Pharmacotherapies are not a recommended first line treatment for PTSD due to their limited efficacy. There is also little evidence to suggest that combining psychological and pharmacological interventions leads to improved outcomes. Nonetheless, Australian and international guidelines for the treatment of PTSD [1308, 1350] recommend that pharmacotherapies be used as an adjunct to trauma-focused psychotherapy if the person has not gained benefit from psychological treatment, or if they express a preference for pharmacotherapy [1308, 1350–1352]. When pharmacotherapies are considered, SSRIs are the recommended first line option, particularly fluoxetine, paroxetine, and sertraline [1303, 1308], followed by the SNRI venlafaxine (see Table 47).
Trials of pharmacotherapy for PTSD co-occurring with AOD use disorders have examined the use of sertraline and paroxetine (SSRI antidepressants), desipramine (TCA), prazosin (alpha1-adrenergic receptor agonist), aprepitant (neurokinin-1 receptor antagonist), topiramate and zonisamide (anticonvulsants), N-acetylcysteine (mucolytic agent), naltrexone (opioid antagonist), and disulfiram (alcohol antagonist).
Early work by Brady and colleagues examining the use of sertraline provided initial evidence of safety and evidence of efficacy among people with less severe alcohol dependence and earlier onset PTSD [1353, 1354]. More recently, Hien and colleagues [780] investigated the use of sertraline in combination with the psychotherapy Seeking Safety. In this study, Seeking Safety plus sertraline was found to be superior to Seeking Safety with placebo in reducing PTSD symptoms, though improvements in alcohol use and dependence were equivalent between groups.
Petrakis and colleagues [1355] conducted an RCT comparing the efficacy of desipramine and paroxetine with and without adjunctive naltrexone among veterans with PTSD and alcohol dependence. Both groups of antidepressants produced a significant decrease in PTSD symptoms, with greater reductions in alcohol use seen among those who received desipramine. Adjunctive use of naltrexone was associated with greater reductions in cravings but did not provide any advantage over placebo in terms of alcohol use.
The limited research that has been conducted among people with co-occurring PTSD and AOD use disorders in relation to prazosin and aprepitant suggests that these agents are no more effective than placebo in relation to either PTSD or alcohol-related outcomes [1356], whereas topiramate [1357], zonisamide (as an adjunct to CPT) [1358], and N-acetylcysteine (as an adjunct to CBT for substance use) [1359] have been associated with greater reductions in PTSD symptom severity and alcohol-related outcomes relative to placebo [1357]. Naltrexone, disulfiram, and the combination of these two medications have been associated with greater reductions in alcohol-related outcomes but not PTSD symptoms, relative to placebo; however, unwanted side effects were more common among people who received the combination of naltrexone and disulfiram [1315, 1360].
In recent years there has been growing interest in the use of psychedelic substances such as MDMA, psilocybin, and ketamine to enhance psychotherapy for the treatment of PTSD and AOD use disorders (alcohol in particular) as single disorders. Despite there being considerable enthusiasm about the potential of these substances bringing a long-awaited breakthrough in psychiatry, to date the predominance of research is limited to small, uncontrolled trials [1361–1364]. Further research is needed to determine clinical efficacy and safety for single, as well as co-occurring conditions.