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Türk Psikiyatri Dergisi 2010;
Turksh Journal of Psychatry
Quetiapine is an atypical antipsychotic approved by the FDA (Food and Drug Administration) for use in the
treatment of schizophrenia, acute mania, and bipolar depression. Pharmacologically, it has antagonistic effects
on serotonin 5-HT1A and 5-HT2A, dopamine D1 and D2, histamine H1, and adrenergic α1 and α2 receptors. In addition
to reports of its use in schizophrenia and bipolar disorder, many studies have examined the use of quetiapine
in the treatment of anxiety disorders and substance use disorders. In the treatment of patients with psychotic
or bipolar disorder with a comorbid substance abuse disorder even though quetiapine was prescribed primarily
for the treatment of the underlying psychotic symptoms, patients taking this medication reported a significant
reduction in substance use. Yet, there are also case reports of quetiapine abuse and dependence; in particular
among prisoners and patients diagnosed with substance abuse. Though quetiapine should be used peroral, it is
also used intranasally and intravenously in these patient groups. Moreover, in some cases quetiapine is combined
with other substances, such as cocaine or marijuana, to increase sedation. This abuse of quetiapine is thought
to occur due to the anxiolytic and sedative effects of the drug. There are no controlled studies on quetiapine
dependence in the literature and it remains unknown whether or not quetiapine causes dependence. This review
aimed to present all published case reports on quetiapine abuse and to discuss the possible mechanisms that
underlie its abuse and dependence.
Key Words: Quetiapine, abuse, dependence, substance use disorders
Que apine in Substance Use Disorders, Abuse and
Dependence Possibility: A Review
Serap ERDOĞAN
Received: 05.04.2009 - Accepted: 31.08.2009
Assist. Prof./MD., Gaziosmanpasa University Faculty of Medicine, Psychiatry Department, Tokat
Serap Erdoğan, MD., e-mail: erd.serap@gmail.com
INTRODUCTION
Quetiapine is considered as an atypical antipsychotic
and has been approved by the FDA (Food and Drug
Administration) for use in the treatment of schizophre-
nia, acute mania, and bipolar depression. Quetiapine, a
dibenzodiazepine derivative, is pharmacologically similar
to clozapine and has an antagonistic effect on serotonin
5-HT1A and 5-HT2A, dopamine D1 and D2, histamine
H1, and adrenergic α1 and α2 receptors (Goldstein 1999;
Reeves and Brister 2007; Riedel et al. 2007). In addition
to its similarity to clozapine, quetiapine has the advantage
of not causing agranulocytosis. Its affinity for 5-HT2A
receptors is much stronger than its affinity for D2 recep-
tors; consequently, it is thought to cause fewer extrapy-
ramidal side effects (Green 1999). Furthermore, hyperpro-
lactinemia that is another side effect of antipsychotics , is less
frequently encountered with quetiapine use.. Unlike other
atypical antipsychotics, the fact that quetiapine tempo-
rarily attaches to postsynaptic D2 receptors and detaches
from them in a short time contributes to its reliable side
effect profile (Kapur et al. 2000). At the lower end of
quetiapine’s suggested dosage level (50-750 mg/day) is
thought that it does not have any significant affinity
for cholinergic muscarinic receptors or benzodiazepine
receptors. Nevertheless, doses above 500 mg/day more
frequently cause anticholinergic effects, such as dysuria,
constipation, and dry mouth (Morin 2007).
Apart from quetiapine’s use in schizophrenia and
bipolar affective disorder, an extensive body of research
on its off-label use exists. In Rowe’s (2007) study, au-
thors added low doses of quetiapine to the treatment of
resistant cases when, in particular, selective serotonin
Abstract
2
re-uptake inhibitors and cognitive behavioral therapy
remained inadequate. Thus, it was reported that quetiap-
ine is suggested for patients with obsessive-compulsive
disorder, prost-traumatic stress disorder, substance use
disorder, personality disorder, and anxiety and depres-
sive disorder. Similarly, a study conducted by Philip et al.
(2008) analyzed prescriptions over a 2-year period and
reported that quetiapine was mostly used off-label in the
treatment of depression, followed by the treatment of bi-
polar and psychotic disorders comorbid with substance
use disorder. In addition, a growing number of case re-
ports on the misuse of quetiapine have been published
(Pierre et al. 2004; Hussain 2005; Morin 2007). It is
noteworthy that these cases generally consist of prison-
ers and patients with a history of multiple substance de-
pendence. When designing and monitoring treatment,
doctors particularly interested in these groups of patients
should be careful about the use of quetiapine alone or in
combination with other substances that might or might
not be addictive.
