Anxiety Disorders

Clinical Snapshot

Anxiety disorders are a group of psychiatric conditions unified by excessive fear or worry that is disproportionate to actual threat, difficult for the patient to control, and causes clinically significant distress or impairment in daily functioning.^[1] They arise from an interaction between psychosocial factors (particularly a personal or family history of anxiety or mood disorders, and a personal history of trauma) and an underlying genetic vulnerability that manifests as neurobiological and neuropsychological dysfunction.^[1] Generalized anxiety disorder (GAD) — the focus of this chapter — is characterized by excessive, hard-to-control worry about everyday concerns (health, finances, family, work) occurring on most days for 6 months or longer, accompanied by physical symptoms such as restlessness, fatigue, poor concentration, irritability, muscle tension, and sleep disturbance. Panic disorder (recurrent, unexpected panic attacks with persistent fear of recurrence) and social anxiety disorder (intense fear of scrutiny or negative evaluation in social or performance situations) are covered wherever their management diverges from GAD's. Anxiety disorders run a chronic, relapsing-remitting course, frequently coexist with depression and substance use disorders, and are commonly under-recognized and under-treated in primary care — a pharmacist who understands the real difference between routine follow-up and a red flag is often the first person to catch either problem.

Recognize the Condition

How generalized anxiety disorder presents

The hallmark of GAD is worry that is excessive, difficult to control, and spread across multiple everyday domains rather than fixed on one specific fear — safety of family members, financial or job security, health, and routine responsibilities are typical themes. The worry itself is often what patients describe as most disabling, more so than any single physical symptom. Associated features include restlessness or feeling keyed up, being easily fatigued, difficulty concentrating or the mind going blank, irritability, muscle tension, and sleep disturbance (difficulty falling or staying asleep, or unsatisfying sleep). Because GAD's symptoms are vague and somatic, it is the anxiety disorder most likely to present alongside other psychiatric or physical comorbidities — depression, another anxiety disorder, chronic pain syndromes, hypertension, cardiovascular disease, and gastrointestinal disorders are all common companions, and GAD is also the most common anxiety disorder in adults over 65.^[1]

The DSM-5-TR anxiety disorder spectrum

GAD is one of several distinct anxiety disorders — each has its own clinical picture and, in several cases, a different first-line treatment approach.

Generalized anxiety disorder

Excessive worry and anxiety about a number of events or activities, occurring on more days than not, for 6 months or longer.

Panic disorder

Recurrent, unexpected, abrupt panic attacks with persistent anxiety about their recurrence or consequences.

Agoraphobia

Marked fear or anxiety about 2 or more situations (public transportation, open spaces, closed spaces, crowds, being outside the home alone) leading to avoidance; can occur with or without panic disorder.

Social anxiety disorder (social phobia)

Intense anxiety provoked by social or performance situations where embarrassment might occur, often leading to avoidance.

Specific phobia

Severe anxiety triggered by a specific feared object or situation (e.g., animals, flying, heights, injections), typically leading to avoidance.

Separation anxiety disorder

Childhood-onset fear of separation from attachment figures that is excessive for the developmental stage.

Selective mutism

Childhood-onset failure to speak in specific social settings (e.g., school) despite speaking normally in others.

Anxiety disorder due to another medical condition

Anxiety or panic attacks directly caused by a medical condition — e.g., thyroid dysfunction, hypoglycemia, heart failure, arrhythmia, COPD, vitamin B12 deficiency, encephalitis.

Substance/medication-induced anxiety disorder

Anxiety or panic attacks directly caused by use of, or withdrawal from, a substance capable of producing anxiety symptoms — e.g., alcohol, amphetamines, anticholinergics, caffeine, cannabis, cocaine, corticosteroids, hallucinogens.

Other specified / unspecified anxiety disorder

Anxiety symptoms causing distress or impairment that do not meet full criteria for a specific anxiety disorder — e.g., limited-symptom panic attacks, or generalized anxiety occurring on fewer days than not.

^[2]

Risk Factors

Family history of an anxiety or mood disorder.
Personal history of trauma or a personal history of an anxiety or mood disorder.
Social isolation.
Lower level of education.
Parental deficiency or overprotection during childhood.
Chronic physical illness, particularly cardiovascular disease or diabetes.
Comorbid substance use, which can both mimic and worsen anxiety symptoms.
Female sex — anxiety disorders are more common in women than men across the lifespan.
Postpartum period — new or worsening anxiety is common and requires specific screening (see Special Populations).

Red Flags & Refer

Refer or escalate urgently for any of the following:

Suicidal ideation, intent, or a plan — anxiety disorders, especially when comorbid with depression, carry a real suicide risk that must be actively screened for, not assumed absent because the primary complaint is "just anxiety."
Psychotic features (hallucinations, delusions) — these are not part of an anxiety disorder and need urgent psychiatric assessment.
Severe functional impairment — inability to work, attend school, leave the house, or care for oneself or dependents.
New anxiety or panic symptoms with a plausible medical cause requiring urgent workup — chest pain, significant tachycardia or arrhythmia, dyspnea, or focal neurologic symptoms should not be assumed to be "just a panic attack" until dangerous causes are excluded.
Suspected anxiety disorder due to another medical condition (thyroid dysfunction, hypoglycemia, heart failure, arrhythmia, COPD, vitamin B12 deficiency, encephalitis, pheochromocytoma) — treat and refer for the underlying medical cause rather than starting an anxiolytic.
Suspected substance intoxication or withdrawal as the cause of the anxiety symptoms — this needs its own medical workup and, where relevant, an addiction-medicine referral, not routine anxiety pharmacotherapy.
Severe anxiety in pregnancy or postpartum, especially with any thought of self-harm or thoughts of harming the infant — refer for urgent psychiatric assessment; postpartum mental health programs are typically able to respond quickly to consultation requests.
Treatment-resistant anxiety despite 2 adequate first-line trials — refer to psychiatry rather than continuing to cycle through agents in primary care.
A current or past substance use disorder in a patient who might otherwise be prescribed a benzodiazepine or pregabalin — this changes the treatment plan and generally rules out these options.

