More than one quarter of children and adolescents experience an uncontrollable traumatic event, e.g., violence at home or school, physical or sexual abuse, motor vehicle accidents, disasters, war, terrorism, refugee trauma (Costello, Erkanli, Fairbank, & Angold, 2002; Cohen, 2010). Of these, 3%–15% of females and 1%–6% of males meet the diagnostic criteria for post-traumatic stress disorder (PTSD) (Costello et al. 2002; Elbe, Bezchlibnyk-Butler, Virani, & Procyshyn, 2014; Katzman et al., 2014).
PTSD symptoms can be categorized into four clusters: intrusive thoughts, e.g., auditory/visual hallucinations, flashbacks, nightmares, unwanted memories/re-experiencing; avoidance of people, places, situations that trigger distressing thoughts; cognitive and mood symptoms, e.g., loss of interest/pleasure in usual activities, feelings of detachment, memory loss, negative view of self/others, sense of a foreshortened future; and hyperarousal, e.g., exaggerated startle response, hypervigilance, inability to concentrate, insomnia, irritability (Elbe et al. , 2014; APA, 2013; Belkin & Schwartz, 2015). Children under six years of age may exhibit different responses to trauma compared to adolescents and adults, with symptoms such as nightmares, regressive behaviors, and re-enactment of the traumatic experience in their play (APA, 2013; Katzman et al., 2014). Risk for suicide attempt is increased in patients with PTSD, particularly in victims of sexual abuse, who are also at increased risk for engaging in high-risk sexual activities (Costello et al., 2002). Comorbid substance use disorders and mood and anxiety disorders are also common (Costello et al., 2002).
Trauma-focused cognitive behavioural therapy (TF-CBT) is the main treatment approach to PTSD in children and adolescents. Sometimes TF-CBT includes use of eye movement desensitization and reprocessing (EMDR) therapy, an evidence based nonpharmacological therapy that helps facilitate the resumption of normal information processing and integration (Cohen, 2010). PTSD drug treatments approved for adults, i.e., selective serotonin reuptake inhibitors (SSRIs), are not yet approved for PTSD in children or adolescents (Elbe et al, 2014). Pharmacotherapy may be considered adjunctively on an off-label basis if there is an inadequate response to TF-CBT or in the presence of a comorbid mood or anxiety disorder(Costello et al., 2002). Only two published randomized controlled trials (RCTs) for treatment of PTSD in children exist (both with sertraline); neither trial demonstrated superiority of sertraline over placebo ( Cohen, Mannarino, Perel, & Staron , 2010; Robb, Cueva, Sporn, Yang & Vanderburg, 2010). While sertraline was well tolerated in these RCTs, the potential for adverse effects (e.g., behavioral activation, irritability, sleep disturbances) must be considered when starting an SSRI in children or adolescents (Cohen, 2010). All SSRIs also carry warnings regarding increased risk for suicidality in children and adolescents (Elbe et al, 2014; US Food & Drug Administration, 2007, www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/UCM096273).
Non-SSRI treatments are also sometimes used adjunctively in children and adolescents with PTSD, although evidence of efficacy is limited to adults (Cohen et al., 2010; Katzman et al. 2014). A benzodiazepine (e.g., lorazepam, clonazepam) is sometimes prescribed on a regular schedule for a short period of time for severe symptoms or when anxiety symptoms (jitteriness) worsen temporarily following SSRI initiation (Bandelow et al., 2012). Long-term benzodiazepine use should be avoided because of the significant risk of dependence in PTSD patients, who are already at increased risk for a substance use disorder.
Prescribers may request help from pharmacists in creating withdrawal plans for patients who have been receiving long-term benzodiazepine treatment. Resources such as the Ashton Manual (www.benzo.org.uk/manual/) contain suggested withdrawal protocols, which usually involve gradual transition to diazepam (the benzodiazepine with the longest half-life) followed by tapering of the diazepam dosage over several weeks or months (Ashton, 2011).
The increased risk for substance use disorders in patients with PTSD has led to examination of the therapeutic potential of adjunctive treatments with reduced abuse liability. Pharmacists may see prescriptions targeting disordered sleep (e.g., trazodone, zopiclone) and hyperarousal such as the alpha-2 adrenergic agonists clonidine or guanfacine and the beta-antagonist propranolol in children and adolescents (Belkin & Schwartz, 2015). Second-generation antipsychotics (SGAs) such as risperidone are sometimes prescribed to reduce fear and aggression related to increased dopamine secretion (Cohen, 2010), but little evidence supports this practice in children. The potential benefits must be weighed against the risk of significant metabolic adverse effects with SGAs in this age group (Ho, Panagiotopoulos, McCrindle, Grisaru, & Prongsheim, 2011).