Quetiapine use among prisoners that were brought
from a closed prison in the town to the psychiatric clinic
of Osmaniye State Hospital for medical examination,
have some similarities to cases of quetiapine abuse re-
ported in the literature. In all, 14 prisoners out of 330
were prescribed quetiapine, and these prisoners were
diagnosed with multiple substance use and antisocial
personality disorder. It was reported that the quetiapine
treatment began before or after imprisonment at various
clinics and that the prisoners insisted on using quetiap-
ine. In fact, some of the prisoners refused to leave the in-
terview room unless they were prescribed quetiapine. In
particular, patients with a history of substance depend-
ence consistently demanded quetiapine from the prison
doctors, and they did not want to use drugs with seda-
tive effects, such as mirtazapine and trazodone, which
were prescribed by psychiatrists. The prison guards and
doctors observed that the prisoners attempted to give
quetiapine to each other. Additionally, during psychi-
atric interviews some prisoners reported that they col-
lected quetiapine given to them as a daily dose, and then
consumed 600-800 mg of quetiapine in a single dose in
order to feel calm.
METHOD
This review, written based on the reports mentioned
above, aimed to examine published case reports on the
possible abuse of quetiapine and quetiapine dependence,
as well as the relationship between substance use disorder
and quetiapine. To meet this objective the Turkish and
foreign psychiatric publications were searched. Turkish
and foreign articles published between 1990 and 2009
were searched through the Turkish national (ULAKBİM
Türk Tıp Dizini, Türk Psikiyatri Dizini) and interna-
tional databases (PubMed, EMBASE, and ISI Web of
Science) using different combinations of the key words
mentioned in the abstract. Case reports, reviews, and
meta-analyses were searched, and those that were appro-
priate for this review were examined.
Quetiapine in the Treatment of Substance Use
Disorders
The use of quetiapine in the treatment of substance
use disorders has been studied in populations of patients
diagnosed with comorbid schizophrenia and bipolar dis-
orders (Brown et al. 2002; Sattar et al. 2004; Martinotti
et al. 2008). Substance use disorders were diagnosed
2-3 times more frequently in patients with schizophre-
nia than in the control group (Potvin et al. 2008). This
high comorbidity rate is thought to originate from the
common biological roots of these two disorders. It was
posited that dopamine sensitivity in the schizophrenic
patients made them more susceptible to the rewarding
effect of the substance (Hanley and Kenna 2008). In ad-
dition, the endogenous cannabinoid system is thought
to play a role in both disorders (Potvin et al. 2008). Simi-
larly, about 50% of patients with bipolar disorder had a
history of substance abuse disorder (Brown et al. 2002).
After antipsychotic treatment was administered to
control psychotic symptoms it was observed that the
quantity of substance used by patients decreased (Volkow
et al. 2002). On the other hand, some studies reported
that antipsychotic use increases the amount of substance
used by patients diagnosed only with a substance use dis-
order (McEvoy et al. 1995). These differing results are
thought to be the result of variation in the mechanisms
of effect of different antipsychotic drugs. While low-po-
tency antipsychotics decrease the quantity of substance
taken, high-potency antipsychotics increase the quantity
taken (Sattar et al. 2004). Green et al. (1999) argue that
this phenomenon is related to the dopaminergic an-
tagonism created by antipsychotic drugs in the reward
pathway in mesocorticolimbic neurons. High-potency
antipsychotics have a stronger antagonistic effect, which
is thought to increase the quantity of substance taken to
reach the satisfaction felling (Martinotti et al. 2008).
Brown et al. (2002) investigated the efficacy of
quetiapine in patients with bipolar affective disorder with
comorbid cocaine dependence or substance abuse. They
3
reported that quetiapine alleviated mood symptoms and
decreased cocaine craving, but that there was no difference
in the amount of money spent for the substance used, the
frequency with which the substance was used, and the fre-
quency of positive urine test results for the substance used.
In another study, patients diagnosed with bipolar I, bipo-
lar II, schizoaffective disorder, and borderline personality
disorder, in addition to alcohol dependence, were given a
daily quetiapine dose of 300-800 mg for 16 weeks follow-
ing detoxification treatment. At the end of the study it was
observed that quetiapine decreased the psychiatric symp-
toms that accompanied alcohol consumption and craving
(Martinotti et al.,2008).
