Journal of Child and Adolescent Psychopharmacology 2014.24:458-461. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 12/31/14. For personal use only.
JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume 24, Number 8, 2014 ª Mary Ann Liebert, Inc. Pp. 458–461 DOI: 10.1089/cap.2014.2482
Advanced Pediatric Psychopharmacology
Expanded Usage of Prazosin in Pre-Pubertal Children with Nightmares Resulting from Posttraumatic Stress Disorder Presenters: Revital Racin, MD1 and Christopher Bellonci, MD1 Discussant: Barbara J. Coffey, MD, MS 2
Chief Complaint and Presenting Problem
M
. was a 10-year-old African American boy with a history of attention deficit hyperactivity disorder (ADHD) and significant childhood trauma referred for hospitalization by his legal guardian for increased aggressive behavior and suicidal ideation. History of Present Illness M. was removed from his biological mother’s home for neglect approximately one and half years prior to hospitalization. He was subsequently placed under the legal guardianship of A., his 21-yearold half-sister. M. has had aggressive behavior problems since he moved to live with A. During the past year, M. has made homicidal statements toward A. and wrote with chalk on their apartment building that he wanted to ‘kill’’ her. He was also physically aggressive toward his peers (e.g., punching an age-mate in the face) and brother (choking him during an altercation) and assaultive with school staff. A. reported that M. tended to ‘‘forget’’ incidents of aggression and often stated that he ‘‘can’t remember what happened.’’ A. stated that M. has had one isolated fire-setting incident when he was 7 years old. Additionally, A. reported that M. often lied, stole, and wrote statements expressing hatred for life and a desire to kill himself. M. was suspended from school as a consequence of his behaviors. A. reported that M.’s aggression and suicidality increased particularly when he was in unstructured environments and when limits were set by authority figures. Limits such as time-outs at home and school had proven ineffective. M. had recently started treatment with an outpatient psychiatrist who diagnosed ADHD and treated him with guanfacine 1 mg in the morning and 0.5 mg in the afternoon and amphetamine mixed salts extended release 5 mg daily. A. and the outpatient child and adolescent psychiatrist reported an increase in aggression, oppositional behavior, and suicidal and homicidal ideation over the course of several weeks prior to admission. M. was referred for voluntary admission to an inpatient child and adolescent psychiatry unit after wrapping a wire around his neck. He had expressed a desire to hang himself at school after getting into trouble. There was no reported precipitant or change in his environment that could explain his increased aggression and suicidality in the weeks leading up to admission. The amphetamine mixed salts had reportedly increased his aggressive behavior, and were discontinued a few days prior to his hospitalization. At the 1 2
time of admission M. was taking guanfacine 1 mg in the morning and 0.5 mg at bedtime, which by A.’s reports only initially ameliorated impulsive and aggressive behaviors. Past Psychiatric History M. had no prior inpatient psychiatric admissions. At the time of admission, M. was seeing a child and adolescent psychiatrist and an individual therapist, and met once weekly with a guidance counselor at his school. Developmental History M. may have been exposed to illicit substances in utero due to a maternal substance abuse history. A full developmental history was not available. Biological mother and legal guardian provided no information regarding his developmental milestones or early development. Educational History M. was currently in the fourth grade and reportedly performing well academically. He did not have a 504 plan and/or an individualized education plan. Although he had a record of suspension, most of his behavioral difficulties were reported to occur during his after school program. At time of admission M. had not undergone academic or neuropsychological testing. Social History M. lived with his biological mother from birth until his removal by the state child welfare agency when he was 8 and a half years old. M. had experienced physical and emotional abuse, exposure to sexual content, and medical and emotional neglect while in his mother’s care. According to reports, mother sold drugs in the home and M. was exposed to adults, including his mother, abusing illicit substances in the home. M. was forced to urinate in bottles so that his mother could use his urine to pass her drug screen. Mother had had multiple male partners, some of whom physically and possibly sexually abused her in front of M. M. also had a history of moving frequently to different homes, cities, and states, and often the precipitating factor for these moves was the threat of child welfare involvement. According to A.’s report, schools had filed neglect reports on multiple occasions when M. failed to attend school on a consistent basis.
Tufts Medical Center, Department of Psychiatry, Boston, Massachusetts. Icahn School of Medicine at Mount Sinai, Department of Psychiatry, New York, New York.
458
ADVANCED PEDIATRIC PSYCHOPHARMACOLOGY M. was removed from his biological mother’s home approximately one and half years prior to this hospitalization. He was subsequently placed under the legal guardianship of A., his 21-year-old halfsister. M., A., and his 7-year-old brother lived in a rented apartment.
