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Pharmacotherapy for posttraumatic stress disorder in children and adolescents
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Pharmacotherapy for posttraumatic stress disorder in children and adolescents
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2017. | This topic last updated: Mar 14, 2017.

INTRODUCTION — Posttraumatic stress disorder (PTSD) in children and adolescents is a severe, often chronic, and impairing mental disorder. PTSD is seen in some children (and not others) after exposure to traumatic experiences involving actual or threatened injury to themselves or others.

PTSD is characterized by intrusive thoughts and reminders of the traumatic experience(s), avoidance of trauma reminders, negative mood and cognitions related to the traumatic experience(s), and physiological hyperarousal that lead to significant social, school, and interpersonal problems. PTSD can occur even in toddlers (one to two years old) [1,2].

This topic will address pharmacotherapy for PTSD in children. The epidemiology, pathogenesis, clinical manifestations, course, assessment, diagnosis, and psychosocial interventions for PTSD in children are addressed separately, as are acute stress disorder and PTSD in adults. (See "Posttraumatic stress disorder in children and adolescents: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis" and "Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical manifestations, course, assessment, and diagnosis" and "Psychotherapy for posttraumatic stress disorder in adults" and "Pharmacotherapy for posttraumatic stress disorder in adults" and "Acute stress disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, and diagnosis" and "Treatment of acute stress disorder in adults".)

APPROACH TO TREATMENT — Our approach to treating posttraumatic stress disorder (PTSD) in children, including selecting among psychotherapies and medications, is described separately. In general, trauma-focused psychotherapy is suggested as first-line treatment for youth with PTSD; adjunctive medications are suggested to treat symptoms that do not adequately respond to psychotherapy. (See "Approach to treating posttraumatic stress disorder in children and adolescents" and "Psychosocial interventions for posttraumatic stress disorder in children and adolescents".)

ANTIDEPRESSANT MEDICATIONS — We agree with the practice parameters developed by the American Academy of Child and Adolescent Psychiatry that clinical trials comparing antidepressant treatment with placebo in pediatric patients with posttraumatic stress disorder (PTSD) are limited and, in general, do not suggest benefit of these medications. [3-5].

SSRIs — Selective serotonin reuptake inhibitors (SSRIs), which have been found to reduce PTSD symptoms in adults with the disorder, do not appear to be efficacious in children with PTSD. No differences in PTSD symptom reduction were seen between patients randomly assigned to receive an SSRI compared with placebo in multiple small randomized trials [4-7], despite promising results in uncontrolled trials [8,9] (see "Pharmacotherapy for posttraumatic stress disorder in adults", section on 'Selective serotonin reuptake inhibitors'):

A clinical trial randomly assigned 24 children and adolescents (age 10 to 17 years) with PTSD who were receiving trauma-focused cognitive-behavioral therapy to receive adjunctive sertraline (mean dose, 150 mg/day; range, 50 to 200 mg/day) or placebo [5]. No difference in PTSD symptom reduction was seen between groups at the end of a 12-week treatment period.

With a goal of preventing the development of PTSD, a clinical trial randomly assigned children and adolescents who experienced thermal burn-related trauma to receive sertraline or placebo [7]. After 24 weeks, parent-reported PTSD symptoms were lower in patients treated with sertraline, although patient-reported symptoms did not differ between groups [7].  

SSRIs may be considered in youth with co-occurring major depressive disorder or anxiety disorders in addition to PTSD.

Other antidepressants — The only non-SSRI antidepressant evaluated in a clinical trial was tested over an inadequate duration. The trial randomly assigned 60 thermally injured children suffering symptoms of acute stress to receive imipramine, fluoxetine, or placebo. After one week of treatment, no difference was seen in patient reported PTSD symptoms (60 and 72 versus 55 percent) [6].

ANTIADRENERGIC MEDICATIONS — Medications that centrally modulate noradrenergic tone are supported by clinical research as potential treatments for posttraumatic stress disorder (PTSD) [10]. Studies of adults with PTSD have found elevated noradrenergic hyperactivity [11,12]. Emerging evidence suggests that noradrenergic disturbances may occur proximal to the trauma and can be detected in traumatized children [13,14].