Other studies focused on the use of quetiapine in pa-
tients with alcohol and substance use disorders, but no
other comorbid psychiatric disorder. Sattar et al. (2004)
gave 50-300 mg/day of quetiapine to 9 patients with al-
cohol and substance dependence (cocaine and metham-
phetamine), in addition to antidepressant and anxiolytic
treatment for such complaints as anxiety and sleep with-
drawal. The researchers reported that 1 patient could not
tolerate the treatment because of increased anxiety, but
that anxiety and sleep withdrawal decreased in the other
8 patients. In a 6-week study conducted to evaluate the
efficacy of quetiapine in cocaine-addicted patients with-
out a psychotic disorder, 22 patients received 300-600
mg/day of quetiapine. Some of the patients could not
finish the study because of quetiapine’s sedative effect.
In particular, during the first week of the study a sig-
nificant decrease in cocaine craving was observed and
patients reported that the quantity of cocaine use de-
creased (Kennedy et al. 2008). Pinkofsky et al. (2005)
conducted a study with patients that were being treated
for opioid dependence, and every 4 hours gave them one
or two 25-mg quetiapine tablets,. According to the re-
sults, 79 of the 107 patients that completed the study
reported a decrease in opioid craving, 52 patients re-
ported decreased anxiety, 24 reported decreased somatic
pain, 22 reported a decrease in sleep withdrawal, and 14
reported increased appetite due to the use of quetiap-
ine. The researchers noted that 4 patients discontinued
quetiapine treatment because they did not benefit from
it and 7 patients stopped because they could not tolerate
the side effects.
A common theme in the studies summarized above is
that quetiapine can be used in the treatment of substance
use disorders. This suggestion brings to mind the abuse
and dependence possibility in the use of quetiapine; and
also there is a growing body of research that reveals these
kinds of case reports in the literature.
Data Related to the Possible Quetiapine Misuse
and Dependence
In the Diagnostic and Statistical Manual of Mental
Disorders (DSM IV), substance dependence criteria in-
clude behavioral (obtaining and using the substance for a
long time, failing to fulfill personal and social obligations
because of substance use, continuing substance use despite
damages and several attempts to quit) and physical (evi-
dence of tolerance and withdrawal when the substance is
nor taken) characteristics. On the other hand, substance
abuse is defined similarly to substance dependence in
terms of the behavioral problems, but does not include
the physical dependence criteria. In both conditions, the
symptoms should have occurred during the last 12-month
period and caused clinically severe deterioration (Ameri-
can Psychiatric Association 1994).
When evaluated in terms of DSM IV criteria it is
noteable that quetiapine abuse and dependence were first
reported among prisoner populations. In the Los Angeles
County Jail, which is referred to as the “world’s biggest
mental health institution”, it is reported that approxi-
mately 30% of prisoners pretend to have a severe psy-
chiatric disorder by reporting symptoms (hearing noises,
having paranoid thoughts) in order to get quetiapine
(Pierre et al. 2004). This is an important point, although
the prevalence of this kind of behavior is not known.
Research revealed that quetiapine is referred to in the
street language used by substance-dependent individuals
by such names as “seroquel”, “quell”, or “susie-Q”, and
that it is called “baby heroin” by prisoners (Reeves and
Brister, 2002; Waters and Joshi, 2007; Hanley and Ken-
na, 2008; Keltner and Vance, 2008). In Turkey, patients
with substance dependence and their doctors report that
one of the street names of quetiapine is “yellow lake.” In
addition, a foreign rap song mentions one of the com-
mercial names for quetiapine among the substances that
might cause dependence (Keltner and Vance 2008).
Quetiapine is not considered a substance that causes
dependence and its use is not under control. Hussain et
al. (2005) reported that quetiapine dependence among
prisoners might be more widespread than is thought, be-
cause obtaining other substances that can cause depend-
ence is more difficult. The fact that quetiapine is used
in the treatment of anxiety and sleep deprivation due to
substance withdrawal, which is frequently seen among
prisoners, is suggested to be another reason. Published
reports on quetiapine abuse will be briefly explained
below. Diagnoses of the cases and the characteristics of
quetiapine use are summarized in Table.
