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Mount Sinai St. Luke's and Roosevelt Hospitals, New York, NY, USAColumbia University Medical Center, College of Physicians and Surgeons, Department of Psychiatry, New York, NY, USA
Non-medical use of atypical antipsychotics by substance abusers has been reported in the literature, although no detailed studies exist. Among 429 addiction treatment inpatients screened, 73 (17.0%) reported misuse of antipsychotics with alcohol, opioids, cocaine, methamphetamine and/or cannabis; 39 (9.1%) within the past year. Of past year misusers, 25 (64.1%) were interviewed. Most were male (76.0%), non-Caucasian (56.0%), and polysubstance abusers (84.0%). Quetiapine, the most abused drug (96.0%), was obtained primarily from doctors (52.0%) and family/friends (48.0%). Reasons for use included to “recover” from other substances (66.7%), “enhance” the effects of other substances (25.0%), and “experiment” (20.8%). The most frequently reported positive effect was “feeling mellow” (75.0%); negative effects were consistent with antipsychotic use (e.g., feeling thirsty, trouble concentrating). Compared to a normative sample of inpatient substance abusers, ASI composite scores were higher. Findings suggest that physicians should assess for use/misuse of atypical antipsychotics among patients with addiction.
Accounts of use of atypical antipsychotics, in combination with alcohol and other drugs, began appearing on informal user blogs and other social media outlets more than a decade ago. A series of case reports subsequently detailed abuse of atypical antipsychotics through intranasal snorting (
The mechanisms underlying abuse of quetiapine (the most frequently misused atypical antipsychotic) remain unclear. Hypothesized pathways include the dopamine reward system common to all addictive substances, the “sedation theory” which suggests that quetiapine is valued because of sedative/anxiolytic properties (
), and the antihistaminic hypothesis that postulates that histamine inhibits the reward system and the antihistaminic properties of quetiapine may have a reinforcing effect (
). However, none of the theories are able to fully explain the misuse of quetiapine, nor answer the question as to why this particular drug appears to be preferable to other atypical antipsychotics (
). The authors also hypothesize that quetiapine may have some “unique intrinsic property” that users find attractive, that the drug's appeal may lie in some specific pharmacological effect, or as an additive effect when used in combination with traditional drugs of abuse.
reported on quetiapine use among 74 opioid treatment program patients who completed face-to-face interviews as part of a larger study. Eighty percent reported prior use of quetiapine. Of these, 75% admitted to abuse/misuse to include alternate routes of administration, mixing the drug with another substance, using more than prescribed and obtaining the drug without a prescription. One in four (28%) reported using quetiapine along with another substance, most often a sedative/anxiolytic. Most clients had been prescribed quetiapine (off-label) to treat insomnia and anxiety and reported taking it for its sedative effects. Although most clients were polysubstance users, misuse of quetiapine was more common among those who also reported misusing prescription sedatives/anxiolytics.
As the literature looking at misuse of atypical antipsychotics among individuals with addiction problems is minimal, it is important to explore this phenomenon in a more organized way. With this in mind, the current study sought to: (1) assess the prevalence of atypical antipsychotic abuse in a diverse group of substance abusers receiving inpatient treatment; (2) characterize patients who were abusing atypical antipsychotics; (3) explore reasons for use; (4) determine the source of atypical antipsychotics; and (5) understand the potential role of provider prescribing practices in patients accessing atypical antipsychotics.
2. Materials and methods
2.1 Research design and setting
This was an IRB-approved cross sectional study. Patients admitted to a locked detoxification and rehabilitation unit of the Addiction Institute of New York (AINY) at Mt. Sinai Roosevelt Hospital in New York City between January and November 2013 were verbally consented and screened for past-year use of atypical antipsychotics. The unit chief provided a list of all new admissions to the researchers several times per week and the two lead authors then attempted to screen all available and willing patients. A total of 429 patients were screened, of whom 25 were deemed eligible for and agreed to complete the Addiction Severity Index (“ASI-lite”), as well as a 45–60 minute structured clinical interview (atypical antipsychotic abuse experiences) designed for this study. All of the patients who were interviewed completed written informed consent. No participant compensation was provided.
