ORIGINAL RESEARCH
Evaluation of Quetiapine Abuse and Misuse Reported to Poison Centers Wendy Klein-Schwartz, PharmD, MPH, Elana K. Schwartz, MA, and Bruce D. Anderson, PharmD, DABAT
Objective: There are case reports of abuse of quetiapine, but no studies address quetiapine abuse or misuse. Most literature on the population that abuses quetiapine describes an older age group with previous substance abuse history, many of whom are in jail. The objective of this study was to evaluate national poison center data on misuse/abuse of quetiapine. Methods: A retrospective study of American Association of Poison Control Centers National Poison Data System data from 2005 to 2011 on single substance quetiapine exposures coded as intentional misuse or abuse and followed to known outcome was performed. Data were evaluated for age, toxicity, management sites, treatments, and medical outcomes. Results: There were 3116 cases meeting inclusion criteria; reason was misuse in 1948 cases and abuse in 1168 cases. The median age was 23 years. Misuse was reported most often in adults, whereas abuse occurred most frequently in adolescents. The male-to-female ratio was 1.7 for abuse and 1.0 for misuse. There were no deaths. Moderate or major toxicity occurred in 23.7% and 27.1% of misuse and abuse cases, respectively. Seventy-six percent were treated in the emergency department and/or received medical admission. Conclusions: Misuse was more common than abuse, except in adolescents for whom abuse was more frequent. Although outcomes were generally good, significant toxicity occurred in 25% of cases and more than 75% of the patients were treated in the emergency department and/or received medical admission. The consequences of nonmedical use of quetiapine are serious in some patients. Key Words: abuse, nonmedical use, quetiapine, toxicity (J Addict Med 2014;8: 195–198)
Q
uetiapine is an atypical antipsychotic used for the treatment of schizophrenia, acute mania, and bipolar disorder. Quetiapine has also been investigated as a treatment for
From the Maryland Poison Center, University of Maryland School of Pharmacy, Baltimore. Received for publication September 30, 2013; accepted December 19, 2013. This research was presented in part at the European Association of Poison Control Centres and Toxicology meeting, Copenhagen, May 29 to 31, 2013. The 3 authors have no conflicts of interest or funding disclosures. Send correspondence and reprint requests to Wendy Klein-Schwartz, 220 Arch Street, Room 01-108, Baltimore, MD 21201. E-mail: wkleinsc@ rx.umaryland.edu. C 2014 American Society of Addiction Medicine Copyright ISSN: 1932-0620/14/0803-0195 DOI: 10.1097/ADM.0000000000000020
patients with substance abuse specifically in patients with mental illness who are dependent on cocaine and/or amphetamines (Hanley and Kenna, 2008). Antipsychotics are not controlled substances and are not usually considered drugs of abuse. However, there is growing evidence of diversion and abuse of quetiapine (Hanley and Kenna, 2008; Tcheremissine, 2008). It is unclear why there seems to be a higher risk of misuse/abuse of quetiapine compared with other antipsychotics and the mechanism of reinforcement of this misuse is also unknown (Fischer and Boggs, 2010; Sansone and Sansone, 2010). Quetiapine is sold on the black market for its sedative and anxiolytic effects and for insomnia. On the street it is known as Quell, Baby Heroin, and Susie-Q. Quetiapine used in combination with cocaine is called “Q-ball” and with marijuana is “Maq ball” (Haridas et al., 2010). The street price of quetiapine is $3 to $8 for a single 25-mg dose (Tarasoff and Osti, 2007). There are case reports and small case series of quetiapine misuse or abuse but no systematic investigations address outcomes in a large number of patients. Evaluating nonmedical use of quetiapine using a single database could provide important information concerning toxicity and patient outcomes. The purpose of this study was to evaluate misuse/abuse-related exposures to quetiapine reported to poison centers in the United States.
METHODS A retrospective review of quetiapine abuse and misuse cases reported to the American Association of Poison Control Centers (AAPCC) National Poison Data System (NPDS) was conducted. The NPDS receives data from all poison centers serving the entire US population. Poison centers receive exposure calls from the public and health care professionals. Specialists in poison information at the poison centers collect data in real time and it is sent electronically to NPDS. Review by the university institutional review board analyst determined that the study did not require full institutional board review because it met the criteria for Not Human Subject Research. The AAPCC NPDS was queried for cases from January 1, 2005, through December 31, 2011 (7 years), involving quetiapine exposures followed to known outcome. The search included all cases in which the substance was coded as quetiapine, Seroquel, or Seroquel XR, based on product codes in Micromedex. Only coded data were available to investigators, not free text fields. Inclusion criteria were nonmedical use of quetiapine as a single substance by history. Nonmedical
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use was defined as either “intentional abuse” or “intentional misuse” as the coded reason for exposure. National Poison Data System defines intentional abuse as improper or incorrect use of a substance in an attempt to gain a high, euphoric effect or some other psychotropic effect and includes recreational use of a substance. Intentional misuse results from improper or incorrect use of a substance for reasons other than psychotropic effects; an example would be deliberately increasing the dosage to enhance its effect. Cases with coingested substances were excluded. De-identified data were received from NPDS in Microsoft Excel 2003 format, data were imported into Microsoft Access 2010, and reports were generated using Crystal Reports 2008. Data were analyzed for age, sex, clinical effects, management site, treatments, and final medical outcomes. Management site was the highest level of care that the patient received and included on-site non–health care facility (HCF), treated and released from emergency department (ED), admitted to non–critical care unit (ie, a general medical/surgical unit), admitted to an intensive care unit, admitted to a psychiatric unit, other, or lost to follow-up/refused referral/unknown. Poison center coding of known medical outcomes included “no effect,” “minor effect,” “moderate effect,” “major effect,” and “death.” “Minor effect” was defined as clinical effects resulting from the exposure, but minimally bothersome. “ Moderate effect” was defined as clinical effects that are more pronounced, more prolonged, or more systemic, and usually some form of treatment is indicated. “Major effect” was defined as signs or symptoms that were life-threatening or resulted in significant residual disability or disfigurement. These medical outcomes were determined by the specialists in poison information when the cases were closed. Quantitative data were summarized by medians and ranges and categorical data by frequencies and percentages. Ages were compared using the Mann-Whitney U test. The χ 2 test was used to compare management sites and medical outcomes. After significance was found, a Tukey pairwise multiple comparison of proportions was performed (Tukey test statistic = Q) to determine which differences were significant. Analyses were done using SAS (version 9.2; SAS Institute Inc, Cary, North Carolina). All reported P values are 2-sided. Statistical significance was defined as P < 0.05.
