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Medications for PTSD
Trauma-focused psychotherapies are the gold standard for treating PTSD in children and adolescents,
as recommended in the 2010 AACAP practice parameters. Many studies support the use of psychotherapy in contrast to the lack of research for medications. First line treatment of PTSD should always consist of psychotherapy but medications are often used in the hopes of further improving symptoms.
Table 1 - Medications for Pediatric PTSD - Provides a summary of drug options.
SSRIs
Two medications are FDA approved for the treatment of PTSD in the adult population, the SSRIs sertraline (Zoloft) and paroxetine (Paxil). No medications are FDA approved for treating children with PTSD. Out of the handful of randomized controlled trials looking at medication use in children and adolescents for PTSD, two include the use of sertraline (Cohen JA et al,J Am Acad Child Adolesc Psychiatry 2007;46(7):811–19 and Robb A et al, J Child Adolesc Psychopharmacol 2010;20(6);463–71).
While they both demonstrated some improvements, they were not significant. The Cohen study was limited to 24 girls with sexual abuse trauma, and the only difference found was in the Child Global Assessment Scale for the sertraline plus therapy group. The Robb study was larger, with 131 patients, but showed no significant benefit with sertraline. In fact, there was a higher dropout rate in the medication group.
In another RCT study, no differences were found between fluoxetine (Prozac), imipramine (Tofranil), and placebo for acute stress symptoms, but this study was extremely short (seven days) and several patients received other anxiolytic meds such as benzodiazepines and beta-blockers (Robert R et al, Burns 2008;34(7):919–28). While it may be helpful to use SSRIs for some children, the benefits are not well established and it is important to monitor for tolerability, particularly in the post black box world. The dosing in this case would be the same as for depression.
Non-SSRI Antidepressants
If you are starting to feel uncomfortable about the lack of evidence-based data, get ready for more uncharted territory. While adult studies have shown some efficacy of non-SSRI antidepressants including MAOIs, SNRIs, TCAs, trazodone (Oleptro), nefazodone (Serzone), and mirtazapine (Remeron), there is very little evidence to generalize this to children. One RCT found imipraminesymptoms in pediatric burn patients; however this was another short study with no placebo comparison, and no follow up beyond seven days (Robert R et al, J Am Acad Child Adolesc Psychiatry 1999;38(7):873–82).
Antipsychotics
The use of atypical antipsychotics has increased exponentially in children, and there is evidence that suggests an increase in dopamine in children with PTSD (De Bellis MD et al, Biol Psychiatry 1999;45(10):1271–84). Some improvements were noted through a report on three children treated with risperidone (Risperdal), a case series of six boys with quetiapine (Seroquel), and even treatment with clozapine (Clozaril), but further evidence is needed. The clozapine study was retrospective, limited to a residential population, and only had 19 patients with a PTSD diagnosis (Kant R et al, J Child Adolesc Psychopharmacol 2004;14(1):57–63). The sedating effects and dopamine blocking may be helpful with fear response and intrusive symptoms of PTSD but the potential benefits must be weighed carefully with the metabolic and extrapyramidal side effects. Typically, you would give these medications at a lower dose compared to treating psychotic disorders.
Antiadrenergics
The use of alpha and beta-adrenergic agents, such as clonidine (Catapres), guanfacine (Tenex), and propranolol (Inderal), has also demonstrated some response in children through a smattering of case studies and one randomized control study of propranolol in 29 children. These medications may help address hyperarousal symptoms in children and the noradrenergic dysregulation that is found with PTSD. Clonidine would start at 0.05 mg at bedtime with an increase in dose frequency of two or three times a day due to the short half life. Recent research has looked at the alpha-antagonist prazosin (Minipress) through case studies in children. Prazosin would be given 1 mg per day at bedtime up to a dose of 4 mg per day and can be particularly helpful with sleep.
