Anxiety and Depression

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This clinical tool helps family physicians and primary care nurse practitioners identify and manage anxiety and depression in adult patients. The tool was developed to help guide conversations with patients and families over a series of visits, as needed.

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Screening and assessment

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Screen patients who express mood or anxiety/depression-related concerns and those who come in for unrelated concerns, but whopresent with risk factors for anxiety and depression. Current evidence does not indicate a recommended screening interval for anxiety and depression.

Balance the use of validated screening tools with facilitating talks with patients about anxiety and depression.

For patients with mild, moderate or severe symptoms, a comprehensive assessment should be conducted.

Guiding principles for the screening and assessment of anxiety and depression:

  • Avoid stigmatizing labels (e.g., “abnormal”, “unusual”). Ensure steps are taken to reduce stigma, discrimination and barriers for patients.
  • Talk about symptoms instead of disorders/diagnoses.
  • Ensure that patients feel comfortable establishing trust with you as their healthcare provider.
  • Ensure services are culturally appropriate or culturally adapted (e.g., language considerations/translators). 
  • Provide various of methods to engage with patients (e.g., in-person, email, telephone, online or remote consultations). 
  • Ensure that discussions occur in settings where confidentiality, privacy and dignity are respected.

Screen patient

Screen for risk factors1, 3

Clinical factors:
  • Personal or family history of anxiety or depression
  • Psychosocial adversity (e.g., stressful life events, childhood trauma)
  • Chronic medical conditions (e.g., cardiovascular disease, diabetes, neurological disorders, chronic pain)
  • Other psychiatric conditions (e.g., bipolar disorder, schizophrenia, substance use disorder)
  • Perinatal/postpartum, premenstrual dysphoric disorder, menopause
Symptom factors:
  • Fatigue
  • Insomnia
  • Unexplained physical symptoms (e.g., unexplained aches and pains)
  • Significant and repeated worry
  • Frequent healthcare use due to any of the above

Complete a validated or recognized screening tool3,4

Anxiety

If anxiety is suspected, proceed with the general anxiety or specific anxiety disorder screening tool for diagnosis and measurement of progress or responses to treatment.

  • General anxiety disorder (GAD): Generalized Anxiety Disorder 7 (GAD-7)
    • Cut off points for minimal (≤4), mild (score 5-9), moderate (score 10-14) and severe anxiety (score ≥15)
  • Social anxiety disorder (SAD): Social Phobia Inventory (SPIN)
    • Cut off points for minimal (score ≤20), mild (score 21-30), moderate (score 31-40), severe (score 41-50) and very severe social phobia (score ≥51)
  • Panic disorder: Panic Disorder Severity Scale (PDSS)
    • Cut off points for none (score <9) and present panic disorder (score ≥9)
  • Specific phobia or agoraphobia: Severity Measure for Specific Phobia (SMSP)
    • Cut off points for none (avg score of 0), mild (avg score of 1), moderate (avg score of 2), severe (avg score of 3) and extreme phobia (avg score of 4)
Depression

If depression is suspected, proceed with the Patient Health Questionnaire 9 (PHQ-9) screening tool for diagnosis and measurement of progress or responses to treatment.

Screening special populations3-5

Older adults

  • Geriatric Depression Scale: Cut off points for does not suggest depression (score < 5), suggests depression (score 5-10) and almost always indicates depression (score ≥10)
  • Cornell Scale for Depression in Dementia: Cut off points for probably major depressive episode (score >10) and definite major depressive episode (score >18)

Peri/postnatal

  • Edinburgh Perinatal/Postnatal Depression Scale (EPDS): Cut off points for not likely (score < 8), possible (score 9-11), fairly high possibility (score 12-13), probable (score ≥ 14) and positive depression (score of 1, 2 or 3 on question 10). Pay close attention to question 10 as scores could indicate suicidality risk which requires further follow-up and intervention)

Assess findings

If ≥mild anxiety or depression, begin or schedule a time to conduct or complete a comprehensive assessment. Consider booking a longer appointment or schedule as the last patient of the day to ensure a less rushed and more relaxed appointment.

If minimal anxiety or depression, book a follow-up appointment or create a reminder to check in at patient’s next appointment to see if their scores change. Consider reevaluating the diagnosis if necessary, as symptoms could be related to something else.

Conduct a comprehensive assessment2-4, 6

Collect clinical history

  • Onset, intensity and history of symptoms (including a snapshot of the last few weeks)
  • Past experiences of, and response(s) to, previous treatments
Understand individual patient-contributing factors
  • Recent or past stressful life events (e.g., work, school,  divorce/breakups, bereavement)
  • Traumatic life events (e.g., adverse childhood events, abuse, trauma)
  • Personal and psychosocial support (e.g., family, friends, community)
  • Lifestyle (e.g., diet, physical activity, sleep, drug use, smoking, social isolation, total screen time work vs social media screen time)
  • Social determinants of health (e.g., housing access , employment, food security and nutrition, income level, racial segregation, social support networks)
  • Perspectives about mental health (e.g., stigma, comfort with management strategies)
  • Provider-patient relationship (e.g., safe space)
  • Current and history of physical health conditions (e.g., endocrine disorders, anemia, thyroid dysfunction, nutrient and vitamin deficiencies, cardiovascular disease, diabetes, neurological disorders, pregnancy and postpartum, perimenopause, menopause, oncological disorders, dementia, Alzheimer’s, Parkinson’s)
  • Refer to the latest lab / test results of the following when appropriate:5,7,8
    • CBC, HBA1c, TSH, Ferritin, B-12, Vitamin D, Electrocardiogram (ECG), Urine Drug Screen (if warranted to rule out substance use disorders)
Community and social resources:

211Ontario: Regional community and support resources.

  • If individual patient factors that affect mental health are detected or suspected, support the patient to address and manage these first.
  • If a physical condition that affects mental health is detected or suspected, screen for and treat the condition while concurrently treating and monitoring mental health symptoms as appropriate.

Screen for risk of suicide or self-harm or harm others

  • “Sometimes when people feel the way you do right now, they start to have thoughts about self harm. Has this ever happened to you?”
  • “Do you have a plan for how you would engage in self-harm?”
  • “In the next 24-48 hours, how likely is it that you will act on your suicidal plan?” (rate on scale of 1 to 10, where 1 = very unlikely and 10 = certain)
  • “With the way you are currently feeling, have you had any thoughts of harming yourself or others?”

Screen for risk of suicide, self-harm or harm to others

  • When considering a patient’s mental health status consider:
    • Risk factors
    • Specific suicidal thoughts and methods
    • Extent of planning and action
    • Present and history
    • Obtaining input from family and caregivers

If the patient is at risk, arrange appropriate help based on their level of need

  • Assess for adequate social support and awareness of resources
  • Advise the patient to create a safety plan and seek further help if the situation becomes worse
  • Let the patient know that we have a legal obligation to report if they are in danger (document that you have mentioned this to the patient)
  • If the patient is identified to be at high risk of harming themselves or others (have a clear intention to act in the next 24-48 hours on a suicide plan), advise them, their family, caregivers and friends to call 911 or go to the Emergency Department (ED)
  • If the patient refuses further assessment and is unwilling to go to the ED:
    1. Communicate with the patient the importance of going to the ED
    2. Complete a Form 1 (if the patient meets criteria) and a brief note to accompany the patient. Consult the CEP’s Keeping Your Patients Safe for tips on completing a Form 1.
    3. Arrange for EMS/police transport of the patient to the ED
Emergency support and suicide prevention resources

For patients:

  • Good2Talk: 1-866-925-5454 (post-secondary students) open 24/7
  • Crisis Line: 1-866-996-0991 (all ages) open 24/7
  • Talk Suicide: 1-833-456-4566
  • Distress and Crisis Ontario: Provides a free, confidential chat program to support patients and offers self-management tips
  • My Safety Plan: For patients experiencing thoughts of suicide but are not in immediate crisis

For family and caregivers:

Provider resources:

Identify any comorbid mental health conditions

  • Attention deficit hyperactivity disorder (ADHD)/attention-deficit disorder (ADD)
  • Post-traumatic stress disorder (PTSD) 
  • Bipolar disorder  
  • Psychosis 
  • Obsessive compulsive disorder (OCD)  
  • Panic disorder  
  • Personality disorders  
  • Adverse childhood experiences
  • Substance use and addictions disorders (e.g., alcohol, drugs, gambling, gaming and problematic screen time)
  • Other
  •  If mental health comorbidities are suspected, consider referral to appropriate mental health services or an eConsult for further assessment and treatment
  • Comorbid mental health disorders significantly increase the risk of suicidal behaviour

Communicate diagnosis to patients

Confirm and communicate a diagnosis to the patient as soon as possible to help with the patient’s understanding of the disorder and to start timely and effective treatment.2

  • To confirm diagnosis, use the DSM-V criteria (Anxiety / Depression)
  • Discuss with the patients how individual factors may affect the development, course and severity of their mental health (e.g., comorbidities, lifestyle, social determinants of health, etc.)
Talking tips
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Talking tips2,5,6

  • Being diagnosed with depression or anxiety is common. Many adults are diagnosed with it every year.
  • The excessive worrying and feelings of anxiousness you experience are felt by many people. There are many ways that we can improve them.
  • The sadness and loss of hope you are experiencing can be very difficult, and I appreciate that you have come today to talk about it. This is an important first step.
  •  I can share information about medications and counselling in many languages. Is there another language you or your family members prefer?