ingested by 97.2% of patients. In 12 cases, quetiapine was taken by more than 1 route. Among the abuse patients, 8 injected and 65 used quetiapine by inhalation/intranasal administration. In contrast, none of the misuse patients injected it and only 7 used quetiapine by inhalation/intranasal administration. The call to the poison center originated from a health care professional in 70.4% of cases, from a residence in 17.8%, other site in 9.3%, and public area/school/workplace/unknown site in 2.5% cases. Although correctional facility calls are included as a subset of other site in NPDS, poison centers develop site-specific codes within this category, so it is not possible to determine how many, if any, were from a correctional facility. Overall, nonmedical use of quetiapine was well tolerated. The most common clinical effect was drowsiness/lethargy (51.2%), followed by tachycardia (24.9%). Other reported clinical effects included slurred speech (7.1%), dizziness/vertigo (5.5%), hypotension (5.2%), agitation/irritable (4.9%), confusion (3.7%), ataxia (3.4%), nausea (2.0%), vomiting (1.5%), conduction disturbances (1.5%), hypertension (1.4%), hallucinations (1.1%), and electrolyte abnormality (1.0%). Electrocardiographic change (other), coma, tremor, and dystonias each occurred in less than 1% of patients. Seizures were uncommon with 9 cases with single seizures and 5 with multiple discrete seizures reported. Respiratory depression and respiratory arrest were reported in 18 patients and 3 patients, respectively. The majority of nonmedical quetiapine users were observed without treatment. Of 2677 cases managed in an HCF, specific treatments included intravenous fluids (712; 26.6%), activated charcoal, single or multiple dose (486; 18.2%), oxygen (117; 4.4%), benzodiazepines (112; 4.2%), naloxone (52; 1.9%), antihistamines (33; 1.2%), other sedation (31; 1.2%), and intubation (28; 1.0%) and ventilation (26; 1.0%). Only 3 patients received vasopressor suggesting that hypotension was usually responsive to intravenous fluids. Table 1 provides data on management sites. Overall, 8.3% were managed on-site non-HCF and 76.0% were treated in the ED and/or received a medical admission. The distribution of abuse versus misuse was significantly different across management sites (χ 2 (4) = 30.1, P < 0.0001). The proportion of abuse cases managed on-site non-HCF (4.9%) was significantly lower than misuse cases (10.4%) (Q = 7.1, adj.
RESULTS There were 3116 cases that met inclusion criteria, of which 1948 (62.5%) were misuse and 1168 (37.5%) were abuse. The median age was 23 years with a range of 4 to 89 years. Excluding the 13 cases with unknown age child or unknown age, the case count by age for misuse and abuse, respectively, were 5 and 0 cases less than 6 years of age; 69 and 32 cases between 6 and 12 years; 566 and 684 cases between 13 and 19 years; and 1299 and 448 cases greater than 19 years of age. Within the 6- to 12-year-old age group, 90.6% and 62.3% of abuse and misuse, respectively, occurred in children aged 10 to 12 years. Median age for abuse was significantly lower at 17 years compared with 26 years for misuse (P < 0.0001), with the majority of misuse in adults and abuse occurring most frequently in adolescents. The male-to-female ratio was 1.7 for abuse and 1.0 for misuse (P < 0.0001). Quetiapine was
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TABLE 1. Management Sites After Quetiapine Misuse and Abuse Management Site On-site non-HCF† Medically managed in HCF Treated/released ED Admit critical care Admit non–critical care unit Admitted to psych Other Lost/refused/unknown‡ Total
Misuse (%)*
Abuse (%)*
Total (%)*
202 (10.4)
57 (4.9)
259 (8.3)
1015 (52.1) 231 (11.9) 195 (10.0) 197 (10.1) 15 (0.8) 93 (4.8) 1948
656 (56.2) 175 (15.0) 97 (8.3) 111 (9.5) 10 (0.9) 62 (5.3) 1168
1671 (53.6) 406 (13.0) 292 (9.4) 308 (9.9) 25 (0.8) 155 (5.0) 3116
* Column percent. ‡Includes lost to follow-up/left AMA/refused referral/unknown. † Significant difference on pairwise comparison (P < 0.05). ED, emergency department; HCF, health care facility, Psych, Psychiatry. C
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P < 0.05). The proportion of abuse and misuse cases managed medically in an HCF (79.5% vs 74.0%) was not significantly different (P > 0.05). None of the other pairwise comparisons were significantly different. Figure 1 shows that most patients (75%) experienced no effect or minor effects. Moderate or major effects occurred in 25.0% of cases. Distribution of outcomes was not significantly different for misuse and abuse (χ 2 (3) = 6.6, P = 0.09).