4
A case report published in 2005 tells of a 34-year-old
woman diagnosed with multiple substance dependence
(alcohol, heroin, and cocaine) and borderline personal-
ity disorder that had attempted suicide more than once
time dissolved two 300-mg quetiapine tablets in water,
which she then boiled and injected. The patient reported
that she slept for 12 hours and didn’t have euphoric, dys-
phoric, or any other effects, except for sedation (Hus-
sein et al. 2005). Another report on the intravenous use
of quetiapine presented a 33-year-old male patient with
multiple substance dependence (cocaine, alcohol, hero-
in, and benzodiazepine) that presented to an emergency
department for detoxification and rehabilitation. The
patient reported that he steals quetiapine prescribed for
his wife (400-800 mg/day), powders it and mixes it with
cocaine, dissolves it in water, filters it through a bandage,
and then injects it. The researchers noted that the pa-
tient used quetiapine in this way in order to experience
hallucinogenic effects (Waters and Joshi 2007).
It is known that quetiapine is used intranasally, as well
as intravenously. A case report by Morin (2007) revealed
that a white powder was found in the room of a 28-year-
old female patient diagnosed with bipolar schizoaffective
disorder, multiple substance abuse (alcohol, cocaine, ec-
stasy, lysergic aside diethylamide [LSD], weight loss pills
including ephedra, and some other drugs described as
“sedative” by the patient), tobacco dependence, and per-
sonality disorder. The patient intranasally took smashed
aspirin and quetiapine (given to her as a part of her treat-
ment) because of the sedative effect of quetiapine. Pierre
et al. (2004) also report that among the prisoners of the
Los Angeles County Jail, some people use quetiapine in-
tranasally.
Pinta and Taylor (2007) report that quetiapine causes
seeking behaviors observed in substance use disorders. It
is reported that a prisoner with opioid dependence and
hepatitis C infection that was taking 800 mg of quetiap-
ine and 0.9 mg of clonidine because of generalized anxi-
ety disorder reacted and could not adapt to the reduction
of quetiapine use, when his doctor wanted to gradually
discontinue quetiapine treatment because of its possible
effects on the patient’s liver. The patient attempted to
obtain quetiapine from other prisoners when quetiapine
treatment was terminated. In addition, when quetiapine
treatment is withdrawn, some prisoners that previously
used quetiapine react to the point of suicidal attempts
(Pinta and Taylor 2007).
In a study by Inciardi et al. (2007) on the abuse of
prescription drugs, they present a cased that reported
taking 4 “seroquel”, 3 “lilly (olanzapine)”, 2 “bar” (2 mg
of alprazolam), alcohol, marihuana, and cocaine at the
same time, having a “perfect” night. This report brings
to mind that the use of antipsychotic drugs in combina-
tion with substances causing dependence started to be a
common behavior.
Reeves and Brister (2007) presented 3 cases that they
consider examples of quetiapine abuse. The first case
was a 49-year-old male patient with a history of alcohol
dependence, and alprazolam and diazepam abuse. The
treatment of substance abuse started while the patient
was in prison, but when the patient was released on pro-
bation he reported having withdrawal symptoms. In re-
sponse, the patient began to obtain quetiapine from his
friends in order to sleep, knowing of its sedative effect
and that it cannot be identified in urine. After a short
while he began to take one 800-mg dose of quetiapine
each night, but his complaints of sleep withdrawal, ir-
ritability lasting all day, anxiety, and headache appeared
when he couldn’t obtain quetiapine. The patient then
presented to a clinician and insisted on being prescribed
at least 400 mg/day of quetiapine.
The second case was a 23-year-old male patient hos-
pitalized because of benzodiazepine dependence. His
detoxification treatment started with lorazepam, but
the patient consistently asked the doctors to give him
quetiapine because he heard that quetiapine is good for
withdrawal symptoms. Then patient then began to steal
quetiapine from his schizophrenic girlfriend and other
patients that used quetiapine in order to use and sell it.
It was noted that the patient used quetiapine when he
couldn’t obtain benzodiazepine and when he felt anxious
and uncomfortable, he sometimes took 1000-1200 mg
of quetiapine in a single dose, and he sometimes took up
to 2400 mg/day. The patient reported that in terms of
its calming effect, 200-300 mg quetiapine was equal to
1 mg of clonazepam.