Assessment & Diagnosis

Differentiating GAD, panic disorder, social anxiety disorder, and normal stress

Feature	Generalized anxiety disorder	Panic disorder	Social anxiety disorder	Normal stress / adjustment reaction
Nature of anxiety	Diffuse, excessive worry spanning multiple everyday domains (health, finances, family, work)	Discrete, unexpected panic attacks — sudden surges of intense fear peaking within minutes	Fear of scrutiny, embarrassment, or negative evaluation in social or performance situations	Anxiety tied to an identifiable, time-limited stressor
Trigger	No single trigger — worry generalizes across situations	Often none identifiable; attacks can occur "out of the blue," though anticipatory anxiety about future attacks develops	Specific social or performance situations (public speaking, eating in public, meeting new people)	The specific stressor itself (exam, job loss, relationship conflict)
Physical symptoms	Muscle tension, restlessness, fatigue, sleep disturbance — gradual and sustained	Palpitations, chest pain, dyspnea, choking sensation, dizziness — abrupt, peaking within minutes	Blushing, trembling, sweating, nausea specific to the feared social situation	Variable, proportionate to the stressor
Duration / course	Most days, for 6 months or longer	Recurrent attacks plus 1 month or more of persistent worry about recurrence or consequences	Persistent, 6 months or longer, specifically situational	Days to weeks; resolves with the stressor or with basic coping support
Avoidance behaviour	The worry itself is disabling; avoidance is less prominent than in panic disorder or social anxiety disorder	Avoidance of situations where escape might be difficult — can progress to agoraphobia	Avoidance of the specific feared social or performance situations	Minimal or absent
Distinguishing clue	Excessive worry the patient finds hard to control, across many domains	A discrete attack with a clear symptom peak within minutes, followed by persistent fear of recurrence	Anxiety and avoidance confined to situations involving possible scrutiny by others	Does not meet the duration, severity, or functional-impairment criteria for any anxiety disorder

These disorders frequently coexist — a patient can meet criteria for more than one at the same time, and GAD in particular commonly presents alongside depression, another anxiety disorder, or a physical disorder such as a pain syndrome, hypertension, cardiovascular disease, or a gastrointestinal disorder.^[1]

History

Characterize the nature and onset of the anxiety symptoms, and the nature and extent of the resulting functional disability.
Screen for comorbid medical or psychiatric conditions — when a comorbid mood disorder is present, it is considered the main disorder, but both conditions must be treated simultaneously rather than sequentially.
Take a full medication history and review lifestyle habits, including tobacco, alcohol, recreational drug use, and sources of caffeine.
Screen specifically for suicidal ideation and for a current or past substance use disorder before selecting pharmacotherapy — both directly change which agents are appropriate.

Physical examination

Examine to rule out endocrine or cardiac disorders and to identify signs of substance use. Treat any physical disorder of recent onset before finalizing a diagnosis of a primary anxiety disorder — a new medical problem can present as, or significantly worsen, anxiety symptoms.

Investigations

No laboratory testing is routinely indicated for anxiety symptoms alone. Order thyroid function testing specifically when hyperthyroidism is clinically suspected — do not order a routine screening panel in a patient with a straightforward anxiety presentation and a normal physical examination.

GAD-7: screening and severity scale

The Generalized Anxiety Disorder 7-item scale (GAD-7) is a short, validated, self-administered questionnaire useful both for screening and for tracking treatment response over time. Each of the 7 items is scored 0-3 based on how often the patient was bothered by it over the previous 2 weeks: 0 = not at all, 1 = several days, 2 = more than half the days, 3 = nearly every day.^[3]

#	Item — over the last 2 weeks, how often bothered by:
1	Feeling nervous, anxious, or on edge
2	Not being able to stop or control worrying
3	Worrying too much about different things
4	Trouble relaxing
5	Being so restless that it is hard to sit still
6	Becoming easily annoyed or irritable
7	Feeling afraid as if something awful might happen

Total score range is 0-21. Score bands: 0-4 minimal anxiety, 5-9 mild, 10-14 moderate, 15-21 severe. A total score of 10 or more is a commonly used threshold prompting further clinical evaluation for probable GAD, and the same total can be used at follow-up visits to track treatment response — a decrease of 5 or more points, or a drop below the 10-point threshold, indicates a meaningful clinical improvement.^[3]

Other validated scales exist for specific disorders and are used mainly in specialist or research settings: the Panic Disorder Severity Scale (PDSS) for panic disorder, the Hamilton Anxiety Rating Scale (HAM-A) for GAD, and the Liebowitz Social Anxiety Scale (LSAS) for social anxiety disorder. The Hospital Anxiety and Depression Scale (HADS) is a useful general self-report option when anxiety and depressive symptoms need to be screened together.^[1]

Treatment Targets

Eliminate or substantially reduce symptomatic anxiety.
Eliminate or reduce anxiety-related functional disability at work, at school, and in relationships.
Achieve full symptomatic remission, not just partial improvement.
Prevent relapse and recurrence.
Identify and treat comorbid conditions (depression, another anxiety disorder, a substance use disorder) concurrently rather than sequentially.

Choose Initial Treatment

Direct treatment rule

Mild or transient anxiety

Anxiety symptoms clearly tied to an identifiable, time-limited stressor, not meeting duration or severity criteria for an anxiety disorder, do not need pharmacotherapy — start with support, problem-solving, relaxation-technique instruction, and reassessment; escalate only if symptoms persist or worsen.

