Post-traumatic Stress Disorder

Clinical Snapshot

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.

Recognize the Condition

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]

Symptom cluster	Examples
Intrusion	Recurrent intrusive memories, distressing dreams, dissociative reactions such as flashbacks, and intense distress or physiological reactivity on exposure to trauma reminders.
Avoidance	Deliberate avoidance of distressing memories, thoughts, feelings, or external reminders (people, places, conversations, activities) associated with the trauma.
Negative alterations in cognition and mood	Distorted blame of self or others, persistent negative emotional state, diminished interest in activities, feelings of detachment from others, and inability to recall key aspects of the event.
Alterations in arousal and reactivity	Hypervigilance, exaggerated startle response, sleep disturbance, irritability or angry outbursts, reckless or self-destructive behaviour, and impaired concentration.

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.

Risk Factors

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.

Red Flags & Refer

Escalate to urgent psychiatric assessment for any of the following:

Active suicidal ideation with a plan, intent, or access to means — needs an immediate safety assessment; do not simply start or adjust a medication and arrange routine follow-up. Risk can emerge or worsen in the first weeks after starting or increasing an SSRI/SNRI, particularly in patients under 25 — a boxed-warning counselling point for every antidepressant used for PTSD, not a theoretical concern.
Severe dissociative symptoms — marked depersonalization, derealization, or dissociative flashbacks — impairing the patient's safety or ability to function.
An acute substance use crisis — intoxication, withdrawal, or overdose risk in a patient self-medicating with alcohol or other substances.
Any indication of harm to self or others, including homicidal ideation.
Psychotic symptoms (hallucinations, delusions) accompanying the presentation.
Evidence of ongoing abuse or an unsafe current situation requiring safety planning.
Severe functional impairment or a complex, treatment-refractory presentation not responding to first-line management — refer for specialist psychiatric input rather than repeating the same approach indefinitely.

Assessment & Diagnosis

Differentiating PTSD from other trauma/stress-related presentations

Feature	PTSD	Acute stress disorder	Adjustment disorder
Qualifying trauma exposure	Required — actual or threatened death, serious injury, or sexual violence	Required — same definition as PTSD	Any identifiable stressor; not restricted to life-threatening trauma
Symptom duration for diagnosis	Beyond 1 month	3 days to 1 month after the trauma	Within 3 months of the stressor; typically resolves within 6 months once the stressor or its consequences end
Symptom pattern	Specific minimum counts across intrusion, avoidance, negative cognition/mood, and arousal/reactivity clusters	Overlapping symptoms across the same clusters plus prominent dissociation, without meeting the full PTSD cluster-count threshold	Distress out of proportion to the stressor, or significant functional impairment, without meeting PTSD's specific symptom-cluster criteria
Key management implication	Trauma-focused psychotherapy ± pharmacotherapy as detailed in this chapter	Supportive management; most cases resolve without formal psychotherapy or medication — reassess for evolution into PTSD if symptoms persist beyond 1 month	Supportive, present-centered management; reassess if symptoms evolve to meet full PTSD criteria

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

Tool	Purpose	Format
PC-PTSD-5	Rapid primary-care screening tool.	5 items
PCL-5	Self-administered; useful for screening, provisional diagnosis, and tracking symptom change during treatment.	Patient-rated
CAPS-5	Clinician-administered; considered the diagnostic gold standard.	20-40 minutes, clinician-rated

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.

Treatment Targets

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.

Choose Initial Treatment

Direct treatment rule

1st line for patients able and willing to engage trauma-focused psychotherapy — cognitive processing therapy, prolonged exposure, or eye movement desensitization and reprocessing — has a stronger evidence base than pharmacotherapy alone and should be offered before or alongside medication whenever accessible.^[2]

Pharmacotherapy as first-line treatment use when trauma-focused psychotherapy is unavailable, not preferred by the patient, or when behavioural stabilization is needed before trauma-focused therapy can safely begin; pharmacotherapy may also be relatively more effective than psychotherapy specifically in combat- or military-related PTSD.^[1]

1st-line pharmacotherapy an SSRI — sertraline or paroxetine — or the SNRI venlafaxine XR; all 3 are equally recommended by current guidance. Paroxetine is the only one of the 3 carrying a formal Health Canada indication specifically for PTSD; sertraline and venlafaxine are supported by the same guideline-level evidence and are commonly used off-label for this indication in Canada.