The third case was a 39-year-old male patient with
bipolar affective disorder. This patient was treated with
quetiapine, but presented to a psychiatric clinic with
complaints of increased flow of thoughts, grandiose de-
lusions, and agitation, and insisted on being prescribed
800 mg d–1 quetiapine. The researchers reported that the
patient had been successfully treated with 400 mg/day
quetiapine, but that the patient confessed he consumed
the entire prescribed dose in a short time because he ex-
ceeded the dose suggested to him, and related his com-
plaints to not being able to find anymore quetiapine.
His treatment medication was changed to aripiprazole,
5
which does not have a sedative effect, but although his
symptoms were controlled, the patient consistently ex-
pressed that he did not like the new drug and wanted to
take quetiapine instead (Reeves and Brister 2007).
Murphy et al. (2008) presented a 29-year-old male
schizophrenic patient treated with 600 mg/day ( single
dose) quetiapine that presented to a psychiatric emergency
department with complaints of sleep disturbance because
he thought that the police were electronically monitoring
his testicles. The patient did get some sleep when he was
medicated. The next day at his assessment it was learned
that the patient did not have any symptoms related to a
psychotic disorder, but that he had been obtaining high
doses of quetiapine from different sources to use and sell.
The researchers warned doctors about people that present
in order to be prescribed quetiapine by describing psy-
chotic symptoms (Murphy et al. 2008).
In Turkey, Evren et al. (2009) report 3 cases they
thought might have abused quetiapine that were fol-
lowed-up at the Alcohol and Drug Addiction Treatment
and Research Center (AMATEM) of Bakirköy State Hos-
pital for Mental and Neurological Diseases. The first case
was a 32-year-old male patient diagnosed with heroin,
marijuana, benzodiazepine, and alcohol abuse, as well as
epilepsy, which was treated with diazepam, an analgesic,
an antiemetic, and an antidiareic to control withdrawal
symptoms, in addition to epilepsy treatment with sodium
valproate and lamotrigine. Mirtazapine was given to the
patient following his complaints of sleep withdrawal, but
the patient consitantly asked the doctors for quetiapine.
After being discharged from the hospital voluntarily he
took quetiapine prescribed by the night doctor as an ex-
tra drug from other inpatients, powdered it and used it
intranasally.
The second case presented with multiple substance de-
pendence, including heroin, that was taking risperidone
for irritability and delusions of persecution, and diazepam,
analgesic, antiemetic, and antidiareic treatment for with-
drawal symptoms. Because of the extrapyramidal side ef-
fects related to risperidone, the patient was prescribed 300
mg/day quetiapine, but his sleep problem continued and
quetiapine treatment was changed to 200 mg/day chlo-
rpromazine. Nonetheless, the patient insisted on being
prescribed quetiapine, and the outpatient clinic records
show that the patient had previously asked for quetiapine.
TABLE. Published quetiapine abuse case reports.
Author, publishing date Patient diagnosis Substances used together with quetiapine Method of use
Hussain et al., 2005 Polysubstance dependence
Depression
Borderline personality disorder
Not indicated Intravenous injection
Waters et al., 2007 Polysubstance dependence Cocaine Intravenous injection
Morin, 2007 Schizoaffective disorder (bipolar type)
Polysubstance abuse
Tobacco dependence
Personality disorder
Aspirin Intranasal
Pierre et al., 2007 Not indicated Not indicated Intranasal
Pinta et al., 2007 Opiate abuse
Generalized anxiety disorder
Clonidine Oral
Inciardi et al., 2007 Not indicated Olanzapine, alprazolam, alcohol, marijuana,
cocaine
Oral
Reeves et al., 2007 Alcohol dependence
Alprazolam, diazepam abuse
Not indicated Oral
Benzodiazepine dependence Not indicated Oral
Bipolar affective disorder Not indicated Oral
Murphy et al., 2008 Not indicated Not indicated Oral
Evren et al., 2009 Heroin dependence, Marijuana,
benzodiazepine, alcohol abuse,
Epilepsy
Sodium valproate, lamotrigine, diazepam,
analgesic, antiemetic, antidiareic drugs,
mirtazapine
Intranasal
Polysubstance dependence Diazepam, analgesic, antiemetic, antidiareic
drugs, risperidone, chlorpromazine
Oral
Polysubstance dependence Diazepam, analgesic, antiemetic,
antidiareic drugs
Oral
6
The third case was a patient with multiple substance
dependence, including heroin. He repeatedly asked for
a higher dose of quetiapine even though he was treated
with 600 mg/day for his sleep withdrawal complaint. It
is reported that the patient had requested high doses of
quetiapine when he was an inpatient, although he did
not have any active psychotic symptoms (Evren et al.