Journal of Child and Adolescent Psychopharmacology 2014.24:458-461. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 12/31/14. For personal use only.
Family History M. had an extensive maternal family history of mental illness, incarcerations, and substance abuse. A., M.’s maternal half-sister, was unaware of the specifics of these issues because she was also removed from her mother’s care at an early age. There is no information regarding father’s history. Medical History M. had no serious medical problems, hospitalizations, or surgery. He had no history of major childhood illnesses, had received all appropriate vaccinations, and reportedly had no growth and developmental abnormalities. An electrocardiogram at the time of admission was normal.
459 M. also attended daily individual supportive psychotherapy and weekly family therapy sessions during his admission. At the time of discharge, M. was taking prazosin 1 mg three times daily, fluoxetine 10 mg daily and OROS methylphenidate 18 mg daily. Wrap-around services and academic testing were recommended to the family at discharge, and were initiated two weeks after his admission. M. was scheduled to continue medication management with his previous outpatient child psychiatrist, individual therapy with his previous therapist, and weekly meetings with his guidance counselor at school. It was also recommended that he receive in-home behavioral therapy in addition to a therapeutic mentor and parental partner for A. At six month follow-up, it was reported that fluoxetine and the morning and late afternoon doses of prazosin had been discontinued due to ineffectiveness; increase in M.’s aggressive behavior during the day resulted in re-hospitalization. Prazosin was subsequently increased to 2 mg orally at bedtime, and M. continued to endorse relief from nightmares and improved quality of sleep. Brief Formulation
Mental Status Exam Mental status examination revealed a cooperative AfricanAmerican child, with no dysmorphic features, whose response to questions about everyday life was accurate but brief. He was appropriately groomed and oriented to time and place. His rate of speech was fast with normal volume, articulation, coherence, and spontaneity of speech. He was fast moving and fidgety during the examination, and exhibited poor eye contact. Mood was sad and affect was congruent with mood. M. endorsed flashbacks, nightmares, and hypervigilance. His flashbacks and nightmares consisted of what he described as ‘‘bad memories.’’ He denied suicidal or homicidal ideation, auditory or visual hallucinations, and depressive symptoms. His thought processes were linear with no perceptual disturbances. Memory was intact, and the neurological examination was within normal limits.
In summary, M. is a 10-year-old African American boy who met diagnostic criteria for PTSD manifest by hypervigilance, flashbacks, difficulty with sleep, and anxiety. M. may have had intrauterine exposure to illicit substances and was subjected to significant childhood trauma. He moved frequently between states, and during the past year his half-sister gained physical and legal custody of him. All of these factors contributed to M.’s insecurity, aggression, and suicidal thoughts. There was a strong genetic predisposition to mental illness, as there was an extensive, although undetailed, family history. M.’s PTSD symptoms improved with individual and family therapy and medication during hospitalization; however, M. did continue to have difficulties managing his aggressive behaviors after discharge, which resulted in rehospitalization and further medication trials. His nighttime dosage of prazosin continued to facilitate initiation and quality of sleep.
Hospital and Treatment Course
Multi-Axial Diagnoses
Upon admission, M. met DSM-IV-TR (American Psychiatric Association, 2000) criteria for posttraumatic stress disorder (PTSD). He reported that he startled easily in reaction to loud noises; scanning, hypervigilance, and daily flashbacks occurred mostly in the late afternoons. M. also suffered from nightmares with vivid imagery of past events. Due to his reported flashbacks and increased hypervigilance in the afternoons, prazosin 1 mg orally was first administered at 3 pm a few days after admission. The day after initiation of prazosin, M. reported that his intrusive memories decreased, which decreased his anger and improved his self-control. He asked for an additional dosage to help with his nightmares two days after initiation, so 1 mg at bedtime was added. His nightmares decreased after the first administration of prazosin at bedtime. Fluoxetine 10 mg orally daily was subsequently initiated to target M.’s depressed mood and PTSD symptoms, and guanfacine was slowly discontinued due to its ineffectiveness. Prazosin 1 mg was added in the morning to target his impulsive behaviors and hyperactivity. However, M. remained fast moving, impulsive, and inattentive. Therefore, a trial of OROS methylphenidate 18 mg was initiated several days prior to discharge, which improved his concentration and hyperactivity. Vital signs were monitored and were stable throughout his hospitalization. There was no evidence of orthostatic hypotension, light-headedness, or excessive sedation.