DISCUSSION Abuse and misuse of psychotherapeutic drugs is a growing problem, usually involving controlled substances such as benzodiazepines, other sedative/anxiolytics, or stimulants. Abuse of antipsychotics is less prevalent and therefore may be underappreciated by clinicians. Quetiapine abuse was first described in incarcerated individuals in a Los Angeles county jail in 2004 and subsequently in other prison settings (Pinta and Taylor, 2007; Reccoppa, 2012). Prisoners may seek quetiapine because it produces sedative, anxiolytic, calming effects, and feeling “high” and is more available than other commonly abused drugs. Quetiapine can also help with symptoms associated with substance abuse withdrawal, which occurs at high rates in the prison population (Pinta and Taylor, 2007; Hanley and Kenna, 2008; Keltner and Vance, 2008). In many reported cases, quetiapine misuse occurs in individuals with a prior substance abuse or alcohol problem. Patients have been described who fabricate psychotic symptoms to obtain the drug (Murphy et al., 2008). Among 74 clients at a methadone maintenance clinic who participated in a survey on quetiapine misuse, 59 reported lifetime use of quetiapine and of these, 21% reported using it only without a prescription and 42% used it both with and without a prescription (McLarnon et al., 2012). Among prescribed users, 38% intentionally took quetiapine in excess at least 1 time and 51% admitted to diverting the drug. Intravenous quetiapine abuse was first reported in 2005 (Hussain et al., 2005). Since then, its abuse orally, intranasally, and by inhalation has also been described (Morin, 2007; Reeves and Brister, 2007; Haridas et al., 2010). In 8 previously reported cases, the route was oral or was unreported but assumed to be oral (Pinta and Taylor, 2007; Reeves and Brister, 2007; Murphy et al., 2008; Papparigopoulos et al., 2008; Chen et al., 2009; Fischer and Boggs, 2010). There are
FIGURE 1. Outcomes by reason: Misuse and abuse. C
Evaluation of Quetiapine Abuse and Misuse
2 cases in which individuals injected quetiapine; one of these patients also used quetiapine intranasally and one used it in combination with cocaine (Hussain et al., 2005; Waters and Joshi, 2007). Intranasal/inhalational administration is described in 3 case reports (Hussain et al., 2005; Morin, 2007; Haridas et al., 2010) and mentioned as the route of administration in 2 reports from correctional institutions (Pierre et al., 2004; Reccoppa, 2010). The most common route for poison center cases was ingestion followed by intranasal/inhalation. Intranasal/inhalation and parenteral were more commonly found in abuse than in misuse cases. Parenteral was infrequent, occurring in less than 1% of abuse cases and not at all in misuse cases. Male adults are the population previously described as those misusing or abusing quetiapine abuse. In 11 cases, the average age was 39 years with a range of 23 to 59 years and 8 were men (Hussain et al., 2005; Morin, 2007; Pinta and Taylor, 2007; Reeves and Brister, 2007; Waters and Joshi, 2007; Murphy et al., 2008; Papparigopoulos et al., 2008; Chen et al., 2009; Fischer and Boggs, 2010; Haridas et al., 2010). Poison center data followed a similar sex distribution for abuse cases with a male predominance for abuse but equal distribution for misuse. An interesting and slightly contradictory finding in the poison center data was that abuse was more common in adolescents whereas misuse was more common in adults. Of 1164 abuse cases with known age, 59% occurred in adolescents aged 13 to 19 years compared with 38% in adults. One explanation for this could be that published cases more often involve incarcerated individuals or those receiving psychiatric and/or substance abuse treatment. This population is more likely to be adult. Poison centers calls are more likely to be from the community so the population served is generally not incarcerated and less likely overall to be receiving mental health services. This also suggests that the current published case reports might be misrepresentative of the general population that abuses quetiapine. In addition, it is possible that there is reporting bias in that cases involving adolescents are more likely to be reported to poison centers than those cases of abuse or misuse in adults. Quetiapine is not approved for use in children younger than 10 years. There were 5 cases of intentional misuse in children younger than 6 years. In children aged 6 to 12 years, there were 68 and 32 cases of misuse and abuse, respectively. All but 3 abuse cases occurred in children aged 10 to 12 years. Ages 9 to 12 years accounted for over three quarters of misuse cases. Although a relatively small proportion of the total cases, misuse or abuse in children is concerning. One might postulate that in the intentional misuse cases, caregivers administered quetiapine to the children for its “quieting” effect. However, with coded data only it is not possible to elucidate the exact circumstances involved in these pediatric exposures. Management site varies depending on the reason for exposures. In the poison center data set, quetiapine misuse was more likely to be treated outside an HCF. The higher frequency of HCF management cases for abuse cases (∼80%) was not statistically different from that for misuse (74%). There was a similar frequency of admission to psychiatry (∼9%). Case reports describe the following treatment sites: 6 individuals were treated at an inpatient psychiatric facility
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(Morin, 2007; Reeves and Brister, 2007; Murphy et al., 2008; Papparigopoulos et al., 2008; Haridas et al., 2010), two were incarcerated (Hussain et al., 2005; Pinta and Taylor, 2007), two were treated at an outpatient clinic (Reeves and Brister, 2007; Fischer and Boggs, 2010), and one was treated in an ED (Waters and Joshi, 2007). Poison center cases present a somewhat different picture as most patients were treated medically, either in the ED or with hospital admission. Limitations of this study include the fact that reporting to poison centers is voluntary and nonmedical use cases may be underreported in NPDS. This is a retrospective review of coded poison center data that relies on history provided by the patient and clinical reports provided by hospital staff. Coded data provided by poison centers may include miscoding or incomplete coding; underreporting of clinical effects and treatments has been previously described (Jaramillo et al., 2010). The free text case note fields of the poison center charts were not available to investigators so it was not possible to review charts for coding errors. Quetiapine is not routinely screened for so there is no laboratory confirmation of the reported exposures. Cases with coingestants were excluded from this study on the basis of history. With the available coded data, it was not possible to determine how many cases in the “other site” category were from a correctional facility. Unknown management site (ie, lost to follow-up, refused referral or unknown) in 5% of cases leaves a gap in our knowledge of the true distribution of this outcome measure.