2009).
Except for case reports, there are no studies on the
characteristics of quetiapine use among prison popula-
tions. In a Turkish study by Kaya et al. (2009), among
37 patients that were brought to the Ankara AMATEM
outpatient clinic from prison and asked to be prescribed
quetiapine, 21.6% developed tolerance to the drug and
40.5% obtained more quetiapine than the legal and sug-
gested dose for treatment. It was reported that when the
patients don’t take the drug, 100% of them have sleep
withdrawal symptoms, 70.3% exhibit nervousness, and
64.9% have withdrawal symptoms such as restlessness.
As these symptoms are in line with DSM-IV substance
dependence criteria, it appears that quetiapine has the
potential for substance abuse and dependence.
DISCUSSION
The mechanisms described below were highlighted
in studies that focused on the therapeutic use of quetiap-
ine in substance use disorders:
1. Quetiapine provides sedation via blockage of H1 re-
ceptors (Reeves and Brister 2007).
2. According to the self-medication hypothesis of
Khantzian, people start to take substances in order
to alleviate the symptoms of anxiety, and then de-
pendence develops. Quetiapine can reduce the effect
of dependence by reducing the symptoms of anxiety
(Khantzian 1985; Martinotti et al. 2008).
3. The affinity of quetiapine for dopamine receptors is
low, and quetiapine detaches a short time after it at-
taches (Morin 2007).
4. Substance-dependent patients have obsessive
thoughts related to the substance they use; the an-
tipsychotic effect of quetiapine helps to reduce these
thoughts (Martinotti et al. 2008).
5. Patients with substance use disorders are also diag-
nosed with personality disorders; quetiapine can in-
directly influence substance use by treating the psy-
chopathology (Evren et al. 2009).
Similarly, the potential for quetiapine abuse was reported
with the following explanations:
1. Quetiapine abuse is most frequently related to its
sedative and anxiolytic characteristics (Pinta and Tay-
lor 2007; Reeves and Brister 2007).
2. It is thought that the motivation for quetiapine abuse
is self-medication for the symptoms of anxiety and
sleep withdrawal, not the desire to get high (Pierre
et al. 2004; Reeves and Brister 2007; Kaya et al.
2009).
3. The fact that quetiapine rapidly detaches from D2 re-
ceptors may contribute to the its potential abuse, and
to the lack of euphoria or dysphoria as withdrawal
symptoms (Morin 2007).
4. The fact that quetiapine use is not under control and
other extensively used substances that might result
in dependence are difficult to obtain might lead to
quetiapine abuse (Inciardi et al. 2007; Pinta and Tay-
lor 2007).
Sedation is a frequently encountered side effect of
quetiapine. Calabrese et al. (2005) report that 29.6% of
patients that took 300 mg/day quetiapine and 32.2% of
patients that took 600 mg/day quetiapine experienced
sedation. The sedative effect of quetiapine significantly
increases when consumed at high doses, especially in
combination with alcohol and other sedative substances.
It is posited that its sedative effect is mostly related to H1
receptor antagonism. In addition, it is thought that anti-
dopaminergic and anti-serotonergic effects might have a
role in its sedative effect. In relation to this, it is known
that quetiapine is sometimes prescribed off-label for the
treatment of sleep withdrawal (Robert et al. 2005; Rowe
2007; Philip et al. 2008). The anxiolytic and sedative
effects of quetiapine help to alleviate such withdrawal
symptoms as anxiety, irritability, and sleep withdrawal
in patients with dependence to central nervous system
(CNS) stimulants or CNS-suppressive substances like
alcohol and opiates. From then on, the patients might
start to abuse quetiapine prescribed for treatment, which
is not controlled for its use.
Researchers argue that quetiapine intranasal or in-
travenous abuse is more common than thought (Pierre
et al. 2004; Hussain et al. 2005). Although there is no
evidence supporting this view, intranasal use of quetiap-
ine might work pharmacokinetically faster than oral use.
Patients might prefer the intranasal use of quetiapine
because its anxiolytic and sedative effects work faster
(Morin 2007).
