Evidence-Based Reviews

Can medications prevent PTSD in trauma victims?

Current Psychiatry. 2007 September;6(9):47-55

References

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Neither propranolol nor gabapentin showed statistically significant benefit in preventing PTSD compared with placebo. Effect sizes with the 2 treatments were too small to suggest that larger samples would produce a statistically significant result.

Prazosin—an alpha-1 adrenergic receptor antagonist—has been evaluated in 3 controlled studies and found to reduce intrusive nightmares typical of chronic PTSD.

Ten combat veterans with chronic PTSD showed significantly improved sleep, fewer severe nightmares, and improved global clinical status after receiving prazosin (mean dose 9.5 mg at bedtime) in a 20-week, placebo-controlled, double-blind, crossover study.¹⁰

Clinical Point

Agents such as propranolol and prazosin that target noradrenergic activity are being explored for possible PTSD prevention

In a larger randomized, parallel group trial,¹¹ the same authors compared prazosin with placebo in 40 combat veterans (mean age 56) with chronic PTSD. After 8 weeks, veterans taking prazosin (mean 13.3 ± 3 mg) had significantly fewer trauma nightmares, improved sleep (including return of normal dreams), and improved global clinical status vs placebo. Overall CAP scores did not decline significantly, however.

In a third placebo-controlled study,¹² a midmorning dose of prazosin was added to the regimens of 11 civilian trauma patients already taking the drug at bedtime to suppress trauma-related nightmares. Their daytime PTSD symptoms improved, as shown by reduced psychological distress in response to verbal trauma cues.

Prazosin can reduce chronic PTSD manifestations of nightmares and disturbed sleep, but it has not been shown to ameliorate the full PTSD syndrome. Prazosin has not been studied as an early PTSD intervention.

Clinical Point

Benzodiazepine trials have found these drugs surprisingly unhelpful (and perhaps harmful) in patients with acute trauma

Other antiadrenergics that reduce the release of norepinephrine—including clonidine and guanfacine—have been studied in open trials as treatment for PTSD. The only controlled study¹³ showed no benefit from guanfacine for PTSD prevention.

De-stressing the HPA axis

Hydrocortisone has been proposed to prevent PTSD by reducing HPA axis activation, acting as a countermeasure to elevated corticotropin-releasing factor found in patients with chronic PTSD.

IV hydrocortisone’s effect on the development of PTSD was compared with placebo in 20 septic shock survivors after discharge from intensive care.¹⁴ One of 9 patients (11%) in the hydrocortisone group was diagnosed with PTSD at follow-up (mean 31 months), compared with 7 of 11 (64%) in the placebo group.

In a similar study, the same researchers gave patients hydrocortisone before, during, and after cardiac surgery. Follow-up interviews revealed significantly lower PTSD and chronic stress symptom scores in the treatment group vs the placebo group.¹⁵

These studies—although provocative—are limited by the narrow range of trauma related to severe medical illness or extensive medical procedures.

Norepinephrine-blocking opioids

When the noradrenergic system is activated, one physiologic response is the activation of endogenous opioid systems, which may promote recovery by inhibiting the HPA axis. Opioid systems might be involved in PTSD, as suggested by:

preclinical evidence that opioids modulate memory¹⁶
studies showing low pain thresholds¹⁷ and abnormal beta-endorphin (an opioid peptide neurotransmitter)¹⁸ and methionine enkephalin (an opioid peptide)¹⁹ levels in PTSD patients.

In theory, opioid administration immediately after trauma may attenuate norepinephrine release, thus thwarting arousal-charged memory consolidation, hyperarousal, and re-experiencing.

One uncontrolled report of pediatric burn victims found a significant association between the morphine dose given for pain during hospitalization and reduced PTSD symptoms 6 months later.²⁰ Decreased pain did not explain the reduction in PTSD, as no significant correlation was seen between pain symptoms and PTSD outcome measures. Similarly, a longitudinal study of substance use among Vietnam War veterans with PTSD found decreased hyperarousal symptoms in heroin users.²¹

Using opioids to prevent PTSD would be feasible and efficient in acute care settings because 80% to 90% of traumatically-injured patients are discharged on opioid analgesics (compared with <10% on beta blockers or corticosteroids).²² However, 20% to 40% of physically injured inpatients are diagnosed with a substance use disorder at some point in life, making the use of opioid analgesics a practical concern.²³

GABA-benzodiazepine paradox

The GABA-benzodiazepine system plays an important role in mediating anxiety, which is consistent with the potent anxiolytic effects of benzodiazepines. Even so, trials of benzodiazepines have found these drugs surprisingly unhelpful—and perhaps harmful—in patients with acute trauma.

Alprazolam did not reduce PTSD symptoms in a small randomized, double-blind study.²⁴ Another trial found that receiving benzodiazepines shortly after trauma exposure was associated with increased PTSD risk in trauma survivors. Nine of 13 patients (69%) who received alprazolam or clonazepam met PTSD diagnostic criteria 6 months after the trauma, compared with 3 of 13 controls (15%).²⁵

Clinical Point

Antidepressants may be useful for acute trauma intervention because early depression symptoms predict PTSD development