Anxiety Disorders

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.

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]

• 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).

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

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]

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]

• 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.

• 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.

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.

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]

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]

1. 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.
2. 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.
3. 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.
4. 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).
5. 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.
6. Persistent treatment resistance after these steps warrants psychiatric referral rather than continued trial-and-error in primary care.

• 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.

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.

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.

Azapirones

Non-benzodiazepine anxiolytic with a low abuse potential.

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.

Gabapentinoids

Beta-blockers

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

Dual-action antidepressants and serotonin modulators

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

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.

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.

Second-generation antipsychotics and adjunctive agents

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

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.