Management New

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Use your clinical judgement to move patients through the stepped-care approach. For the psychological and pharmacological management of anxiety and depression. Individualize therapy based on a patient’s symptom severity, concerns and preferences. This may involve skipping steps to achieve appropriate treatment for an individual patient. Routinely follow-up and monitor changes in the patient’s symptoms and quality of life. Empower patients to make decisions with you about their treatment plan.2

Talking tips
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Talking tips

Ask the patients questions, such as:5

  • What is your experience with other periods of low mood/anxiety?
  • Is there anything that helps you feel better?
  • Is there anything that might be making your mood/anxiety worse?
  • What are you hoping to gain from your management plan?
  • What do you think you need to get back on track?
  • Do you have any ideas or preferences for treatment?

Guiding principles for the management of anxiety and depression:

  • Understand the patient’s context and life circumstances, such as:6
  • Cost considerations
  • Account for how coexisting conditions may impact treatment options.

Psychological treatment options

Anxiety2, 3, 9

Depression1, 4, 5, 10

Refer adult patients who are experiencing mild to moderate depression, anxiety, and anxiety-related problems to publicly funded, short-term, evidence-based services that are based on the treatment principles of cognitive behavioural therapy (CBT) through the Ontario Structured Psychotherapy (OSP) Program. Find your regional OSP network below.

OSP services follow a stepped-care approach. They include in-person or virtual self-help resources facilitated or guided by a mental health professional and one-on-one or group CBT sessions.

OSP Networks and Referral Process

Waypoint Centre for Mental Health Care

CarePoint Health (Brampton, Halton, Mississauga)

Canadian Mental Health Association – York and South Simcoe

Centre for Addiction and Mental Health

OSP West Region (St. Joseph’s Healthcare Hamilton and St. Joseph’s Health Care London)

 

The Royal Ottawa Mental Health Centre

Ontario Shores Centre for Mental Health Services

Health Sciences North

St. Joseph’s Care Group


Resources for patients and caregivers9

Free resources available for patients and their caregivers are listed below:
Community and social

ConnexOntario: Mental health system navigation and information. Mental health: 1-800-531-2600 | Addictions: 1-800-565-8603

eMentalHealth.ca: Directory of publicly-funded regional service coordination and case management services.

Hope for Wellness: Mental health counselling and community-based cultural and emotional support for Indigenous people. 1-855-242-3310

Talk4Healing: 24/7 talk, text, and chat to support Indigenous women by Indigenous women. 1-888-200-9997

thehealthline.ca: Regional mental health organizations, clinics, workshops, conferences and support groups.

Educational supports for patients and caregivers
Online app and resources

BounceBack Ontario:  Available through the OSP Program. Guided self-led resources to support adults and youth manage low mood, mild to moderate depression and anxiety, stress or worry. Delivered by phone with a coach and through online videos.

MindShift CBT App: CBT-based tools for worry, panic, perfectionism, social anxiety and phobias. Available on the App Store and Google Play.

My Anxiety Plan (MAP): Virtual, individual non-facilitated and facilitated self-help program for adults with mild to moderate anxiety.

Greenspace: Matches patients to therapists in the GTA. Matching is free. Therapy fees apply.

PocketWell: Free app for tracking mood from Wellness Together Canada.

Pharmacological treatment options

Factors to consider when choosing a medication1, 5

Patient factors:
  • Previous experience with antidepressants (e.g., response, side effects). Consider a pharmacy review for information on the discontinuation of past medications.
  • Family history of a positive response to particular medication(s)
  • Clinical features/specifiers/dimensions
  • Comorbid conditions
  • Patient preference(s)
  • Other factors (e.g., age, pregnancy/breastfeeding, suicide risk)
  • Comparative efficacy
  • Comparative tolerability, warnings, contraindications and precautions
  • Potential interactions with other medications
  • Simplicity of use
  • Cost and availability

Support from a pharmacist or mental health expert may be helpful in complex cases or if there is uncertainty.

Talking tip5
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Talking tip

Choosing to use medications for condition, blood pressure or our mood can be difficult. Do you feel this way? What are some of your concerns?

Role of pharmacogenetic testing for medication selection1

There is a paucity of large-scale randomized controlled trial (RCT) evidence for pharmacogenetic testing. Pharmacogenetic testing may be considered in specific cases, including a patient’s inability to tolerate multiple medications or repeated lack of response to high doses of medications.

First-line medication options1,3–5, 7, 9, 11–30

The following medications are considered first line in the CANMAT 2016 MDD Guidelines and 2014 Anxiety Guidelines.1,7 Some international guidelines recommend all SSRIs and SNRIs broadly (+/- agents) as first-line for MDD, anxiety or both.6,8,28 CANMAT classifies the SNRI levomilnacipran (Fetzima®) as second-line for MDD due to lack of comparative and relapse-prevention data.1 Other options (e.g., amitriptyline, trazodone) are not first-line in any of the reviewed guidelines due to side effects.

Available evidence for drug selection has many limitations, including limited head-to-head trials between drugs and potential for bias. If you have questions about drug selection, consult a pharmacist or specialist through eConsult.

***Click to view*** first-line medication options in table format.

Selective Serotonin Reuptake Inhibitors (SSRI)
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  • Selective Serotonin Reuptake Inhibitors (SSRI)
    Citalopram (Celexa®)

    10 mg, 20 mg, 40 mg tablet

    First-line for

    • Major depressive disorder
    • Panic disorder (+/- agoraphobia)

    Coverage

    • ODB ✓
    • NIHB ✓

    Cost for usual dose ($/100 days)

    • $24-60

    Overall tolerability*

    • Well-tolerated

    Activating or sedating

    • Activating/sedating

    Interaction risk

    • + (CYP)
    • Caution: combined QT-prolongation risk

    Features**

    • A preferred pharmacological options in pregnancy
    View dosing, side effects, warning and contraindications
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    Citalopram (Celexa®)

    Dosing***
    • Initial: 10-20 mg daily (am/pm)
    • Usual: 20–40 mg daily
    • Max: 40 mg daily (20 mg in older adults, liver disease, concurrent CYP 2C19 inhibitors)
    Side effects
    • CNS: headache, sleep disturbance, drowsiness, nervousness, dizziness, somnolence, fatigue
    • GI: nausea, vomiting, diarrhea
    • Anticholinergic: dry mouth, constipation, blurred vision, hyperhidrosis
    • CV: orthostatic hypotension, tachycardia
    • Urogenital: sexual dysfunction
    Warnings and contraindications
    • QTc prolongation risk
    • Contraindicated in patients with known QT prolongation or congenital long QT syndrome
    • Anxiety/agitation may worsen initially (first 1-2 weeks)
    • GI bleeding (consider gastroprotective agent if high risk)
    • Hyponatremia (especially in elderly)
    • Fractures (especially in first 6 weeks)
    • Suicidal thinking and self-harm (patients 30 years and under)
  • Selective Serotonin Reuptake Inhibitors (SSRI)
    Escitalopram (Cipralex®)

    10 mg, 20 mg tablet

    First-line for

    • Major depressive disorder
    • Generalized anxiety disorder
    • Social anxiety disorder
    • Panic disorder (+/- agoraphobia)

    Coverage

    • ODB ✓
    • NIHB ✓

    Cost for usual dose ($/100 days)

    • $26-45

    Overall tolerability*

    • Very well-tolerated

    Activating or sedating

    • Activating/sedating

    Interaction risk

    • + (CYP)
    • Caution: combined QT-prolongation risk

    Features**

    • A preferred pharmacological option in pregnancy
    View dosing, side effects, warning and contraindications
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    Escitalopram (Cipralex®)

    Dosing***
    • Initial: 5-10 mg daily (am/pm)
    • Usual: 10-20 mg daily
    • Max: 20 mg daily (10 mg in older adults, liver disease, concurrent CYP 2C19 inhibitors)
    Side effects
    • CNS: headache, sleep disturbance, drowsiness, nervousness, dizziness, somnolence, fatigue
    • GI: nausea, vomiting, diarrhea
    • Anticholinergic: dry mouth, constipation, blurred vision, hyperhidrosis
    • CV: orthostatic hypotension, tachycardia
    • Urogenital: sexual dysfunction
    Warnings and contraindications
    • QTc prolongation risk
    • Contraindicated in patients with known QT prolongation or congenital long QT syndrome
    • Anxiety/agitation may worsen initially (first 1-2 weeks)
    • GI bleeding (consider gastroprotective agent if high risk)
    • Hyponatremia (especially in elderly)
    • Fractures (especially in first 6 weeks)
    • Suicidal thinking and self-harm (patients 30 years and under)
  • Selective Serotonin Reuptake Inhibitors (SSRI)
    Fluoxetine (Prozac®)