CONCLUSIONS In this 7-year retrospective study of poison cases, misuse was more common than abuse, except in adolescents for whom abuse was more frequent. Although outcomes were generally good, significant toxicity occurred in 25% of cases and 76% were treated in the ED and/or received medical admission. The consequences of nonmedical use of quetiapine are serious in some patients.
DISCLAIMER The AAPCC (http://www.aapcc.org) maintains the national database of information logged by the country’s 57 Poison Centers. Case records in this database are from selfreported calls: they reflect only information provided when the public or health care professionals report an actual or potential exposure to a substance (eg, an ingestion, inhalation, or topical exposure), or request information/educational materials. Exposures do not necessarily represent a poisoning or overdose. The AAPCC is not able to completely verify the accuracy
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of every report made to member centers. Additional exposures may go unreported to Poison Centers and data referenced from the AAPCC should not be construed to represent the complete incidence of national exposures to any substance(s).
ACKNOWLEDGMENTS We thank Larry Gonzales, BS, senior IT specialist at the Maryland Poison Center, for his assistance with data analysis and Yolande Tra, PhD, for her assistance with statistical analysis. REFERENCES Chen CY, Shiah IS, Lee WK, et al. Dependence on quetiapine in combination with zolpidem and clonazepam in bipolar depression. Psychiatry Clin Neurosci 2009;63:427–428. Fischer BA, Boggs DL. The role of antihistaminic effects in the misuse of quetiapine: a case report and review of the literature. Neurosci Biobehav Rev 2010;34:555–558. Hanley MJ, Kenna GA. Quetiapine: treatment for substance abuse and drug of abuse. Am J Health Syst Pharm 2008;65:611–618. Haridas A, Kushon D, Gurmu S, et al. Smoking quetiapine: A “maq ball”? Prim Psychiatry 2010;17:38–39. Hussain MZ, Waheed W, Hussain S. Intravenous quetiapine abuse. Am J Psychiatry 2005;162:1755–1756. Jaramillo JE, Marchbanks B, Willis B, et al. Evaluation of completeness of selected poison control center data fields. J Med Syst 2010;34:499–507. Keltner NL, Vance DE. Incarcerated care and quetiapine abuse. Perspect Psychiatric Care 2008;44:202–206. McLarnon ME, Fulton HG, MacIsaac C, et al. Characteristics of quetiapine misuse among clients of a community-based methadone maintenance program. J Clin Psychopharmacol 2012;32:721–723. Morin AK. Possible intranasal quetiapine misuse. Am J Health Syst Pharm 2007;64:723–725. Murphy D, Baily K, Stone M, et al. Addictive potential of quetiapine. Am J Psychiatry 2008;165:918. Papparigopoulos T, Karaiskos D, Liappas J. Quetiapine: another drug with potential for misuse? A case report. J Clin Psychiatry 2008;69:162–163. Pierre JM, Shnayder I, Wirshing DA, et al. Intranasal quetiapine abuse. Am J Psychiatry 2004;161:1718. Pinta ER, Taylor RE. Quetiapine addiction? Am J Psychiatry 2007;164:174– 175. Reccoppa L. Less abuse potential with XR formulation of quetiapine? Am J Addict 2010;20:178. Reeves RR, Brister JC. Additional evidence of the abuse potential of quetiapine. South Med J 2007;100:834–836. Sansone RA, Sansone LA. Is seroquel developing an illicit reputation for misuse/abuse? Psychiatry 2010;7:13–16. Tarasoff G, Osti K. Black market value of antipsychotics, antidepressants, and hypnotics in Las Vegas, Nevada. Am J Psychiatry 2007;164:350. Tcheremissine OV. Is quetiapine a drug of abuse? Reexamining the issue of addiction. Expert Opin Drug Saf 2008;7:739–748. Waters BM, Joshi KG. Intravenous quetiapine-cocaine use (“Q-Ball”). Am J Psychiatry 2007;164:173–174.