2.2 Participants
Inclusion criteria for the study consisted of the following: (1) English-speaking; (2) ≥18 years old; (3) current problem with alcohol, cocaine/crack, methamphetamine, cannabis and/or opiates; and (4) misuse of atypical antipsychotics within the past 12 months; misuse was defined as use without a prescription or with a prescription but not as prescribed (e.g., wrong dose, wrong indication).
2.3 Measures
The measures used were the Brief Screen for Atypical Antipsychotic Use, Addiction Severity Index Lite (ASI-Lite) and the Atypical Antipsychotic Abuse Experiences ([AAAE];
), a structured interview was developed for this study as no standardized interview was available. The Brief Screen assessed: (1) past 12 month substance use; (2) past 12 month atypical antipsychotic use; (3) reasons for atypical antipsychotic use; and (4) presence of a psychotic disorder. The ASI (
) assesses problem severity in 7 areas impacted by substance abuse to include: (1) medical; (2) employment; (3) legal; (4) alcohol; (5) drugs; (6) family/social; and (7) psychiatric. Composite scores can be generated from ASI data and used for normative comparisons to nationally representative samples. The AAAE interview is a structured set of questions pertaining to history of use of seven atypical antipsychotic medications, alone or in combination with alcohol, cocaine, marijuana, methamphetamine and/or opioids. The domains covered in the questionnaire included: (1) age at first use; (2) duration of use; (3) frequency of use; (4) dose; (5) route of administration; (6) source of drug; (7) preference for different atypical antipsychotics (if more than one atypical antipsychotic used); (8) combinations of atypical and traditional drugs of abuse tried; (9) temporal relationship in use of atypical and traditional drugs of abuse (i.e., before, during or after); (10) reasons for use (i.e., euphoria, “come down”); and (11) side effects. If the atypical antipsychotic was prescribed, patients also were asked (12) for what psychiatric condition and if the participant had that problem; and (13) perceived likelihood of becoming “addicted” to the atypical antipsychotic.
2.4 Analysis
Descriptive statistics (i.e., means, standard deviation, and percentages) were utilized to provide summary characteristics of the sample and their drug use patterns. Composite scores were calculated for the seven sections of the ASI. Composite scores were composed of the sum of key questions within each section including number of days experiencing problems, how troubled patients were by these problems, and how important treatment was, which were weighted equally (
). Six individuals were excluded from the family composite score as they did not have complete information. All analyses were conducted using SPSS 21 (
A total of 429 patients were screened. Of these, 73 (17.0%) reported abusing atypical antipsychotic medication, with 39 (9.1%) reporting use within the last 12 months. These 39 were deemed eligible and 25 (64.1%) enrolled in the study and completed the clinical interviews. Reasons that eligible patients did not enroll in the study included too little time to complete the interview prior to discharge and refusal to participate due to lack of financial compensation. Among the screening sample (N = 429) who obtained atypical antipsychotics from a medical provider, use was mostly “off label” to treat insomnia, anxiety, mood, and behavioral symptoms. Only 7.0% of screened patients were prescribed atypical antipsychotics for psychotic symptoms.
3.2 Characteristics of enrolled sample
Table 1 shows demographic and clinical characteristics of the sample. Three-quarters of participants (76.0%) were male. The majority of the sample identified as non-White (44.0% Caucasian, 32.0% Hispanic, and 20.0% Black/African American). Their mean age was 41.2 (SD = 9.6). Only 20.0% were employed (either full time or part time). Half (52.0%) reported co-morbid chronic medical problems and more than a quarter of the sample (28.0%) were receiving a pension for a physical disability, a reflection of the high percentage of co-morbid medical problems. Based on the ASI, 64.0% of patients reported having depression and 68.0% anxiety; 48.0% had a previous suicide attempt. However, only 8.0% reported a history of hallucinations which might indicate a psychotic process but which also could be drug-induced. Twelve percent (12.0%) of patients received a pension for psychiatric problems.