Adequate trial before judging response titrate to an effective dose and continue for a minimum of 8 weeks — full benefit can take up to 2-3 months to emerge. Do not switch or abandon a first-line agent before this window has elapsed at an adequate dose.

Nightmares or sleep disturbance persisting despite first-line antidepressant therapy and sleep-hygiene measures add prazosin at bedtime as an adjunct, titrated gradually. Prazosin is not a substitute for first-line SSRI/SNRI therapy, and current evidence supports it specifically for nightmare and sleep symptoms rather than overall PTSD symptom improvement.^[2]

Do not use benzodiazepines as routine monotherapy or adjunctive treatment for PTSD — current guidance recommends against them given a lack of demonstrated benefit for core PTSD symptoms and the high rate of comorbid substance use disorder in this population; avoid entirely when substance use disorder is present.^[2]

Partial response after 2 adequate first-line trials consider augmentation — mirtazapine or trazodone if sleep or appetite symptoms are prominent, or specialist-directed second-generation antipsychotic augmentation (aripiprazole preferred if used) reserved for refractory cases given uncertain current evidence for this specific strategy.

Non-Pharmacologic Treatment

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]

Recommended trauma-focused modalities

Cognitive processing therapy (CPT)

The patient examines and works to modify the appraisals, beliefs, and emotions that developed as a result of the traumatic event.

Prolonged exposure (PE)

The patient confronts trauma-related memories and situations, imaginally or in vivo, in a structured, planned sequence across treatment sessions.

Eye movement desensitization and reprocessing (EMDR)

The patient recalls the traumatic memory and associated negative cognitions while engaging in bilateral stimulation (classically, following the clinician's finger movements).

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]

Pharmacologic Treatment Options

Drug / intervention	Role	Dose / use	Important adverse effects	Teaching points
Sertraline Preferred	1st-line SSRI	Initial 25-50 mg PO daily; usual 50-200 mg/day	GI upset, sexual dysfunction, insomnia, diaphoresis	Take with food to reduce GI upset. Used off-label for PTSD in Canada despite guideline-level 1st-line status — no formal Health Canada PTSD indication.
Paroxetine Preferred	1st-line SSRI; only agent with a formal Health Canada PTSD indication	Initial 20 mg PO daily; may increase in 10 mg increments to a maximum of 50 mg/day	Anticholinergic effects, sexual dysfunction, weight gain, discontinuation symptoms	Potent CYP2D6 inhibitor. Taper gradually — do not stop abruptly.
Venlafaxine XR Preferred	1st-line SNRI	Initial 37.5-75 mg PO daily; usual 75-225 mg/day	Nausea, insomnia, dose-related blood pressure increase, pronounced discontinuation symptoms	Taper slowly — short half-life gives a high discontinuation-symptom risk.
Fluoxetine Alternative	Alternative SSRI with trial evidence, though not on the current top-tier recommended list	Initial 10-20 mg PO daily; usual 20-40 mg/day	GI upset, insomnia, anxiety on initiation	Long half-life allows a more forgiving taper than other SSRIs — consider when strict taper adherence is a concern.
Prazosin Special situation	Adjunct for PTSD-related nightmares and sleep disturbance, added to 1st-line antidepressant therapy	Initial 1 mg PO at bedtime; increase by 1-2 mg increments at bedtime as tolerated (usual effective range 3-15 mg at bedtime)	Orthostatic hypotension, especially after the first dose; dizziness	Give the first dose at bedtime under supervision given first-dose syncope risk. Not a substitute for 1st-line antidepressant therapy — evidence supports nightmare/sleep benefit specifically, not overall PTSD symptom improvement.
Mirtazapine Alternative	Augmentation or alternative, particularly with comorbid insomnia or low appetite	Initial 15-30 mg PO at bedtime; usual 30-45 mg/day	Sedation, increased appetite and weight gain	Most sedating at lower doses — a lower starting dose can be used specifically to target insomnia.
Trazodone Alternative	Adjunct specifically for insomnia not responding to nonpharmacologic measures	Initial 25-50 mg PO at bedtime; may increase to 100 mg at bedtime as needed/tolerated	Drowsiness, orthostatic hypotension, rare priapism	For sleep only — not an evidence-based treatment for core daytime PTSD symptoms.
Aripiprazole Special situation	Specialist-directed augmentation for partial response to 1st-line pharmacotherapy	Initial 2-5 mg PO daily; titrate in increments of up to 5 mg/day every 7 days to a maximum of 15 mg/day	Akathisia, extrapyramidal symptoms, orthostatic hypotension, activation/insomnia	Reserve for specialist-directed use — current evidence review found insufficient benefit to routinely recommend antipsychotic augmentation. Dose in the morning to reduce activating effects.

