Journal of Traumatic Stress, VoL 9, No. 4, 1996

Brief Report

The Use of Anticonvulsants in Posttraumatic Stress Disorder: Case Study and Overview

Nicholas Ford 1

A case of posttraumatic stress disorder is described in which a favorable response to the anticonvulsants carbemazepine and sodium valproate occurred. The literature on the use of anticonvulsants in this disorder is reviewed.

KEY WORDS: carbemazepine; sodium valproate; posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is characterized by phases of intru- sion and avoidance on a background of significantly increased arousal (Horowitz, Wilner, & Kaltreider, 1980). Multiple psychobiologic mecha- nisms have been implicated, including alterations of the catecholamine and opioid systems and this has guided treatment approaches using agents in- fluencing these systems (Southwick, Bremner, Kaystal, & Chamey, 1994).

The course of this illness may be protracted (Archibald & Tudden- ham, 1965) and associated with other psychiatric diagnoses such as major depression, brief reactive psychoses, alcohol dependence and other anxiety disorders (McFarlane & Papay, 1992). There may be a range of social handicaps including marital breakdown, loss of employment and social iso- lation.

Treatment, both psychotherapeutic and pharmacological, is eclectic. There is often use of multiple drugs to treat different aspects of the syn- drome and comorbid illness. Treatment failures are not uncommon (Sutherland & Davidson, 1994).

This paper reports the use of carbemazepine and sodium valproate in a man with PTSD whose symptoms had failed to respond to two tricyclic antidepressants.

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Case Report

A 37-year-old married man was referred for psychiatric evaluation because of suicidal ideation. Six months previously he had given up his work as a policeman following a series of incidents in which his life had repeatedly been endangered. His work at the time involved long periods of covert surveillance in which there was an obsessive need for silence. On several occasions he had been discovered by the objects of his surveillance and he had been threatened with firearms, and had believed his life was at risk. This had occurred during a period of intense involvement in his work, and working long hours.

Since that time, he had suffered daily from intrusive recollections of the threatening incidents. His sleep was disturbed, with recurrent night- mares. Intense anxiety occurred when he was confronted with cues or reminders of his work. This included media reports, and loud noises of any kind, particularly the ringing of telephones. He had become agoraphobic, with panic attacks which occurred in social situations and public settings. There was a very prominent startle response with subjective distress, and associated with irritability and edginess.

He was depressed, with marked impairment of concentration and sleep. His appetite was unimpaired, but there was suicidal ideation with feelings of hopelessness. He felt he had lost control, which he attributed to the startle response, nightmares and recollections. This had led to mari- tal conflict, largely due to his irritability and verbal aggression toward his children. He had become withdrawn, rarely venturing outside his home. Alcohol abuse was denied by both the patient and his spouse. He com- plained of severe migraine headaches which first developed shortly after he had ceased work.

A diagnosis of PTSD was made, with secondary diagnoses of adjust- ment disorder with depressed mood and agoraphobia with panic attacks. He was hospitalized.

His past history included an admission to the hospital soon after ceas- ing work. At that time he had been diagnosed as suffering from a PTSD and major depression related to his work experience. He had been treated with trimipramine, and clomipramine. His depression had improved, but his anxiety symptoms had not. There was no past history of epilepsy, and a previous electroencephalogram, taken whilst on clomipramine, was re- ported as normal.

One month prior to the index admission his symptoms had worsened, and he became increasingly depressed. At the time of initial contact he had not responded to a dose increase of clomipramine. In hospital, he failed to improve with the addition of thioridazine and alprazolam.

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Throughout this time his mood remained depressed, and he stayed largely within his room. He remained preoccupied with thoughts of suicide and his work, although these occurred less frequently than prior to admission. He was jumpy, restless, and slept poorly due to nightmares and easy rous- ing from noise around the ward. Sessions with a psychologist, which had been commenced 2 weeks prior to admission, produced little improve- ment.

In the third week of admission, carbemazepine was added to the other medications. The relatively untested nature of this treatment was emphasized to the patient and his wife, as was the potential for side effects. The dose of carbemazepine was increased to 400 mg/day giving steady state levels of 27 ~tmoles/L. Three days after commencing this dose he began to become more relaxed with an improvement in sleep and mood, a decrease in nightmares, and a diminishing startle response. He started to spend time out of the ward, and at one point took trial leave with his family. Unfortunately, routine monitoring showed a two- fold rise in alkaline phosphatase, with a fourfold rise in transaminases. Carbemazepine was withdrawn, with a reversal of the liver function test abnormalities. Over the following 2 weeks there was a return of the startle response, irritability, nightmares, and sleep disturbance. His de- pression worsened.

Clomipramine was ceased and paroxetine begun, in conjunction with thioridazine and alprazolam. His depression again improved and he was no longer suicidal. However, at discharge he remained edgy and con- tinued to have disturbed sleep, nightmares, and intrusive recollections, although to a lesser degree than on admission. He continued to be ago- raphobic.

Over the next 5 months he continued on this medication and in psy- chotherapy with a psychologist. There was little improvement, and his irritability and startle response worsened to the extent that he could not tolerate the noise of his children. He became increasingly depressed and suicidal, despite adequate compliance and an increased dose of paroxetine. The nightmares and intrusive recollections had become more intense and distressing.

He was readmitted to the hospital, and sodium valproate was com- menced and increased to 500 mg twice daily, achieving steady-state levels of 520 ~moles/L. Two days after reaching this dose his edginess began to decrease and he began to leave his room. Over the next 2 weeks his mood and sleep improved. The nightmares ended, and al- though intrusive recollections continued they were less frequent and distressing. He was discharged and followed up as an outpatient.