Axis I:
PTSD ADHD, combined presentation, by history Axis II: Deferred Axis III: None Axis IV: Level of psychosocial stressors: Severe; extensive history of unstable housing and trauma exposure Axis V: Current Global Assessment of Functioning (GAF): 40 Discussion According to DSM-5 diagnostic criteria (APA 2013), PTSD includes exposure to actual or threatened death, serious injury, or sexual violence in one (or more) of the following ways: directly experiencing the traumatic event(s), witnessing, in person, the event(s) as it occurred to others, or learning that the traumatic event(s) occurred to a close family member or close friend. In cases of actual or threatened death of a family member or friend, the event(s) must have been violent or accidental. Experiencing repeated or extreme exposure to aversive details of the traumatic event(s) also meets criteria. Exposure to traumatic events is not uncommon for many children and adolescents. More than one in four children experience a significant traumatic event before reaching adulthood (Krystal and Davidson 2007). In fact, a study of 1,420 children ages 9, 11, and 13 who were followed annually until the age of 16 reported that nearly
Journal of Child and Adolescent Psychopharmacology 2014.24:458-461. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 12/31/14. For personal use only.
460 two thirds experienced at least one traumatic event (Breslau, Andreski, Peterson 1991). A 2002 national sample of adolescents (12–17 years old) indicated that 3.7% of male and 6.3% of female adolescents met full diagnostic criteria for PTSD (Costello, Erkanli, Fairbank, Angold 2002). One study of a sample of adolescents and young adults reported that the overall lifetime prevalence of PTSD in the general youth population was 9.2% (Litz and Gray 2004). Sleep disturbance is an essential symptom of PTSD; recent evidence suggests that disrupted sleep may play an important role in the development of PTSD following a traumatic event (Gehman and Harb 2010). Sleep disturbance and nightmares occur in a majority of adults with PTSD, and in children, nightmares are one of the diagnostic criteria in the re-experiencing cluster of PTSD. PTSD-related nightmares often cause high levels of distress in children and adolescents, impacting their social and emotional functioning and overall sense of wellbeing. In the past, it was thought that PTSD-related nightmares would improve as the PTSD symptom complex improved, but this is no longer thought to be the case. If nightmares do not improve following therapy or other psychopharmacologic treatment, clinical practice calls for targeted treatment options for the sleep problems themselves. Reduction of nightmares is reported to improve the quality of sleep, subsequently improving overall clinical status of those who suffer from PTSD. Recent investigation of the neurobiology of PTSD suggests there is evidence for noradrenergic hyperactivity (Krystal and Neumeister 2009). Alpha-1 adrenergic receptors are located in the hippocampus, amygdala, and prefrontal cortex, which have been implicated in the pathophysiology of PTSD and PTSD-related nightmares. Prazosin antagonizes peripheral alpha-1 adrenergic receptors, and is the only available drug of this class that crosses the blood- brain barrier, with activity at central nervous system alpha-1 adrenergic receptors. Central noradrenergic tone is significantly reduced during slow wave sleep and essentially absent during rapid eye movement (REM) sleep, but in patients with PTSD, there are findings consistent with increased noradrenergic activity. This can cause increased phasic motor activity, stage shifts and arousals during REM sleep (Ross 1994 and Breslau 2004) and REM fragmentation during early PTSD development (Mellman, Kullickbell, Ashlock 1995). This disruption can cause trauma nightmares (Mellman 1995; Mellman 2002) and interfere with normal cognitive processing of traumatic events (Stickgold 2007). Prazosin is thought to act centrally during sleep to reduce the nightmares and other events that lead to distressed awakening in patients with PTSD because of its ability to reduce adrenergic activity in the central nervous system that may contribute to hyperarousal symptoms and sleep disturbances. Prazosin has been investigated as a treatment for sleep problems, flashbacks, and hyperarousal associated with PTSD. Although used for other medical problems, there is evidence to suggest promising outcomes for its use in treatment of nightmares and other comorbid sleep disturbances (Raskind 2003; Miller 2008; Strawn 2008, 2011; Taylor 2008). It is now a commonly used drug for PTSD nightmares and non-nightmare-distressed awakenings in the veteran population. Two double-blind, placebo controlled trials (Raskind 2003, 2007) of prazosin in military veterans demonstrated promising outcomes in the reduction of posttraumatic nightmares. These trials suggest that prazosin is substantially more effective than placebo for nightmares in veterans with PTSD. Similarly designed trials for pediatric PTSD sleep-related disorders could test its effectiveness in this population. M.’s response to prazosin illustrates its potential utility for treatment of nightmares in the pre-pubertal population. Prazosin
