Abstract
Chief Complaint and Presenting Problem
F
History of Present Illness
F.'s parents reported that he was diagnosed with ADHD as a child, consistent with his early history of hyperactivity, short attention span, and fidgetiness. He reportedly made careless mistakes, had trouble playing quietly, and trouble taking turns. He recalled becoming bored easily, especially in school, and he disliked mental activity that required sustained effort. In addition, parents reported that F. had a history of lying, rule and curfew breaking, and shoplifting; a past diagnosis of conduct disorder had also been made.
In this context, F. reported that his first opiate use was at the age of 9 years when he ingested a family member's medication; his regular substance use began at the age of 13 years. F. reported that he started smoking tobacco when he was 13 and was smoking around 20 cigarettes a day by the time of this evaluation. He also started smoking marijuana at age 13; he reported a history of smoking 2 g of marijuana at least once a week in the past, but none over recent months. In addition he experimented with inhalants briefly when he was 13; he started using Triple C (containing dextromethorphan, acetaminophen, and pseudoephedrine) when he was 13, and ingested up to two to three bottles at a time at a frequency of two to three times a week. When he was 14, he experimented with oral methamphetamines and methylene-dioxy-meth-amphetamine, and also started using benzodiazepines, such as clonazepam, and would occasionally use opiates. F. reported that he drank alcohol occasionally. He denied ever using intravenous drugs. There was no history of abusing any other analgesic drugs.
Most recently F. reported that he was started on 50 mg quetiapine to initiate sleep a few months before admission. He reported that he experienced a “buzz” from this medication, and described this experience as similar to what he experienced with opiate ingestion. He claimed that he resisted the temptation to increase the dose of this medication for 2 months after its initiation. He subsequently increased the dose to 100 mg and reported that he liked the feeling. He reported that when he requested a dose increase from his family physician, the dose was increased to 300 mg once daily; he then gradually increased his quetiapine to 400 mg three times a day over a period of 3 months. He also procured quetiapine from friends and reported that he sometimes provided sexual favors to a middle-aged woman in exchange for quetiapine.
F. reportedly felt dysphoric and craved on days when he was unable to obtain quetiapine, or when he would attempt to reduce his use. He reported that he experienced palpitations on 400 mg three times a day, but continued taking the medication. Since his first use, quetiapine quickly became his primary drug of abuse. While on quetiapine, he reported one episode of opiate use. Before F.'s current hospitalization, he claimed being offered four 0.5 mg alprazolam tablets by a peer at school. When he ingested the alprazolam and 400 mg of quetiapine, he became drowsy and subsequently unresponsive, resulting in an emergency department evaluation. As a result he was hospitalized. During this admission, his urine drug screen was positive for benzodiazepines, but was negative for any other drugs of abuse. His complete metabolic panel and complete blood count were within the normal range. His acetaminophen level and salicylate levels did not reveal any evidence of overdose. Ethanol was undetectable and his head computed tomography was normal.
F. had no significant history of mood or anxiety symptoms, tics, body image distortions, or eating disorder symptoms. There was no recent history of psychotic symptoms, but F. recalled hearing his name being called when he was on illicit drugs.
Past Psychiatric History
Parents report that F. was treated by his pediatrician in early childhood with mixed amphetamine salts (MAS) for his diagnosis of ADHD; MAS reportedly reduced his hyperactivity but were associated with irritability. Consequently, he was switched to atomoxetine up to 60 mg, which he remained on for approximately a year; it was discontinued a few days before his first hospitalization. F. had received outpatient therapy for around 18 months before this hospitalization.
F. was hospitalized for 3 days when he was 15 years old after an episode of suicidal ideation with a plan to jump off a bridge, which was precipitated by an argument with his father. F. reportedly experienced mild dysphoria triggered by the hospitalization, which quickly improved. During this hospitalization, F.'s atomoxetine was officially discontinued, as F. had himself stopped taking it. He was subsequently started on bupropion extended release 150 mg once daily for ADHD and a possible depressive disorder.