Mood Stabilizers
When considering complex PTSDand the emotional dysregulation that is often present, the use of mood stabilizers seems reasonable. Studies in children include an RCT for divalproex sodium (Depakote) which showed symptom improvement at higher blood levels (Steiner H et al, Child Psychiatry Hum Dev 2007;38(3):183–93), and an open label study for carbamazepine (Tegretol) which also showed some improvements (Looff D et al, J Am Acad Child Adolesc Psychiatry 1995;34(6):703–4). The divalproex study used data from a previous trial and was limited to 12 incarcerated, conduct disorder boys, while the Looff study included 28 children, of whom several also received other psychotropic medications. Adult studies have shown some efficacy with lamotrigine (Lamictal), tiagabine (Gabitril), and topiramate (Topamax). Overall, the results have not been as promising as expected, and further research is needed.
Benzodiazepines
As PTSD falls under the DSM category of anxiety disorders, the use of benzodiazepines may be considered. However, there are essentially no studies that look at the efficacy of benzodiazepines in children for PTSD. This may be due to several reasons, including the increased risk of disinhibition in children, the limited amount of research in treating children with benzodiazepines for any indication, and the lack of evidence supporting its use in adult patients with PTSD. Another consideration is the significant rate of comorbid substance abuse with PTSD.
Opiates
While on the topic of potential substances of abuse, a naturalistic study looked at the use of morphine and the development of PTSD in hospitalized children with acute burns and found a reduction in PTSD symptoms with higher doses of morphine (Saxe G et al, J Am Acad Child Adolesc Psychiatry 2001;40(10):915–21). This may be due to an association with fear conditioning and memory consolidation. While this study followed the 24 children six months out, it would be difficult to sell the use of morphine in children without physical pain.
Other Possible Agents
Other medications that have been considered include cyproheptadine (Periactin), an antihistamine and 5-HT2 antagonist, with several case reports in adults and one case report in children. Improvements were found in intrusive symptoms, specifically nightmares. Dysregulation of the HPA axis suggests possible use of medications that act on corticotrophin-releasing.
Child Psychiatryas recommended in the 2010 AACAP practice parameters. Many studies support the use of psychotherapy in contrast to the lack of research for medications. First line treatment of PTSD should always consist of psychotherapy but medications are often used in the hopes of further improving symptoms.
Table 1 - Medications for Pediatric PTSD - Provides a summary of drug options.
SSRIs
Two medications are FDA approved for the treatment of PTSD in the adult population, the SSRIs sertraline (Zoloft) and paroxetine (Paxil). No medications are FDA approved for treating children with PTSD. Out of the handful of randomized controlled trials looking at medication use in children and adolescents for PTSD, two include the use of sertraline (Cohen JA et al,J Am Acad Child Adolesc Psychiatry 2007;46(7):811–19 and Robb A et al, J Child Adolesc Psychopharmacol 2010;20(6);463–71).
While they both demonstrated some improvements, they were not significant. The Cohen study was limited to 24 girls with sexual abuse trauma, and the only difference found was in the Child Global Assessment Scale for the sertraline plus therapy group. The Robb study was larger, with 131 patients, but showed no significant benefit with sertraline. In fact, there was a higher dropout rate in the medication group.
In another RCT study, no differences were found between fluoxetine (Prozac), imipramine (Tofranil), and placebo for acute stress symptoms, but this study was extremely short (seven days) and several patients received other anxiolytic meds such as benzodiazepines and beta-blockers (Robert R et al, Burns 2008;34(7):919–28). While it may be helpful to use SSRIs for some children, the benefits are not well established and it is important to monitor for tolerability, particularly in the post black box world. The dosing in this case would be the same as for depression.