RACIN, BELLONCI, AND COFFEY has been used in children and adolescents to treat congestive heart failure and hypertension, and is well tolerated from a hemodynamic standpoint. The onset of action related to reduction of nightmare frequency and severity was rapid, occurring within one day. No adverse effects were noted. The effect was sustained over the course of the hospitalization and for 6 months afterward. Improvement of M.’s sleep, flashbacks, and hyper-vigilance contributed to subsequent improvement of his mood, self-confidence and self-control during the hospital stay. In the only other case report that described use of prazosin in a pre-pubertal child at the time of this publication there were concerns over weight gain with long-term administration (Strawn 2009). We did not follow M. after hospitalization to know whether weight gain became a concern. Low-dose prazosin may be effective in youth with PTSD as an adjunctive treatment. Systematic studies of prazosin for the treatment of youth with PTSD are warranted based on adult studies and a growing number of case reports in adolescents and children. Disclosures There are no conflicts of interest and no disclosures to report. Dr. Coffey has received research support from Eli Lily Pharmaceutical, NIMH, NINDS, Tourette Syndrome Association, Otsuka, Shire, Bristol-Myers, Pfizer, and Boehringer Ingelheim. Acknowledgment We would like to acknowledge and thank Zoey Shaw, Laura Ibanez Gomez, and Natasha Kostek for their assistance in review and preparation of the manuscript. References American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th edition. Text Revision. Washington, DC: American Psychiatric Association, 2000. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th edition. Washington, DC: American Psychiatric Association, 2013. Breslau N, Davis GC, Andreski P, Peterson E: Traumatic events and posttraumatic stress disorder in an urban population of young adults. Arch Gen Psychiatry 48:216–222, 1991. Breslau N, Roth T, Burduvali E, Kapke A, Schultz L, Roehrs T: Sleep in lifetime posttraumatic stress disorder: A community-based polysomnographic study. Arch Gen Psychiatry 61:508–516, 2004. Brkanac Z, Pastor JE, Storck M: Prazosin in PTSD. J Am Acad Child Adolesc Psychiatry 42:384–385, 2003. Copeland WE, Keeler G, Angold A, Costello EJ: Traumatic events and posttraumatic stress in childhood. Arch Gen Psychiatry 64:577– 584, 2007. Costello EJ, Erkanli A, Fairbank JA, Angold A: The prevalence of potentially traumatic events in childhood and adolescents. J Trauma Stress 15:99–112, 2002. Fraleigh LA, Hendratta VD, Ford JD, Connor DF: Prazosin for the treatment of posttraumatic stress disorder-related nightmares in an adolescent male. J Child Adolesc Psychopharmacol 19:475–476, 2009. Gehrman PR, Harb GC: Treatment of nightmares in the context of posttraumatic stress disorder. J Clin Psychol 66:1185–1194, 2010. Krystal AD, Davidson J. The use of prazosin for the treatment of trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder: Biol Psychiatry 61:925–927, 2007. Krystal JH, Neumeister A: Noradrenergic and serotonergic mechanisms in the neurobiology of posttraumatic stress disorder and resilience. Brain Res 1293:13–23, 2009.
Journal of Child and Adolescent Psychopharmacology 2014.24:458-461. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 12/31/14. For personal use only.
ADVANCED PEDIATRIC PSYCHOPHARMACOLOGY Kung S, Espinel Z, Lapid MI: Treatment of nightmares with prazosin: A systematic review. Mayo Clin Proc 87:890–900, 2012. Litz BT, Gray MI. Early Intervention for trauma in adults: A framework for first aid and secondary prevention. In: Litz BT, ed. Early Intervention for Trauma and Traumatic Loss. New York: Guilford Press; 87–111, 2004. Mellman TA, Kulick-Bell R, Ashlock L, Nolan B: Sleep events among veterans with combat-related posttraumatic stress disorder. Am J Psychiatry 152:110–115, 1995. Mellman TA, Bustamante V, Fins AI, Pigeon WR, Nolan B: REM sleep and the early development of posttraumatic stress disorder. Am J Psychiatry 159:1696–1701, 2002. Miller Lj: Prazosin for the treatment of posttraumatic stress disorder sleep disturbances. Pharmacotherapy 28:656–666, 2008. Oluwabusi OO, Sedky K, Benett DS: Prazosin treatment of nightmares and sleep disturbances associated with postraumatic stress disorder: Two adolescent cases. J Child Adolesc Psychopharmacol 22:399–402, 2012. Raskind MA, Peskind ER, Kanter ED, Petrie EC, Radant A, Thompson CE, Dobie DJ, Hoff D, Rein RJ, Straits-Troster K, Thomas RG, McFall MM: Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin. Am J Psychiatry 160:371–373, 2003. Raskin MA, Peskind ER, Hoff DJ, Hart KL, Holmes HA, Warren D, Shofer J, O’Connell J, Taylor F, Gross C, Rohde K, McFall ME: A parallel group of placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with posttraumatic stress disorder. Biol Psychiatry 61:928–934, 2007.