Developmental History
F. was the product of an uncomplicated pregnancy. Motor milestones were achieved at the appropriate ages. He recalled receiving speech therapy as a child for a possible speech sound disorder.
Educational History
F. had always attended public school and received regular education. He was a junior attending an alternative school for his addiction problems. He had been an average student, but there was a decline in grades over the course of the preceding academic year. There was no history of special educational needs; however, he had a history of truancy.
Social History
F. lived with his biological parents and an 18-year-old sister with whom he had a “fair” relationship. He reported that he was sexually active and had had more than six relationships. There was no gang involvement; his relationships were short term and he often associated with peers who used drugs. F. had been charged with “Minor in Possession” and “Shoplifting” last year. He received tickets for possession of tobacco and breaking curfew.
Family History
A sibling had anxiety and mother had been diagnosed with depression. An aunt had a history of alcohol or illicit substance use.
Past Medical History
F. had no serious medical problems, hospitalizations, or surgery. He did receive treatment for a fractured arm when he was 5 years old. He had no history of significant childhood illness and had received appropriate vaccinations.
An electrocardiogram in hospital revealed a QTc (a measure of the depolarization and repolarization rhythm of the ventricles) of 420 milliseconds. There was no evidence of any weight gain over 6 months. Other than initial insomnia, there was no evidence of any sleep disorder.
Mental Status Examination
Mental status examination revealed a 16-year-old adolescent boy without dysmorphic features. He exhibited age-appropriate secondary sexual characteristics. There were no abnormal movements. He was alert, pleasant, and cooperative. He was reported to have been drowsy earlier but this had improved. There was no evidence of intoxication or withdrawal from substances noted at the time of interview. Good rapport was easily established and maintained. His speech was spontaneous, normal in rate, tone, and flow. His mood was euthymic and affect was reactive. F. reported good mood and energy levels and denied any loss of interest. He denied excessive guilt, recent appetite, or weight changes. He reported that he enjoys spending time with friends, although some of them use illicit substances. He denied mood swings, euphoria, decreased need for sleep, or flight of ideas when not using illicit substances.
F.'s thought process was logical and goal directed. There was no suicidal or homicidal ideation, delusions or hallucinations. There were no obsessions or compulsions, but F. reported cravings for quetiapine.
F. was oriented to time, place, and person; memory was predominately intact for immediate, recent, and remote memory, but he struggled to piece together details of the previous day's events. F.'s abstract thinking was appropriate for his age. In terms of insight and judgment, F. acknowledged the risks involved in using quetiapine and the manner in which he procured it. He understood that he had been unsuccessful in reducing its use, and endorsed a desire to reduce it.
Brief Formulation
In summary, F. was a 16-year-old boy with ADHD and opiate and cannabis use disorders, and was referred for a recent history of escalating recreational quetiapine use. F. also met diagnostic criteria for conduct disorder and experienced mood regulation difficulties in the past several years. He had started using illicit substances at the age of 13 that gradually worsened over the past 3 years; quetiapine was his most recent substance of choice.
From a biological perspective, a family history of substance use disorder in an aunt and depressive and anxiety disorders in mother and a sibling rendered F. vulnerable to development of mood/anxiety and substance use disorders. There were no other significant medical issues. From a psychosocial perspective, F. had developed relationships with peers who were using drugs, which was likely a significant factor in the perpetuation of his own use of substances. Unfortunately his substance use led to a decline in academic, social, and emotional functioning.
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Diagnosis
Attention-deficit hyperactivity disorder
Conduct disorder, past
Severe other substance use disorder (quetiapine)
Benzodiazepine use disorder
Opiate use disorder
Cannabis use disorder
Nicotine use disorder
Discussion
Quetiapine is an atypical antipsychotic, often associated with sedation, which is indicated for treatment of psychotic disorders, including schizophrenia and bipolar disorder. There have been reports of quetiapine-seeking behavior in adult patients with a comorbid substance use disorder (Sansone and Sansone 2010). Quetiapine has nicknames including “Quell,” “Suzie Q,” or “baby Heroin” (Sansone and Sansone 2010). It is called “Q-ball” when mixed with other substances such as heroin or cocaine (Sansone and Sansone 2010).