Clonidine and guanfacine — There are no randomized clinical trials of the alpha-2 adrenergic agonists clonidine and guanfacine in children with PTSD. An uncontrolled trial suggested that guanfacine may reduce intrusive and hyperarousal symptoms in children with PTSD symptoms. Nineteen children 6 to 18 years of age with PTSD symptoms were treated with 1 to 4 mg (mean daily dose: 1.19 mg; 0.03 mg/kg) of guanfacine extended release at bedtime [15]. After eight weeks, the patients experienced reductions in re-experiencing, avoidant, and hyperarousal symptoms of PTSD on the UCLA Reaction Index. The medication was well tolerated.

These medications are used to treat ADHD and nonspecific sleep disturbances in children and in our clinical experience are generally well tolerated, with the most common side effects being dry mouth and sedation [10]. Extended-release versions of guanfacine and clonidine are available. Clonidine is typically initiated at 0.05 to 0.1 mg at bedtime; extended release guanfacine is initiated at 1 mg at bedtime. (See "Attention deficit hyperactivity disorder in children and adolescents: Treatment with medications", section on 'Stimulants versus other medications'.)

Prazosin — Dyssomnias, including nightmares and frequent nighttime awakenings, are common among youth with PTSD. Case reports and a retrospective case series of 34 youth ages 5 to 17 years of age suggest that prazosin, an alpha-1 adrenergic antagonist, may be effective and well tolerated in treating sleep disturbances in youth with PTSD [16-20]. In the case series of 34 children and adolescents with PTSD, most youth responded to doses of ≤5 mg, with approximately a third of youth, primarily adolescents, requiring more than 5 mg/day [20]. In our clinical experience, improving the child’s sleep can greatly improve daytime functioning, reduce daytime symptoms, and increase the child’s ability to engage in evidence based trauma psychotherapy.

In adults, prazosin has been found to be efficacious and generally well tolerated at dose ranges of 10 to 15 mg at night in the treatment of PTSD-associated sleep disturbances (trouble falling/staying asleep, nightmares) [21-25]. (See "Pharmacotherapy for posttraumatic stress disorder in adults", section on 'Alpha-adrenergic receptor blockers'.)

Prazosin should be initiated at 1 mg 30 minutes before bedtime in children due to concern for first dose hypotension, and may be increased by 1 mg every three to four days for the first two weeks, starting lower and titrating up more slowly in younger children and/or in children and adolescents experiencing nausea, dizziness, or other side effects related to changes in blood pressure.

Gradual titration of prazosin will minimize orthostatic side effects. There is no evidence of a dose-response relationship for prazosin-related improvement in nightmares in pediatric PTSD, although our practice is to increase the dose, as tolerated, to at least 5 mg, over the course of four to eight weeks prior to concluding that the medication trial has been ineffective. Blood pressure and pulse should be monitored at baseline and during clinical encounters in prazosin-treated patients, especially if side effects are reported. If prazosin is effective, but morning dizziness or other orthostatic symptoms are present, prazosin may be administered 30 to 60 minutes earlier in the evening and/or the dose can be slowly decreased.

In our experience, prazosin can be continued through the duration of evidence-based trauma-focused psychotherapy. At the termination of psychotherapy, prazosin should be re-evaluated and titrated as clinically appropriate.

Propranolol — The beta-blocker propranolol may be an effective treatment for PTSD symptoms in children, but randomized clinical trials are needed. A prospective trial, utilizing an on-off-on design reported PTSD symptom reduction associated with propranolol treatment in 11 children with PTSD symptoms [26]. A randomized clinical trial to prevent PTSD development in 29 pediatric injury patients found no difference in response between propranolol and placebo [27].

SECOND-GENERATION ANTIPSYCHOTICS — Limited, uncontrolled trials of second-generation antipsychotic medications in youth with posttraumatic stress disorder (PTSD) symptoms have found mixed results and high rates of treatment-emergent adverse events [28,29].

Side effects of second-generation antipsychotics include weight gain, insulin resistance, dyslipidemia (including hypercholesterolemia and hypertriglyceridemia), and for many agents include hyperprolactinemia and extrapyramidal symptoms as well. Given the adverse effects of these medications, weighing the drug’s risks and possible benefits is particularly important. Children exposed to childhood trauma are at risk for chronic health problems such as childhood obesity independent of medication use [30], and thus at additional risk with second-generation antipsychotic use.