461 Ross RJ, Ball WA, Dinges DF, Kribbs NB, Morrison AR, Silver SM, Mulvaney: Motor dysfunction during sleep in posttraumatic stress disorder. Sleep 17:723–732, 1994. Stickgold R: Of sleep, memories and trauma. Nat Neurosci 10:540– 542, 2007. Strawn JR, Geracioti TD: Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder. Depress Anxiety 25:260–271, 2008. Strawn JR, Delbello MP, Geracioti TD: Prazosin treatment of an adolescent with posttraumatic stress disorder. J Child Adolesc Psychopharmacol 19:599–600, 2009. Strawn JR, Keeshin BR: Successful treatment of posttraumatic stress disorder with prazosin in a young child. Ann Pharmacother 45:1590–1591, 2011. Taylor FB, Martin P, Thompson C, Williams J, Mellman TA, Gross C, Peskind ER, Raskind MA: Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: A placebo-controlled study. Biological Psychiatry 63:629–632, 2008.
Address correspondence to: Barbara J. Coffey, MD, MS Icahn School of Medicine at Mount Sinai One Gustave L. Levy Place, Box 1230 New York, New York 10029 E-mail: [email protected]
JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume 24, Number 8, 2014 ª Mary Ann Liebert, Inc. Pp. 458–461 DOI: 10.1089/cap.2014.2482
Advanced Pediatric Psychopharmacology
Expanded Usage of Prazosin in Pre-Pubertal Children with Nightmares Resulting from Posttraumatic Stress Disorder Presenters: Revital Racin, MD1 and Christopher Bellonci, MD1 Discussant: Barbara J. Coffey, MD, MS 2
Chief Complaint and Presenting Problem
M
. was a 10-year-old African American boy with a history of attention deficit hyperactivity disorder (ADHD) and significant childhood trauma referred for hospitalization by his legal guardian for increased aggressive behavior and suicidal ideation. History of Present Illness M. was removed from his biological mother’s home for neglect approximately one and half years prior to hospitalization. He was subsequently placed under the legal guardianship of A., his 21-yearold half-sister. M. has had aggressive behavior problems since he moved to live with A. During the past year, M. has made homicidal statements toward A. and wrote with chalk on their apartment building that he wanted to ‘kill’’ her. He was also physically aggressive toward his peers (e.g., punching an age-mate in the face) and brother (choking him during an altercation) and assaultive with school staff. A. reported that M. tended to ‘‘forget’’ incidents of aggression and often stated that he ‘‘can’t remember what happened.’’ A. stated that M. has had one isolated fire-setting incident when he was 7 years old. Additionally, A. reported that M. often lied, stole, and wrote statements expressing hatred for life and a desire to kill himself. M. was suspended from school as a consequence of his behaviors. A. reported that M.’s aggression and suicidality increased particularly when he was in unstructured environments and when limits were set by authority figures. Limits such as time-outs at home and school had proven ineffective. M. had recently started treatment with an outpatient psychiatrist who diagnosed ADHD and treated him with guanfacine 1 mg in the morning and 0.5 mg in the afternoon and amphetamine mixed salts extended release 5 mg daily. A. and the outpatient child and adolescent psychiatrist reported an increase in aggression, oppositional behavior, and suicidal and homicidal ideation over the course of several weeks prior to admission. M. was referred for voluntary admission to an inpatient child and adolescent psychiatry unit after wrapping a wire around his neck. He had expressed a desire to hang himself at school after getting into trouble. There was no reported precipitant or change in his environment that could explain his increased aggression and suicidality in the weeks leading up to admission. The amphetamine mixed salts had reportedly increased his aggressive behavior, and were discontinued a few days prior to his hospitalization. At the 1 2
time of admission M. was taking guanfacine 1 mg in the morning and 0.5 mg at bedtime, which by A.’s reports only initially ameliorated impulsive and aggressive behaviors. Past Psychiatric History M. had no prior inpatient psychiatric admissions. At the time of admission, M. was seeing a child and adolescent psychiatrist and an individual therapist, and met once weekly with a guidance counselor at his school. Developmental History M. may have been exposed to illicit substances in utero due to a maternal substance abuse history. A full developmental history was not available. Biological mother and legal guardian provided no information regarding his developmental milestones or early development. Educational History M. was currently in the fourth grade and reportedly performing well academically. He did not have a 504 plan and/or an individualized education plan. Although he had a record of suspension, most of his behavioral difficulties were reported to occur during his after school program. At time of admission M. had not undergone academic or neuropsychological testing. Social History M. lived with his biological mother from birth until his removal by the state child welfare agency when he was 8 and a half years old. M. had experienced physical and emotional abuse, exposure to sexual content, and medical and emotional neglect while in his mother’s care. According to reports, mother sold drugs in the home and M. was exposed to adults, including his mother, abusing illicit substances in the home. M. was forced to urinate in bottles so that his mother could use his urine to pass her drug screen. Mother had had multiple male partners, some of whom physically and possibly sexually abused her in front of M. M. also had a history of moving frequently to different homes, cities, and states, and often the precipitating factor for these moves was the threat of child welfare involvement. According to A.’s report, schools had filed neglect reports on multiple occasions when M. failed to attend school on a consistent basis.
