Gabapentin and Posttraumatic Stress Disorder

Case Report

A 37-year-old Latin American woman, unemployed, was evaluated at our medication clinic in April 2000. She had moved from a small town to a city of approximately 200 000 people. At the time of the index examination, the patient was taking venlafaxine 37.5 mg twice a day and clonazepam 0.5 mg twice a day. She had been taking venlafaxine for approximately 20 months and clonazepam for 2 months to treat depression and PTSD. The symptoms had begun after a motor vehicle accident in October 1998. In the accident, her car was struck from behind and pushed into a lane of oncoming traffic, where it was struck by a school bus. She did not lose consciousness, but sustained injuries to her abdomen and left knee requiring hospitalization.

Approximately 7 months after the accident, the woman was examined by a psychiatrist who diagnosed major depression, single episode, moderate; fluoxetine 20 mg/d was begun at that time. Due to worsened anxiety and gastrointestinal adverse effects, fluoxetine was discontinued after 2 days and treatment with venlafaxine 37.5 mg twice a day was begun. According to the medical records, 1 month later she was free of depressive symptoms. Approximately 4 months later, clonazepam 0.5 mg twice a day was started, which the patient reportedly continued to take during the entire period prior to the index examination. The reason for initiating clonazepam was not given in her previous treatment records.

At the time of the index examination, the depression appeared to be in remission, but the patient continued to report PTSD symptoms consisting of flashbacks, increased vigilance, insomnia, and anxiety. Her flashbacks were constantly triggered by sounds (sirens, skidding tires, helicopters), the smell of hospitals, and viewing vehicles in her rear view mirror.

Her medical history was significant for hysterectomy, cholecystectomy, repair of cervical vertebrae (C5–C6), and unilateral carpal tunnel syndrome. She denied a history of seizures. There was no prior history of any psychiatric disorder; however, her family history was positive for depression. She had no history of alcohol or sedative/hypnotics abuse. The patient met the diagnostic criteria for major depression in remission and chronic PTSD. ¹ Her complete blood cell count with differential and thyroid-stimulating hormone revealed normal values. Liver function test values were also normal except for mild elevation of alkaline phosphatase. Renal function tests were not ordered. An electroencephalogram (EEG) was not performed.

In the following 2 months, the woman remained on a fixed dose of venlafaxine 37.5 mg twice a day, to which gabapentin was added. Gabapentin was selected to avoid chronic use of benzodiazepine compounds. She was started on gabapentin 100 mg at bedtime for 7 days and was instructed to increase the dose to 200 mg at bedtime. However, she continued taking only 100 mg at bedtime and reported a significant reduction in the frequency of the flashbacks. When asked to measure her improvement on a 1–10 scale, the woman rated her response as 7. During this period of 2 months, the clonazepam dose was gradually reduced and the drug discontinued without withdrawal symptoms. When the dose of gabapentin was increased to 300 mg at bedtime, she reported flashbacks only once a day. Due to the recurrence of dysphoria, the venlafaxine dose was increased to 37.5 mg 3 times a day.

In the intervening 15 months, the patient continued to report intermittent anxiety and insomnia. The dose of gabapentin was gradually increased. Approximately 8 months following the index evaluation, she started a part-time job and reported only a few flashbacks. Approximately 4 months later, she began working full-time. During this period, she was taking gabapentin 300 mg twice a day and 600 mg at bedtime, experiencing only occasional flashbacks. She continued, however, to report insomnia and anxiety. She tolerated gabapentin without any adverse effects. No standard rating scale was used to quantify the symptoms, and she did not receive any type of psychotherapy during the course of the drug therapy.

At the last follow-up visit approximately 28 months after the index evaluation, the woman was in remission of the depressive symptoms while taking venlafaxine 75 mg twice a day, but reported daily recurrence of flashbacks after she had been off gabapentin for 2 months (due to her inability to afford the medication). She was given a limited supply of venlafaxine samples and referred to a medication assistance program (samples of gabapentin were not available). She has not maintained contact with our clinic since her last visit.

Discussion

While the patient's response may have been related to a placebo effect or spontaneous improvement of her symptoms, the possibility of therapeutic effects of venlafaxine cannot be completely ruled out. In a single case report, venlafaxine, up to 225 mg/d, reduced nightmares and avoidance behavior in a 50-year-old combat veteran with PTSD and recurrent major depression. ⁴ In a recently reported uncontrolled study, Smajkic et al. ⁵ reported improvement in 5 patients with PTSD (Bosnian refugees residing in Chicago) with depression who were treated with venlafaxine 37.5 mg twice a day for 2 weeks, followed by 75 mg twice a day for 4 weeks. Depressive symptoms did not improve.