Diagnosed generalized anxiety disorder

GAD, 1st line cognitive behavioural therapy (CBT) or an SSRI/SNRI, chosen by patient preference, access, and prior treatment response — both have comparable efficacy as monotherapy, and current evidence does not support routinely combining them as the initial GAD treatment.^[1]

Diagnosed panic disorder (with or without agoraphobia)

Panic disorder, 1st line an SSRI/SNRI combined with CBT from the start — most evidence favours starting combination therapy over either treatment alone for panic disorder specifically, the opposite pattern from GAD.^[1]

Diagnosed social anxiety disorder

SAD, 1st line an SSRI/SNRI; CBT tailored to social anxiety disorder is also first-line. Evidence on combining the two in social anxiety disorder is inconclusive, so either monotherapy is a reasonable starting point.^[1]

Situational or performance-only anxiety

Special situation use when anxiety occurs only around a specific, predictable performance event (public speaking, auditions, a stage performance) with no anxiety symptoms between events: a single dose of a beta-blocker (propranolol or atenolol), taken shortly before the event, not a scheduled daily medication.

Severe illness, suicidal risk, or treatment-resistant presentation

Special situation pharmacotherapy is generally preferred over psychotherapy alone, and psychiatric consultation is indicated.

Short-term benzodiazepine bridge

Special situation — use only for rapid relief of severe acute anxiety or panic while waiting for an antidepressant to take effect, or to blunt the temporary increase in anxiety and restlessness that can occur when starting an SSRI/SNRI: a benzodiazepine for the first few weeks of treatment, tapered off once the antidepressant is effective. This is never a routine or long-term treatment strategy on its own — see Pharmacologic Treatment Options and Drug Tables for tapering guidance.^[4]

Non-Pharmacologic Treatment

Provide psychoeducation about the specific anxiety disorder, its treatment, its aggravating factors, and the early warning signs of relapse — this should accompany every treatment plan, pharmacologic or not.
Cognitive behavioural therapy (CBT) tailored to the specific diagnosis is generally the preferred psychotherapy and is first-line for GAD, panic disorder, and social anxiety disorder; a full course commonly runs 20 or more sessions for GAD.^[1]
Exposure therapy is the treatment of choice for specific phobia and is often sufficient on its own.
Mindfulness-based therapy has demonstrated effectiveness and is a reasonable option when CBT access is limited, or as an adjunct.
Where face-to-face CBT is not accessible, internet-delivered CBT (ICBT) is a reasonable alternative — a Cochrane review found therapist-supported ICBT produced a clinically significant improvement in anxiety compared with a waitlist or an online discussion-group control, with no significant difference found between face-to-face CBT, therapist-supported ICBT, and unguided ICBT.^[5]
Stress-reduction techniques, including relaxation training and time-management training, are often helpful at the start of treatment.
Regular aerobic exercise several times per week can help reduce anxiety symptoms, although it is significantly less effective than CBT on its own and should not replace CBT or pharmacotherapy in a diagnosed anxiety disorder.
Reduce and monitor caffeine and other stimulant intake.
Counsel against using alcohol to self-manage anxiety — it disrupts sleep architecture (reducing deep sleep) despite its short-term sedating effect, and abruptly stopping or reducing heavy or chronic alcohol use can itself provoke a temporary increase in anxiety.
Cannabis, cocaine, hallucinogens, and anabolic steroids can induce or worsen anxiety and should be discontinued; refer to an addiction treatment service when needed.
Reinforce sleep hygiene and a consistent, balanced daily routine.

Pharmacologic Treatment Options

Drug / intervention	Role	Dose / use	Important adverse effects	Teaching points
Escitalopram Preferred	GAD, panic disorder, and social anxiety disorder — 1st-line SSRI	Initial 5 mg PO once daily; increase to 10 mg after 1-2 weeks; target 10-20 mg once daily (max 20 mg/day; 10 mg/day if age ≥65)	Nausea, sexual dysfunction, hyponatremia (especially elderly), QTc prolongation at higher doses	Start at half the usual depression starting dose to limit early anxiety/agitation; full anxiolytic effect can take 8-12 weeks.
Sertraline Preferred	GAD, panic disorder, and social anxiety disorder — 1st-line SSRI	Initial 25 mg PO once daily; target 50-200 mg once daily	GI upset, sexual dysfunction, sweating	Take with food to improve tolerability; the low starting dose specifically reduces early panic-disorder symptom exacerbation.
Paroxetine Preferred	GAD, panic disorder, and social anxiety disorder — 1st-line SSRI	Initial 10 mg PO once daily; target 20-60 mg once daily	Sedation, anticholinergic effects (dry mouth, constipation), sexual dysfunction, weight gain, discontinuation symptoms if stopped abruptly	Avoid in pregnancy (associated with congenital cardiac malformations) — see Special Populations.
Venlafaxine XR Preferred	GAD, panic disorder, and social anxiety disorder — 1st-line SNRI	Initial 37.5 mg PO once daily; target 75-225 mg once daily (doses above 150 mg/day are needed for a meaningful norepinephrine effect)	Hypertension (dose-related), nausea, sweating, sexual dysfunction	Taper very gradually when stopping — one of the more difficult antidepressants to discontinue smoothly.
Duloxetine Preferred	GAD — 1st-line SNRI	Initial 30 mg PO once daily; target 60-120 mg once daily	Nausea, dry mouth, hypertension	Contraindicated if creatinine clearance under 30 mL/min; monitor blood pressure and heart rate weekly during the first month and with dose increases.
Pregabalin Alternative	GAD (2nd line) and social anxiety disorder (2nd line, high dose only)	GAD: initial 50 mg PO TID, target 150-600 mg/day divided. Social anxiety disorder: target ≥600 mg/day divided — doses of 150-300 mg/day have not shown efficacy.	Dizziness, sedation, peripheral edema, weight gain	Never prescribe to a patient with a current or past opioid use disorder — real misuse/abuse risk in this population specifically.
Buspirone Alternative	GAD — 2nd line / adjunct	Initial 5 mg PO BID-TID; titrate gradually; target 10-60 mg/day divided	Dizziness, nausea, headache	Onset of action is 2-4 weeks — must be taken on a scheduled basis, never PRN; counsel the patient not to expect immediate relief. Not effective for social anxiety disorder.
Clonazepam Special situation	Short-term benzodiazepine bridge — panic disorder, GAD, social anxiety disorder	Initial 0.25 mg PO BID; target 1-2 mg/day divided (up to 4 mg/day for panic disorder)	Sedation, psychomotor impairment, dependence, withdrawal	Reserve for the first few weeks of treatment; taper gradually rather than stopping abruptly — never the sole long-term treatment.
Lorazepam Special situation	Short-term benzodiazepine bridge — acute anxiety or panic	Initial 0.5-1 mg PO 2-3 times daily; target 2-6 mg/day divided	Sedation, psychomotor impairment, dependence, withdrawal	Preferred benzodiazepine in significant hepatic impairment, since it is cleared by glucuronidation alone; taper gradually when stopping.
Propranolol Special situation	Situational / performance anxiety only	10-40 mg PO as a single dose, 30-60 minutes before the anxiety-provoking event	Bradycardia, hypotension, fatigue	Not effective for generalized social anxiety disorder unrelated to a specific performance situation — test the dose in a low-stakes situation first.
Quetiapine XR Special situation	GAD — 3rd-line monotherapy	Initial 50 mg PO once daily; target 50-150 mg once daily	Sedation, weight gain, dyslipidemia, hyperglycemia	Reserve for treatment-resistant GAD given the metabolic burden; monitor weight, lipids, and glucose.