Not recommended: benzodiazepines have no demonstrated efficacy for core PTSD symptoms, are associated with rebound insomnia and anxiety on discontinuation, and carry a genuine misuse/dependence risk in a population with a high rate of comorbid substance use disorder — current guidance recommends against their use, whether as monotherapy or as a routine adjunct.^[2]

Special Populations

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.

Monitoring & Follow-Up

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]

Treatment Failure / Next Step

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.
Confirm adherence and explore specific barriers (adverse effects, cost, stigma, lack of perceived benefit).
Reassess for an untreated comorbid condition (depression, substance use disorder, chronic pain, insomnia) that may be driving apparent non-response.
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.
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.
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.
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.

Common Errors to Avoid

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.

Clinical Decision Algorithm

Initial assessment and treatment selection

Trauma exposure with symptoms persisting beyond 1 month, meeting DSM-5 PTSD criteria

Assess for active suicidality, self-injurious behaviour, psychosis, or a substance use crisis needing stabilization first

Stabilization needed

Stabilize first — manage the acute safety or substance use crisis before starting trauma-focused psychotherapy

No stabilization needed

Offer trauma-focused psychotherapy (CPT, PE, or EMDR) as 1st line

Psychotherapy unavailable, not preferred, or insufficient alone

Start 1st-line pharmacotherapy — sertraline, paroxetine, or venlafaxine XR — titrated to an effective dose

Psychotherapy accessible and accepted

Trauma-focused psychotherapy alone, or combined with pharmacotherapy per patient preference and clinical need

Pharmacotherapy response assessment

1st-line SSRI/SNRI at an effective dose for a minimum of 8 weeks

Full response

Continue the same dose; continue for at least 6-12 months after response to reduce relapse risk

Partial response

Optimize to the maximum tolerated dose

Still inadequate: add augmentation — mirtazapine/trazodone for sleep, prazosin for nightmares, or specialist-directed aripiprazole

No response

Confirm adherence and comorbidities, then switch to a different 1st-line agent

Still refractory after 2 adequate trials: refer to psychiatry

Managing PTSD-related nightmares and sleep disturbance

Nightmares or sleep disturbance present

Sleep hygiene and cognitive behavioural therapy for insomnia first

Persistent despite nonpharmacologic measures and 1st-line antidepressant therapy

Add prazosin at bedtime — start 1 mg, titrate by 1-2 mg increments to an effective dose (usual range 3-15 mg at bedtime)

Response

Continue prazosin as an adjunct; recheck orthostatic blood pressure with each dose increase

No response after adequate titration

Consider trazodone at bedtime as an alternative, or refer to psychiatry/sleep medicine — prazosin evidence is mixed and not every patient responds

Resolves with sleep hygiene and 1st-line therapy alone

No additional sleep-targeted medication needed

Drug Tables

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.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Sertraline	Initial: 25-50 mg PO daily Usual: 50-200 mg PO daily	GI upset, sexual dysfunction, insomnia, diaphoresis, headache	Concurrent use with MAOIs, linezolid, or methylene blue is contraindicated (serotonin syndrome risk); use caution combining with other serotonergic agents; increased GI bleeding risk with NSAIDs/antiplatelet agents.	Not formally Health Canada-indicated for PTSD (Canadian monograph covers depression, panic disorder, and OCD) despite equally-recommended guideline-level 1st-line status.
Paroxetine	Initial: 20 mg PO daily Dose range: May increase in 10 mg increments to a maximum of 50 mg/day	Anticholinergic effects (dry mouth, constipation), sexual dysfunction, weight gain, somnolence	Concurrent use with MAOIs, linezolid, or methylene blue is contraindicated (serotonin syndrome risk); use caution combining with other serotonergic agents; increased GI bleeding risk with NSAIDs/antiplatelet agents. Potent CYP2D6 inhibitor.	The only SSRI with a formal Health Canada indication specifically for PTSD.
Fluoxetine	Initial: 10-20 mg PO daily Usual: 20-40 mg PO daily	GI upset, anorexia, insomnia, anxiety/agitation on initiation	Concurrent use with MAOIs, linezolid, or methylene blue is contraindicated (serotonin syndrome risk); use caution combining with other serotonergic agents; increased GI bleeding risk with NSAIDs/antiplatelet agents. Potent CYP2D6 inhibitor.	Alternative agent with trial evidence; longer half-life allows a more rapid, forgiving taper than other SSRIs.
Fluvoxamine	Initial: 50-100 mg PO daily Usual: 100-300 mg PO daily	GI upset, somnolence, insomnia, sexual dysfunction	Concurrent use with MAOIs, linezolid, or methylene blue is contraindicated (serotonin syndrome risk); use caution combining with other serotonergic agents; increased GI bleeding risk with NSAIDs/antiplatelet agents. Potent CYP1A2 inhibitor.	Second-line alternative with trial evidence specifically in combat-related PTSD.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