Non-SSRI Antidepressants
If you are starting to feel uncomfortable about the lack of evidence-based data, get ready for more uncharted territory. While adult studies have shown some efficacy of non-SSRI antidepressants including MAOIs, SNRIs, TCAs, trazodone (Oleptro), nefazodone (Serzone), and mirtazapine (Remeron), there is very little evidence to generalize this to children. One RCT found imipraminesymptoms in pediatric burn patients; however this was another short study with no placebo comparison, and no follow up beyond seven days (Robert R et al, J Am Acad Child Adolesc Psychiatry 1999;38(7):873–82).
Antipsychotics
The use of atypical antipsychotics has increased exponentially in children, and there is evidence that suggests an increase in dopamine in children with PTSD (De Bellis MD et al, Biol Psychiatry 1999;45(10):1271–84). Some improvements were noted through a report on three children treated with risperidone (Risperdal), a case series of six boys with quetiapine (Seroquel), and even treatment with clozapine (Clozaril), but further evidence is needed. The clozapine study was retrospective, limited to a residential population, and only had 19 patients with a PTSD diagnosis (Kant R et al, J Child Adolesc Psychopharmacol 2004;14(1):57–63). The sedating effects and dopamine blocking may be helpful with fear response and intrusive symptoms of PTSD but the potential benefits must be weighed carefully with the metabolic and extrapyramidal side effects. Typically, you would give these medications at a lower dose compared to treating psychotic disorders.
Antiadrenergics
The use of alpha and beta-adrenergic agents, such as clonidine (Catapres), guanfacine (Tenex), and propranolol (Inderal), has also demonstrated some response in children through a smattering of case studies and one randomized control study of propranolol in 29 children. These medications may help address hyperarousal symptoms in children and the noradrenergic dysregulation that is found with PTSD. Clonidine would start at 0.05 mg at bedtime with an increase in dose frequency of two or three times a day due to the short half life. Recent research has looked at the alpha-antagonist prazosin (Minipress) through case studies in children. Prazosin would be given 1 mg per day at bedtime up to a dose of 4 mg per day and can be particularly helpful with sleep.
Mood Stabilizers
When considering complex PTSDand the emotional dysregulation that is often present, the use of mood stabilizers seems reasonable. Studies in children include an RCT for divalproex sodium (Depakote) which showed symptom improvement at higher blood levels (Steiner H et al, Child Psychiatry Hum Dev 2007;38(3):183–93), and an open label study for carbamazepine (Tegretol) which also showed some improvements (Looff D et al, J Am Acad Child Adolesc Psychiatry 1995;34(6):703–4). The divalproex study used data from a previous trial and was limited to 12 incarcerated, conduct disorder boys, while the Looff study included 28 children, of whom several also received other psychotropic medications. Adult studies have shown some efficacy with lamotrigine (Lamictal), tiagabine (Gabitril), and topiramate (Topamax). Overall, the results have not been as promising as expected, and further research is needed.
Benzodiazepines
As PTSD falls under the DSM category of anxiety disorders, the use of benzodiazepines may be considered. However, there are essentially no studies that look at the efficacy of benzodiazepines in children for PTSD. This may be due to several reasons, including the increased risk of disinhibition in children, the limited amount of research in treating children with benzodiazepines for any indication, and the lack of evidence supporting its use in adult patients with PTSD. Another consideration is the significant rate of comorbid substance abuse with PTSD.
Opiates
While on the topic of potential substances of abuse, a naturalistic study looked at the use of morphine and the development of PTSD in hospitalized children with acute burns and found a reduction in PTSD symptoms with higher doses of morphine (Saxe G et al, J Am Acad Child Adolesc Psychiatry 2001;40(10):915–21). This may be due to an association with fear conditioning and memory consolidation. While this study followed the 24 children six months out, it would be difficult to sell the use of morphine in children without physical pain.
Other Possible Agents
Other medications that have been considered include cyproheptadine (Periactin), an antihistamine and 5-HT2 antagonist, with several case reports in adults and one case report in children. Improvements were found in intrusive symptoms, specifically nightmares. Dysregulation of the HPA axis suggests possible use of medications that act on corticotrophin-releasing.
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