Special Populations

Pregnancy

Screen for anxiety symptoms before conception where possible, and repeat screening during pregnancy and especially postpartum — anxiety disorder prevalence does not fall during pregnancy, and severity can wax or wane with environmental events. Preconception treatment may be offered for anxiety disorders causing significant distress or interfering with normal functioning; panic disorder with agoraphobia specifically can prevent a patient from attending medical appointments because of phobic avoidance.^[1]

Nonpharmacologic treatment is preferred first-line for mild-to-moderate anxiety in pregnancy: CBT and interpersonal therapy have demonstrated benefit, and meditation- or relaxation-based approaches may be more acceptable to some pregnant patients than pharmacotherapy.^[6] If anxiety symptoms are severe and cause significant impairment or distress, pharmacotherapy can be appropriate and effective. When an antidepressant is already being taken for an anxiety disorder before pregnancy, it can generally be continued at the same dose rather than stopped. If starting antidepressant treatment during pregnancy, citalopram, escitalopram, and sertraline are the preferred agents; avoid paroxetine, given its association with congenital cardiac malformations.^[6] Third-trimester SSRI/SNRI exposure has been linked to a transient neonatal behavioural syndrome (tremor, agitation, increased muscle tone, feeding or breathing difficulty); the care team at delivery should be aware of maternal use.

Benzodiazepines in pregnancy: avoid in the first trimester specifically. If used later in pregnancy because symptom severity affects maternal or fetal safety, use the lowest effective dose for the shortest duration, and avoid combining a benzodiazepine with an antidepressant when possible — the combination in the first trimester carries a statistically increased, though clinically low, risk of major non-specific malformations compared to either agent alone.^[1]

Breastfeeding

Nonpharmacologic options should be used whenever possible in the postpartum period, particularly in breastfeeding patients. If drug therapy is necessary, paroxetine or sertraline are preferred, since low amounts transfer into breast milk and are typically undetectable in the breastfed infant's plasma.^[6] Avoid benzodiazepines in breastfeeding given the risk of accumulation, sedation, and impaired temperature regulation in the infant. If a patient is unable or unwilling to care for the infant, or expresses any thought of harming herself or the infant, this is an urgent psychiatric referral — see Red Flags & Refer.

Children and adolescents

Before starting treatment, complete a full assessment including a meeting with the child and a parent/caregiver, and a differential diagnosis to rule out physical conditions that can mimic anxiety — hyperthyroidism, migraine, asthma, diabetes, central nervous system disorders, cardiac disorders, systemic lupus erythematosus, pheochromocytoma, lead poisoning, and dysmenorrhea. Also rule out ADHD, bipolar disorder, obsessive-compulsive disorder, psychosis, and autism spectrum disorder, and investigate use of substances that can cause anxiety (caffeine, tobacco, over-the-counter products, drugs, alcohol).^[1]

Ages 6-18, 1st line CBT, especially for mild-to-moderate anxiety disorders. SSRIs (and possibly SNRIs) are treatment options for more severe cases or when CBT is not available or insufficient; combining CBT with an antidepressant may be more effective than either alone for severe or incapacitating anxiety, when urgency to treat is high, or with partial response to monotherapy.^[1]

The SSRIs with sufficient pediatric evidence are fluoxetine, fluvoxamine, paroxetine, and sertraline; duloxetine and venlafaxine have the most pediatric SNRI evidence, though venlafaxine is potentially associated with a greater suicide risk than other agents in this age group and has been linked to fatal overdose. No SSRI or SNRI carries a Health Canada-approved indication for pediatric anxiety — all carry a warning about increased risk of suicidal ideation and behaviour in patients under 18; closer monitoring for behavioural and emotional changes, including self-harm risk, is required whenever an antidepressant is used in this age group.^[1]

Older adults

GAD is the most common anxiety disorder in people over 65. Use benzodiazepines with particular caution in this population — age-related pharmacokinetic changes increase the risk of psychomotor and cognitive impairment, falls, and fractures. Start SSRIs/SNRIs at a lower dose with slower titration; citalopram and escitalopram carry a Health Canada-mandated lower maximum dose in patients 65 and older (citalopram 20 mg/day, escitalopram 10 mg/day) because of dose-related QTc-prolongation risk. Lorazepam is a reasonable benzodiazepine choice in hepatic impairment given its glucuronidation-only clearance, but the fall/cognitive-impairment risk of any benzodiazepine remains elevated in this age group regardless of which agent is chosen.