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

Drug	Dosage	Adverse effects	Drug interactions	Comments
Venlafaxine XR	Initial: 37.5-75 mg PO daily Usual: 75-225 mg PO daily	Nausea, insomnia, dizziness, asthenia, dose-related blood pressure increase	Do not use with MAOIs. Substrate of CYP2D6 and CYP3A4.	1st-line SNRI. Taper slowly — short half-life gives a high discontinuation-symptom risk.
Desvenlafaxine	Initial/usual: 50 mg PO daily Maximum: 100 mg PO daily	Nausea, sleep disturbance, drowsiness, nervousness, dizziness, dry mouth	Do not use with MAOIs. Substrate of CYP3A4.	Pharmacologically related alternative SNRI; less directly studied for PTSD than venlafaxine.

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]

Drug	Dosage	Adverse effects	Drug interactions	Comments
Prazosin	Initial: 1 mg PO at bedtime Titration: Increase by 1-2 mg PO at bedtime increments until an effective dose is reached Usual effective range: 3-15 mg PO at bedtime	Orthostatic hypotension (particularly after the first dose), dizziness	Additive orthostatic hypotension with other antihypertensives or PDE5 inhibitors (sildenafil, tadalafil, vardenafil)	Give the first dose at bedtime under supervision given first-dose syncope risk. Prior or current alpha1-antagonist use increases the risk of intraoperative floppy iris syndrome during cataract surgery — inform the ophthalmologist even if the drug was stopped before surgery.

Serotonin Modulator

Drug	Dosage	Adverse effects	Drug interactions	Comments
Trazodone	Initial: 25-50 mg PO at bedtime Titration: May increase to 100 mg PO at bedtime as needed/tolerated	Drowsiness, orthostatic hypotension, nausea, dry mouth, rare priapism	Toxicity may be increased by CYP3A4 inhibitors (clarithromycin, erythromycin, ketoconazole, grapefruit juice); effectiveness may be reduced by CYP3A4 inducers (carbamazepine, phenytoin, rifampin)	For PTSD-related insomnia specifically, not core daytime symptoms.

Dual-Action Antidepressant

Drug	Dosage	Adverse effects	Drug interactions	Comments
Mirtazapine	Initial: 15-30 mg PO at bedtime Usual: 30-45 mg PO daily	Somnolence, increased appetite/weight gain, dizziness	Do not use with MAOIs; additive sedation with other CNS depressants including alcohol and benzodiazepines. Substrate of CYP1A2, CYP2D6, and CYP3A4.	Particularly useful with comorbid insomnia, low appetite, or weight loss; may be more effective as an adjunct than as monotherapy. Most sedating at lower doses.

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.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Phenelzine (irreversible)	Initial: 15-30 mg PO daily Usual: 45-90 mg PO daily	Insomnia, dizziness, orthostatic hypotension, edema, sexual dysfunction	Hypertensive crisis with sympathomimetics, tyramine, or levodopa; contraindicated with serotonergic drugs (SSRIs, SNRIs, TCAs, meperidine, tryptophan) — serotonin syndrome risk	Requires strict dietary tyramine restriction throughout treatment.
Moclobemide (reversible)	Initial: 200-300 mg PO daily Usual: 450-600 mg PO daily Maximum: 900 mg PO daily	Nausea, insomnia, dizziness	Hypertensive crisis with sympathomimetics, tyramine, or levodopa; contraindicated with serotonergic drugs — serotonin syndrome risk	No dietary restriction required at usual doses (under 600 mg/day), unlike irreversible MAOIs.

