Post-traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a trauma- and stressor-related disorder that develops after exposure to actual or threatened death, serious injury, or sexual violence — directly, by witnessing it happen to someone else, by learning it happened to a close relative or friend, or through repeated or extreme exposure to aversive details of the event, as in first responders or military personnel.^[1] Symptoms span 4 clusters — intrusion, avoidance, negative alterations in cognition and mood, and alterations in arousal and reactivity — and must persist beyond 1 month with clinically significant functional impairment to meet diagnostic criteria (see Recognize the Condition for the full criteria).

Trauma-focused psychotherapy — cognitive processing therapy, prolonged exposure, or eye movement desensitization and reprocessing — is the preferred first-line treatment and has a stronger evidence base than medication alone.^[2] Pharmacotherapy remains a genuine first-line option in its own right — not a fallback — when psychotherapy is unavailable, not preferred by the patient, or when stabilization is needed first, and this chapter focuses on the pharmacologic side of management that pharmacists are positioned to lead.

DSM-5 symptom clusters

Diagnosis requires exposure to a qualifying trauma plus symptoms from 4 clusters: at least 1 intrusion symptom, at least 1 avoidance symptom, at least 2 negative cognition/mood symptoms, and at least 2 arousal/reactivity symptoms, persisting beyond 1 month and causing clinically significant distress or impairment in social, occupational, or other important functioning.^[1]

Onset and course

Symptoms most often begin within the first 3 months after the trauma, but delayed-onset PTSD — where the full diagnostic threshold is not met until 6 months or more after the event — occurs in a meaningful minority of cases. Without treatment, the course is variable: some patients experience gradual natural improvement, while others develop a chronic, fluctuating illness.

Moral injury

A diagnostically separate construct describing the distress that follows an event that violates a person's deeply held moral beliefs — for example, causing or failing to prevent harm, or witnessing acts that conflict with one's values. Moral injury is often concurrent with PTSD, particularly in military-related presentations, and can worsen overall symptom severity; adaptive disclosure-based interventions are an emerging, specifically targeted approach (see Non-Pharmacologic Treatment).

This chapter addresses PTSD in adults; children 6 years of age or younger are diagnosed using separate DSM-5 criteria not covered here.

• Severity, duration, and personal proximity of the traumatic exposure — direct, life-threatening, or repeated/prolonged trauma (combat exposure, sexual assault, childhood abuse) carries higher risk than a single, less severe exposure.
• Occupational exposure to repeated trauma — military personnel, first responders (paramedics, police, firefighters), and healthcare workers in trauma or critical-care settings.
• Prior trauma history, especially childhood trauma.
• Pre-existing psychiatric illness, including a personal or family history of anxiety, depression, or substance use disorder.
• Peritraumatic dissociation or an extreme peritraumatic emotional response.
• Lack of social support during and after the traumatic event.
• Ongoing life stress or additional adversity in the aftermath of the trauma.
• Female sex.
• Genetic and familial vulnerability to stress-related psychiatric illness.

Differentiating PTSD from other trauma/stress-related presentations

History

• Explore the nature, timing, and circumstances of the trauma with sensitivity and at the patient's pace — a complete history may genuinely take several sessions, and pushing for detail before trust is established can be counter-therapeutic.
• Characterize symptom onset, nature, and functional impact on work, relationships, and daily functioning.
• Screen explicitly for comorbid depression, other anxiety disorders, and substance use disorder — these frequently coexist and change the treatment plan.
• Ask directly about suicidal ideation, self-harm, and current safety at every assessment.

Screening and diagnostic tools

Physical examination and investigations

• Physical examination to exclude endocrine or cardiac conditions that can mimic arousal/anxiety symptoms, and to look for signs of substance misuse.
• Screen directly for substance use given the high rate of comorbid substance use disorder in this population.
• Baseline laboratory tests: CBC, electrolytes, glucose, liver function tests including GGT (alcohol-use screening), thyroid function tests, renal function tests, ferritin, vitamin B12, and ECG — mainly to exclude medical mimics and screen for the increased rate of comorbid medical illness in psychiatric populations, since PTSD itself has no diagnostic laboratory test.
• Routine neuroimaging is not indicated in the absence of focal neurologic findings or an atypical presentation suggesting a structural cause.

• Reduce the frequency and severity of intrusion, avoidance, negative cognition/mood, and arousal/reactivity symptoms.
• Reduce or eliminate PTSD-related functional disability — occupational, social, and relational.
• Reduce nightmare frequency and improve overall sleep quality.
• Treat comorbid conditions (depression, other anxiety disorders, substance use disorder, chronic pain) rather than treating PTSD in isolation.
• Support patient safety and reduce the risk of self-harm or suicide.
• Prevent relapse once symptom control is achieved.