7
On one hand, using prescribed drugs in combina-
tion with illegal substances prevents the toxic side effects
that might be caused by overdosing; on the other hand it
helps to intensify the desired effects. An example of this
is the intravenous use of cocaine together with heroin
(known as a “speedball”) (Waters and Joshi 2007). In a
case mentioned previously in this review, it is thought
that quetiapine was used instead of heroin together with
cocaine (the combination of cocaine and quetiapine is
known as a “Q-ball”). When the anxiolytic and sedative
effects of quetiapine reduces the dysphoria developed
due to the lack of cocaine in a short while, it might also
create a hallucinogenic effect as reported by the use itself.
The composition of the hallucinogenic effect mechanism
cannot be explained (Waters and Joshi 2007).
It is noteworthy that the case reports of quetiapine
abuse mostly involve patients with a substance use disor-
der. Only 1 case with bipolar affective disorder was ob-
served to increasingly use quetiapine (Reeves and Brister
2007). This might be because patients with a substance
use disorder use quetiapine for its sedative and anxiolytic
effects in order to reduce the irritability they experience
when they cannot take other substances (because they are
in prison, or cannot obtain other substances). It is pos-
sible to argue that the sedative and anxiolytic effects of
quetiapine (for which it is preferred in clinical settings)
might be why it’s used in the streets as well. These atti-
tudes toward quetiapine are considered to be similar the
abuse of anticholinergic drugs and low-potency antip-
sychotics such chlorpromazine and thioridazine, which
occurred in the past when atypical antipsychotics were
not commonly used (Pierre et al. 2004). In addition, it
has been reported that some patients had to be excluded
from studies because they couldn’t tolerate the sedation
associated with quetiapine (Kennedy et al. 2008). This
finding suggests that quetiapine abuse might not always
be related to the desire for sedation. In the treatment of
all substance use disorders, two crucial factors are pa-
tient motivation for treatment and patient expectations
of the treatment. Considering these factors, quetiapine
might become a replacement substance or abuse might
continue with quetiapine in patients with a low toler-
ance for anxiety, or expect to be away from the substance
for a short time, or can’t use the substance because of
the conditions (being in prison, in hospital, or under
surveillance because of the supervised liberty, or finan-
cial problems) they live in even though they don’t expect
to be treated. The cases mentioned above show that the
behavioral characteristics of patients are primarily associ-
ated with substance use disorders. In the process of de-
veloping dependence, the role of the mesolimbic reward
system is critical.
The mesolimbic reward system originates in the
ventral tegmental area, and is related to the nucleus ac-
cumbens and the prefrontal cortex. The pathways in this
system contain dopaminergic neurons. The concentra-
tion of extracellular dopamine increases in the brain in
alcohol and substance dependence, even though it occurs
via different mechanisms (Blum et al., 2000). It is clear
that this mechanism is not activated in the process of
possible quetiapine abuse or dependence. Nevertheless,
the fact that quetiapine rapidly detaches from D2 recep-
tors might contribute not to have euphoria or dysphoria
due to the lack of the drug, but also to the potential of
quetiapine’s abuse (Morin 2007).
Quetiapine abuse is increasing and this might be
because clinicians prescribe fewer benzodiazepine, bar-
biturate, and stimulant drugs for substance dependence
treatment and in prisons because of their addictive char-
acteristics. The increase in quetiapine abuse might also
be related to increased use of quetiapine because of its
anxiolytic and sedative effects, and because it is thought
that it won’t result in dependence. In order to evaluate
this it might be useful to track quetiapine’s off-label pre-
scription use for the treatment of the symptoms of anxi-
ety, irritability, and sleep withdrawal over time.
CONCLUSION
Quetiapine is a drug approved by the FDA (Food
and Drug Administration) for use in the treatment of
schizophrenia, acute mania, and bipolar depression. Its
effectiveness in the treatment of substance use and anxi-
ety disorders has also been reported. It is reported that
quetiapine is increasingly abused, especially by patients
diagnosed with substance use disorders and by prisoners.
This observation, along with the lack of evidence that
quetiapine use causes abuse and dependence leaves clini-
cians with a dilemma concerning prescribing quetiapine
to treat these groups of patients. This dilemma contains
the risks of supporting the dependence of the patient,
and not using a drug that can be beneficial for the pa-
tient. This review aimed to examine published reports
on quetiapine abuse or dependence, and to present an
overview of this subject by discussing the possible mech-
anisms responsible. Additional studies that focus on pa-
tients with substance use disorders that are treated vol-
untarily or by court order, and controlled double-blind
studies involving people that have never used quetiapine
are needed.
8
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