Tufts Medical Center, Department of Psychiatry, Boston, Massachusetts. Icahn School of Medicine at Mount Sinai, Department of Psychiatry, New York, New York.
458
ADVANCED PEDIATRIC PSYCHOPHARMACOLOGY M. was removed from his biological mother’s home approximately one and half years prior to this hospitalization. He was subsequently placed under the legal guardianship of A., his 21-year-old halfsister. M., A., and his 7-year-old brother lived in a rented apartment.
Journal of Child and Adolescent Psychopharmacology 2014.24:458-461. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 12/31/14. For personal use only.
Family History M. had an extensive maternal family history of mental illness, incarcerations, and substance abuse. A., M.’s maternal half-sister, was unaware of the specifics of these issues because she was also removed from her mother’s care at an early age. There is no information regarding father’s history. Medical History M. had no serious medical problems, hospitalizations, or surgery. He had no history of major childhood illnesses, had received all appropriate vaccinations, and reportedly had no growth and developmental abnormalities. An electrocardiogram at the time of admission was normal.
459 M. also attended daily individual supportive psychotherapy and weekly family therapy sessions during his admission. At the time of discharge, M. was taking prazosin 1 mg three times daily, fluoxetine 10 mg daily and OROS methylphenidate 18 mg daily. Wrap-around services and academic testing were recommended to the family at discharge, and were initiated two weeks after his admission. M. was scheduled to continue medication management with his previous outpatient child psychiatrist, individual therapy with his previous therapist, and weekly meetings with his guidance counselor at school. It was also recommended that he receive in-home behavioral therapy in addition to a therapeutic mentor and parental partner for A. At six month follow-up, it was reported that fluoxetine and the morning and late afternoon doses of prazosin had been discontinued due to ineffectiveness; increase in M.’s aggressive behavior during the day resulted in re-hospitalization. Prazosin was subsequently increased to 2 mg orally at bedtime, and M. continued to endorse relief from nightmares and improved quality of sleep. Brief Formulation
Mental Status Exam Mental status examination revealed a cooperative AfricanAmerican child, with no dysmorphic features, whose response to questions about everyday life was accurate but brief. He was appropriately groomed and oriented to time and place. His rate of speech was fast with normal volume, articulation, coherence, and spontaneity of speech. He was fast moving and fidgety during the examination, and exhibited poor eye contact. Mood was sad and affect was congruent with mood. M. endorsed flashbacks, nightmares, and hypervigilance. His flashbacks and nightmares consisted of what he described as ‘‘bad memories.’’ He denied suicidal or homicidal ideation, auditory or visual hallucinations, and depressive symptoms. His thought processes were linear with no perceptual disturbances. Memory was intact, and the neurological examination was within normal limits.
In summary, M. is a 10-year-old African American boy who met diagnostic criteria for PTSD manifest by hypervigilance, flashbacks, difficulty with sleep, and anxiety. M. may have had intrauterine exposure to illicit substances and was subjected to significant childhood trauma. He moved frequently between states, and during the past year his half-sister gained physical and legal custody of him. All of these factors contributed to M.’s insecurity, aggression, and suicidal thoughts. There was a strong genetic predisposition to mental illness, as there was an extensive, although undetailed, family history. M.’s PTSD symptoms improved with individual and family therapy and medication during hospitalization; however, M. did continue to have difficulties managing his aggressive behaviors after discharge, which resulted in rehospitalization and further medication trials. His nighttime dosage of prazosin continued to facilitate initiation and quality of sleep.
