The committee identified three RCTs of the tricyclic antidepressants imipramine, desipramine, and amitriptyline that included placebo controls (Davidson et al., 1990; Kosten et al., 1991; Reist, 1989). Participants in the tricyclic antidepressant studies all suffered from combat-related trauma (all U.S.). Age was reported in two of the three studies and ranged from 28 to 64 years with a mean age of about 38 years. None of the studies reported duration of illness or time since exposure. Race/ethnicity was only reported in one study and participants were predominantly white (88 percent) (Kosten et al., 1991).
The treatment period for these studies ranged from 4 to 6 weeks. None of the studies conducted follow-up after completion of treatment. One study measured adverse events associated with the treatment condition (Davidson et al., 1990). The main PTSD outcome measures used in the tricyclic antidepressant studies was IES. All three trials used a weak study design. The studies analyzed only those who completed treatment and suffered from high dropout rates; thus the committee found it impossible to judge whether the modest improvements were valid.
The committee identified one RCT of mirtazapine, showing a modest benefit of treatment; but the study was small and did not use a robust method for handling the dropout rates and managing missing values (Davidson et al., 2003). The committee identified one RCT of nefazodone, showing a modest benefit of treatment; but the study was small, of short duration, and did not use a robust method for handling dropouts and managing missing values (Davis et al., 2004). Finally, the committee identified two large RCTs of venlafaxine. However, both had dropout rates exceeding 30 percent with weak treatment of missing values (LOCF) and showed very small changes in CAPS, although they were statistically significant (Davidson et al., 2006a, 2006b).
Synthesis: The committee found that the overall body of evidence regarding other antidepressants to be low quality because of study limitations and a small number of studies for each drug. The committee is not confident in the presence of an effect and believes that any estimate of effect is uncertain. Further research is very likely to have an important impact on confidence in the estimate of effect of any of these agents and is likely to change the estimate.
Conclusion: The committee concludes that the evidence is inadequate to determine the efficacy of other antidepressants in the treatment of PTSD.