C
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Evaluation of Quetiapine Abuse and Misuse Reported to Poison Centers Wendy Klein-Schwartz, PharmD, MPH, Elana K. Schwartz, MA, and Bruce D. Anderson, PharmD, DABAT
Objective: There are case reports of abuse of quetiapine, but no studies address quetiapine abuse or misuse. Most literature on the population that abuses quetiapine describes an older age group with previous substance abuse history, many of whom are in jail. The objective of this study was to evaluate national poison center data on misuse/abuse of quetiapine. Methods: A retrospective study of American Association of Poison Control Centers National Poison Data System data from 2005 to 2011 on single substance quetiapine exposures coded as intentional misuse or abuse and followed to known outcome was performed. Data were evaluated for age, toxicity, management sites, treatments, and medical outcomes. Results: There were 3116 cases meeting inclusion criteria; reason was misuse in 1948 cases and abuse in 1168 cases. The median age was 23 years. Misuse was reported most often in adults, whereas abuse occurred most frequently in adolescents. The male-to-female ratio was 1.7 for abuse and 1.0 for misuse. There were no deaths. Moderate or major toxicity occurred in 23.7% and 27.1% of misuse and abuse cases, respectively. Seventy-six percent were treated in the emergency department and/or received medical admission. Conclusions: Misuse was more common than abuse, except in adolescents for whom abuse was more frequent. Although outcomes were generally good, significant toxicity occurred in 25% of cases and more than 75% of the patients were treated in the emergency department and/or received medical admission. The consequences of nonmedical use of quetiapine are serious in some patients. Key Words: abuse, nonmedical use, quetiapine, toxicity (J Addict Med 2014;8: 195–198)
Q
uetiapine is an atypical antipsychotic used for the treatment of schizophrenia, acute mania, and bipolar disorder. Quetiapine has also been investigated as a treatment for
From the Maryland Poison Center, University of Maryland School of Pharmacy, Baltimore. Received for publication September 30, 2013; accepted December 19, 2013. This research was presented in part at the European Association of Poison Control Centres and Toxicology meeting, Copenhagen, May 29 to 31, 2013. The 3 authors have no conflicts of interest or funding disclosures. Send correspondence and reprint requests to Wendy Klein-Schwartz, 220 Arch Street, Room 01-108, Baltimore, MD 21201. E-mail: wkleinsc@ rx.umaryland.edu. C 2014 American Society of Addiction Medicine Copyright ISSN: 1932-0620/14/0803-0195 DOI: 10.1097/ADM.0000000000000020
patients with substance abuse specifically in patients with mental illness who are dependent on cocaine and/or amphetamines (Hanley and Kenna, 2008). Antipsychotics are not controlled substances and are not usually considered drugs of abuse. However, there is growing evidence of diversion and abuse of quetiapine (Hanley and Kenna, 2008; Tcheremissine, 2008). It is unclear why there seems to be a higher risk of misuse/abuse of quetiapine compared with other antipsychotics and the mechanism of reinforcement of this misuse is also unknown (Fischer and Boggs, 2010; Sansone and Sansone, 2010). Quetiapine is sold on the black market for its sedative and anxiolytic effects and for insomnia. On the street it is known as Quell, Baby Heroin, and Susie-Q. Quetiapine used in combination with cocaine is called “Q-ball” and with marijuana is “Maq ball” (Haridas et al., 2010). The street price of quetiapine is $3 to $8 for a single 25-mg dose (Tarasoff and Osti, 2007). There are case reports and small case series of quetiapine misuse or abuse but no systematic investigations address outcomes in a large number of patients. Evaluating nonmedical use of quetiapine using a single database could provide important information concerning toxicity and patient outcomes. The purpose of this study was to evaluate misuse/abuse-related exposures to quetiapine reported to poison centers in the United States.
METHODS A retrospective review of quetiapine abuse and misuse cases reported to the American Association of Poison Control Centers (AAPCC) National Poison Data System (NPDS) was conducted. The NPDS receives data from all poison centers serving the entire US population. Poison centers receive exposure calls from the public and health care professionals. Specialists in poison information at the poison centers collect data in real time and it is sent electronically to NPDS. Review by the university institutional review board analyst determined that the study did not require full institutional board review because it met the criteria for Not Human Subject Research. The AAPCC NPDS was queried for cases from January 1, 2005, through December 31, 2011 (7 years), involving quetiapine exposures followed to known outcome. The search included all cases in which the substance was coded as quetiapine, Seroquel, or Seroquel XR, based on product codes in Micromedex. Only coded data were available to investigators, not free text fields. Inclusion criteria were nonmedical use of quetiapine as a single substance by history. Nonmedical
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use was defined as either “intentional abuse” or “intentional misuse” as the coded reason for exposure. National Poison Data System defines intentional abuse as improper or incorrect use of a substance in an attempt to gain a high, euphoric effect or some other psychotropic effect and includes recreational use of a substance. Intentional misuse results from improper or incorrect use of a substance for reasons other than psychotropic effects; an example would be deliberately increasing the dosage to enhance its effect. Cases with coingested substances were excluded. De-identified data were received from NPDS in Microsoft Excel 2003 format, data were imported into Microsoft Access 2010, and reports were generated using Crystal Reports 2008. Data were analyzed for age, sex, clinical effects, management site, treatments, and final medical outcomes. Management site was the highest level of care that the patient received and included on-site non–health care facility (HCF), treated and released from emergency department (ED), admitted to non–critical care unit (ie, a general medical/surgical unit), admitted to an intensive care unit, admitted to a psychiatric unit, other, or lost to follow-up/refused referral/unknown. Poison center coding of known medical outcomes included “no effect,” “minor effect,” “moderate effect,” “major effect,” and “death.” “Minor effect” was defined as clinical effects resulting from the exposure, but minimally bothersome. “ Moderate effect” was defined as clinical effects that are more pronounced, more prolonged, or more systemic, and usually some form of treatment is indicated. “Major effect” was defined as signs or symptoms that were life-threatening or resulted in significant residual disability or disfigurement. These medical outcomes were determined by the specialists in poison information when the cases were closed. Quantitative data were summarized by medians and ranges and categorical data by frequencies and percentages. Ages were compared using the Mann-Whitney U test. The χ 2 test was used to compare management sites and medical outcomes. After significance was found, a Tukey pairwise multiple comparison of proportions was performed (Tukey test statistic = Q) to determine which differences were significant. Analyses were done using SAS (version 9.2; SAS Institute Inc, Cary, North Carolina). All reported P values are 2-sided. Statistical significance was defined as P < 0.05.
