19.14 for
other (or unknown) substance use disorder with other (or unknown) substance–induced de-
pressive disorder or F19.24 for a moderate or severe other (or unknown) substance use dis-
order with other (or unknown) substance–induced depressive disorder.
Specify current severity:
305.90 (F19.10) Mild:  Presence of 2–3 symptoms.
304.90 (F19.20) Moderate: Presence of 4–5 symptoms.
304.90 (F19.20) Severe:  Presence of 6 or more symptoms.
Specifiers
“In a controlled environment” app lies as a further specifier of remission if the individual is
both in remission and in a controlled environm ent (i.e., in early remission in a controlled


environment or in sustained remission in a controlled environmen t). Examples of these
environments are closely supe rvised and substanc e-free jails, therapeutic communities,
and locked hospital units.


Other (or Unknown) Substance Use Disorder 579
Diagnostic Features
The diagnostic class other (or unknown) su bstance use and related disorders comprises
substance-related disorders unrelated to alco hol; caffeine; cannabis; hallucinogens (phen-
cyclidine and others); inhalants; opioids; sedative, hypnotics, or anxiolytics; stimulants
(including amphetamine and cocaine); or tobacco. Such substances include anabolic ste-
roids; nonsteroidal anti-inflammatory drugs; cortisol; antiparkinsoni an medications; an-
tihistamines; nitrous oxide; amyl-, butyl-, or isobutyl-nitrites; betel nut, which is chewed
in many cultures to produce mild euphoria an d a floating sensation;  kava (from a South
Pacific pepper plant), which produces sedation , incoordination, weight loss, mild hepati-
tis, and lung abnormalities; or cathinones (including khât plant agents and synthetic chem-
ical derivatives) that produce stimulant effe cts. Unknown substance- related disorders are
associated with unidentified substances, such as intoxications in which the individual can-
not identify the ingested drug, or substance use disorders involving either new, black mar-
ket drugs not yet identified or familia r drugs illegally sold under false names.
Other (or unknown) substance use disorder is  a mental disorder in which repeated use
of an other or unknown substance typically continues, despite the individual’s knowing
that the substance is causing serious problems  for the individual. Th ose problems are re-
flected in the diagnostic criteria . When the substance is known, it should be reflected in the
name of the disorder upon coding (e.g., nitrous oxide use disorder).
Associated Features Supporting Diagnosis


Associated Features Supporting Diagnosis
A diagnosis of other (or unknown) substance us e disorder is supporte d by the individual’s
statement that the substance involved is not among the nine classes listed in this chapter; by re-
curring episodes of intoxication with negative results in standard drug  screens (which may not
detect new or rarely used substances); or by the presence of symptoms characteristic of an un-
identified substance that has newly appeared in the individual’s community.
Because of increased access to nitrous oxide (“laughing ga s”), membership in certain
populations is associated with diagnosis of ni trous oxide use disorder. The role of this gas
as an anesthetic agent leads to misuse by so me medical and dental professionals. Its use as
a propellant for commercial products (e.g., whipped cream dispensers) contributes to
misuse by food service workers. With recent  widespread availability of the substance in
“whippet” cartridges for use in home whipped cream dispensers, ni trous oxide misuse by
adolescents and young adults is significant, especially among those who also inhale vola-
tile hydrocarbons. Some continuously usin g individuals, inhaling from as many as 240
whippets per day, may present with serious medical complications and mental conditions,
including myeloneuropathy, spinal cord su bacute combined degeneration, peripheral
neuropathy, and psychosis. These conditions are also associated with a diagnosis of ni-
trous oxide use disorder.
Use of amyl-, butyl-, and iso butyl nitrite gases has been  observed among homosexual
men and some adolescents, especially those with conduct disorder. Membership in these
populations may be associated with a diagnosis of amyl-, butyl-, or is obutyl-nitrite use dis-
order. However, it has not been determined that these substances produce a substance use


order. However, it has not been determined that these substances produce a substance use
disorder. Despite tolerance, these gases may no t alter behavior through central effects, and
they may be used only for their peripheral effects.
Substance use disorders generall y are associated with elevated risks of suicide, but there
is no evidence of unique risk factors for suicide with other (or unknown) substance use
disorder.
Prevalence
Based on extremely limited data, the prevalence of other (or unknown) substance use disorder


disorder.
Prevalence
Based on extremely limited data, the prevalence of other (or unknown) substance use disorder
is likely lower than that of use disorders involv ing the nine substance classes in this chapter.


580 Substance-Related and Addictive Disorders
Development and Course
No single pattern of development or course  characterizes the pharmacologically varied
other (or unknown) substance use disorders.  Often unknown substance use disorders will
be reclassified when the unknown substance eventually is identified.
Risk and Prognostic Factors
Risk and prognostic factors for other (or un known) substance use disorders are thought to
be similar to those for most substance use disorders and include the presence of any other
substance use disorders, conduct disorder, or antisocial personality disorder in the indi-
vidual or the individual’s family; early onse t of substance problems ; easy availability of
the substance in the individual’s environment; childhood maltreatment or trauma; and ev-
idence of limited early self-control and behavioral disinhibition.
Culture-Related Diagnostic Issues
Certain cultures may be associated with ot her (or unknown) substance use disorders in-
volving specific indigenous substances with in the cultural region, such as betel nut.
Diagnostic Markers
Urine, breath, or saliva tests may correctly identify a commonly used substance falsely
sold as a novel product. However, routine clin ical tests usually cannot identify truly un-
usual or new substances, which may requir e testing in specialized laboratories.
Differential Diagnosis
Use of other or unknown substances without meeting criteria for other (or unknown)
substance use disorder. Use of unknown substances is not rare among adolescents, but
most use does not meet the diag nostic standard of two or mo re criteria for other (or un-
known) substance use disorder in the past year.
Substance use disorders. Other (or unknown) substanc e use disorder may co-occur
with various substance use diso rders, and the symptoms of the disorders may be similar