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).

Drug	Dosage	Adverse effects	Drug interactions	Comments
Aripiprazole	Initial: 2-5 mg PO daily Titration: Increase gradually in increments of up to 5 mg/day every 7 days Maximum: 15 mg PO daily	Akathisia, extrapyramidal symptoms, orthostatic hypotension, headache, GI complaints, activation/insomnia	Strong CYP2D6/CYP3A4 inducers (carbamazepine, phenytoin, rifampin) can substantially decrease levels; strong CYP2D6/CYP3A4 inhibitors (ketoconazole, quinidine, fluoxetine, paroxetine) can substantially increase levels	Lower rate of weight gain and anticholinergic effects than other agents in this class. Dose in the morning to reduce activating effects.
Quetiapine XR	Initial: 50 mg PO daily for 2 days, then 150 mg PO daily Titration: May increase to 300 mg PO daily on or after day 4	Sedation, dizziness, weight gain, orthostatic hypotension, possible increased cataract risk	Additive sedation with other CNS depressants; strong CYP3A4 inhibitors (clarithromycin, erythromycin, grapefruit juice, ketoconazole) increase levels; strong CYP3A4 inducers (carbamazepine, phenytoin, rifampin) reduce levels	More sedating than other agents in this class.
Olanzapine	Initial: 2.5 mg PO daily Titration: Increase gradually as needed Usual: 2.5-5 mg PO daily, maximum 10 mg/day	Weight gain, sedation, anticholinergic effects, increased risk of diabetes and dyslipidemia, orthostatic hypotension	Additive sedation with other CNS depressants; CYP1A2/CYP2D6 inhibitors (diltiazem, fluvoxamine, paroxetine) can increase levels; cigarette smoking induces CYP1A2 and may require a higher dose	Higher likelihood of sedation, weight gain, and anticholinergic effects than other agents in this class.

Not included in this table: benzodiazepines and cannabis/cannabinoid products are deliberately not listed here with a dose, because current guidance recommends against using either for PTSD — see Pharmacologic Treatment Options and Common Errors to Avoid for the reasoning.^[2]

References

Clinical Practice Guideline for the Treatment of Posttraumatic Stress Disorder (PTSD) in Adults — American Psychological Association. Washington (DC): American Psychological Association; 2017
The Management of Posttraumatic Stress Disorder and Acute Stress Disorder: Synopsis of the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline — Annals of Internal Medicine (Schnurr PP, Hamblen JL, Wolf J, et al.). Ann Intern Med 2024;177(3):363-374
Canadian Network for Mood and Anxiety Treatments 2024 Clinical Practice Guideline for the Management of Perinatal Mood, Anxiety, and Related Disorders — Canadian Journal of Psychiatry (Vigod SN, Frey BN, Clark CT, et al.). Can J Psychiatry 2025;70(6):429-489
A pilot trial of prazosin, an alpha-1 adrenergic antagonist, for comorbid alcohol dependence and posttraumatic stress disorder — Alcoholism: Clinical and Experimental Research (Simpson TL, Malte CA, Dietel B, et al.). Alcohol Clin Exp Res 2015;39(5):808-817
Risk of relapse after antidepressant discontinuation in anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder: systematic review and meta-analysis of relapse prevention trials — BMJ (Batelaan NM, Bosman RC, Muntingh A, et al.). BMJ 2017;358:j3927
Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans — New England Journal of Medicine (Raskind MA, Peskind ER, Chow B, et al.). N Engl J Med 2018;378(6):507-517
Prazosin for treatment of post-traumatic stress disorder: a systematic review and meta-analysis — CNS Spectrums (Reist C, et al.). CNS Spectr 2021;26(4):338-344
Post-traumatic stress disorder — National Institute for Health and Care Excellence. NICE guideline NG116; published 5 December 2018, evidence surveillance reconfirmed currency April 2025
World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders – Version 3. Part II: OCD and PTSD — World Journal of Biological Psychiatry (Bandelow B, Allgulander C, Baldwin DS, et al.). World J Biol Psychiatry 2023;24(2):118-134
Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders — BMC Psychiatry, Canadian Anxiety Guidelines Initiative Group (Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M, et al.). BMC Psychiatry 2014;14(Suppl 1):S1

Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.