    10 mg, 20 mg, 40 mg, 60 mg tablet
    4 mg/mL oral solution

    First-line for

    • Major depressive disorder
    • Panic disorder (+/- agoraphobia)

    Coverage

    • ODB ✓ (excludes 10mg tablet)
    • NIHB ✓

    Cost for usual dose ($/100 days)

    • $45-152

    Overall tolerability*

    • Well-tolerated

    Activating or sedating

    • Activating

    Interaction risk

    • +++

    Features**

    • Easy to discontinue (self-taper)
    View dosing, side effects, warning and contraindications
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    Fluoxetine (Prozac®)

    Dosing***
    • Initial: 10-20 mg daily (am)
    • Usual: 20 mg daily
    • Max: 80 mg daily (lower dose recommended for older adults)
    Side effects
    • CNS: insomnia, headache, sleep disturbance, drowsiness, nervousness, dizziness, somnolence, fatigue
    • GI: nausea, vomiting, diarrhea
    • Anticholinergic: dry mouth, constipation, blurred vision, hyperhidrosis
    • CV: orthostatic hypotension, tachycardia
    • Urogenital: sexual dysfunction
    • Other: agitation, anorexia
    Warnings and contraindications
    • Higher rates of confusion
    • QTc prolongation risk
    • Anxiety/agitation may worsen initially (first 1-2 weeks)
    • GI bleeding (consider gastroprotective agent if high risk)
    • Hyponatremia (especially in elderly)
    • Fractures (especially in first 6 weeks)
    • Suicidal thinking & self-harm (patients 30 years and under)
  • Selective Serotonin Reuptake Inhibitors (SSRI)
    Fluvoxamine (Luvox®)

    50 mg, 100 mg tablet

    First-line for

    • Major depressive disorder
    • Social anxiety disorder
    • Panic disorder (+/- agoraphobia)

    Coverage

    • ODB ✓
    • NIHB ✓

    Cost for usual dose ($/100 days)

    • $55-132

    Overall tolerability*

    • Poorly-tolerated

    Activating or sedating

    • Sedating

    Interaction risk

    • +++

    Features**

    • No notable features
    View dosing, side effects, warning and contraindications
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    Fluvoxamine (Luvox®)

    Dosing***
    • Initial: 25-50 mg daily (hs)
    • Usual: 100–200 mg daily
    • Max: 300 mg daily
      • Divide doses above 150 mg (max 150 mg at bedtime)
      • Hepatic/renal disease: increase dose slowly & monitor carefully
    Side effects
    • CNS: headache, sleep disturbance, drowsiness, nervousness, dizziness, somnolence, fatigue
    • GI: severe GI upset, nausea, vomiting, diarrhea
    • Anticholinergic: anticholinergic potential, dry mouth, constipation, blurred vision, hyperhidrosis
    • CV: orthostatic hypotension, tachycardia
    • Urogenital: sexual dysfunction
    • Other: anorexia
    Warnings and contraindications
    • Caution when using for older adults
    • Anxiety/agitation may worsen initially (first 1-2 weeks)
    • GI bleeding (consider gastroprotective agent if high risk)
    • Hyponatremia (especially in elderly)
    • Fractures (especially in first 6 weeks)
    • Suicidal thinking & self-harm (patients 30 years and under)
  • Selective Serotonin Reuptake Inhibitors (SSRI)
    Paroxetine (Paxil®)

    10 mg, 20 mg, 30 mg tablet
    CR: 12.5 mg, 25 mg tablet

    First-line for

    • Major depressive disorder
    • Generalized anxiety disorder
    • Social anxiety disorder
    • Panic disorder (+/- agoraphobia)

    Coverage

    • ODB ✓ (excludes 10mg and CR tablets)
    • NIHB ✓ (excludes CR tablets)

    Cost for usual dose ($/100 days)

    • $27-125
    • CR: $252 – 790

    Overall tolerability*

    • Poorly-tolerated

    Activating or sedating

    • Sedating

    Interaction risk

    • +++

    Features**

    • A preferred pharmacological options for breastfeeding
    View dosing, side effects, warning and contraindications
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    Paroxetine (Paxil®)

    Dosing***
    • Initial: 10-20 mg daily (hs)
    • Usual: 20 mg daily (40 mg for GAD)
    • Max: 50 mg daily (40 mg for older adults/debilitated patients)
    Dosing (CR)
    • Initial: 12.5-25 mg daily (hs)
    • Usual: 25 mg daily (50 mg for GAD)
    • Max: 62.5 daily (50 mg for older (adults/debilitated patients)
    Side effects
    • CNS: headache, sleep disturbance, drowsiness, nervousness, dizziness, somnolence, fatigue
    • GI: nausea, vomiting, diarrhea
    • Anticholinergic: anticholinergic potential, dry mouth, constipation, blurred vision, hyperhidrosis
    • CV: orthostatic hypotension, tachycardia
    • Urogenital: sexual dysfunction
    • Other: weight gain, withdrawal effects
    Warnings and contraindications
    • Avoid in older adults and pregnancy
    • Anxiety/agitation may worsen initially (first 1-2 weeks)
    • GI bleeding (consider gastroprotective agent if high risk)
    • Hyponatremia (especially in elderly)
    • Fractures (especially in first 6 weeks)
    • Suicidal thinking & self-harm (patients 30 years and under)
  • Selective Serotonin Reuptake Inhibitors (SSRI)
    Sertraline (Zoloft®)

    25 mg, 50 mg, 100 mg capsule

    First-line for

    • Major depressive disorder
    • Generalized anxiety disorder
    • Social anxiety disorder
    • Panic disorder (+/- agoraphobia)

    Coverage

    • ODB ✓
    • NIHB ✓

    Cost for usual dose ($/100 days)

    • $26-81

    Overall tolerability*

    • Very well-tolerated

    Activating or sedating

    • Activating

    Interaction risk

    • ++

    Features**

    • A preferred pharmacological option for older adults, pregnancy and breastfeeding
    • May be a preferred option in CV disease
    View dosing, side effects and warnings
    Close

    Sertraline (Zoloft®)

    Dosing***
    • Initial: 25-50 mg daily (am/pm)
    • Usual:
      • MDD: 50-100 mg daily
      • GAD: 50-150 mg daily
      • SAD & panic: 50-200 mg dailyx
    • Max: 200 mg daily
    Side effects
    • CNS: headache, sleep disturbance, drowsiness, nervousness, dizziness, somnolence, fatigue
    • GI: nausea, vomiting, diarrhea
    • Anticholinergic: dry mouth, constipation, blurred vision, hyperhidrosis
    • CV: orthostatic hypotension, tachycardia
    • Urogenital: sexual dysfunction
    Warnings and contraindications
    • Anxiety/agitation may worsen initially (first 1-2 weeks)
    • GI bleeding (consider gastroprotective agent if high risk)
    • Hyponatremia (especially in elderly)
    • Fractures (especially in first 6 weeks)
    • Suicidal thinking & self-harm (patients 30 years and under)

*Overall tolerability is based on availability of evidence that primarily evaluates drop-out rates from trials. Specific drug side effects and patient factors may influence overall tolerability in practice.
** Consider in addition to other patient and medication factors
***Titration information:
Depression: for most agents – increase dose no more frequently than once a week.        
Anxiety OR if sensitive to side effects, or has kidney disease, liver disease, advanced age, or other factors warranting caution: start with the lowest dose and increase every 1-2 weeks

Serotonin Norepinephrine Reuptake Inhibitors (SNRI)
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  • Serotonin Norepinephrine Reuptake Inhibitors (SNRI)
    Desvenlafaxine (Pristiq®)

    50 mg, 100 mg tablet

    First-line for

    • Major depressive disorder

    Coverage

    • ODB X
    • NIHB X

    Cost for usual dose ($/100 days)

    • $268

    Overall tolerability*

    • Poorly tolerated

    Activating or sedating

    • Activating > sedating

    Interaction risk

    • +

    Features**

    • No notable features
    View dosing, side effects, warning and contraindications
    Close

    Desvenlafaxine (Pristiq®)