with various substance use diso rders, and the symptoms of the disorders may be similar
and overlapping. To disentangle symptom pattern s, it is helpful to  inquire about which
symptoms persisted during periods when some  of the substances were not being used.
Other (or unknown) substance/medication-induced disorder. This diagnosis should
be differentiated from instances when the indi vidual’s symptoms meet full criteria for one
of the following disorders, and that disorder is caused by an other or unknown substance:
delirium, major or mild  neurocognitive disorder, psychoti c disorder, depressive disorder,
anxiety disorder, sexual dysf unction, or sleep disorder.
Other medical conditions. Individuals with substance us e disorders, including other
(or unknown) substance use disorder, may present with symptoms of many medical dis-
orders. These disorders also may occur in the absence of other (or unknown) substance use
disorder. A history of little or no use of ot her or unknown substances helps to exclude
other (or unknown) substance use disord er as the source of these problems.
Comorbidity
Substance use disorders, including other (o r unknown) substance use disorder, are com-
monly comorbid with one another, with adol escent conduct disorder  and adult antisocial
personality disorder, and with suicid al ideation and suicide attempts.


Other (or Unknown) Substance Intoxication 581
Other (or Unknown) Substance Intoxication
Diagnostic Criteria
A. The development of a reversible substance-specific syndrome attributable to recent in-
gestion of (or exposure to) a substance that is not listed elsewhere or is unknown.
B. Clinically significant problematic behavioral or psychological changes that are attribut-
able to the effect of the substance on the central nervous system (e.g., impaired motor
coordination, psychomotor agitation or retardation, euphoria, anxiety, belligerence,
mood lability, cognitive impairment, impaired judgment, social withdrawal) and develop
during, or shortly after, use of the substance.
C. The signs or symptoms are not attributable to another medical condition and are not bet-
ter explained by another mental disorder, in cluding intoxication with another substance.
Coding note:  The ICD-9-CM code is 292.89. The ICD-10-CM code depends on whether
there is a comorbid other (or unknown) substance use disorder involving the same sub-
stance. If a mild other (or unknown) substance use disorder is comorbid, the ICD-10-CM
code is F19.129,  and if a moderate or severe other (or unknown) substance use disorder is
comorbid, the ICD-10-CM code is F19.229. If there is no comorbid other (or unknown) sub-
stance use disorder involving the same substance, then the ICD-10-CM code is F19.929.
Note:  For information on Risk and Prognostic Factors, Culture-Related Diagnostic Issues,
and Diagnostic Markers, see the correspondin g sections in other (or unknown) substance
use disorder.
Diagnostic Features


use disorder.
Diagnostic Features
Other (or unknown) substance intoxication is a clinically significant mental disorder that
develops during, or immediately after, use of either a) a substance not elsewhere ad-
dressed in this chapter (i.e., alcohol; caff eine; cannabis; phencyclidine and other halluci-
nogens; inhalants; opioids; sedatives, hypnotics , or anxiolytics; stimulants; or tobacco) or
b) an unknown substance. If the substance is known, it should be reflected in the name of
the disorder upon coding.
Application of the diagnostic criteria for other (or unknow n) substance intoxication is
very challenging. Criterion A requires development of a reversible “substance-specific
syndrome,” but if the substance is unknown, that syndrome usually will be unknown. To
resolve this conflict, clinicians may ask the in dividual or obtain co llateral history as to
whether the individual has experienced a similar episode after using substances with the
same “street” name or from the same source . Similarly, hospital emergency departments
sometimes recognize over a few days numerous presentations of a severe, unfamiliar in-
toxication syndrome from a newly available,  previously unknown substance. Because of
the great variety of intoxicating substances, Criterion B can provide only broad examples
of signs and symptoms from some intoxications, with no  threshold for the number of
symptoms required for a diagnosis; clinical judgment guides those decisions. Criterion C
requires ruling out other medical conditio ns, mental disorders, or intoxications.
Prevalence
The prevalence of other (or unknown) substance intoxication is unknown.
Development and Course
Intoxications usually appear and then peak minu tes to hours after use of the substance, but
the onset and course vary with the substanc e and the route of administration. Generally,


582 Substance-Related and Addictive Disorders
substances used by pulmonary inhalation and intravenous injection have the most rapid
onset of action, while those ingested by mouth and requiring metabolism to an active
product are much slower. (For example, after ingestion of certain mushrooms, the first
signs of an eventually fatal intoxication may not appear for a few days.) Intoxication ef-
fects usually resolve within hours to a very  few days. However, the body may completely
eliminate an anesthetic gas such as nitrous ox ide just minutes after use ends. At the other
extreme, some “hit-and-run” intoxicating su bstances poison systems, leaving permanent
impairments. For example, MPTP (1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine), a con-
taminating by-product in the synthesis of a certain opioid, kills dopaminergic cells and in-
duces permanent parkinsonism in user s who sought opioid intoxication.
Functional Consequences of
Other (or Unknown) Substance Intoxication
Impairment from intoxication with any subs tance may have serious consequences, includ-
ing dysfunction at work, social indiscretions, problems in interpersonal relationships, fail-
ure to fulfill role obligations, traffic accide nts, fighting, high-risk behaviors (i.e., having
unprotected sex), and substance or medication  overdose. The pattern of consequences will
vary with the particular substance.
Differential Diagnosis
Use of other or unknown substance, without meeting criteria for other (or unknown)
substance intoxication. The individual used an other or unknown substance(s), but the
dose was insufficient to produce symptoms that meet the diag nostic criteria required for
the diagnosis.