Table 1Demographic and clinical characteristics of the enrolled sample (n = 25).
As shown in Table 2 the vast majority of participants (84.0%) were polysubstance abusers (both current and lifetime) with 84.0% reporting a history of IV drug use. In the last 30 days, 76.0% had used alcohol, 56.0% cocaine, 28.0% opiates, 20.0% cannabis, and 12.0% amphetamines. The average lifetime duration of regular substance use (i.e., ≥3 times per week, binge behavior, or problematic irregular use) was 13.3 years (SD = 12.5) for alcohol, 10.0 years (SD = 9.0) for heroin, 9.0 years (SD = 9.8) for cocaine, 8.7 years (SD = 10.0) for cannabis, and 0.5 years (SD = 1.6) for amphetamines. The mean number of lifetime treatment episodes was 5.9 (SD = 5.7) for alcohol and 5.8 (SD = 5.2) for drugs.
Table 2Lifetime and current substance use of the enrolled sample (n = 25).
Table 3 shows the reasons for atypical antipsychotic abuse, preferred antipsychotic/drug and alcohol combinations, source of antipsychotics, and perceived likelihood of antipsychotic addiction. The most common preferred drugs to use with atypical antipsychotics were opioids (34.8%), cocaine (30.4%), and alcohol (21.7). The most common specific atypical antipsychotic/drug combinations were quetiapine with alcohol and opioids (24.0%), quetiapine with cocaine (24.0%) and quetiapine with opioids (16.0%). Patients reported they used atypical antipsychotics to “recover” from the use of other substances (66.7%), to “enhance” the effects of other substances (25.0%) and to “experiment” (20.8%). Unfortunately, it was not possible to determine which combinations of drugs were being used for which purposes due to how this question was asked on the AAAE. Atypical antipsychotic drugs were obtained from both licit (i.e., physician, 52.0%) and illicit sources to include family/friends (48.0%) or a drug dealer/on the street (28.0%). Quetiapine (96.0 %) was, by far, the most abused atypical antipsychotic, followed by olanzapine (28.0%), risperidone (20.0%) and aripiprazole (20.0%) and this was true regardless of source (licit or illicit). The newer atypical antipsychotics (e.g., asenapine, iloperidone, lurasidone) were rarely mentioned by participants and do not appear to have reached the stage of experimentation. While the median number of times atypical antipsychotics were used was high (median = 50; range 3–1000 times), only 20.8% reported anticipating a “high likelihood” of addiction resulting from use of atypical antipsychotic medications.
Table 3Characteristics of atypical antipsychotic use of the enrolled sample (n = 25).
3.3 Positive and negative effects of atypical antipsychotic use
Patients reported both positive and negative emotional effects of their atypical antipsychotic use in conjunction with alcohol and other drugs of abuse. The most frequently endorsed positive effects were feeling happy (33.3%), friendly (29.2%), and sexy/horny (25.0%) and the most frequently endorsed negative effects were depression (16.7%), anxiety (25.0%) and irritability (25.0%). Other commonly reported effects, while not psychological, likely were desired, as their prevalence was quite high. These effects included feeling mellow (75.0%) and slowed down (75.0%). Patients also were asked about side effects attributed to the atypical antipsychotic (i.e., effects they would not normally experience if using drugs and alcohol alone) and these included dry mouth (80.0%), lethargy (64.0%), and clouded thinking (56.0%). These reported side effects are consistent with taking antipsychotic medications in general.