Hospital and Treatment Course
Multi-Axial Diagnoses
Upon admission, M. met DSM-IV-TR (American Psychiatric Association, 2000) criteria for posttraumatic stress disorder (PTSD). He reported that he startled easily in reaction to loud noises; scanning, hypervigilance, and daily flashbacks occurred mostly in the late afternoons. M. also suffered from nightmares with vivid imagery of past events. Due to his reported flashbacks and increased hypervigilance in the afternoons, prazosin 1 mg orally was first administered at 3 pm a few days after admission. The day after initiation of prazosin, M. reported that his intrusive memories decreased, which decreased his anger and improved his self-control. He asked for an additional dosage to help with his nightmares two days after initiation, so 1 mg at bedtime was added. His nightmares decreased after the first administration of prazosin at bedtime. Fluoxetine 10 mg orally daily was subsequently initiated to target M.’s depressed mood and PTSD symptoms, and guanfacine was slowly discontinued due to its ineffectiveness. Prazosin 1 mg was added in the morning to target his impulsive behaviors and hyperactivity. However, M. remained fast moving, impulsive, and inattentive. Therefore, a trial of OROS methylphenidate 18 mg was initiated several days prior to discharge, which improved his concentration and hyperactivity. Vital signs were monitored and were stable throughout his hospitalization. There was no evidence of orthostatic hypotension, light-headedness, or excessive sedation.
Axis I:
PTSD ADHD, combined presentation, by history Axis II: Deferred Axis III: None Axis IV: Level of psychosocial stressors: Severe; extensive history of unstable housing and trauma exposure Axis V: Current Global Assessment of Functioning (GAF): 40 Discussion According to DSM-5 diagnostic criteria (APA 2013), PTSD includes exposure to actual or threatened death, serious injury, or sexual violence in one (or more) of the following ways: directly experiencing the traumatic event(s), witnessing, in person, the event(s) as it occurred to others, or learning that the traumatic event(s) occurred to a close family member or close friend. In cases of actual or threatened death of a family member or friend, the event(s) must have been violent or accidental. Experiencing repeated or extreme exposure to aversive details of the traumatic event(s) also meets criteria. Exposure to traumatic events is not uncommon for many children and adolescents. More than one in four children experience a significant traumatic event before reaching adulthood (Krystal and Davidson 2007). In fact, a study of 1,420 children ages 9, 11, and 13 who were followed annually until the age of 16 reported that nearly
Journal of Child and Adolescent Psychopharmacology 2014.24:458-461. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 12/31/14. For personal use only.
460 two thirds experienced at least one traumatic event (Breslau, Andreski, Peterson 1991). A 2002 national sample of adolescents (12–17 years old) indicated that 3.7% of male and 6.3% of female adolescents met full diagnostic criteria for PTSD (Costello, Erkanli, Fairbank, Angold 2002). One study of a sample of adolescents and young adults reported that the overall lifetime prevalence of PTSD in the general youth population was 9.2% (Litz and Gray 2004). Sleep disturbance is an essential symptom of PTSD; recent evidence suggests that disrupted sleep may play an important role in the development of PTSD following a traumatic event (Gehman and Harb 2010). Sleep disturbance and nightmares occur in a majority of adults with PTSD, and in children, nightmares are one of the diagnostic criteria in the re-experiencing cluster of PTSD. PTSD-related nightmares often cause high levels of distress in children and adolescents, impacting their social and emotional functioning and overall sense of wellbeing. In the past, it was thought that PTSD-related nightmares would improve as the PTSD symptom complex improved, but this is no longer thought to be the case. If nightmares do not improve following therapy or other psychopharmacologic treatment, clinical practice calls for targeted treatment options for the sleep problems themselves. Reduction of nightmares is reported to improve the quality of sleep, subsequently improving overall clinical status of those who suffer from PTSD. Recent investigation of the neurobiology of PTSD suggests there is evidence for noradrenergic hyperactivity (Krystal and Neumeister 2009). Alpha-1 adrenergic receptors are located in the hippocampus, amygdala, and prefrontal cortex, which have been implicated in the pathophysiology of PTSD and PTSD-related nightmares. Prazosin antagonizes peripheral alpha-1 adrenergic receptors, and is the only available drug of this class that crosses the blood- brain barrier, with activity at central nervous system alpha-1 adrenergic receptors. Central noradrenergic tone is significantly reduced during slow wave sleep and essentially absent during rapid eye movement (REM) sleep, but in patients with PTSD, there are findings consistent with increased noradrenergic