    Dosing***
    • Initial: 50 mg daily
    • Usual: 50 mg daily
    • Max: 100 mg daily
    Side effects
    • CNS: headache, sleep disturbance, drowsiness, nervousness, dizziness, somnolence, fatigue
    • GI: nausea, vomiting, diarrhea, decreased appetite
    • Anticholinergic: dry mouth, constipation, blurred vision, hyperhidrosis
    • CV: increased blood pressure, orthostatic hypotension
    • Urogenital: sexual dysfunction
    Warnings and contraindications
    • Anxiety/agitation may worsen initially (first 1-2 weeks)
    • Increased risk of bone fractures
  • Serotonin Norepinephrine Reuptake Inhibitors (SNRI)
    Duloxetine (Cymbalta®)

    30 mg, 60 mg capsule

    First-line for

    • Major depressive disorder
    • Generalized anxiety disorder

    Coverage

    • ODB ✓
    • NIHB ✓

    Cost for usual dose ($/100 days)

    • $48-167

    Overall tolerability*

    • Neutral

    Activating or sedating

    • Activating > sedating

    Interaction risk

    • + +

    Features**

    • A preferred pharmacological option for older adults
    • Helpful for some types of pain
    View dosing, side effects, warning and contraindications
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    Duloxetine (Cymbalta®)

    Dosing***
    • Initial: 30 mg daily (may be considered for tolerability)
    • Usual: 60 mg daily
    • Max: 60 mg daily (120 mg daily for GAD)
    Side effects
    • CNS: headache, sleep disturbance, drowsiness, nervousness, dizziness, somnolence, fatigue
    • GI: nausea, vomiting, diarrhea, decreased appetite
    • Anticholinergic: dry mouth, constipation, blurred vision, hyperhidrosis
    • CV: increased blood pressure, orthostatic hypotension
    • Urogenital: sexual dysfunction
    Warnings and contraindications
    • Anxiety/agitation may worsen initially (first 1-2 weeks)
    • Increased risk of bone fracture
  • Serotonin Norepinephrine Reuptake Inhibitors (SNRI)
    Venlafaxine (Effexor®)

    37.5 mg, 75 mg, 150 mg capsule

    First-line for

    • Major depressive disorder
    • Generalized anxiety disorder
    • Social anxiety disorder
    • Panic disorder (+/- agoraphobia)

    Coverage

    • ODB ✓
    • NIHB ✓

    Cost for usual dose ($/100 days)

    • $19-69

    Overall tolerability*

    • Poorly tolerated

    Activating or sedating

    • Activating > sedating

    Interaction risk

    • +

    Features**

    • Helpful for some types of pain
    View dosing, side effects, warning and contraindications
    Close

    Venlafaxine (Effexor®)

    Dosing***
    • Initial: 37.5 mg daily (75 mg daily for Panic)
      • MDD: if needed to adjust to the medication
      • GAD: for 4-7 days
      • SAD: for 7 days
      • Panic: for 4-7 days may be considered for tolerability
    • Titration: increase by ≤ 75 mg daily, as needed
      • MDD: at intervals of 4 days – 2 weeks
      • GAD & Panic: at interval of ≥ 4 days
      • SAD: at interval of ≥ 7 days
    • Usual: 75 mg daily
    • Max: 225 mg daily
    Side effects
    • CNS: headache, sleep disturbance, drowsiness, nervousness, dizziness, somnolence, fatigue
    • GI: nausea, vomiting, diarrhea, decreased appetite
    • Anticholinergic: dry mouth, constipation, blurred vision, hyperhidrosis
    • CV: increased blood pressure, orthostatic hypotension
    • Urogenital: sexual dysfunction
    Warnings and contraindications
    • Anxiety/agitation may worsen initially (first 1-2 weeks)
    • Increased risk of bone fracture

*Overall tolerability is based on availability of evidence that primarily evaluates drop-out rates from trials. Specific drug side effects and patient factors may influence overall tolerability in practice.
** Consider in addition to other patient and medication factors
***Titration information:
Depression: for most agents – increase dose no more frequently than once a week.
Anxiety OR if sensitive to side effects, or has kidney disease, liver disease, advanced age, or other factors warranting caution: start with the lowest dose and increase every 1-2 weeks

Other classes
Scroll (left-right) for details
  • Norepinephrine Dopamine Reuptake Inhibitor (NDRI)
    Bupropion (Wellbutrin®)

    SR: 100 mg, 150 mg tablet
    XL (ER): 150 mg, 300 mg capsule

    First-line for

    • Major depressive disorder

    Coverage

    Cost for usual dose ($/100 days)

    • SR: $66-207
    • XL: $41-72

    Overall tolerability*

    • Well tolerated

    Activating or sedating

    • Activating

    Interaction risk

    • ++

    Features**

    • Low risk of sexual dysfunction
    • Low risk of hyponatremia
    • Also indicated for smoking cessation
    View dosing, side effects, warning and contraindications
    Close

    Bupropion (Wellbutrin®)

    Dosing (SR)***
    • Initial: 100-150 mg daily
    • Usual: 100-150 mg daily
    • Max: 300 mg daily (doses > 150 mg daily should be given BID with at least 8 hours between doses. A single dose should not exceed 150 mg)
    Dosing (XL, given once daily)***
    • Initial: 150 mg daily
    • Usual: 150–300 mg daily
    • Max: 450 mg daily
    Side effects
    • CNS: headache, sleep disturbance, nervousness, dizziness, fatigue
    • GI: nausea, vomiting, diarrhea, decreased appetite
    • Anticholinergic: dry mouth, constipation, blurred vision, hyperhidrosis
    • CV: Increased blood pressure, orthostatic hypotension
    Warnings and contraindications
    • Contraindicated in patients with seizure disorder or at higher risk for seizures (e.g, anorexia nervosa or bulimia)

     

  • Noradrenergic and Specific Serotonergic Antidepressant (NaSSA)
    Mirtazapine (Remeron®)

    15 mg, 30 mg, 45 mg tablet
    15 mg, 30 mg, 45 mg orally disintegrating tablet (ODT)

    First-line for

    • Major depressive disorder

    Coverage

    • ODB ✓ (excludes 15mg and 45mg tablets)
    • NIHB ✓

    Cost for usual dose ($/100 days)

    • $26-134 (tablet)
    • $54-143 (ODT)

    Overall tolerability*

    • Neutral

    Activating or sedating

    • Sedating

    Interaction risk

    • +

    Features**

    • Low risk of sexual dysfunction
    • Can help increase appetite and weight
    • May be helpful
    View side dosing effects, warning and contraindications
    Close

    Mirtazapine (Remeron®)

    Dosing***
    • Initial: 15 mg daily
    • Usual: 15–45 mg daily
    • Maximum: 45 mg daily
    Side effects
    • CNS: headache, sleep disturbance, nervousness, dizziness, fatigue
    • GI: nausea, vomiting, diarrhea, increased appetite
    • Anticholinergic: dry mouth, constipation, blurred vision, hyperhidrosis
    • CV: orthostatic hypotension
  • Calcium Modulator, GABA Anxiolytic
    Pregabalin (Lyrica®)

    25 mg, 50 mg, 75 mg, 150 mg, 300 mg capsule

    First-line for

    • Generalized anxiety disorder
    • Social anxiety disorder

    Coverage

    • ODB ✓
    • NIHB ✓

    Cost for usual dose ($/100 days)

    • $25-99

    Overall tolerability*

    • Neutral

    Activating or sedating

    • Sedating

    Interaction risk

    • 0/+

    Features**

    • Helpful for some types of pain
    View dosing, side effects, warning and contraindications
    Close

    Pregabalin (Lyrica®)

    Dosing***
    • Initial: 150 mg daily (75 mg BID or 50 mg TID)
      • some experts recommend 50 mg daily
    • Titration: Increase weekly
    • Usual:
      • GAD: 300 mg daily (150 mg BID)
      • SAD: 600 mg daily (300 mg BID)
    • Max: 600 mg daily (300 mg BID)
    Side effects
    • CNS: headache, sleep disturbances, memory impairment, ataxia, diplopia, dizziness, somnolence, sedation, fatigue
    • GI: nausea, vomiting, diarrhea, weight gain
    • Anticholinergic: dry mouth, blurred vision
    • Other: skin rash, peripheral edema, weight gain
    Warnings
    • Angioedema
    • Hypersensitivity reactions
    • Caution in renal impairment
    • New-onset congestive heart failure in CV-compromised adults
    • Reduced GI motility (caution with concurrent opioid use)
  • Serotonin Receptor Antagonist and Serotonin Reuptake Inhibitor (SARI)
    Vortioxetine (Trintellix®)

    5 mg, 10 mg, 20 mg tablet
    No generic available

    First-line for

    • Major depressive disorder

    Coverage

    • ODB ✓
    • NIHB ✓

    Cost for usual dose ($/100 days)

    • $320-363

    Overall tolerability*

    • Poorly tolerated

    Activating or sedating

    • Activating/sedating

    Interaction risk

    • ++

    Features**

    • No notable features
    View dosing, side effects, warning and contraindications
    Close