There have been previous reports of quetiapine's addictive potential in prison settings (Pinta and Taylor 2007). Its inhalational and intravenous use has been reported (Pierre et al. 2004; Hussain et al. 2005). There is a case report of an emergency room presentation with malingering psychotic symptoms with quetiapine use (Murphy et al. 2008). The risk of quetiapine addiction seems to be higher in those with preexisting abuse of other drugs.
A PubMed search did not reveal previous case reports of quetiapine use disorder in the child and adolescent population. F. exhibited escalating use, tolerance, withdrawal, craving, failed attempts to stop, and continued use despite harmful effects, thus meeting diagnostic criteria for Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)'s severe other substance use disorder (American Psychiatric Association 2013). It is interesting that his use of other illicit substances was minimal while he was on quetiapine. His first urine drug screen was positive for benzodiazepines, consistent with his recent benzodiazepine use, but was negative for other substances.
The neurobiology of quetiapine's reinforcement is not clear (Sansone and Sansone 2010); dopaminergic release in the reward-mediating dopaminergic mesolimbic pathway and sedation mediated through antihistamine pathways may play a role (Sansone and Sansone 2010). As an atypical antipsychotic, quetiapine increases the risk of metabolic syndrome (Simon et al. 2009) and carries a dose-dependent QTc prolongation risk (Hasnain et al. 2014). Fortunately, F. did not experience QTc prolongation despite ingestion of 1200 mg. Around 30% of patients on quetiapine gain weight in the first 6 months of treatment, but F. did not gain weight with his quetiapine use (Arango et al. 2014). However, on ingestion of 400 mg in combination with 2 mg alprazolam, F. did experience significant sedation, requiring hospitalization.
Quetiapine exerts its sedative action through histaminic blockade; alprazolam acts by promoting gamma-aminobutyric acid activity (Schatzberg et al. 2013). Perhaps sedation was sought after by this youth; unlike other sedative-hypnotic agents, quetiapine is not detected in the commonly used urine drug screens. This might further the appeal of use for those undergoing regular drug testing. The relatively lower risk of extrapyramidal side effects makes quetiapine more tolerable than other antipsychotics (Schatzberg et al. 2013). Interestingly, abuse of olanzapine, another second-generation antipsychotic, has also been reported in the adult population (Kumsar and Erol 2013). Olanzapine and quetiapine are common in being markedly sedative.
The American Association of Poison Control Centers National Poison Data System reported 684 phone calls about quetiapine abuse in 13- to 19-year-olds from 2005 to 2011 (Klein-Schwartz et al. 2014). Nevertheless, there is a dearth of literature on quetiapine addiction in adolescents. The absence of case reports in this population perhaps reflects a reporting bias.
ADHD increases the risk of substance use by two and half times (Lee et al. 2011) and the risk is increased further by the presence of conduct disorder. Adolescents with ADHD plus conduct disorder have a five times higher risk of substance use than adolescents with ADHD alone (Lee et al. 2011). F.'s history of ADHD and conduct disorder was additionally increased by his family history of substance use.
In the context of increasing use of second-generation antipsychotics in children and adolescents over the past decade (Olfson et al. 2012), child and adolescent psychiatrists need to be vigilant of abuse potential and diversion risk with quetiapine. Enhanced vigilance is suggested in those who carry a higher vulnerability to substance use disorders.
Footnotes
Acknowledgments
We would like to acknowledge and thank Natasha Toralba Kostek and Maxwell Luber for their assistance in review and preparation of the article.
Disclosures
Dr. Mary does not have any disclosures. Dr. Kolli had received a Janssen mentorship grant to study the impact of psychosocial interventions on antipsychotic use in schizophrenia and has no disclosures for this article.