Topiramate in Combat-Related Posttraumatic Stress Disorder
BACKGROUND: Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder that is common among combat veterans and may lead to very poor sleep and disturbing nightmares.
OBJECTIVE: To examine the safety and effectiveness of topiramate as add-on therapy for the management of combat-related PTSD and to examine the effects of topiramate on sleep and alcohol consumption.
METHODS: We conducted an 8-week open-label pilot study of topiramate for male combat veterans (N = 43) with PTSD, with analysis of veterans who completed the protocol. Psychometric, sleep, and alcohol consumption assessments were conducted at baseline and at week 8.
RESULTS: Twenty-nine subjects completed the 8-week study. Significant reductions in Clinician Administered PTSD Scale scores were observed at the 8-week endpoint (from 86.3 ± 21.1 to 67.1 ± 25.1; p < 0.01). Decreases were seen in both Stanford Sleepiness Scale scores (from 10.5 ± 0.72 to 9.0 ± 0.58; p = 0.08) and Mississippi PTSD scores (from 120.4 ± 6.5 to 111.5 ± 20.9; p = 0.08), but the extent of the changes did not attain statistical significance for either scale. There was a significant reduction in the proportion of patients with nightmares (from 100% to 62%; p < 0.001) and patients who experienced anxiety that interfered with falling asleep (from 90% to 62%; p < 0.05). The proportion of patients with high-risk drinking patterns also decreased (from 31% to 14%). Two serious adverse events were reported during the study: an increase in low back pain and an episode of acute confusion.
CONCLUSIONS: When used in addition to other empiric therapy, topiramate may be effective at reducing general symptoms of combat-related PTSD and reducing high-risk alcohol intake and nightmares. Further randomized controlled trials of topiramate for the treatment of combat-related PTSD are warranted.
Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder common among combat veterans. It is often associated with other psychiatric disorders, including depression and alcoholism. The prevalence of PTSD in Australia is approximately 3.3%; among Australian veterans of the Vietnam War, the lifetime prevalence is approximately 17%. This debilitating condition is difficult to manage. In clinical settings in Australia and other countries, treatment of PTSD usually involves a combination of nonpharmacologic interventions, often used with pharmacologic interventions.
Psychological interventions such as trauma-focused cognitive behavioral therapy, eye movement desensitization and reprocessing, and stress management are often first-line treatment for PTSD and have been shown to be effective at reducing symptoms. Pharmacotherapy is also commonly used for the management of PTSD, often in combination with psychotherapy. Pharmacotherapy used for PTSD may be undertaken with various agents, including selective serotonin-reuptake inhibitors (SSRIs) as well as other antidepressants (eg, mirtazapine, tricyclic antidepressants, monoamine oxidase inhibitors), and has been shown to reduce the core symptoms of PTSD, although there is a need for further controlled trials. The SSRIs are widely regarded as first-line pharmacotherapy for management of PTSD.
Prazosin, an α-adrenoreceptor antagonist, has been shown to be effective in treating PTSD, especially with respect to nightmares and sleep disturbances. Some benefit has been reported with clonidine, but issues of poor tolerability may have led to a lack of further research.
Patients with PTSD often report very poor sleep and are frequently troubled by disturbing nightmares. Preliminary evidence suggests a possible role for the anticonvulsant drug topiramate in the management of some features of PTSD, including nightmares. Topiramate has a number of potential mechanisms of action that may have therapeutic effect in PTSD: inhibition of sodium and calcium channels, enhanced γ-aminobutyric acid neuroinhibition, glutamate inhibition at kainate and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, and antikindling effect. However, to date there has been very little research addressing the clinical usefulness of topiramate in treatment of PTSD. Despite some evidence that topiramate may be helpful in attenuating nightmares associated with non-combat-related PTSD, only limited research has been published assessing this approach in relation to combat-related PTSD. Topiramate is not currently approved by any regulatory authority for the treatment of PTSD.
Finally, combat exposure is associated with increased risk of alcohol dependence. For example, in a comparison of subjects exposed to combat, with and without subsequent PTSD, the average prevalence of alcoholism was 33% in those without PTSD and 71% in those with PTSD. There is some evidence that topiramate may assist in the management of alcoholism.
The primary aim of this open-label pilot study was to observe the effect of topiramate as add-on therapy for the treatment of PTSD. Secondary objectives were to examine the effect of topiramate on sleep quality, focusing substantially on self-reports of nightmares and abnormal dream experiences, as well as alcohol consumption in combat-related PTSD in Australian veterans.