    Vortioxetine (Trintellix®)

    Dosing***
    • Initial: 10 mg daily (5 mg daily in older adults; consider decreasing to 5 mg if higher dose is not tolerated)
    • Usual: 10–15 mg daily
    • Max: 20 mg daily
    Side effects
    • CNS: headache, sleep disturbance, nervousness, dizziness, fatigue
    • GI: nausea, vomiting, diarrhea, abdominal pain, bloating, decreased appetite
    • Anticholinergic: dry mouth, constipation, hyperhydrosis
    • CV: orthostatic hypotension
    • Other: cough, flu-like symptoms, pruritus, joint and muscle pain
    Warnings and contraindications
    • Anxiety/agitation may worsen initially (first 1-2 weeks)
    • Increased risk of bone fractures
    • Caution in narrow-angle glaucoma

*Overall tolerability is based on availability of evidence that primarily evaluates drop-out rates from trials. Specific drug side effects and patient factors may influence overall tolerability in practice.
** Consider in addition to other patient and medication factors
***Titration information:
Depression: for most agents – increase dose no more frequently than once a week.        
Anxiety OR if sensitive to side effects, or has kidney disease, liver disease, advanced age, or other factors warranting caution: start with the lowest dose and increase every 1-2 weeks

Role of benzodiazepines for anxiety disorders3,5,7

Benzodiazepines should not be routinely prescribed for anxiety disorders.

Benzodiazepines may be useful as an adjunctive therapy early in treatment for acute crises. Due to concerns about tolerance, dependency, sedation, cognitive impairment, and other side effects, benzodiazepines should be restricted to short-term use. They should be used with caution, especially with patients with a history of substance use disorder. Patients should also be warned about the safety risks of driving and using benzodiazepines (i.e. drowsiness, reduced concentration). Older adults may be at increased risk of falls and fractures and memory impairment with benzodiazepines. Except for alprazolam (which may be harder to discontinue), short-acting agents are preferable to long-acting agents.

Talking tips
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Talking tips5

  • If we are to start [benzodiazepine name], it would only be for a short time, until the effects of the [antidepressant/anti-anxiety medication name] are seen.
  • This is because [benzodiazepine name] can cause more long-term side effects, including fatigue, addiction, and difficulty with thinking clearly, learning and remembering.

Medication counselling

The idea of starting a medication can cause anxiety for some patients. This can be compounded by the fact that medication side effects can make patients feel worse before there is an expected benefit.1 Options to address anxiety related to medications include:5

  • Provide information about the recommended treatment option(s) verbally and in writing.
  • Probe for questions or concerns.
  • If appropriate, the patient may want time to process the information before proceeding.
  • Provide choice (e.g., treatment type, initiation timing, follow-up timing). If the patient is struggling to make decisions due to their underlying condition, consider limiting the number of options and adjusting this approach based on clinical judgement.

Before starting a treatment, discuss the following with the patient, and if desired, their family or caregiver(s):1-5,9

Medication option(s)
Expected benefit(s) of the particular medication
Overall plan to “start low and go slow” to the “target” dose
Onset of action
  • Depression: 2-4 weeks1
  • Anxiety: 2-8 weeks7
Full effect(s)
  • Depression: 4-8 weeks4,5
  • Anxiety: 6-12 weeks or more3,7
  • Older adults may take longer to respond9
Talking tips
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Talking tips3,5

Onset of effect

  • It may take ___ weeks [depression: 2-4; anxiety: 2-8] to notice some improvement with medication. This is partly because we are starting with a small dose of ___ mg to make sure it’s a good fit for you.
  • The full benefits will come after you’ve been taking the “target” dose or ___ mg of the medication. Because of this, it may take a total of ___ weeks [depression: 4-8 weeks; anxiety: 6-12 weeks] to notice the full effect.

Duration

  • Studies have shown that people do best if they continue medication for __ [depression: 6-9 months from the time they are feeling better; anxiety: 12-24 months]. After that, many people can work with their healthcare provider to reduce the dose of medication over a month or two and eventually stop taking it.
  • It is important not to stop taking the medication “cold turkey” because you may experience withdrawal symptoms. We can work together to reduce the dose over time so this is less likely to happen.
Cost/coverage of the treatment
  • Understand your patient’s access to private health insurance
  • Reach out to drug companies to inquire about their compassionate use programs
  • Connect your patient with Ontario Works and Ontario Disability Support Program for financial assistance with drug coverage
Side effects/risks of treatment and how to manage
  • Common side effects that are likely to go away within a week or two of each dose change (e.g., GI upset, sedation, increased anxiety, sleeping difficulties). See Side effect management.
  • Serious side effects (e.g., serotonin syndrome, unmasking bipolar disorder, neuroleptic malignant syndrome,  hyponatremia)
Follow-up and monitoring
  • Why regular monitoring is needed
  • Options for monitoring, as appropriate (i.e., phone call, virtual, in person, support staff)
  • Frequency of follow-up. See Follow-up/monitoring for the overall approach
  • How to self-monitor (e.g., keep track of symptoms and feelings in a mood diary)
  • Contingency plans if additional support is needed between appointments
Treatment duration
  • Depression: 6-9 months after symptom remission1
  • Anxiety: 12-24 months7
Precautions
  • SSRIs have been associated with thoughts of suicide or self-harm early on in treatment for a small number of people under the age of 30. Discuss & create a safety plan.
  • Caution with driving until impact on the central nervous system (CNS) is known (e.g., sedation, cognitive impairment).
  • Caution with other CNS-active substances: alcohol, cannabinoids, over-the-counter (OTC) products, etc.
  • Ask a pharmacist to confirm any known interactions with herbal treatments.
  • Avoid abrupt discontinuation due to risk of withdrawal symptoms.

Side effect management1, 5

Medication side effects can lead to significant distress and treatment discontinuation. In extreme cases, these negative experiences may impact a patient’s consideration of another medication or their relationship with their healthcare provider and the healthcare system. Side effects should be discussed with patients before treatment initiation. Consider booking a follow-up appointment within 2 weeks of initiation to discuss side effect management.

Troubleshooting side effects1, 5
  • Consider whether the symptom is a side effect vs the underlying condition or improvement of the condition being treated
  • Switch the time of day taken
  • Consider taking the medication with food 
  • Treat the side effect if short-term
  • Titrate more slowly (and do so in the future too)
  • Lower the dose
  • Consider drug interactions
  • Switch medications (see first-line medications options table)
  • Consult a pharmacist or expert as needed
  • Pharmacogenetic testing (if available) may be considered if patients have severe side effects to multiple medications.
Talking tips
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Talking tips5

  • Are there side effects that you are worried about?
  • Some people have side effects for the first few weeks of starting or increasing the dose of their medication. This is why we start with a low dose and increase the dose if and when you are comfortable.
  • The most common side effects are _____.  For many people, these will settle out as their body gets used to the medication.
  • I’ll give you some information to help lower the chances of side effects and some tips for how to deal with the side effects. Sometimes, it is as easy as taking with food or switching the time of day that you take the medication. Your pharmacist may have ideas to help.
  • We can touch base often to adjust the medication and see how it is working for you.

Specific side effect management for symptoms1, 5

Short-term or long-term: usually short-term

Management:

  • Take with food
  • Consider alternate dose timing
  • Eat smaller, more frequent meals
  • Drink plenty of fluids
  • Switch to another medication or use a long-acting formulation
  • Short-term use of OTC antacids or antinauseants

Short-term or long-term: usually short-term

Management:

  • Take with food
  • Ensure hydration
  • Consider alternate dose timing
  • Short-term use of loperamide

Short-term or long-term: usually short-term

Management:

  • Ensure hydration
  • Regular exercise
  • Dietary fibre and laxatives may be used

Short-term or long-term: long-term

Management:

  • Confirm not due to increased appetite with treatment of mental health condition
  • Diet and exercise
  • Switch medication if not manageable

Short-term or long-term: Usually short-term

Management:

  • Consider dosing at bedtime
  • Brief nap during the day
  • Dose reduction
  • Switch medication if not manageable

Short-term or long-term: Usually short-term

Management:

  • Consider dosing at morning
  • Avoid caffeinated food or drinks later in the day
  • Regular exercise several hours before bedtime
  • Sleep hygiene
  • Switch medication if not manageable

Management:

  • Consider dosing at morning

Short-term or long-term: usually short-term

Management:

  • Consider dosing in morning
  • If agitation/anxiety occur further dose increases should be done with caution
  • If agitation/anxiety are bothersome or not resolving, consider alternative agents
  • The risks & benefits of short-term benzodiazepines may be considered for SSRI-related activation in select patients with anxiety.7 See “role of benzodiazepines for anxiety disorders”. Consider consulting an expert

Short-term or long-term: short or long-term

Management:

  • Confirm not due to underlying condition(s)
  • Wait and watch for improvement
  • Take a once-daily dose after sexual activity
  • Lower the dose
  • Switch medication if not manageable (switch to bupropion or mirtazapine)
  • Conflicting evidence for adjunct bupropion

Short-term or long-term: usually short-term

Management:

  • Consider switching dose timing

Short-term or long-term: long-term

Management:

  • Ensure hydration
  • Reduce dose or consider switching medications

Short-term or long-term: short or long-term

Management:

  • Exercise and outdoor activities
  • Diet and exercise
  • Work with a therapist
  • Reduce dose or consider switching medications

Short-term or long-term: short or long-term

Management:

  • Provide education on how to identify and manage
  • Keep a glass of water at the bedside to drink when waking
  • Get up gradually from sitting or lying down
  • Perform leg pumps before getting up
  • Reduce dose or consider switching medications31

Short-term or long-term: short-term

Management:

  • Sip water regularly
  • Chew sugarless gum or suck on sugarless candy/ice
  • Avoid tobacco, alcohol and caffeinated beverages
  • Breathe through nose
  • Dental hygiene
  • Reduce dose or switch medication if not manageable
  • Use an OTC artificial saliva product

Warnings and precautions

An association with falls and fractures has been noted for patients taking SSRIs long-term. The risk of fractures has been noted to be elevated in the first 6 weeks of treatment.1

Management: Provide education and strategies to lower the general risk as relevant for the patient.5

SSRIs have been associated with an increased risk of upper GI bleeding, especially in older adults, patients with a history of GI bleeding and patients taking other agents that may increase risk (e.g., non-steroidal anti-inflammatory drugs, steroids).

Management: Educate regarding this potential side effect and consider a gastroprotective agent if an SSRI is chosen for these patients.1, 2

 

Older adults may be at a higher risk of hyponatremia with SSRIs.1

Management: Caution when using with older adults and in patients taking other agents that lower sodium. Consider baseline serum sodium levels and repeat at 2-4 weeks. Thereafter repeat yearly or as appropriate.5

In the absence of known risk factors, the risk of Torsades de Pointes (TdP) is very low.1 However, when other risk factors exist, the risk of TdP may occur at even low therapeutic doses of antidepressants and has even occurred with QTc intervals within the normal range.1

Management: For QT-prolonging antidepressants, request an ECG if the patient has risk factors, such as a history of Tdp, arrhythmias, chronic kidney disease and age.5

While serotonin syndrome is rare, it can occur in cases of overdose or when multiple serotonergic agents are used (e.g., SSRIs, SNRIs, TCAs, tramadol, OTC products).1

Serotonin Syndrome Patient handout from UWaterloo Pharmacy 5-in5

Management: Particular caution should be taken when changing or adding another serotonergic agent, especially if the agent being discontinued has a long half-life (e.g., fluoxetine).8 Educate the patient and monitor for signs and symptoms.5

SSRIs have been associated with thoughts of suicide or self harm early on in treatment in a small number of people under the age of 30. Weekly monitoring should be employed with treatment initiation until the condition has stabilized.. Discuss and create a safety plan.1 See “Emergency Support and Suicide Prevention” in the Assessment section.

Special populations

Peri/post natal

This section pertains to patients who develop depression or anxiety while trying to conceive or who are pregnant or breastfeeding. This section excludes patients who have postpartum depression. At the time of pregnancy, all medications should be reviewed (i.e., by a peripartum psychiatrist). Patients who are already receiving SSRI treatment should not be taken off of their treatment medication(s) when they become pregnant.5  A shared decision-making approach should consider the risks and benefits of pharmacological management, including the risks of not treating. In cases of high risk or uncertainty, there should be a low threshold for referral to an expert for support (OTN eConsult).

Psychological management

Anxiety

  • Despite the lack of data on the efficacy of psychological interventions in perinatal patients with anxiety disorders, CBT or behavioural therapy are considered safe alternatives during pregnancy.7

Depression (excluding postpartum depression)

  • For patients who wish to become pregnant, are pregnant, or are breastfeeding, depression-focused psychological interventions alone are recommended. Depending on the severity of symptoms, depression-focused psychological interventions should be considered the first-line treatment.
  • First-line treatment for mild to moderate antenatal depression: CBT or IPT.1
Pharmacological management

Anxiety and Depression (excluding postpartum depression)

Before prescribing medication, weigh the risks of pharmacological treatment to the fetus and newborn against the potential risks of untreated anxiety and depression.1,7 Refer to the LactMed® database for information on exposure to medications and during lactation. Refer to Medicines in Pregnancy for information on exposure to medications during pregnancy.

Special considerations:

  • In pregnant patients, if pharmacological treatment is indicated, citalopram, escitalopram, and sertraline are preferred second-line treatments after CBT or IPT.1 Valproate and paroxetine must not be used.7,10
  • Empower patients and encourage them to think about their treatment as an important element of their health and wellness and their child’s.5
  • In breastfeeding patients, if pharmacological treatment is indicated, sertraline or paroxetine are preferred. Despite the limited evidence, the excretion of such prescription medication in breast milk results in very low amounts being transferred to the baby and few isolated instances of adverse events.7
  • Refer to the pharmacy with a prescription, noting that the patient is breastfeeding and request that they be counselled.5 
  • St. John’s Wort must not be used in pregnant and breastfeeding women.10

Depression (excluding postpartum depression)

  • First-line treatment for severe antenatal depression: pharmacological treatment, either alone or in combination with CBT or IPT.1

Older Adults

Depression and anxiety disorders are commonly present simultaneously present among patients aged 65 or older.7 Determine the onset of depression. Late-onset depression is more chronic with a higher relapse rate and higher levels of medical comorbidity, cognitive impairment and mortality.1 Monitor cognition at the initial assessment and over time. Late-onset depression might be an early symptom of dementia.1

Medications and risks
Before prescribing medication, weigh the risks associated with antidepressant use against their potential benefits.

Consider pharmacokinetic changes with aging and patient factors such as hepatic and renal function and body mass. Also consider comorbidities and the use of other medications which could increase the risk of side effects (e.g., anticholinergic, sedation, orthostatic hypotension, and neurological effects).1, 7, 30

Due to these pharmacokinetic changes, including an increased risk of  impaired balance and falls early in treatment, initiate older adults at a low dose and increase doses slowly with regular follow-up.30

When prescribing an SSRI or SNRI, patients should be screened for hyponatremia. A serum level should be obtained before starting medication if there is a positive history. In general, a serum sodium level should be done within 2-4 weeks of initiating an SSRI or SNRI.32

Risks: 

  • Increased susceptibility to adverse drug events and drug-drug interactions7
  • Increased risk of  impaired balance and falls early in treatment30
  • Increased risk of fractures7
  • Increased risk of mortality in older patients with dementia7
  • Increased risk of rare side effects such as bone loss, serotonin syndrome, extrapyramidal side effects, and neuroleptic malignant syndrome1
Psychological management

Anxiety (the efficacy of psychological and pharmacological treatments is similar)7

  • Relaxation training
  • CBT (with learning- and memory-aids)
  • Supportive therapy
  • Cognitive therapy
  • Exercise for prevention7

Depression (excluding postpartum depression)

  • Problem-solving theray: discrete, time-limited, structured psychological intervention that focuses on learning to cope with specific problem areas and where therapist and patient work collaboratively to identify and prioritize key problem areas.10
  • Interventions that reduce social isolation and loneliness (e.g., reminiscence therapy, physical exercise programs, video conferences with family, horticultural therapy and gender-based social groups)32
  • Social prescribing (referring patients with social, emotional and practical needs to local, non-clinical services typically from the voluntary or community sectors)32
  • Increased physical activity (e.g., Fountain of Health)32
Pharmacological management

Anxiety (efficacy of psychological and pharmacological treatments is similar)28

Medication has similar effectiveness as in younger adults.7

  • For GAD: pregabalin (significant improvements), duloxetine, venlafaxine, citalopram, escitalopram, sertraline (more effective than CBT at 1-year follow-up), buspirone, fluvoxamine.7
  • For panic disorder: paroxetine (as effective as CBT), citalopram, escitalopram, fluvoxamine, and mirtazapine (for older adults with major depressive disorder).7

Depression (excluding postpartum depression)

  • First-step: duloxetine, mirtazapine, sertraline, venlafaxine, and vortioxetine.1 Of these agents, sertraline and duloxteine are preferred. Escitalopram and citalopram are useful options as well, but must be balanced with concerns around QTc prolongation.32
  • Second-step (if multiple first-step treatments are ineffective): switch to bupropion, fluoxetine, paroxetine,or quetiapine.1

Follow-up/monitoring New

Jump to:

Depression

Overall approach

Follow-up frequency for patients using pharmacological treatment:4 

  • First 6 weeks OR until response and tolerability are established: at least every 2 weeks
  • After 6 weeks OR after response and tolerability are confirmed: every 4 weeks
Ongoing treatment options 

Treatment response:
At least a 50% reduction in the patient’s baseline score on a validated depression rating scale indicates early improvement/response to antidepressant treatment. The evidence is mixed regarding the benefits of switching at 2-4 weeks for non-response to the first antidepressant tried.1 Whereas symptom remission is when the patient’s score is in the nondepressed range.1

Partial or non-response:1, 5, 28
Ask: Is the treatment being taken as prescribed?