Pharmacists may be surprised to receive a prescription for prazosin for a child, as it is formally approved only for treatment of hypertension in adults (see product monographs. However, this alpha-1 adrenergic antagonist has been studied in six small RCTs in combat veterans and adult civilians for treatment of sleep disturbances and nightmares associated with PTSD (Khachatryan, Groll, Booij, Sepehry, & Schütz, 2016). These symptoms also cause significant distress in children and adolescents with PTSD, and their impact on daytime functioning and well-being can persist after other symptoms subside (Cohen, 2010). Child and adolescent psychiatrists have shown increasing interest in using prazosin for these PTSD symptoms. A handful of published case reports describe beneficial responses and good tolerability (aside from transient dizziness early in treatment) with prazosin at a dose of 1–4 mg at bedtime (Brkanac, Pastor, & Storck, 2003; Fraleigh, Hendratta, Ford, & Connor, 2009; Strawn, Delbello, & Geracioti, 2009; Strawn & Keeshin, 2011; Oluwabusi, Sedky, & Bennett, 2012; Racin, Bellonci, & Coffey, 2014). Children and adolescents who are normotensive at baseline usually tolerate the hypotensive effects of medications well. However, pharmacists should still counsel caregivers and patients taking prazosin or other adrenergic blockers regarding precautions to mitigate dizziness and prevent syncope. These include avoiding dehydration by maintaining good fluid intake; taking bedtime doses just before lying down; rising slowly from a sitting or lying position; using caution with hot baths, showers, hot tubs, or saunas; sitting down if feeling dizzy or lightheaded; and ensuring regular blood pressure checks during the dose titration period.
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Ashton, C. H. (2011). Benzodiazepines: How they work and how to withdraw (aka the Ashton Manual). Retrieved from www.benzo.org.uk/manual/contents.htm.<7p>
Bandelow, B., Sher, L., Bunevicius, R., Hollander, E., Kasper, S., Zohar, J., . . . WFSBP Task Force on Anxiety Disorders, OCD and PTSD. (2012). Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and post-traumatic stress disorder in primary care. International Journal of Psychiatry in Clinical Practice, 16, 77–84.
Belkin, M. R., & Schwartz, T. L. (2015). Alpha-2 receptor agonists for the treatment of posttraumatic stress disorder. Drugs Context, 4, 212286.
Brkanac, Z., Pastor, J. F., & Storck, M. (2003). Prazosin in PTSD. Journal of the American Academy of Child and Adolescent Psychiatry, 42, 384–5.
Cohen, J. A. (2010). Practice parameter for the assessment and treatment of children and adolescents with posttraumatic stress disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 49, 414–30.
Cohen, J. A., Mannarino, A. P., Perel, J. M., & Staron, V. (2007). A pilot randomized controlled trial of combined trauma-focused CBT and sertraline for childhood PTSD symptoms. Journal of the American Academy of Child and Adolescent Psychiatry, 46, 811–9.
Costello, E. J., Erkanli, A., Fairbank, J. A., & Angold, A. (2002). The prevalence of potentially traumatic events in childhood and adolescence. Journal of Traumatic Stress, 15, 99–112.
Elbe, D., Bezchlibnyk-Butler, K., Virani, A. S., & Procyshyn, R. M. (2014). Clinical handbook of psychotropic drugs for children and adolescents, 3rd ed. Boston, MA: Hogrefe Publishing.
Fraleigh, L. A., Hendratta, V. D., Ford, J. D., & Connor, D. F. (2009). Prazosin for the treatment of posttraumatic stress disorder-related nightmares in an adolescent male. Journal of Child and Adolescent Psychopharmacology, 19, 475–6.
Ho, J., Panagiotopoulos, C., McCrindle, B., Grisaru, S., & Prongsheim, T. (2011). Management recommendations for metabolic complications associated with second generation antipsychotic use in children and youth. Journal of the Canadian Academy of Child and Adolescent Psychiatry, 20, 234–41.
Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., Van Ameringen, M. . . . Walker, J. R. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry, 14 (Suppl. 1), S1.
Khachatryan, D., Groll, D., Booij, L., Sepehry, A. A., & Schütz, C. G. (2016). Prazosin for treating sleep disturbances in adults with posttraumatic stress disorder: A systematic review and meta-analysis of randomized controlled trials. General Hospital Psychiatry, 39, 46–52.
Oluwabusi, O. O., Sedky, K., & Bennett, D. S. (2012). Prazosin treatment of nightmares and sleep disturbances associated with posttraumatic stress disorder: two adolescent cases Journal of Child and Adolescent Psychopharmacology, 22, 399–402.
Racin, P. R., Bellonci, C., & Coffey, D. B. (2014). Expanded usage of prazosin in pre-pubertal children with nightmares resulting from posttraumatic stress disorder. Journal of Child and Adolescent Psychopharmacology, 24, 458–61.
Robb, A. S., Cueva, J. E., Sporn, J., Yang R., & Vanderburg, D. G. (2010). Sertraline treatment of children and adolescents with posttraumatic stress disorder: a double-blind, placebo-controlled trial. Journal of Child and Adolescent Psychopharmacology, 20, 463–71.
Strawn, J. R., Delbello, M. P., & Geracioti, T. D. (2009). Prazosin treatment of an adolescent with posttraumatic stress disorder. Journal of Child and Adolescent Psychopharmacology, 19, 599-600.
Strawn, J. R., & Keeshin, B. R. (2011). Successful treatment of posttraumatic stress disorder with prazosin in a young child. Annals of Pharmacotherapy, 45, 1590–1
Dean Elbe is a Doctor of Pharmacy and a Board-Certified Psychiatric Pharmacist working as a Clinical Pharmacy Specialist in child and adolescent mental health at the BC Children’s Hospital in Vancouver, BC. He is an international speaker on food–medication interactions and child and adolescent psychopharmacology. Dean’s research interests include developing clinical tools for clinicians and members of the public to obtain factual information about drug interactions between prescription medications and substances of abuse.