A case report of adjunctive risperidone reported improvement in PTSD symptoms in a boy with severe PTSD; however, risperidone was associated with treatment-emergent hyperprolactinemia that necessitated discontinuation of therapy [31].

ANTICONVULSANT MEDICATIONS — Carbamazepine [32] and divalproex [33] have been evaluated in small, open-label trials or retrospective data analyses of youth with posttraumatic stress disorder (PTSD). As examples:

A secondary analysis of data from a larger study of youth with conduct disorder treated with divalproex described the response of 12 youth with co-occurring PTSD (mean age: 12±1 years). Subjects in the original trial had been randomly assigned to receive low dose (≤250 mg/day; mean serum valproic acid level: 15.6 ug/ml [subtherapeutic]) divalproex or high dose (500 to 1500 mg/day; mean serum valproic acid level: 71.5 ug/ml) divalproex. Patients with conduct disorder and PTSD who received the high dose experienced greater reductions in core PTSD symptoms compared with those receiving low dose. Five of six patients treated with high-dose divalproex were classified as responders, while no patients treated with low-dose divalproex were classified as responders based on Clinical Global Impression-Improvement scale scores.  

In a retrospective evaluation of carbamazepine in 28 youth with sexual abuse-related PTSD residing in a state psychiatric hospital, carbamazepine was well tolerated at doses that produced serum levels between 10 to 11.5 ug/mL [32]. Twenty-two of 28 patients “became asymptomatic” while improvement was noted in the remaining six children.

These studies were performed in settings of intensive psychiatric services and high comorbidity. These limitations, the lack of randomized clinical trials, associated side effects, and the need for ongoing monitoring of drug levels limit the clinical utility of anticonvulsant medications in pediatric patients with PTSD.

OTHER MEDICATIONS — Several additional medications, including glutamatergic modulators and serotonin antagonists have been evaluated in pediatric patients with posttraumatic stress disorder (PTSD); however, the data do not support their utility.

Adjunctive D-cycloserine, an N-methyl-D-aspartic acid partial agonist, was evaluated in a randomized, placebo-controlled trial of 57 youth (age: 7 to 18 years) with PTSD who were receiving trauma-focused cognitive-behavioral therapy [34]. D-cycloserine appeared to hasten PTSD symptom recovery in the context of exposure-based sessions; however, no difference was seen in PTSD symptoms at three-month follow-up.

A case report suggested benefit for the 5-HT2 antagonist and antihistamine, cyproheptadine, in pediatric patients with PTSD [35].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Anxiety disorders in children".)

SUMMARY AND RECOMMENDATIONS

Our approach to treating posttraumatic stress disorder (PTSD) in children, including selecting among psychotherapies and medications, is described separately. In general, trauma-focused psychotherapy is suggested as first-line treatment for youth with PTSD; adjunctive medications are suggested to treat symptoms that do not adequately respond to psychotherapy. (See "Approach to treating posttraumatic stress disorder in children and adolescents".)

Multiple small clinical trials have generally not found antidepressants (mostly selective serotonin reuptake inhibitors [SSRIs]) to reduce PTSD symptoms in children with the disorder or prevent the development of PTSD. In adults, multiple clinical trials have found SSRIs to be efficacious in reducing PTSD symptoms. SSRIs may be considered for use in youth with co-occurring major depressive disorder or anxiety disorders. (See "Overview of prevention and treatment for pediatric depression" and "Pharmacotherapy for anxiety disorders in children and adolescents".)

Case series suggest that prazosin, an alpha-1 adrenergic antagonist, may be effective for sleep disruption or nightmares when prescribed at night in children with PTSD. In adults with PTSD, multiple clinical trials have found prazosin to be efficacious for these symptom. (See 'Prazosin' above and "Pharmacotherapy for posttraumatic stress disorder in adults", section on 'Alpha-adrenergic receptor blockers'.)

An uncontrolled trial has suggested that guanfacine may reduce intrusive and hyperarousal symptoms in children with PTSD symptoms. Experience with guanfacine and clonidine in children to treat other mental disorders suggests that these medications are well tolerated. (See 'Clonidine and guanfacine' above.)

Evidence of efficacy for other medications in children with PTSD, including second-generation antipsychotics and anticonvulsant medication, has not been sufficient to justify their use, particularly in light of the side effect profile of these medications. (See 'Second-generation antipsychotics' above and 'Anticonvulsant medications' above and 'Other medications' above.)  

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