  • No: explore reasons why not and provide support. Adjust treatment plan if needed
  • Yes: 
    • Consider:
      • Is the diagnosis correct?
      • Factors that may complicate response (e.g., social factors, comorbid conditions, drug interactions)
    • Consider increasing the dose of medication if:
      • The target dose has not been reached
      • The medication is being tolerated well
      • This is not the first medication tried
      • Functional deficit and symptoms are mild (no urgency for effect)
      • The patient is comfortable with increasing the dose
    • Note: less frequent dose increases may be preferable for patients who are anxious or medically compromised 
    • Review opportunities to switch to, intensify, or add non-pharmacological treatment, including psychological interventions, exercise and light therapy. See Psychological treatment options for depression.
    • If the above options not preferred, an adjunctive medication or medication switch can be considered as follows:1,5
Adjunct

When to consider:

  • Not the first antidepressant tried
  • Tolerated well
  • >25% improvement on symptom scale
  • Urgency for efficacy (severe symptoms)
  • Additional symptoms that could be addressed by an additional drug
  • The patient prefers to add-on

Advantages

  • Fast onset for effectiveness
  • More convenient to start
  • Easier for a provider to implement
  • Able to target symptoms not fully addressed

Disadvantages

  • Higher CNS load
  • Risk of additive side effects
  • High interaction risk
  • Likely less convenient overall (2 drugs)
  • Possibly higher cost
  • Less certainty of effect
  • Harder to discontinue (2 drugs)
Switch

When to consider:

  • First antidepressant tried
  • Bothersome side effects
  • <25% improvement on symptom scale
  • No urgency for efficacy
  • No additional symptoms being targeted
  • The patient prefers to switch

Advantages

  • Lower overall CNS load
  • Low interaction risk (high to start)
  • Likely more convenient overall (1 drug)
  • Possibly lower cost
  • More certainty of effect
  • Easier to discontinue (1 drug)

Disadvantages

  • Slow onset for effectiveness
  • Risk of additive side effects
  • Risk of withdrawal 
  • Less convenient to start
  • Harder for a provider to implement

*For the initial antidepressant trial. In subsequent trials, lack of response (<25% improvement) may not be a factor for choosing between switch and adjunctive strategies

First-line adjunctive medications options for depression1,27,29,33-35

The evidence and recommendations for adjunctive treatment strategies are mixed and must be balanced with the risk of adding an additional medication.1,28 The following medications are considered first line adjunctive agents in the CANMAT 2015 MDD Guidelines.1 Other options include an alternative class of antidepressant.6,28 Consider patient and medication factors in the approach to adjunct medication selection. If you have questions about adjunctive medications, consult a pharmacist or specialist through eConsult.

The evidence and recommendations for augmentation strategies are mixed and must be balanced with the risk of adding an additional medication.1, 28 Consider patient and medication factors in the approach to adjunct medication selection.

***Click to view*** first-line adjunctive medication options in table format.

Atypical antipsychotics1,5,33–35
Scroll (left-right) for details
  • Atypical antipsychotics
    Aripiprazole (Abilify®)

    2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg tablet

    Coverage

    • ODB ✓
    • NIHB ✓

    Cost for usual dose ($/100 days)

    • $96-146

    Interaction risk

    • ++

    Characteristics to consider

    • May be activating or sedating
    • May cause impulse control disorders (e.g., problem gambling) or complex sleep-related behaviours
    • Useful if there is comorbid psychosis
    View dosing, side effects and warnings
    Close

    Aripiprazole (Abilify®)

    Dosing
    • Initial: 2-5 mg daily
    • Titration: Increase gradually by ≤ 5 mg daily, at intervals of ≥ 1 week
    • Usual: 5-15 mg daily
    • Max: 15 mg daily
    Side effects
    • CNS: insomnia, agitation, dizziness, headache, sleep apnea, complex sleep-related behaviours
    • GI: nausea, diarrhea
    • Anticholinergic: constipation, dry mouth
    • CV: orthostatic hypotension
    • Neurologic: extrapyramidal symptoms (EPS; akathisia, parkinsonism), tremor
    • Dermatologic: severe cutaneous adverse reactions
    • Other: nasopharyngitis
    Warnings
    • Stroke risk in elderly with dementia
    • QTc prolongation
    • Neuroleptic malignant syndrome (NMS)
    • Impulse control disorders (e.g., problem gambling)
  • Atypical antipsychotics
    Quetiapine (Seroquel®)

    IR: 25 mg, 100 mg, 150 mg, 200 mg, 300 mg tablet
    XR: 50 mg, 150 mg, 200 mg, 300 mg, 400 mg tablet

    Coverage

    • ODB ✓
    • NIHB ✓

    Cost for usual dose ($/100 days)

    • $40-115 (IR)
    • $62-114 (XR)

    Interaction risk

    • +++

    Characteristics to consider

    • May be helpful for insomnia (balance this with the risk of daytime sedation)
    • QTc prolongation risk
    • Causes more orthostatic hypotension, anticholinergic effects, metabolic effects and weight gain than aripiprazole or risperidone
    • May have an antiemetic effect
    • Cataract risk (eye exams at baseline and every 6 months)
    • Useful if there is comorbid psychosis
    View dosing, side effects and warnings
    Close

    Quetiapine (Seroquel®)

    Dosing
    • Initial: 50 mg daily
    • Titration: Initial dose may be doubled daily until usual/max dose achieved
    • Usual: 150-300 mg per day
    • Max: 300 mg daily

    (BID for IR and once daily for XR)’

     

    Side effects
    • CNS: sedation, dizziness, headache, sleep apnea
    • Anticholinergic: constipation, gastric or urinary retention
    • CV: orthostatic hypotension, tachycardia
    • Neurologic: EPS
    • Dermatologic: severe cutaneous adverse reactions
    • Metabolic: increased risk of diabetes and dyslipidemia, may reduce thyroid hormone levels, hepatic transaminase elevation, weight gain
    • Urogenital: sexual dysfunction
    Warnings
    • Stroke risk in elderly with dementia
    • QTc prolongation
    • NMS
    • Possible increased risk of cataracts
  • Atypical antipsychotics
    Risperidone (Risperdal®)

    0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg tablet
    1 mg/mL oral solution
    0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg orally disintegrating tablet (ODT)

    Coverage

    • ODB ✓
    • NIHB ✓

    Cost for usual dose ($/100 days)

    • $30-74 (tablets)
    • $85-238 (oral solution)
    • $64-172 (ODT)

    Interaction risk

    • ++

    Characteristics to consider

    • May be activating or sedating
    • Lower risk of QTc prolongation vs. quetiapine at therapeutic dose
    • Causes more ESP than aripiprazole or quetiapine
    • Risk of floppy iris syndrome after cataract surgery
    • Useful if there is comorbid psychosis
    View dosing, side effects and warnings
    Close

    Risperidone (Risperdal®)

    Dosing
    • Initial: 0.5 mg/day
    • Titration: Increase over 3 weeks to target 1-2mg daily. May be increased to 3 mg if response to 2 mg is inadequate.
    • Usual: 1-3 mg daily
    • Max: 3 mg daily
    Side effects
    • CNS: insomnia, agitation, anxiety, dizziness, headache
    • GI: nausea, dyspepsia, vomiting, abdominal pain
    • Anticholinergic: constipation
    • CV: orthostatic hypotension
    • Neurologic: EPS
    • Dermatologic: severe cutaneous adverse reactions
    • Metabolic: increased risk of diabetes and dyslipidemia
    • Urogenital: sexual dysfunction
    • Other: dose-related hyperprolactinemia, rhinitis
    Warnings
    • Stroke risk in elderly with dementia
    • QTc prolongation
    • NMS
    • Risk of intraoperative floppy iris syndrome in patients undergoing cataract surgery
Guidance for switching medications

Drug selection:

There is a paucity of evidence to guide whether to switch to an alternate first-line drug within the same class versus switching to a different class of first-line medication after the first medication is tried.1

Consider:

  • Reasons for switching (e.g., tolerability or lack of effect)
  • Specific features of alternate options as they pertain to your patient’s clinical picture

Cross-tapering:

Due to the risk of additive side effects, serotonin syndrome, withdrawal effects and drug interactions, consider asking a pharmacist or clinical expert for support with cross-tapers.5

Cross-tapers may occur over weeks or months depending on several factors, including:5

  • How long has the patient been taking the medication?
  • Urgency of completing the cross taper (e.g., severity of mental health condition and side effects)?
  • What is the risk of destabilizing the mental health condition with changes based on the patient’s clinical factors?
  • What is the half-life of the drug involved?
  • What is the propensity for withdrawal effects with the medications involved?
  • What is the risk of side effects with the new medication?
  • What drug interactions may impact the taper?
  • What is the patient’s preference?