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At follow-up 8 months postdischarge he was living with his family, and reported only occasional intrusive thoughts. Medication had been ceased. He felt he was largely recovered and had made some plans to re- turn to work, although in a different area.

Discuss ion

In treating this man there was a clear association between the com- mencement of anticonvulsants and marked improvement in symptoms, particularly those of startle response, irritability, sleep disturbance, and de- pression. Following cessation of carbemazepine his symptoms returned, leading to discharge on a cumbersome drug regime. The introduction of sodium valproate was associated with improvement. Sedation was not com- plained of with either drug, arguing against this as an acute effect producing improvement.

With both anticonvulsants the dose was increased to produce blood levels within the range quoted for epilepsy. Improvement was seen within 2 days of reaching this dose.

It is possible on each occasion that this man's PTSD symptoms im- proved secondary to improvement in his depression. Both carbemazepine and sodium valproate have been found useful in bipolar affective disorders (American Psychiatric Association [APA], 1994). There are isolated reports of carbemazepine having an antidepressant effect and also augmenting tri- cyclics in depression, but the time course is much slower than reported here. Sodium valproate has not been reported as an effective antidepres- sant (APA, 1994).

However, the patient's own description is of a marked improvement in startle response, leading to a decreased responsiveness to environmental cues and lowered irritability and arousal. The cognitive content of his de- pression tended to revolve around the loss of control produced by this symptom. It was also responsible initially for much of his social withdrawal, particularly the decision to leave his family.

Both sodium valproate and carbemazepine have been reported to be of use in a wide variety of psychiatric disturbances. In addition to their well known use in the affective disorders, they have been used in anxiety disorders, withdrawal states and behavioral dyscontrol syndromes, particu- larly when there is an unstable electroencephalogram (Keck, McElroy, & Friedman, 1992; Klein, Colin, Stolk, & Lenox, 1994). Although the use of anticonvulsants in PTSD has been suggested by Friedman (1988) and Silver, Sandberg, and Hales (1990), only three reports of use in FFSD were found on searching the literature, none of which were placebo controlled.

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The use of sodium valproate in PTSD was reported by Fesler (1991). In that study 14 Vietnam veterans in a FrSD clinic were treated with so- dium valproate over a 16-month period. Significant improvement was seen in both hyperarousal and phobic avoidance in those 11 patients who con- tinued the drug. Reexperiencing phenomena did not seem to have improved. No comment was made about improvement in mood although many of these patients had a past history of depression. Sodium valproate was well tolerated in this study, with only one patient ceasing due to side effects (nausea and vomiting). The time course of improvement was not described, although one detailed case study suggested a month lag to im- provement.

Lipper et al. (1986) reported the use of carbemazepine in 10 inpa: tients with PTSD. There was a significant level of improvement in intrusive recollections, sleep disturbance and startle response, but not in avoidance. This was a different profile of action to that reported for sodium valproate by Fesler (1991). Sleep and depression were reported to have improved, however much of the apparent improvement in depression was thought to be artifactual, and related to improvement on the sleep items on the Ham- ilton depression scale. Irritability improved, which is consistent with carbemazepine's effects in other psychiatric disorders as described by Keck et al. (1992). Although Lipper et al. did not report an incidence of side effects, carbemazepine has a high incidence of untoward effects, and is less well tolerated than valproate (Rail & Schleiffer, 1990).

Wolff, Alavi, and Mosnaim (1988) reported on improvements in im- pulsivity and angry outbursts in 10 Vietnam veterans with PTSD treated with carbemazepine. Their patients were also noted to have had normal electroencephalograms.

Putative mechanisms for improvement in PTSD with the anticonvul- sants focus around known effects of these drugs in epilepsy. Both activate GABA receptors, sodium valproate more generally than carbemazepine, enhancing inhibitory CNS transmission (Keck et al., 1992). This is thought to underlie the reversal of the lowering of discharge threshold in kindled cells by these drugs. Kindled limbic structures engaged in repetitive dis- charge might account for some of the phenomena of FrSD (Friedman, 1988). Post, Weiss, and Chuang (1992) have speculated that kindling may be the mechanism behind progressively developing symptoms in psychiatric disorders, and underlies the chronic relapsing nature of disorders such as bipolar disorder, and by inference, PTSD (Friedman, 1988). van der Kolk, Greenberg, and Boyd (1985) have demonstrated that long-term potentia- tion of pathways from the locus ceruleus to the hippocampus and amygdala occurs in animal models of inescapable shock, and speculate that similar processes occur in FIND.

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Two of the clinical reports suggest different profiles of action for so- dium valproate and carbemazepine, the mechanisms of which are obscure. Carbemazepine seemed to have an action on the intrusive dimension of symptoms, although sodium valproate lacked this (Fesler, 1991; Lipper et al., 1986).

There are reports suggesting facilitation of benzodiazepine withdrawal with carbemazepine in some anxiety states (Klein et al., 1994; Schweitzer, Rickels, Case, & Greenblatt, 1992). It has been suggested that sodium val- proate may have a similar action (Keck et al., 1992). It is possible that alprazolam withdrawal may have been facilitated in this patient by sodium valproate, although the improvement in his condition and the absence of a prior history of substance abuse may be sufficient to explain this effect.

This is a single case report, and describes previous data obtained from only 30 patients world wide. FI'SD can be highly resistant to intervention, and is significantly debilitating. There is an associated toll on the families of those involved, with demonstrated third generation effects, as well as medical costs. The anticonvulsants are potentially toxic drugs, but the data suggest that anticonvulsants have some useful properties in treatment re- sistant PTSD, particularly where irritability and a startle response are prominent.

Acknowledgments

The author wishes to thank Kerry Pincombe and Alexander McFarlane for their helpful criticisms of the manuscript.

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