3.4 Comparison of ASI composite scores to nationally representative inpatient sample
Composite scores for the seven domains of the ASI (i.e., medical, employment, legal, alcohol, drugs, family/social, psychiatric) were calculated and compared to a nationally representative sample of substance abuse treatment inpatients (
). Fig. 1 shows that the current sample has higher ASI composite scores across all domains except legal, compared to a nationally representative inpatient sample.
Fig. 1ASI composite scores of current enrolled sample (n = 25) and a nationally representative sample of addiction inpatients (n = 3133).
This study is one of the first to describe patterns of and reasons for misuse of atypical antipsychotics among substance abusers. Screening data, collected from a large and diverse sample of patients from an inpatient rehabilitation and detoxification unit, revealed that 17% had a history of misusing atypical antipsychotics in combination with alcohol and/or other drugs of abuse, with 9.1% having done so within the prior year. More generally, spending on antipsychotics grew by 1.4 billion in 2010 compared to 2009, with top brands including Seroquel, Abilify, and Zyprexa (Abilify and Seroquel were also among the top 10 of all prescribed medications in terms of spending) (
). This suggests high rates of off-label prescriptions given that schizophrenia and other psychotic illnesses are relatively uncommon. Overall prevalence rates from this study, combined with national spending data, raise concerns about the availability of these medications and provide a rational for a more detailed study of users.
Among patients meeting criteria for past year use who consented to be interviewed, the percentage who obtained atypical antipsychotics from licit vs. illicit sources was similar, with the vast majority of prescription holders using these medications off-label to manage symptoms such as insomnia, anxiety, and mood. This is similar to findings from
study conducted in methadone maintenance clients. In the current study, sources of atypical antipsychotics included doctors (52.0%), family/friends (48.0%), or dealers (28.0%). These percentages may be compared to those reported for prescription pain killers [14% doctors, 52% family/friends, 4.8% dealers (
)]. Differences in “source” for these two drug classes, both with abuse liability, suggest that doctors are less reticent to prescribe atypical antipsychotics than opioid analgesics, perhaps viewing them as more innocuous than they are. While misuse prevention strategies clearly must begin in the home, with family members being advised to keep all medications secure, we also recommend that doctors exert caution when writing prescriptions for atypical antipsychotics, especially for patients with current or past substance use disorders, as they clearly have both abuse liability and street value. Future research should test the abuse liability of these agents to determine if they should be considered for scheduling.
Similar to findings from a study conducted among methadone maintenance clients (
), study participants were primarily male and polysubstance abusers. In addition, participants had high rates of co-morbid chronic medical and psychiatric problems, multiple treatment episodes and low rates of employment and social support. The finding of higher ASI composite scores compared to those for a national sample of substance abuse inpatients is intriguing, although the reasons for this are obscure. As we did not have comparable ASI data for patients who were not abusing atypical antipsychotics, it is unclear whether this finding of greater acuity is characteristic of our patient population as a whole or whether it is specific to those using atypical antipsychotics. Further investigation is needed to answer this question. Should other studies confirm greater impairment among patients abusing atypical antipsychotics, population-specific interventions (including psychoeducation about atypical antipsychotics), may need to be implemented.
Consistent with previously published data, quetiapine was the most commonly misused atypical antipsychotic, regardless of source (licit or illicit). Most of the legally obtained atypical antipsychotics were prescribed for off-label use, although reported indications varied by drug. For instance, among the screening patients (N = 429), 24.6% were prescribed quetiapine for sleep, whereas only 7.0% were taking it for psychotic symptoms. In contrast, risperidone primarily was prescribed for anxiety (41.2%) and aripiprazole for mood disturbances (42.9%), although no evidence exists of differential effectiveness for these drugs for these conditions. The newer antipsychotics, including asenapine, had much lower rates of abuse. Physician prescribing patterns likely are being influenced by formularies and costs. For instance, quetiapine XRs covered for 81.0% of commercially insured patients nationwide with no prior authorization, whereas newer drugs may not be available on formulary (
). Complicating matters, direct advertising of atypical antipsychotics, such as aripiprazole, in combination with SSRIs for treatment of depression, may stimulate the public to request specific antipsychotic drugs from their primary care providers who may have less knowledge of and experience with prescribing psychiatric medications. It seems probable that, the more direct advertising occurs and the longer the newer drugs are on the market, the more experimentation (and potential misuse) of these agents will be seen.