Trauma-focused psychotherapy (first-line)

These modalities directly address the traumatic memory itself, rather than teaching general coping skills, and are more effective than non-trauma-focused approaches.^[2]

Other evidence-supported approaches

Present-centered therapy, written exposure therapy, and Ehlers' cognitive therapy have a suggestion for use, a lower level of support than the 3 recommended trauma-focused therapies above. Internet-based CBT is a reasonable option when a patient does not require stabilization first but is unable to access in-person or virtual psychotherapy promptly.

Supportive psychotherapy that does not directly address the trauma is no more effective than a waiting list and should not be relied upon as the sole treatment.

Behavioural stabilization first, when needed

Active suicidality, self-injurious behaviour, or psychosis may need to be stabilized before trauma-focused psychotherapy begins — starting trauma processing before stabilization can worsen comorbid depression or substance use symptoms.

Sleep and lifestyle measures

Sleep hygiene and cognitive behavioural therapy for insomnia are the first step for sleep disturbance, tried before adding a sleep-targeted medication. Regular exercise as an adjunct measure reduces PTSD symptoms and comorbid depressive symptoms.

Immediate post-trauma period

In the first 4 weeks after a traumatic event, most people do not need formal psychotherapy or medication — support the patient's natural resilience and existing social supports. Single-session psychological debriefing delivered in a group format in the first 2 weeks after trauma may impede natural recovery and is not recommended.

Family and moral injury

Refer partners, children, or other affected family members to counselling when indicated. Consider adaptive disclosure interventions addressing moral injury as an emerging adjunct, particularly in military-related PTSD.

Complementary therapies

Not recommended cannabis and cannabinoid-based products — evidence for PTSD is limited, and cannabis use is associated with an increased risk of psychiatric comorbidity; do not recommend it as treatment.^[2]

Pregnancy

Screen for PTSD and anxiety symptoms before conception where possible, and repeat screening during pregnancy and especially postpartum — many patients do not spontaneously disclose distress. Trauma-focused psychotherapy can be used without restriction throughout pregnancy and is preferred whenever the patient's condition allows.

1st line in pregnancy, if medication is needed citalopram, escitalopram, or sertraline.^[3]

Use cautiously in pregnancy paroxetine — associated with a small increase in cardiac and cleft lip/palate malformation risk, particularly with first-trimester exposure. Avoid starting it in pregnancy when an equally effective alternative is available; a switch in a patient already stable on it should be individualized rather than automatic.

Third-trimester exposure to any SSRI/SNRI can produce transient neonatal adaptation symptoms — tremor, increased muscle tone, feeding difficulty, respiratory distress — which is usually self-limiting and is not, on its own, a reason to withhold necessary treatment.

Breastfeeding

Nonpharmacologic treatment remains preferred. If medication is needed, sertraline, escitalopram, or citalopram are preferred given low breast-milk concentrations.^[3]

This chapter's scope

This chapter addresses PTSD in adults. Children 6 years of age or younger are diagnosed using separate DSM-5 criteria, and pediatric PTSD pharmacotherapy — including prazosin and most of the SSRI/SNRI dosing above — is not established for routine use; refer to child/adolescent psychiatry rather than extrapolating adult dosing.

Older adults

Start at lower doses and titrate more slowly given greater sensitivity to anticholinergic effects (paroxetine) and orthostatic hypotension (prazosin, mirtazapine, trazodone) — both raise fall risk in this population. Screen for polypharmacy and drug interactions given the higher likelihood of concurrent chronic-disease medications.

Renal and hepatic impairment

Consult the current product monograph for renally or hepatically cleared agents (venlafaxine, desvenlafaxine) and use lower starting doses with slower titration in significant impairment.

Comorbid substance use disorder

Very common in PTSD and should not delay or preclude evidence-based treatment — comorbid substance use disorder does not reduce the effectiveness of trauma-focused psychotherapy or first-line pharmacotherapy and should not be used as a reason to withhold either.^[2]

Avoid benzodiazepines specifically in this population given real misuse/dependence risk on top of the lack of core-symptom efficacy.

Prazosin has pilot-trial evidence for reducing drinking specifically in patients with comorbid PTSD and alcohol use disorder, though it did not significantly improve overall PTSD symptoms in that same trial — a reasonable adjunct to consider in this specific comorbidity pattern, not a substitute for concurrent addiction-focused treatment or referral to a concurrent disorder program.^[4]

Military and combat-related PTSD

Pharmacotherapy may be relatively more effective compared with psychotherapy in this population than in civilian trauma populations, and moral injury is a common, diagnostically separate but often concurrent contributor worth specifically assessing.