ingested by 97.2% of patients. In 12 cases, quetiapine was taken by more than 1 route. Among the abuse patients, 8 injected and 65 used quetiapine by inhalation/intranasal administration. In contrast, none of the misuse patients injected it and only 7 used quetiapine by inhalation/intranasal administration. The call to the poison center originated from a health care professional in 70.4% of cases, from a residence in 17.8%, other site in 9.3%, and public area/school/workplace/unknown site in 2.5% cases. Although correctional facility calls are included as a subset of other site in NPDS, poison centers develop site-specific codes within this category, so it is not possible to determine how many, if any, were from a correctional facility. Overall, nonmedical use of quetiapine was well tolerated. The most common clinical effect was drowsiness/lethargy (51.2%), followed by tachycardia (24.9%). Other reported clinical effects included slurred speech (7.1%), dizziness/vertigo (5.5%), hypotension (5.2%), agitation/irritable (4.9%), confusion (3.7%), ataxia (3.4%), nausea (2.0%), vomiting (1.5%), conduction disturbances (1.5%), hypertension (1.4%), hallucinations (1.1%), and electrolyte abnormality (1.0%). Electrocardiographic change (other), coma, tremor, and dystonias each occurred in less than 1% of patients. Seizures were uncommon with 9 cases with single seizures and 5 with multiple discrete seizures reported. Respiratory depression and respiratory arrest were reported in 18 patients and 3 patients, respectively. The majority of nonmedical quetiapine users were observed without treatment. Of 2677 cases managed in an HCF, specific treatments included intravenous fluids (712; 26.6%), activated charcoal, single or multiple dose (486; 18.2%), oxygen (117; 4.4%), benzodiazepines (112; 4.2%), naloxone (52; 1.9%), antihistamines (33; 1.2%), other sedation (31; 1.2%), and intubation (28; 1.0%) and ventilation (26; 1.0%). Only 3 patients received vasopressor suggesting that hypotension was usually responsive to intravenous fluids. Table 1 provides data on management sites. Overall, 8.3% were managed on-site non-HCF and 76.0% were treated in the ED and/or received a medical admission. The distribution of abuse versus misuse was significantly different across management sites (χ 2 (4) = 30.1, P < 0.0001). The proportion of abuse cases managed on-site non-HCF (4.9%) was significantly lower than misuse cases (10.4%) (Q = 7.1, adj.
RESULTS There were 3116 cases that met inclusion criteria, of which 1948 (62.5%) were misuse and 1168 (37.5%) were abuse. The median age was 23 years with a range of 4 to 89 years. Excluding the 13 cases with unknown age child or unknown age, the case count by age for misuse and abuse, respectively, were 5 and 0 cases less than 6 years of age; 69 and 32 cases between 6 and 12 years; 566 and 684 cases between 13 and 19 years; and 1299 and 448 cases greater than 19 years of age. Within the 6- to 12-year-old age group, 90.6% and 62.3% of abuse and misuse, respectively, occurred in children aged 10 to 12 years. Median age for abuse was significantly lower at 17 years compared with 26 years for misuse (P < 0.0001), with the majority of misuse in adults and abuse occurring most frequently in adolescents. The male-to-female ratio was 1.7 for abuse and 1.0 for misuse (P < 0.0001). Quetiapine was
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TABLE 1. Management Sites After Quetiapine Misuse and Abuse Management Site On-site non-HCF† Medically managed in HCF Treated/released ED Admit critical care Admit non–critical care unit Admitted to psych Other Lost/refused/unknown‡ Total
Misuse (%)*
Abuse (%)*
Total (%)*
202 (10.4)
57 (4.9)
259 (8.3)
1015 (52.1) 231 (11.9) 195 (10.0) 197 (10.1) 15 (0.8) 93 (4.8) 1948
656 (56.2) 175 (15.0) 97 (8.3) 111 (9.5) 10 (0.9) 62 (5.3) 1168
1671 (53.6) 406 (13.0) 292 (9.4) 308 (9.9) 25 (0.8) 155 (5.0) 3116
* Column percent. ‡Includes lost to follow-up/left AMA/refused referral/unknown. † Significant difference on pairwise comparison (P < 0.05). ED, emergency department; HCF, health care facility, Psych, Psychiatry. C
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P < 0.05). The proportion of abuse and misuse cases managed medically in an HCF (79.5% vs 74.0%) was not significantly different (P > 0.05). None of the other pairwise comparisons were significantly different. Figure 1 shows that most patients (75%) experienced no effect or minor effects. Moderate or major effects occurred in 25.0% of cases. Distribution of outcomes was not significantly different for misuse and abuse (χ 2 (3) = 6.6, P = 0.09).