Regarding the specific reasons for misuse of atypical antipsychotics, two-thirds of patients reported they were attempting to attenuate the negative effects of other substances. The scientific literature regarding antipsychotics as therapeutic agents among substance dependent people has produced mixed results. In a double-blind, placebo-controlled trial with 224 alcohol-dependent patients, no difference was found between quetiapine or placebo (plus medical management) for reducing alcohol use (
). In a study exploring quetiapine as an agent to alleviate negative symptoms of opioid detoxification (n = 107), however, investigators found quetiapine to be generally well tolerated and helped to reduce opioid craving, anxiety, and insomnia (
. Since the specifics of self-medication were not explored in the current study, it is unclear what percent of patients were attempting to mitigate withdrawal symptoms associated with other drug use as opposed to dealing with the pharmacological effects of the drugs themselves. Another quarter of patients endorsed using atypical antipsychotics to enhance the effects of other drugs. Although detailed information about the effects sought was not collected, indirect information may be gleaned from the list of top effects reported, the most common being “to feel mellow.” Finally, one-fifth of participants stated they were merely experimenting with atypical antipsychotics. It is unknown how many experimenters may go on to regular use; however, the fact that some patients had used atypical antipsychotics in the hundreds of times is further evidence of abuse liability. Further investigation is needed to clarify reasons for use on a drug by drug basis, looking at various combinations as well temporal relationships (before, during, or after) taking other drugs of abuse.
4.1 Limitations
The present study advances our knowledge of the characteristics, drug source, preferences and reasons for misuse of antipsychotic medications among individuals with substance use disorders. Several limitations should be noted, however, and rectified in future studies. First, generalizability of the sample is limited due to an unsystematic (i.e., convenience sample) recruitment method within a single detoxification/rehabilitation unit of an inner-city community hospital with a relatively small sample size. Larger studies are needed to determine if these findings, particularly prevalence rates and reasons for and patterns of antipsychotic misuse, hold up over time and across populations. The sample did appear to be representative of patients treated on the unit, including presenting with a wide range of substance use. Another drawback of the study was our inability to link specific drug effects or reasons for use with different combinations of drugs used; this occurred because people reported using multiple combinations of atypical antipsychotics and traditional drugs of abuse and the data collection tool (AAAE) was not structured to capture this level of detail. Future research, conducted with larger samples, should carefully parse out desired and observed effects for each drug combination. As previously noted, study participants generated higher ASI severity scores (i.e., were more impaired) than those in a nationally representative comparison group of inpatient substance abusers. The reasons for this discrepancy are unclear due to the unsystematic sampling method. Future studies should endeavor to replicate this finding among other samples of atypical antipsychotic abusers using random sampling methods.
4.2 Conclusion
This study contributes much needed information on the misuse of atypical antipsychotics among patients with substance use disorders. Findings suggest providers should consider using other strategies to manage symptoms in known (or suspected) substance abusers who do not have psychotic disorders and for whom alternatives exist. Further, providers should consider routinely screening for atypical antipsychotic misuse among patients with a history of substance use disorders and judiciously monitor those who are maintained on these medications for treatment of co-occurring psychotic disorders.
Acknowledgments
We would like to acknowledge Bonnie Hendrickson for her assistance in preparing the manuscript for submission. We would also like to acknowledge Alicia Murray, DO for writing the original protocol and creating an early version of the data collection tool. A limited portion of the manuscript data was presented as a poster at the 2013 AAAP meeting.
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