Renal and hepatic impairment

Duloxetine is contraindicated at creatinine clearance under 30 mL/min. Gabapentin and pregabalin both require renal dose adjustment. Lorazepam, cleared solely by hepatic glucuronidation with no active metabolites, is generally the preferred benzodiazepine in significant hepatic impairment; diazepam and other benzodiazepines that undergo oxidative hepatic metabolism can accumulate.

Substance use disorder, current or past

Avoid benzodiazepines where possible in this population, given the elevated misuse and dependence risk. Pregabalin should never be prescribed to a patient with a current or past opioid use disorder — case reports of misuse (including nasal inhalation) and a specifically elevated abuse risk in this population make this an absolute avoidance, not a relative caution.^[1]

Monitoring & Follow-Up

Reassess with the GAD-7 (or the disorder-specific validated scale) at follow-up visits to track objective treatment response, alongside clinical assessment of functional improvement. Response is generally defined as a 50% or greater improvement on a validated scale from baseline. Set the expectation with the patient upfront that adverse effects of an SSRI/SNRI often appear at initiation, while the anxiolytic benefit is delayed — some symptom improvement may appear after 2-8 additional weeks at target dose, but the full anxiolytic effect can take up to 8-12 weeks or more, meaningfully slower than the antidepressant effect in major depressive disorder.^[7] Communicating this clearly at the first visit is one of the most effective things a pharmacist can do to prevent premature discontinuation.

Monitor closely for suicidal ideation or other indicators of suicidal behaviour, particularly in patients under 25 and at any dose change — this applies across the age spectrum, though the boxed warning for increased suicidality with antidepressants specifically applies under age 18 in Canada.

Most patients need to continue pharmacotherapy for at least 12-24 months after achieving remission to consolidate functional recovery and reduce relapse risk; continuing treatment for up to 1 year after remission has shown a clear benefit for both relapse rate and time to relapse. When discontinuation is eventually considered, taper the antidepressant gradually over several months, not weeks — sudden dose reduction or discontinuation can trigger a withdrawal syndrome and a resurgence of anxiety symptoms.

For any patient on a benzodiazepine, monitor specifically for tolerance to sedation with continued use, early signs of dependence, and (in older adults) fall risk at every visit; a benzodiazepine without an explicit taper plan already in the chart is itself a monitoring flag warranting a medication review.^[4]

Treatment Failure / Next Step

Confirm the diagnosis is still correct — re-screen for a missed comorbid depression, an emerging substance use disorder, or a medical mimic — and confirm the patient actually completed an adequate trial: target dose maintained for at least 8-12 weeks, not a partial dose or a shortened trial.
Partial response (some benefit at optimal dose): augment with a second agent (e.g., pregabalin, buspirone, or low-dose quetiapine added to the current antidepressant) rather than switching — clinical experience supports augmentation specifically when there has been measurable, if incomplete, improvement.
No response at optimal dose and duration: switch to a different first-line SSRI/SNRI rather than augmenting — patients who fail to respond to one agent can still respond to an agent from another class, and switching (not augmenting) is the recommended next step when there has been no meaningful benefit at all.
If a second full first-line trial also fails: move to a 2nd-line agent (pregabalin or buspirone) or, for refractory GAD specifically, a 3rd-line option (quetiapine XR monotherapy, or augmentation with olanzapine or pregabalin added to the antidepressant — see Drug Tables for combination dosing).
At every failure step, reassess adherence and ongoing psychosocial stressors before escalating pharmacotherapy — nonadherence and an unaddressed ongoing stressor are common, correctable causes of apparent treatment failure.
Persistent treatment resistance after these steps warrants psychiatric referral rather than continued trial-and-error in primary care.

Common Errors to Avoid

Starting an SSRI/SNRI at the usual depression starting dose in an anxious patient — this commonly causes early activation and a transient worsening of anxiety, leading to premature discontinuation; start lower and titrate slower than for depression.
Not warning the patient upfront that adverse effects typically appear early while anxiolytic benefit is delayed — this single counselling point prevents a large share of early, avoidable discontinuations.
Using a benzodiazepine as sole or long-term monotherapy instead of a short-term bridge while an antidepressant takes effect.
Continuing a benzodiazepine indefinitely without ever documenting an explicit taper plan.
Prescribing pregabalin to a patient with a current or past opioid use disorder.
Assuming buspirone can be used PRN — it requires scheduled dosing and has a 2-4 week onset, so it will not help an acute panic episode.
Missing an organic or substance-induced cause of new-onset anxiety by treating symptomatically without an adequate workup.
Augmenting after zero response (should switch instead), or switching after a partial response (should augment instead) — mixing up these two failure pathways delays effective treatment.
Using paroxetine in pregnancy.
Combining an SSRI/SNRI with an MAOI, or switching between them, without an adequate washout period — serotonin syndrome risk.
Stopping antidepressant treatment before 12-24 months of sustained remission, risking early relapse.
Treating panic disorder and GAD as though they call for the same initial strategy — panic disorder benefits from starting CBT and an antidepressant together, while GAD generally does not need routine combination at initiation.