DISCUSSION Abuse and misuse of psychotherapeutic drugs is a growing problem, usually involving controlled substances such as benzodiazepines, other sedative/anxiolytics, or stimulants. Abuse of antipsychotics is less prevalent and therefore may be underappreciated by clinicians. Quetiapine abuse was first described in incarcerated individuals in a Los Angeles county jail in 2004 and subsequently in other prison settings (Pinta and Taylor, 2007; Reccoppa, 2012). Prisoners may seek quetiapine because it produces sedative, anxiolytic, calming effects, and feeling “high” and is more available than other commonly abused drugs. Quetiapine can also help with symptoms associated with substance abuse withdrawal, which occurs at high rates in the prison population (Pinta and Taylor, 2007; Hanley and Kenna, 2008; Keltner and Vance, 2008). In many reported cases, quetiapine misuse occurs in individuals with a prior substance abuse or alcohol problem. Patients have been described who fabricate psychotic symptoms to obtain the drug (Murphy et al., 2008). Among 74 clients at a methadone maintenance clinic who participated in a survey on quetiapine misuse, 59 reported lifetime use of quetiapine and of these, 21% reported using it only without a prescription and 42% used it both with and without a prescription (McLarnon et al., 2012). Among prescribed users, 38% intentionally took quetiapine in excess at least 1 time and 51% admitted to diverting the drug. Intravenous quetiapine abuse was first reported in 2005 (Hussain et al., 2005). Since then, its abuse orally, intranasally, and by inhalation has also been described (Morin, 2007; Reeves and Brister, 2007; Haridas et al., 2010). In 8 previously reported cases, the route was oral or was unreported but assumed to be oral (Pinta and Taylor, 2007; Reeves and Brister, 2007; Murphy et al., 2008; Papparigopoulos et al., 2008; Chen et al., 2009; Fischer and Boggs, 2010). There are
FIGURE 1. Outcomes by reason: Misuse and abuse. C
Evaluation of Quetiapine Abuse and Misuse
2 cases in which individuals injected quetiapine; one of these patients also used quetiapine intranasally and one used it in combination with cocaine (Hussain et al., 2005; Waters and Joshi, 2007). Intranasal/inhalational administration is described in 3 case reports (Hussain et al., 2005; Morin, 2007; Haridas et al., 2010) and mentioned as the route of administration in 2 reports from correctional institutions (Pierre et al., 2004; Reccoppa, 2010). The most common route for poison center cases was ingestion followed by intranasal/inhalation. Intranasal/inhalation and parenteral were more commonly found in abuse than in misuse cases. Parenteral was infrequent, occurring in less than 1% of abuse cases and not at all in misuse cases. Male adults are the population previously described as those misusing or abusing quetiapine abuse. In 11 cases, the average age was 39 years with a range of 23 to 59 years and 8 were men (Hussain et al., 2005; Morin, 2007; Pinta and Taylor, 2007; Reeves and Brister, 2007; Waters and Joshi, 2007; Murphy et al., 2008; Papparigopoulos et al., 2008; Chen et al., 2009; Fischer and Boggs, 2010; Haridas et al., 2010). Poison center data followed a similar sex distribution for abuse cases with a male predominance for abuse but equal distribution for misuse. An interesting and slightly contradictory finding in the poison center data was that abuse was more common in adolescents whereas misuse was more common in adults. Of 1164 abuse cases with known age, 59% occurred in adolescents aged 13 to 19 years compared with 38% in adults. One explanation for this could be that published cases more often involve incarcerated individuals or those receiving psychiatric and/or substance abuse treatment. This population is more likely to be adult. Poison centers calls are more likely to be from the community so the population served is generally not incarcerated and less likely overall to be receiving mental health services. This also suggests that the current published case reports might be misrepresentative of the general population that abuses quetiapine. In addition, it is possible that there is reporting bias in that cases involving adolescents are more likely to be reported to poison centers than those cases of abuse or misuse in adults. Quetiapine is not approved for use in children younger than 10 years. There were 5 cases of intentional misuse in children younger than 6 years. In children aged 6 to 12 years, there were 68 and 32 cases of misuse and abuse, respectively. All but 3 abuse cases occurred in children aged 10 to 12 years. Ages 9 to 12 years accounted for over three quarters of misuse cases. Although a relatively small proportion of the total cases, misuse or abuse in children is concerning. One might postulate that in the intentional misuse cases, caregivers administered quetiapine to the children for its “quieting” effect. However, with coded data only it is not possible to elucidate the exact circumstances involved in these pediatric exposures. Management site varies depending on the reason for exposures. In the poison center data set, quetiapine misuse was more likely to be treated outside an HCF. The higher frequency of HCF management cases for abuse cases (∼80%) was not statistically different from that for misuse (74%). There was a similar frequency of admission to psychiatry (∼9%). Case reports describe the following treatment sites: 6 individuals were treated at an inpatient psychiatric facility
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Klein-Schwartz et al.
