Rationale:

• SSRIs do not benefit all patients with PTSD; some do better with more sedating medications, and they may need doses at the higher end of the safe-dose range.

Evidence:

• The alternatives with the best evidence to support their use are mirtazapine and venlafaxine (35; 36; 37; 38; 39).
• No substantive data support the use of buspirone, and no data are available on strategies for adding or substituting medications (26; 28; 40; 41; 42).
• Prazosin has been associated with reductions in nightmares and global PTSD severity in both open and placebo-controlled trials (43; 44; 45; 46), and should be considered as adjunctive therapy in patients for whom nightmares are prominent.
• A systematic review of evidence supporting pharmacologic intervention in patients who fail to respond to or do not tolerate SSRIs found that risperidone had the best evidence to favor its use in an adjunctive role (24).

Comments:

• Some evidence exists to support secondary consideration of sedating TCAs and the monoamine oxidase inhibitor phenelzine for PTSD, but the greater propensity of these medications for significant adverse effects makes them less desirable alternatives.
• The insomnia of chronic PTSD can be resistant to medication. Older antipsychiatric agents are not recommended and data are limited regarding newer ones such as risperidone and olanzapine.