Clinical Decision Algorithm

Algorithm A — Initial assessment and differentiation

Patient presents with anxiety symptoms

Assess for a medical or substance cause (thyroid dysfunction, hypoglycemia, cardiac/pulmonary disease, B12 deficiency, intoxication or withdrawal); treat/stabilize any recent-onset physical disorder before finalizing an anxiety diagnosis

Red flags present

Suicidal ideation, psychotic features, or severe functional impairment — refer/escalate urgently

No red flags

Characterize the anxiety pattern: diffuse multi-domain worry vs. discrete panic attacks vs. social/performance-specific fear

Diffuse worry, most days, ≥6 months

Likely generalized anxiety disorder — proceed to Algorithm B

Discrete panic attacks + ≥1 month persistent fear of recurrence

Likely panic disorder — proceed to Algorithm C

Fear confined to social/performance situations

Likely social anxiety disorder — proceed to Algorithm D

Algorithm B — Generalized anxiety disorder management

GAD confirmed

Mild-moderate severity

CBT alone OR an SSRI/SNRI alone, by patient preference — do not routinely combine as initial therapy

Severe, suicidal risk, or history of treatment resistance

Pharmacotherapy preferred; obtain psychiatric consultation

If an SSRI/SNRI is chosen: start at a low dose and titrate over 1-2 weeks toward the usual depression target dose

Reassess with the GAD-7 (or clinical response) at 8-12 weeks at target dose

Response ≥50% improvement

Continue current regimen; treat for 12-24 months before considering a taper

Partial response

Augment with a second agent (pregabalin, buspirone, or low-dose quetiapine) rather than switching

No response

Switch to a different first-line SSRI/SNRI rather than augmenting

If a second full first-line trial also fails: move to 2nd-line agents (pregabalin, buspirone) or 3rd-line quetiapine XR / augmentation, and refer to psychiatry for refractory GAD

Algorithm C — Panic disorder management

Panic disorder (with or without agoraphobia) confirmed

Start an SSRI/SNRI together with CBT as initial therapy — combination is preferred from the start, unlike GAD

Start the antidepressant at the lowest possible dose — patients with panic disorder are especially prone to an early exacerbation of anxiety/agitation that can cause premature discontinuation

Severe or acute symptoms at initiation

Add a short-term benzodiazepine bridge (clonazepam or lorazepam) for the first few weeks, tapered once the antidepressant is effective

Tolerable at initiation

Continue antidepressant titration alone

Reassess at 8-12 weeks; if no response, switch to another first-line SSRI or to venlafaxine before considering a TCA

Algorithm D — Social anxiety disorder management

Social anxiety disorder confirmed

Generalized social anxiety (multiple situations, not performance-specific)

SSRI/SNRI and/or CBT specifically tailored to social anxiety disorder

Situational/performance-only anxiety (e.g., public speaking) with no symptoms between events

Single-dose beta-blocker (propranolol or atenolol) 30-60 minutes before the event — no daily medication needed

Reassess generalized SAD at 8-12 weeks; if no response, switch to another first-line agent or add pregabalin (2nd line, effective only at doses ≥600 mg/day)

Drug Tables

How to use this table: Doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. Indications reflect clinical evidence and may extend beyond a specific drug's Health Canada-approved indication — confirm the approved indication in the linked Drug Database entry. Select any drug name to open its complete Pharmasist Drug Database page.

Selective serotonin reuptake inhibitors (SSRIs)

First-line for GAD, panic disorder, and social anxiety disorder as a class. Start at a lower dose than used for depression and titrate weekly to every 2 weeks toward the usual antidepressant target dose — this specifically limits the early anxiety/agitation exacerbation these agents can cause on initiation. All SSRIs carry a serotonin syndrome risk with MAOIs and other serotonergic drugs, and an increased GI bleeding risk when combined with an NSAID or antiplatelet agent.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Citalopram	Initial: 10 mg PO once daily Target: 20-40 mg once daily Maximum: 40 mg/day (20 mg/day if age ≥65)	Nausea, sexual dysfunction, hyponatremia (SIADH), QTc prolongation	Combination with an MAOI is contraindicated; low CYP2D6 inhibition potential	Health Canada dose ceiling reflects QTc-prolongation risk.
Escitalopram	Initial: 5 mg PO once daily Target: 10-20 mg once daily Maximum: 20 mg/day (10 mg/day if age ≥65)	Nausea, sexual dysfunction, hyponatremia (SIADH), QTc prolongation	Combination with an MAOI is contraindicated; low CYP2D6 inhibition potential	Generally well tolerated among the SSRIs, given high receptor selectivity.
Fluoxetine	Initial: 10 mg PO once daily Target: 20-60 mg once daily	Activation/insomnia, sexual dysfunction, GI upset	Potent CYP2D6 inhibitor; long half-life delays full washout when switching agents	More activating than most SSRIs — consider morning dosing.
Fluvoxamine	Initial: 25 mg PO once daily Target: 100-300 mg/day	Sedation, significant GI upset (nausea, diarrhea)	Potent inhibitor of CYP1A2 and other CYP enzymes — extensive interaction potential	More sedating than most SSRIs.
Paroxetine	Initial (immediate-release): 10 mg PO once daily Target (immediate-release): 20-60 mg once daily Initial (controlled-release): 12.5 mg PO once daily Target (controlled-release): 25-50 mg once daily	Sedation, anticholinergic effects, sexual dysfunction, weight gain, discontinuation symptoms	Potent CYP2D6 inhibitor	Shortest half-life of the SSRIs — highest risk of a discontinuation syndrome if stopped abruptly. Avoid in pregnancy.
Sertraline	Initial: 25 mg PO once daily Target: 50-200 mg once daily	GI upset, sexual dysfunction, sweating	Weak CYP2D6 inhibitor — fewer interactions than fluoxetine/paroxetine/fluvoxamine	Take with food to improve tolerability.