(Morin, 2007; Reeves and Brister, 2007; Murphy et al., 2008; Papparigopoulos et al., 2008; Haridas et al., 2010), two were incarcerated (Hussain et al., 2005; Pinta and Taylor, 2007), two were treated at an outpatient clinic (Reeves and Brister, 2007; Fischer and Boggs, 2010), and one was treated in an ED (Waters and Joshi, 2007). Poison center cases present a somewhat different picture as most patients were treated medically, either in the ED or with hospital admission. Limitations of this study include the fact that reporting to poison centers is voluntary and nonmedical use cases may be underreported in NPDS. This is a retrospective review of coded poison center data that relies on history provided by the patient and clinical reports provided by hospital staff. Coded data provided by poison centers may include miscoding or incomplete coding; underreporting of clinical effects and treatments has been previously described (Jaramillo et al., 2010). The free text case note fields of the poison center charts were not available to investigators so it was not possible to review charts for coding errors. Quetiapine is not routinely screened for so there is no laboratory confirmation of the reported exposures. Cases with coingestants were excluded from this study on the basis of history. With the available coded data, it was not possible to determine how many cases in the “other site” category were from a correctional facility. Unknown management site (ie, lost to follow-up, refused referral or unknown) in 5% of cases leaves a gap in our knowledge of the true distribution of this outcome measure.
CONCLUSIONS In this 7-year retrospective study of poison cases, misuse was more common than abuse, except in adolescents for whom abuse was more frequent. Although outcomes were generally good, significant toxicity occurred in 25% of cases and 76% were treated in the ED and/or received medical admission. The consequences of nonmedical use of quetiapine are serious in some patients.
DISCLAIMER The AAPCC (http://www.aapcc.org) maintains the national database of information logged by the country’s 57 Poison Centers. Case records in this database are from selfreported calls: they reflect only information provided when the public or health care professionals report an actual or potential exposure to a substance (eg, an ingestion, inhalation, or topical exposure), or request information/educational materials. Exposures do not necessarily represent a poisoning or overdose. The AAPCC is not able to completely verify the accuracy
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of every report made to member centers. Additional exposures may go unreported to Poison Centers and data referenced from the AAPCC should not be construed to represent the complete incidence of national exposures to any substance(s).
ACKNOWLEDGMENTS We thank Larry Gonzales, BS, senior IT specialist at the Maryland Poison Center, for his assistance with data analysis and Yolande Tra, PhD, for her assistance with statistical analysis. REFERENCES Chen CY, Shiah IS, Lee WK, et al. Dependence on quetiapine in combination with zolpidem and clonazepam in bipolar depression. Psychiatry Clin Neurosci 2009;63:427–428. Fischer BA, Boggs DL. The role of antihistaminic effects in the misuse of quetiapine: a case report and review of the literature. Neurosci Biobehav Rev 2010;34:555–558. Hanley MJ, Kenna GA. Quetiapine: treatment for substance abuse and drug of abuse. Am J Health Syst Pharm 2008;65:611–618. Haridas A, Kushon D, Gurmu S, et al. Smoking quetiapine: A “maq ball”? Prim Psychiatry 2010;17:38–39. Hussain MZ, Waheed W, Hussain S. Intravenous quetiapine abuse. Am J Psychiatry 2005;162:1755–1756. Jaramillo JE, Marchbanks B, Willis B, et al. Evaluation of completeness of selected poison control center data fields. J Med Syst 2010;34:499–507. Keltner NL, Vance DE. Incarcerated care and quetiapine abuse. Perspect Psychiatric Care 2008;44:202–206. McLarnon ME, Fulton HG, MacIsaac C, et al. Characteristics of quetiapine misuse among clients of a community-based methadone maintenance program. J Clin Psychopharmacol 2012;32:721–723. Morin AK. Possible intranasal quetiapine misuse. Am J Health Syst Pharm 2007;64:723–725. Murphy D, Baily K, Stone M, et al. Addictive potential of quetiapine. Am J Psychiatry 2008;165:918. Papparigopoulos T, Karaiskos D, Liappas J. Quetiapine: another drug with potential for misuse? A case report. J Clin Psychiatry 2008;69:162–163. Pierre JM, Shnayder I, Wirshing DA, et al. Intranasal quetiapine abuse. Am J Psychiatry 2004;161:1718. Pinta ER, Taylor RE. Quetiapine addiction? Am J Psychiatry 2007;164:174– 175. Reccoppa L. Less abuse potential with XR formulation of quetiapine? Am J Addict 2010;20:178. Reeves RR, Brister JC. Additional evidence of the abuse potential of quetiapine. South Med J 2007;100:834–836. Sansone RA, Sansone LA. Is seroquel developing an illicit reputation for misuse/abuse? Psychiatry 2010;7:13–16. Tarasoff G, Osti K. Black market value of antipsychotics, antidepressants, and hypnotics in Las Vegas, Nevada. Am J Psychiatry 2007;164:350. Tcheremissine OV. Is quetiapine a drug of abuse? Reexamining the issue of addiction. Expert Opin Drug Saf 2008;7:739–748. Waters BM, Joshi KG. Intravenous quetiapine-cocaine use (“Q-Ball”). Am J Psychiatry 2007;164:173–174.
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