Abstract and Introduction
Abstract
BACKGROUND: Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder that is common among combat veterans and may lead to very poor sleep and disturbing nightmares.
OBJECTIVE: To examine the safety and effectiveness of topiramate as add-on therapy for the management of combat-related PTSD and to examine the effects of topiramate on sleep and alcohol consumption.
METHODS: We conducted an 8-week open-label pilot study of topiramate for male combat veterans (N = 43) with PTSD, with analysis of veterans who completed the protocol. Psychometric, sleep, and alcohol consumption assessments were conducted at baseline and at week 8.
RESULTS: Twenty-nine subjects completed the 8-week study. Significant reductions in Clinician Administered PTSD Scale scores were observed at the 8-week endpoint (from 86.3 ± 21.1 to 67.1 ± 25.1; p < 0.01). Decreases were seen in both Stanford Sleepiness Scale scores (from 10.5 ± 0.72 to 9.0 ± 0.58; p = 0.08) and Mississippi PTSD scores (from 120.4 ± 6.5 to 111.5 ± 20.9; p = 0.08), but the extent of the changes did not attain statistical significance for either scale. There was a significant reduction in the proportion of patients with nightmares (from 100% to 62%; p < 0.001) and patients who experienced anxiety that interfered with falling asleep (from 90% to 62%; p < 0.05). The proportion of patients with high-risk drinking patterns also decreased (from 31% to 14%). Two serious adverse events were reported during the study: an increase in low back pain and an episode of acute confusion.
CONCLUSIONS: When used in addition to other empiric therapy, topiramate may be effective at reducing general symptoms of combat-related PTSD and reducing high-risk alcohol intake and nightmares. Further randomized controlled trials of topiramate for the treatment of combat-related PTSD are warranted.
Introduction
Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder common among combat veterans. It is often associated with other psychiatric disorders, including depression and alcoholism. The prevalence of PTSD in Australia is approximately 3.3%; among Australian veterans of the Vietnam War, the lifetime prevalence is approximately 17%. This debilitating condition is difficult to manage. In clinical settings in Australia and other countries, treatment of PTSD usually involves a combination of nonpharmacologic interventions, often used with pharmacologic interventions.
Psychological interventions such as trauma-focused cognitive behavioral therapy, eye movement desensitization and reprocessing, and stress management are often first-line treatment for PTSD and have been shown to be effective at reducing symptoms. Pharmacotherapy is also commonly used for the management of PTSD, often in combination with psychotherapy. Pharmacotherapy used for PTSD may be undertaken with various agents, including selective serotonin-reuptake inhibitors (SSRIs) as well as other antidepressants (eg, mirtazapine, tricyclic antidepressants, monoamine oxidase inhibitors), and has been shown to reduce the core symptoms of PTSD, although there is a need for further controlled trials. The SSRIs are widely regarded as first-line pharmacotherapy for management of PTSD.
Prazosin, an α-adrenoreceptor antagonist, has been shown to be effective in treating PTSD, especially with respect to nightmares and sleep disturbances. Some benefit has been reported with clonidine, but issues of poor tolerability may have led to a lack of further research.
Patients with PTSD often report very poor sleep and are frequently troubled by disturbing nightmares. Preliminary evidence suggests a possible role for the anticonvulsant drug topiramate in the management of some features of PTSD, including nightmares. Topiramate has a number of potential mechanisms of action that may have therapeutic effect in PTSD: inhibition of sodium and calcium channels, enhanced γ-aminobutyric acid neuroinhibition, glutamate inhibition at kainate and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, and antikindling effect. However, to date there has been very little research addressing the clinical usefulness of topiramate in treatment of PTSD. Despite some evidence that topiramate may be helpful in attenuating nightmares associated with non-combat-related PTSD, only limited research has been published assessing this approach in relation to combat-related PTSD. Topiramate is not currently approved by any regulatory authority for the treatment of PTSD.
Finally, combat exposure is associated with increased risk of alcohol dependence. For example, in a comparison of subjects exposed to combat, with and without subsequent PTSD, the average prevalence of alcoholism was 33% in those without PTSD and 71% in those with PTSD. There is some evidence that topiramate may assist in the management of alcoholism.
The primary aim of this open-label pilot study was to observe the effect of topiramate as add-on therapy for the treatment of PTSD. Secondary objectives were to examine the effect of topiramate on sleep quality, focusing substantially on self-reports of nightmares and abnormal dream experiences, as well as alcohol consumption in combat-related PTSD in Australian veterans.
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