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

First-line, comparable efficacy to SSRIs. Monitor blood pressure and heart rate weekly during the first month of treatment and with each dose increase.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Venlafaxine XR	Initial: 37.5 mg PO once daily Target: 75-225 mg once daily	Hypertension (dose-related), nausea, sweating, sexual dysfunction	Combination with an MAOI is contraindicated; weak CYP2D6 inhibitor	Doses above 150 mg/day are needed for a meaningful norepinephrine effect. Taper very gradually — high discontinuation-syndrome risk.
Duloxetine	Initial: 30 mg PO once daily Target: 60-120 mg once daily	Nausea, dry mouth, hypertension	Combination with an MAOI is contraindicated; moderate CYP2D6 inhibitor	Contraindicated if creatinine clearance under 30 mL/min.

Azapirones

Non-benzodiazepine anxiolytic with a low abuse potential.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Buspirone	Initial: 5 mg PO BID-TID, titrated gradually Target: 10-60 mg/day divided	Dizziness, fatigue, agitation (especially early), nausea	Metabolized by CYP3A4; avoid combination with an MAOI given serotonin syndrome risk	Onset of action is 2-4 weeks. Must be taken on a scheduled basis — never effective PRN. Not effective for social anxiety disorder.

Benzodiazepines

Effective for anxiety, but a second-line choice given abuse potential, sedation, cognitive impairment, dependence, withdrawal, and fall risk. Use as a short-term measure during the first few weeks of treatment only where possible; if continued longer because an agent is effective and well tolerated while awaiting antidepressant response, review regularly and taper as soon as reasonable. All benzodiazepines require a gradual taper — never abrupt discontinuation — and carry additive CNS/respiratory depression risk with opioids, alcohol, and other sedating drugs. Avoid in a patient with a current or past substance use disorder, and use with particular caution in older adults given elevated fall, fracture, and cognitive-impairment risk.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Alprazolam	GAD — initial: 0.25-0.5 mg PO BID-TID GAD — target: 0.5-4 mg/day divided Panic disorder — initial: 0.5 mg PO TID or 0.5-1 mg at bedtime Panic disorder — target: average 5-6 mg/day, up to 10 mg/day	Sedation, psychomotor impairment, memory impairment, dependence, withdrawal	Strong CYP3A4 inhibitors (ketoconazole, itraconazole) are contraindicated in combination	Fastest onset of the group but also the highest interdose-rebound and abuse-potential profile — clonazepam or lorazepam are generally preferred first.
Bromazepam	Initial: 1.5-3 mg PO TID Target: 6-18 mg/day divided	Sedation, fatigue, ataxia, dizziness	Additive CNS depression with other sedating drugs	Second-line option for GAD and social anxiety disorder.
Clonazepam	Initial: 0.25 mg PO BID Target: 1-2 mg/day divided (up to 4 mg/day for panic disorder)	Sedation, psychomotor impairment, muscle weakness, dependence, withdrawal	Additive CNS depression with other sedating drugs	Long half-life gives smoother anxiolysis with less interdose rebound — generally a preferred agent alongside lorazepam.
Diazepam	Initial: 2-5 mg PO BID-TID Target: usual maximum 40 mg/day divided	Sedation, ataxia, fatigue	CYP2C19/CYP3A4 inhibitors (e.g., cimetidine, fluoxetine) increase levels via reduced clearance of the parent drug and its active metabolite	Long half-life with active metabolites — sedation can accumulate with repeated dosing, especially in the elderly or hepatic impairment.
Lorazepam	Initial: 0.5-1 mg PO 2-3 times daily Target: 2-6 mg/day divided, up to 10 mg/day in select patients	Sedation, psychomotor impairment, muscle weakness, dependence, withdrawal	Fewer CYP-mediated interactions than most benzodiazepines — cleared by glucuronidation alone	Preferred agent, alongside clonazepam, and specifically preferred in hepatic impairment.

Gabapentinoids

Drug	Dosage	Adverse effects	Drug interactions	Comments
Pregabalin	GAD — initial: 50 mg PO TID GAD — target: 150-600 mg/day divided Social anxiety disorder — target: ≥600 mg/day divided (150-300 mg/day has not shown efficacy)	Dizziness, sedation, ataxia, peripheral edema, weight gain	Additive CNS/respiratory depression with opioids and alcohol	Never prescribe to a patient with a current or past opioid use disorder — real misuse/abuse risk in this population.
Gabapentin	Initial: 300 mg/day PO Target: 900-3600 mg/day divided	Sedation, dizziness, ataxia, peripheral edema	Additive CNS/respiratory depression with opioids and alcohol; magnesium/aluminum antacids reduce absorption	Second-line, limited evidence, for social anxiety disorder.

Beta-blockers

For occasional, situational use only — not useful for generalized social anxiety disorder unrelated to a specific performance situation.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Propranolol	Dosing: 10-40 mg PO as a single dose, 30-60 minutes before the event	Bradycardia, hypotension, fatigue	Additive bradycardia with diltiazem/verapamil/digoxin; can mask hypoglycemia symptoms in diabetes	Test the dose in a low-stakes situation before relying on it for an important event.
Atenolol	Dosing: 25-50 mg PO as a single dose, 60 minutes before the event	Bradycardia, hypotension	Additive bradycardia with diltiazem/verapamil/digoxin	Alternative to propranolol for the same situational indication.

Dual-action antidepressants and serotonin modulators

Second-line, limited evidence base relative to the SSRIs/SNRIs above.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Mirtazapine	Initial: 15 mg/day PO Target: 15-60 mg/day	Sedation, increased appetite/weight gain, dry mouth	Combination with an MAOI is contraindicated	Second-line option for social anxiety disorder; minimal sexual dysfunction relative to SSRIs.
Trazodone	Initial: 25-50 mg PO at bedtime Target: up to 150-200 mg/day divided	Sedation, orthostatic hypotension, priapism (rare)	Combination with an MAOI is contraindicated; additive sedation with other CNS depressants	Limited evidence specifically for GAD; sedation is dose-limiting.