activity. This can cause increased phasic motor activity, stage shifts and arousals during REM sleep (Ross 1994 and Breslau 2004) and REM fragmentation during early PTSD development (Mellman, Kullickbell, Ashlock 1995). This disruption can cause trauma nightmares (Mellman 1995; Mellman 2002) and interfere with normal cognitive processing of traumatic events (Stickgold 2007). Prazosin is thought to act centrally during sleep to reduce the nightmares and other events that lead to distressed awakening in patients with PTSD because of its ability to reduce adrenergic activity in the central nervous system that may contribute to hyperarousal symptoms and sleep disturbances. Prazosin has been investigated as a treatment for sleep problems, flashbacks, and hyperarousal associated with PTSD. Although used for other medical problems, there is evidence to suggest promising outcomes for its use in treatment of nightmares and other comorbid sleep disturbances (Raskind 2003; Miller 2008; Strawn 2008, 2011; Taylor 2008). It is now a commonly used drug for PTSD nightmares and non-nightmare-distressed awakenings in the veteran population. Two double-blind, placebo controlled trials (Raskind 2003, 2007) of prazosin in military veterans demonstrated promising outcomes in the reduction of posttraumatic nightmares. These trials suggest that prazosin is substantially more effective than placebo for nightmares in veterans with PTSD. Similarly designed trials for pediatric PTSD sleep-related disorders could test its effectiveness in this population. M.’s response to prazosin illustrates its potential utility for treatment of nightmares in the pre-pubertal population. Prazosin
RACIN, BELLONCI, AND COFFEY has been used in children and adolescents to treat congestive heart failure and hypertension, and is well tolerated from a hemodynamic standpoint. The onset of action related to reduction of nightmare frequency and severity was rapid, occurring within one day. No adverse effects were noted. The effect was sustained over the course of the hospitalization and for 6 months afterward. Improvement of M.’s sleep, flashbacks, and hyper-vigilance contributed to subsequent improvement of his mood, self-confidence and self-control during the hospital stay. In the only other case report that described use of prazosin in a pre-pubertal child at the time of this publication there were concerns over weight gain with long-term administration (Strawn 2009). We did not follow M. after hospitalization to know whether weight gain became a concern. Low-dose prazosin may be effective in youth with PTSD as an adjunctive treatment. Systematic studies of prazosin for the treatment of youth with PTSD are warranted based on adult studies and a growing number of case reports in adolescents and children. Disclosures There are no conflicts of interest and no disclosures to report. Dr. Coffey has received research support from Eli Lily Pharmaceutical, NIMH, NINDS, Tourette Syndrome Association, Otsuka, Shire, Bristol-Myers, Pfizer, and Boehringer Ingelheim. Acknowledgment We would like to acknowledge and thank Zoey Shaw, Laura Ibanez Gomez, and Natasha Kostek for their assistance in review and preparation of the manuscript. References American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th edition. Text Revision. Washington, DC: American Psychiatric Association, 2000. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th edition. Washington, DC: American Psychiatric Association, 2013. Breslau N, Davis GC, Andreski P, Peterson E: Traumatic events and posttraumatic stress disorder in an urban population of young adults. Arch Gen Psychiatry 48:216–222, 1991. Breslau N, Roth T, Burduvali E, Kapke A, Schultz L, Roehrs T: Sleep in lifetime posttraumatic stress disorder: A community-based polysomnographic study. Arch Gen Psychiatry 61:508–516, 2004. Brkanac Z, Pastor JE, Storck M: Prazosin in PTSD. J Am Acad Child Adolesc Psychiatry 42:384–385, 2003. Copeland WE, Keeler G, Angold A, Costello EJ: Traumatic events and posttraumatic stress in childhood. Arch Gen Psychiatry 64:577– 584, 2007. Costello EJ, Erkanli A, Fairbank JA, Angold A: The prevalence of potentially traumatic events in childhood and adolescents. J Trauma Stress 15:99–112, 2002. Fraleigh LA, Hendratta VD, Ford JD, Connor DF: Prazosin for the treatment of posttraumatic stress disorder-related nightmares in an adolescent male. J Child Adolesc Psychopharmacol 19:475–476, 2009. Gehrman PR, Harb GC: Treatment of nightmares in the context of posttraumatic stress disorder. J Clin Psychol 66:1185–1194, 2010. Krystal AD, Davidson J. The use of prazosin for the treatment of trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder: Biol Psychiatry 61:925–927, 2007. Krystal JH, Neumeister A: Noradrenergic and serotonergic mechanisms in the neurobiology of posttraumatic stress disorder and resilience. Brain Res 1293:13–23, 2009.
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Address correspondence to: Barbara J. Coffey, MD, MS Icahn School of Medicine at Mount Sinai One Gustave L. Levy Place, Box 1230 New York, New York 10029 E-mail: [email protected]