The presence of our patient's flashback symptoms at the time of the index examination and their recurrence after gabapentin was stopped support the role of gabapentin in suppressing the flashbacks.

Several AEDs have been used in treating PTSD symptoms. Lipper et al. ⁶ studied 10 veterans with PTSD who were treated with carbamazepine (serum concentrations 5–10 μg/mL) for 4 weeks. Seven patients reported “moderate to very much improved” with respect to their nightmares, flashbacks, and intrusive recollections. The authors proposed that a kindling mechanism may underlie PTSD symptoms and the therapeutic effects of carbamazepine were mediated by its antikindling property. Another report described a 30-year-old Vietnam veteran with PTSD who had been experiencing persistent nightmares associated with frequent awakenings. His EEG revealed bitemporal epileptiform sharp waves; carbamazepine was started. Within 2 days after a therapeutic concentration was reached, he did not report nightmares and nocturnal awakenings were not observed. ⁷ Wolf et al. ⁸ studied 8 Vietnam veterans with PTSD who were treated with carbamazepine 800–1200 mg/d (serum concentration 8–12 μg/mL). The patients reported only a reduction of angry outbursts and better impulse control. All patients had normal EEGs.

Valproate has shown effectiveness for treatment of PTSD. Szymanski and Olympia ⁹ reported reduction of irritability in 2 patients with PTSD and intermittent explosive disorder treated with divalproex. Another report described a 37-year-old man with PTSD who responded to sodium valproate 1000 mg/d. Within 2 days, his sleep improved and his nightmares ceased. There was also a reduction in the frequency of his intrusive memories. ¹⁰ Fesler et al. ¹¹ reported 14 Vietnam veterans with PTSD who were treated with divalproex for 2 months. The dose ranged from 250 to 2000 mg/d (mean serum concentration 70 μg/mL). Nine patients reported a significant overall improvement. Clark et al. ¹² reported reduction of intrusive thoughts and hyperarousal in 11 male combat veterans who were treated with divalproex (serum concentration 50–150 μg/mL) for 8 weeks.

Other AEDs have also been used for treatment of PTSD. In a 12-week, double-blind study, 5 of 10 patients who were given lamotrigine (up to 500 mg/d) reported improvement in their avoidance behavior. ¹³ Therapeutic effects of topiramate were reported in 3 patients with PTSD by suppressing nightmares and intrusive memories. ¹⁴ In a retrospective study of 35 patients with PTSD, Berlant and van Kammen ¹⁵ reported complete elimination of nightmares in 50% and intrusive recollections in 54% of patients treated with topiramate. Thirty-two of those patients had a comorbid diagnosis of mood disorder.

There are only a few published reports on gabapentin use in patients with PTSD. One described a 41-year-old man with the diagnoses of PTSD and cocaine abuse who had abused gabapentin (up to 1500 mg/d for 3 mo) to reduce his craving for cocaine. Gabapentin did decrease the craving, but its effect on his PTSD symptoms (if any) was not specified. ¹⁶ Berigan ¹⁷ reported a 48-year-old man with chronic PTSD, opioid abuse, and chronic hepatitis C whose PTSD symptoms had not responded to fluoxetine 40 mg/d and clonidine 0.1 mg 3 times a day taken for 1 year. After gabapentin (300 mg at bedtime for first 3 days and twice a day thereafter) was added, the patient reported decreased nightmares and resolution of flashbacks within several days. Brannon et al. ¹⁸ reported a 50-year-old electrician who developed PTSD 6 months after a severe electrical injury. His symptoms consisted of frequent dreams and avoiding electrical outlets. After failing to respond to fluoxetine 20 mg/d for 1 month, followed by a 1-month trial of cyproheptadine 4 mg at bedtime, he was treated with gabapentin (up to 1200 mg/d). The patient experienced a significant reduction in the frequency of his nightmares. An EEG was not obtained. In a retrospective study, Hamner et al. ¹⁹ reported that mild to marked improvement occurred in 27 patients with PTSD and comorbid depression treated with gabapentin 300–3600 mg/d as adjunct therapy. The duration of treatment ranged from 1 month to 36 months.

Summary

In a patient with chronic PTSD and major depression in remission, gabapentin treatment appears to have significantly reduced the frequency of flashbacks. Several clinical studies and a few case reports suggest that some AEDs are of clinical benefit in PTSD patients. With the exception of 1 double-blind study using lamotrigine, ¹³ these studies were not controlled. They do, however, raise the possibility that a subset of patients with PTSD may benefit from AEDs. Future controlled studies on larger numbers of patients are warranted.

ADDENDUM: Since the acceptance of this article, Berigan ²⁰ has reported an overall improvement in a 46-year-old male patient with chronic PTSD treated with oxcarbazepine 900 mg/d for 4 months.