Tricyclic antidepressants (TCAs)

Efficacy similar to SSRIs for panic disorder and GAD but reserved as second/third-line given a significant adverse-effect profile and toxicity in overdose.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Imipramine	Initial: 10-25 mg PO daily Target: 100-300 mg/day	Anticholinergic effects, orthostatic hypotension, QTc prolongation, sedation	Combination with an MAOI is contraindicated; CYP2D6 inhibitor	Toxic in overdose — use caution in a patient with suicidal ideation.
Clomipramine	Initial: 10-25 mg PO daily Target: 100-250 mg/day	Anticholinergic effects, orthostatic hypotension, QTc prolongation, sedation	Combination with an MAOI is contraindicated; CYP2D6 inhibitor	Toxic in overdose — use caution in a patient with suicidal ideation.
Desipramine	Initial: 25 mg PO daily Target: 100-300 mg/day	Anticholinergic effects, orthostatic hypotension, QTc prolongation, sedation	Combination with an MAOI is contraindicated; CYP2D6 inhibitor	Third-line — supported by only a single study for panic disorder. Toxic in overdose.

Monoamine oxidase inhibitors (MAOIs)

Second/third-line given dietary restrictions, drug interactions, and adverse-effect burden. A minimum washout period is required when switching to or from a serotonergic antidepressant (typically 2 weeks; 5 weeks after fluoxetine given its long half-life) to avoid serotonin syndrome.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Phenelzine	Initial: 15 mg PO daily Target: 15-90 mg/day	Orthostatic hypotension, weight gain, sexual dysfunction, insomnia	Tyramine or sympathomimetic exposure can precipitate hypertensive crisis; contraindicated with serotonergic drugs (SSRIs, SNRIs, TCAs, triptans)	Requires strict dietary tyramine restriction. Contraindicated if creatinine clearance under 30 mL/min.
Moclobemide	Initial: 150 mg PO BID Target: 300-600 mg/day divided	Insomnia, nausea, dizziness	Lower hypertensive-crisis risk than irreversible MAOIs, but still requires caution with serotonergic drugs	Reversible MAOI — fewer dietary restrictions than phenelzine. Second-line for social anxiety disorder.

Second-generation antipsychotics and adjunctive agents

Third-line or adjunctive only, given the adverse-effect burden relative to first- and second-line agents.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Quetiapine XR	Initial: 50 mg PO once daily Target: 50-150 mg once daily	Sedation, weight gain, dyslipidemia, hyperglycemia, orthostatic hypotension	Metabolized by CYP3A4 — caution with strong inhibitors/inducers	Monitor weight, lipids, and glucose regularly given the metabolic burden.
Vilazodone	Initial: 10 mg PO once daily with food Target: 20-40 mg once daily with food	Insomnia, GI upset, diarrhea	Moderate CYP2C19 inhibitor; maximum 20 mg/day with a strong CYP3A4 inhibitor	Second-line for GAD; take with food to maximize absorption. Long-term comparative data are limited.

Refractory GAD — adjunctive combination therapy

For GAD that has not responded to sequential first- and second-line monotherapy trials — add one of the following to the existing, optimized antidepressant rather than switching again.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Olanzapine augmentation	Combo (adjunct to antidepressant): olanzapine 2.5-10 mg PO daily + existing antidepressant at optimized dose	Sedation, weight gain, metabolic syndrome	Additive sedation with other CNS depressants	Reserve for refractory cases given the metabolic burden; requires ongoing metabolic monitoring.
Pregabalin augmentation	Combo (adjunct to antidepressant): pregabalin 150-600 mg/day PO divided + existing antidepressant at optimized dose	Dizziness, sedation, peripheral edema, weight gain	Additive CNS/respiratory depression with opioids and alcohol	Never use in a patient with a current or past opioid use disorder.

Shown not effective — do not select for these indications: buspirone and desvenlafaxine have not demonstrated efficacy in social anxiety disorder, despite buspirone's role in GAD. Propranolol and atenolol are not effective for generalized social anxiety disorder unrelated to a specific performance situation. Hydroxyzine has shown efficacy comparable to benzodiazepines and buspirone in limited trial data, but its adverse-effect profile means it is not typically included in current GAD pharmacotherapy. Valproate has only limited evidence in GAD and is not a routine treatment option. Ketamine has shown effect in a single small trial for refractory social anxiety disorder; given the limited evidence base and the requirement for specialist/clinic-based administration, it is accessed through psychiatric referral rather than routine community dispensing.

References

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
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) — American Psychiatric Association. American Psychiatric Publishing, 2022
A brief measure for assessing generalized anxiety disorder: the GAD-7 — Archives of Internal Medicine (Spitzer RL, Kroenke K, Williams JW, Löwe B). Arch Intern Med 2006;166(10):1092-1097
Deprescribing benzodiazepine receptor agonists: Evidence-based clinical practice guideline — Canadian Family Physician (Pottie K, Thompson W, Davies S, Grenier J, Sadowski CA, Welch V, et al.). Can Fam Physician 2018;64(5):339-351
Therapist-supported Internet cognitive behavioural therapy for anxiety disorders in adults — Cochrane Database of Systematic Reviews (Olthuis JV, Watt MC, Bailey K, Hayden JA, Stewart SH). Cochrane Database Syst Rev 2016;3:CD011565
Canadian Network for Mood and Anxiety Treatments (CANMAT) 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
World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders – version 3, Part I: Anxiety disorders — World Journal of Biological Psychiatry (Bandelow B, Allgulander C, Baldwin DS, et al.). World J Biol Psychiatry 2023;24(2):79-117

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