A Guide to the Literature on Pharmacotherapy for Ptsd

We are beginning to reap the benefits of the upsurge in multiand single-site clinical trials with newer pharmacological agents that began in the mid-1990s. Although we eagerly await publications on large industry-sponsored trials currently in progress, this is a good time to take stock of the current and older literature on pharmacotherapy for PTSD. The two major developments are publica­ tion of guidelines on best pharmacotherapeutic prac­ tices in PTSD and recent approval by the Food and Drug Administration (FDA) of sertraline as a treat­ ment for PTSD. Best practices. Two recent publications address the question of best practices in pharmacotherapy from somewhat different perspectives. The empirical evidence on drug efficacy is thoroughly evaluated in a chapter by Friedman et al. (in press) that will appear in the forthcoming treatment guideline com­ missioned by the International Society for Trau­ matic Stress Studies (ISTSS). This comprehensive overview evaluates results from both randomized and open label trials and determines the level of evidence for the efficacy of each medication that has been the focus of an article in the PTSD treatment literature. A very different kind of overview is represented in a recent monograph summarizing the responses of an expert consensus panel of 57 international experts to a questionnaire on prescrib­ ing preferences for PTSD (Foa et al., 1999). There are some very interesting differences between these two practice guidelines. Conclusions in the ISTSS chapter (Friedman et al., in press) are based on empirical data derived from monotherapy efficacy studies. In contrast, the panel of experts (Foa et al., 1999) offer opinions based on clinical experience on complex treatment questions about treatment strat­ egies for partial and non-responders to medication treatment as well as on questions about what to prescribe for patients with co-morbid psychiatric, medical, and chemical abuse/dependency disor­ ders. Selective serotonin reuptake inhibitors (SSRIs). FDA approval of sertraline as the first medication indi­ cated for treating PTSD patients is an important milestone in our field. The data that convinced the FDA to take this action came from two large multisite trials in which approximately 200 subjects (in each trial) were randomly assigned to either sertraline or placebo, respectively. A description of the first of these studies is currently in press (Brady et al., in press). Since results of the second trial are still being prepared for publication, I have included an ab­ stract of the data that were presented at a scientific meeting (Davidson, Londborg, et al., 1997). Both studies demonstrate what others have previously reported from single-site trials with sertraline, paroxetine, fluvoxamine, and fluoxetine: that selec­ tive serotonin reuptake inhibitors have a broad spec­ trum of action on all three (re-experiencing, avoidant/numbing, and hyperarousal) clusters of PTSD symptoms (Davidson, Malik, et al., 1997; Marmar et al., 1996; Marshall et al., 1998; Rothbaum et al., 1996). Van der Kolk and associates (1994), who conducted the first randomized clinical trial with the SSRI fluoxetine, also found clear evidence for the efficacy of this agent, although their results suggest a more constricted spectrum of action since it re­ duced numbing and hyperarousal, but not re-expe­ riencing or avoidant PTSD symptoms. Randomized clinical trials (RCTs). I have presented abstracts of all the randomized clinical trials con­ ducted with PTSD patients since I believe that that is the best and most valuable data in this field. Citations on SSRI trials have already been discussed. Chronologically speaking, the first trials were with older antidepressants, tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). Three studies with TCAs, all with Vietnam veteran subjects, report positive results with imipramine (Kosten et al., 1991), mild-to-moderate effects with amitriptyline (Davidson et al., 1990), and negative results with desipramine (Reist et al., 1989). Two trials with the MAOI phenelzine report very posi­ tive results in one study (Kosten et al., 1991) and negative results in a methodologically flawed inves­ tigation (Shestatzky et al., 1988). Although interest in these older agents has waned because of the more recent interest generated by SSRIs and other new agents, it is important to consider the fact that nei­ ther TCAs nor MAOIs have been systematically evaluated and that there may be good reasons to include them in future drug trials. Other RCTs worth noting are a negative trial with the benzodiazepine, alprazolam (Braun et al., 1990), a negative trial with the second messenger, inositol, which had previously shown promise in treatment of depression and panic disorder (Kaplan et al., 1996), and a negative trial with the serotonin antago­ nist cyproheptadine, which had previously appeared