• Use the PCL-5 (self-administered) or CAPS-5 (clinician-administered) to track symptom change against baseline at each follow-up.
• Reassess after a genuinely adequate trial — minimum 8 weeks at an adequate dose; full benefit may take 2-3 months.
• Confirm adherence and screen for treatment-emergent adverse effects, particularly sexual dysfunction and sedation or insomnia, which are common reasons for early discontinuation.
• Reassess suicide risk explicitly at every visit, especially in the first weeks after starting or changing a medication dose.
• Check orthostatic blood pressure (supine and standing) at prazosin initiation and after each dose increase.
• If a second-generation antipsychotic is used for augmentation, monitor weight, fasting glucose, and lipids at baseline and at regular intervals.
• Reassess comorbid conditions (depression, substance use, chronic pain, insomnia) at the same visits — improvement in one domain without improvement in another suggests the comorbid condition needs its own targeted treatment.
• Continue an effective antidepressant for at least 6-12 months after response, and consider continuing up to 1 year specifically to reduce relapse risk before tapering.^[5]

1. Confirm an adequate trial actually occurred — correct diagnosis, adequate dose, and a minimum of 8 weeks (up to 2-3 months for full effect) — before concluding a medication has failed.
2. Confirm adherence and explore specific barriers (adverse effects, cost, stigma, lack of perceived benefit).
3. Reassess for an untreated comorbid condition (depression, substance use disorder, chronic pain, insomnia) that may be driving apparent non-response.
4. Confirm trauma-focused psychotherapy has been offered, and offer or re-offer it if not already in place — switching to or adding psychotherapy can succeed where medication alone has not.
5. No response after an adequate trial: switch to a different first-line agent — from one SSRI to another, or between an SSRI and the SNRI venlafaxine.
6. Partial response after 2 adequate first-line trials: consider augmentation — mirtazapine or trazodone for prominent sleep or appetite symptoms, prazosin specifically for persistent nightmares, or specialist-directed second-generation antipsychotic augmentation (aripiprazole preferred if used) for refractory hyperarousal or re-experiencing symptoms.
7. Still refractory after these steps: refer to psychiatry for specialist-directed strategies, which may include a monoamine oxidase inhibitor trial (phenelzine or moclobemide) given their dietary-restriction and interaction burden, or a formal treatment-resistance work-up.

• Prescribing a benzodiazepine as first-line or routine adjunct therapy for PTSD.
• Judging an SSRI/SNRI trial a failure before an adequate dose and duration (minimum 8 weeks) has been reached.
• Using prazosin as monotherapy for overall PTSD symptoms rather than as a targeted adjunct for nightmares and sleep disturbance.
• Not counselling on first-dose orthostatic hypotension risk before starting prazosin.
• Recommending cannabis or cannabinoid products for PTSD.
• Stopping paroxetine or venlafaxine abruptly instead of tapering — both carry a real discontinuation-symptom risk.
• Assuming sertraline and venlafaxine are formally Health Canada-approved for PTSD — only paroxetine carries that specific indication in Canada, even though all 3 are equally recommended by current clinical guidance.
• Overlooking or delaying treatment because of comorbid substance use disorder — it should change drug selection (avoid benzodiazepines) but should not delay evidence-based psychotherapy or first-line pharmacotherapy.
• Missing emergent or worsening suicidal ideation, especially in patients under 25 and especially in the first weeks of SSRI/SNRI treatment.
• Recommending psychological debriefing in the immediate post-trauma period — it may impede natural recovery rather than help.
• Starting trauma-focused psychotherapy before addressing active suicidality, self-injurious behaviour, or psychosis that needs stabilization first.

How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.

Selective Serotonin Reuptake Inhibitors (SSRIs)

First-line agents (sertraline, paroxetine) and alternatives (fluoxetine, fluvoxamine). May take 2-3 months to achieve maximum effect; discontinue gradually.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

First-line venlafaxine XR; desvenlafaxine is pharmacologically related but less directly studied for PTSD specifically.

Alpha1-Adrenergic Antagonist

Used specifically for PTSD-related nightmares, as an adjunct to 1st-line antidepressant therapy, never as monotherapy for overall PTSD. Evidence is genuinely mixed — the largest RCT to date found no significant benefit over placebo for nightmares or overall PTSD symptoms,^[6] while a subsequent meta-analysis of 6 randomized trials found a significant benefit for nightmares and sleep quality.^[7]

Serotonin Modulator

Dual-Action Antidepressant

Monoamine Oxidase Inhibitors

Specialist-initiated, third-line agents given their dietary-restriction and drug-interaction burden. Never combine with an SSRI, SNRI, or other serotonergic agent without a full washout.

Second-Generation Antipsychotics (augmentation only)

Reserve for specialist-directed augmentation of a 1st-line antidepressant in partial responders. Current guidance is more cautious than older practice — a 2023 evidence review found insufficient benefit to routinely recommend antipsychotic augmentation for PTSD, a shift from earlier, more favourable positioning.^[2] Never use as monotherapy for PTSD. Monitor weight, fasting glucose, and lipids at baseline and regularly thereafter, and counsel on antipsychotic-associated body-temperature dysregulation (hydration, sun protection, heat-stroke prevention).