Post-traumatic stress disorder (PTSD) is a mental health condition that can develop after witnessing or experiencing a life-threatening event like war, a natural disaster, a car accident or sexual assault. PTSD affects 3-4% of the general population, and the incidence is higher in certain groups including Aboriginal and Torres Strait Islanders, people with substance abuse disorders, emergency service personnel, serving and ex-service military, and prisoners.

PTSD is associated with increased morbidity, use of healthcare services, and increased suicide risk, as well as premature death. PTSD is commonly associated with other comorbidities including depression, anxiety, alcohol and other substance abuse disorders, tobacco smoking, poor diet, and physical inactivity.

The symptoms of PTSD usually appear soon after the traumatic event. However, they may not appear until months or years after the event or may emerge over time in response to multiple traumatic experiences. One of the main features of PTSD are re-experiencing symptoms. This may include flashbacks of the traumatic event, intrusive thoughts, or emotional distress or physical reactivity after exposure to traumatic reminders. Most flashbacks occur at night and contribute to the presence of nightmares and sleep disturbances in PTSD. Other symptoms include hyperarousal, avoidance of situations that may remind people of the event, and a change in a person’s mood, behaviour, and feelings.

Nightmares and Sleep Disturbances in PTSD

It is estimated that 70-87% of people who suffer from PTSD experience sleep disruption and nightmares. Nightmares can be extremely distressing and disturbing. While they can have a profound negative effect on an individual’s sleep; they also affect mental health, physical health, and quality of life.

Nightmares experienced by people with PTSD are often frightening dreams involving threats to survival, security, or self-esteem. Trauma-related nightmares in PTSD are more severe than non-trauma-related nightmares as they are more frequent in nature and have been found to decrease the maintenance of sleep.

The onset of nightmares in PTSD is intrinsically linked to noradrenaline levels in the central nervous system (CNS). Higher noradrenaline levels in the CNS have been found in patients with PTSD and are associated with greater severity of PTSD symptoms. This increased CNS noradrenergic activity may contribute to the disruption of normal rapid eye movement sleep, in turn leading to nightmares.

Treatment of PTSD

PTSD is a difficult condition to treat and requires an integrated approach of psychotherapy and pharmacotherapy (medications). Cognitive behavioural therapy (CBT) is often considered one of the most effective treatments for PTSD.

There are a number of different types of CBT such as Cognitive Processing Therapy (CPT) and Prolonged Exposure (PE) therapy. CPT involves changing how people think and feel about the trauma, while prolonged exposure (PE) involves sufferers talking about the trauma repetitively until the memories are no longer upsetting.

Unfortunately, the common PTSD symptoms of nightmares and sleep disturbances are often resistant to treatment. In primary care, the recommended first-line pharmacotherapy agents for treating PTSD are selective serotonin reuptake inhibitors (SSRI) such as paroxetine. The response of PTSD to antidepressants is usually slower than for depression and they should be trialled for at least eight to twelve weeks. However, SSRIs are often ineffective or only partially effective for sleep problems. Second-line pharmacological interventions include the use of mirtazapine or tricyclic antidepressants. Phenelzine may be considered for resistant cases under specialist care. Sedative-hypnotics such as benzodiazepines may be helpful in the short-term. However, their use is not encouraged as the risk of tolerance and addiction likely outweigh any potential benefits.

The role of Prazosin

Prazosin is a highly lipophilic alpha1-adrenergic receptor antagonist (blocker) that crosses the blood brain barrier. As alpha1-adrenergic receptors are increasingly activated by elevated noradrenaline levels in the CNS of people with PTSD, prazosin can be used to minimise this activity.

Prazosin is currently approved for the treatment of hypertension, congestive heart failure, Raynaud’s phenomenon, Raynaud’s disease, and benign prostatic hyperplasia. Therefore, its use in the treatment of PTSD-associated nightmares is considered “off-label.” Randomised controlled trials provide evidence that prazosin is effective and safe in the treatment of nightmares and sleep disturbances with PTSD. Likewise, prazosin is found to improve overall clinical status, sleep quality, and patient’s sense of well-being and ability to function in daily activities. Significant changes in blood pressure were not observed in clinical trial participants.

Guidelines state that prazosin should be introduced to a patient’s treatment plan using the “start low, go slow” rule. The recommended starting dose to minimise the risk of adverse drug reactions is 1mg before bed. The dose may then be increased by 1mg every two to three nights until a clinical response is obtained. Average daily doses of prazosin reached during PTSD studies were 19.6mg for males and 8.7mg for females. However, there are reports of higher doses being used. The optimum dose is unknown, although a dose-related response appears to be evident.

Overall, prazosin is well tolerated. Common side effects include dizziness, headache, drowsiness, lack of energy, palpitations, and nausea. In addition, ‘first dose syncope’ (fainting) occurs in 1% of people initiated on doses of 2mg or higher. Therefore, prazosin should commence at a dose of 1mg or less.

Conclusion

PTSD is a difficult condition to treat and requires an integrated approach of cognitive behavioural therapy and pharmacotherapy. Unfortunately, common PTSD symptoms of nightmares and sleep disturbances are often resistant to treatment. The off-label use of the alpha1-adrenergic receptor blocker, prazosin, has shown promise in the treatment of PTSD-related trauma nightmares. The overall improvement in clinical status, coupled with its attractive side effect profile, make prazosin an agent worthy of further investigation for the management of PTSD.

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