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Why did we examine topiramate as an agent that may have efficacy in Posttraumatic Stress Disorder (PTSD)?

Topiramate, an anticonvulsant agent, has been studied as a primary and adjunctive treatment for PTSD, yet little is known regarding the efficacy of this treatment approach.  The neurochemical basis for PTSD is hypothesized to involve kindling of the limbic nuclei and increased susceptibility to arousal. Anticonvulsants have been investigated as potential augmentation or monotherapy strategies to treat PTSD due to their anxiolytic and anti- kindling effects.

In contrast to most SSRIs and atypical antipsychotics, topiramate can display weight-reducing properties (Jones, 2015), and is usually well-tolerated at lower doses.  However, at higher doses (especially over 600 mg/day), patients often report sedation and impaired cognition (Jones, 2015). These treatment-limiting adverse effects could make prescribing higher doses of topiramate to treat PTSD problematic, as is observed in other conditions such as epilepsy (Kim et al., 2006).

Although RCTs have not showed conclusive evidence of topiramate’s mood stabilizing properties (Pigott et al., 2016), open-label trials have suggested efficacy in this area (Grunze et al., 2001; Maidment, 2002; Vieta et al., 2001). Furthermore, RCTs show topiramate’s efficacy in borderline personality disorder to reduce impulsivity, interpersonal problems, anger, and anxiety (Lieb et al, 2010). These properties may make topiramate well-suited to treat those patients with concurrent PTSD, impulsivity, and/or emotional reactivity, and further investigation is warranted in this area. Additionally, as topiramate has been successfully used to treat alcohol use disorders, evaluating the efficacy of topiramate among those with co-occurring PTSD and alcohol use seems particularly warranted. Batki et al. (2014) found that topiramate was associated with reduction in frequency of alcohol use and alcohol craving in PTSD patients.

What were the results of the meta-analysis?

Randomized controlled trials (RCTs) comparing topiramate as adjuvant therapy or monotherapy to placebo with minimum duration of six weeks were reviewed. Studies used a rating scale of PTSD symptoms at intake and at the end of treatment. Trials with veteran subjects and civilian subjects were included.

Topiramate had a small significant reduction of hyperarousal symptoms of PTSD. It tended to reduce overall PTSD symptoms and re-experiencing symptoms of PTSD, but these results were not statistically significant. A stratified analysis did not show a difference in treatment outcomes between veterans and non-veterans with PTSD.

What were the limitations of the meta-analysis?

There are notable limitations of this meta-analysis. There are only six RCTs included, which are limited in their scope due to small sample sizes of less than 40 subjects. Studies differed in the employment of combat or noncombat populations, use of topiramate as monotherapy or adjunctive therapy, and range of dosing. The variability among trials makes it difficult to extrapolate results clinically. Additionally, there was significant heterogeneity and differences in retention rates. Furthermore, many of these trials excluded patients with co-morbid illnesses such as bipolar, psychotic, and active substance use disorders, despite their high comorbidity with PTSD. Further research will clarify the role of topiramate and other anticonvulsants in the treatment of PTSD.

Discussion questions:

  1. With topiramate’s commonly reported side effects of cognitive slowing and sedation, would you consider using topiramate to treat PTSD?
  2. Would tailoring pharmacologic interventions for PTSD based on symptom cluster (hyperarousal; re-experiencing; and avoidance) be an effective approach to treatment?
  3. The DSM V introduces another cluster of symptoms for PTSD (Criterion D: Negative alterations in cognitions and mood). How might this affect pharmacological approaches to treating PTSD, and rating scales of PTSD symptoms?

Reference Article

Varma, A., Moore, M. B., Miller, C. W. T. and Himelhoch, S. (2018), Topiramate as Monotherapy or Adjunctive Treatment for Posttraumatic Stress Disorder: A Meta-Analysis. JOURNAL OF TRAUMATIC STRESS. doi:10.1002/jts.22251

Author Biography

Archana Varma, MD is a psychiatrist at Sheppard Pratt Health System and psychoanalytic candidate at the Washington Baltimore Institute for Psychoanalysis.

Michael Moore, MD is an outpatient psychiatrist at Inova Behavioral Health in Fairfax, Virginia. His interests include treatment of mood disorders, psychotic disorders, post-traumatic stress disorder, and addictions.