Putting it into practice:5

  • Develop a plan with the patient. Consider including an expert in pharmacological treatment options (e.g., pharmacist, mental health expert).
  • Discuss the risks and benefits of the plan with the patient 
  • Provide the cross-taper plan in writing. 
  • Provide guidance for side effect management of the new medication and any potential withdrawal effects of the medication being stopped (see discontinuation and withdrawal symptoms) if relevant.
  • Discuss serotonin syndrome symptoms if multiple serotonergic medications are involved in the cross-taper (see warnings and precautions: serotonin syndrome under side effect management).
  • Follow-up within 1 week of each dose change to review side effects and symptoms.

Anxiety

Overall approach
Ongoing treatment options

Response:

Continue treatment7

Partial or non-response:3, 5, 7

Ask: Is the treatment being taken as prescribed?

  • No: explore reasons why not and provide support. Adjust treatment plan if needed
  • Yes: 
    • Review options for intensifying psychological treatment 
    • Consider increasing the dose of medication to condition-related target* if:
      • The target dose has not been reached
      • The medication is being tolerated well
      • This is not the first medication tried
      • Functional deficit and symptoms are mild (no urgency for effect)
      • The patient is comfortable with increasing the dose
    • If increasing is not preferred, switching to an alternate medication is recommended (see guidance for switching medications).

*While initial medication dosing for anxiety is often lower than dosing for depression, the usual and maximum doses for anxiety are sometimes higher than those used for depression (see drug cards).

Adjunctive treatment is generally reserved for second-line management after multiple first-line agents have been tried.7 A clinical expert should be consulted in cases where second-line treatment or second-line adjunctive therapy is being considered.3

Duration of pharmacological treatment

Anxiety17

  • GAD: Treatment should be continued for at least one to two years to maintain symptom remission and prevent relapse.
  • Panic Disorder: Review with the patient every 8-12 weeks.2
    • Optimal treatment duration is not well defined8
    • Consider a minimum continuation for 6 months after remission and up to a year. Avoidance behaviour should be resolved before the medication is withdrawn and relapse of avoidance behaviours should be monitored.
    • Long-term treatment can be considered – weighing the risks and benefits.
Discontinuation guidance

Due to the risk of withdrawal symptoms, the dose of medication should generally be gradually reduced over an extended period. This may be weeks, months, or even years, depending on the duration of treatment, the medication involved, and patient factors.5

If a medication is being stopped to switch to another antidepressant due to lack of effectiveness or side effects, dose reductions may be done more quickly (e.g., over days). Symptoms emerging during the transition period may be due to either discontinuation/withdrawal effects OR side effects to the new medication.

A pharmacist or mental health expert can be helpful in providing guidance as it relates to the individual drug and patient. 

The website Medstopper.com offers advice regarding tapering plans and possible withdrawal symptoms. 

Putting it into practice:5

  • Develop a plan with the patient. Consider including an expert in pharmacological treatment options (e.g., pharmacist, mental health expert).
  • Discuss the risks and benefits of the plan with the patient. 
  • Provide the plan and withdrawal symptom management information in writing.
  • Follow-up within 1-2 weeks of each dose change to review withdrawal effects and emerging mental health symptoms.

Discontinuation & withdrawal symptoms for anxiety and depression

Discontinuation & withdrawal symptoms8

Symptoms29

  • Flu-like symptoms (e.g., malaise, headache, fatigue, chills, sweating, tremor, loss of appetite)

Management5

Provide reassurance and support to patients, including but not limited to:

  • Symptom management
  • Additional follow-up
  • Pause, adjust, or stop the tapering plan according to patient preference
  • Arranging contingency plans for subsequent dose reductions

In some cases, it may be helpful to:

  • Increase the dose of the medication
  • Consult an expert for further advice  (e.g., cross-taper, managing discontinuation symptoms, etc.)

Symptoms29

  • “Electric shock sensations” (especially with SNRIs), paresthesias, numbness, blurred vision, palinopsia, auditory disturbances

Management5

Provide reassurance and support to patients, including but not limited to:

  • Symptom management
  • Additional follow-up
  • Pause, adjust, or stop the tapering plan according to patient preference
  • Arranging contingency plans for subsequent dose reductions

In some cases, it may be helpful to:

  • Increase the dose of the medication
  • Consult an expert for further advice  (i.e., cross-taper, managing discontinuation symptoms, etc.)

Symptoms29

  • Light-headedness, dizziness, vertigo

Management5

Provide reassurance and support to patients, including but not limited to:

  • Symptom management
  • Additional follow-up
  • Pause, adjust, or stop the tapering plan according to patient preference
  • Arranging contingency plans for subsequent dose reductions

In some cases, it may be helpful to:

  • Increase the dose of the medication
  • Consult an expert for further advice  (i.e., cross-taper, managing discontinuation symptoms, etc.)

Symptoms29

  • Nausea, vomiting, diarrhea

Management5

Provide reassurance and support to patients, including but not limited to:

  • Symptom management
  • Additional follow-up
  • Pause, adjust, or stop the tapering plan according to patient preference
  • Arranging contingency plans for subsequent dose reductions

In some cases, it may be helpful to:

  • Increase the dose of the medication
  • Consult an expert for further advice  (i.e., cross-taper, managing discontinuation symptoms, etc.)

Symptoms29

  • Insomnia, nightmares, excessive dreaming

Management5

Provide reassurance and support to patients, including but not limited to:

  • Symptom management
  • Additional follow-up
  • Pause, adjust, or stop the tapering plan according to patient preference
  • Arranging contingency plans for subsequent dose reductions

In some cases, it may be helpful to:

  • Increase the dose of the medication
  • Consult an expert for further advice  (i.e., cross-taper, managing discontinuation symptoms, etc.)

Appendix: complementary therapies and natural health products New

Jump to:

Complementary therapies and self management

Considerations for complementary and alternative medicine (CAM):5

Patient values and wishes are a priority in treatment selection. While there is evidence for some types of CAM, as with any treatment, the potential for harm must be considered.

Consider the advantages:

  • Patient places high value on treatment
  • Likelihood of the treatment addressing factors related to the patient’s symptoms
  • Evidence for treatment

Consider the disadvantages:

  • Cost
  • Risk of negative impact 

Talk to patients about complementary therapies that can help alleviate symptoms of anxiety and depression.1, 4, 5

  • Exercise 
    • First-line monotherapy for mild to moderate depression
    • Second-line adjunctive therapy for moderate to severe depression
    • Typical or studied dose and duration: at least 30 minutes of moderate-intensity exercise at least 3 times weekly for a minimum of 9 weeks is considered effective.
  • Light therapy 
    • First-line monotherapy for seasonal depression
    • Second-line adjunctive therapy or monotherapy for moderate to severe depression
    • Typical or studied dose and duration: Standard protocol is 10,000 lux (light intensity) for 30 minutes per day during the early morning for up to 6 weeks. A response is usually seen within 1 to 3 weeks.
  • Yoga 
    • Second-line adjunctive therapy for mild to moderate depression
    • Typical or studied dose and duration: At least 2 to 4 sessions a week over 2 to 3 months. 
  • Sleep hygiene
    • Recommended habits and  practices of maintaining a regular sleep schedule: avoiding excess eating, drinking, or smoking before going to sleep and establishing a proper sleep environment. 
  • Nutrition
    •  Maintaining a healthy, balanced diet and correcting any  nutritional deficiencies.

Other complementary therapies1

  • Acupuncture
    • Third-line adjunctive therapy for mild to moderate depression
    • Typical or studied dose and duration: typically 20 to 30 minutes in session duration, and ranging from 10 to 30 sessions, decreasing in frequency over time from daily to weekly intervals

Natural health products (NHPs) 1, 36

Considerations for NHPs:
A pharmacist can support you and patients in navigating herbal treatments. Some general considerations include the following:

  • Is it a quality product?
  • Is there a potential for harm?
    • Risk of bleeding and liver damage are the most common warnings for herbal products (direct to evidence resources).
  • Is there a potential for drug interactions? (e.g., St. John’s Wort)
  • How many ingredients are listed?
    • Products with more than one ingredient have a higher risk of interactions and side effects.
  • How much does the product cost?
  • Is there evidence of the product’s efficacy?
Talking tips
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Talk tips

Herbal Products5

  • There are many products that are safe, and some have been studied for mental health.
  • Even though herbal products are natural, they may have side effects, interfere with your medications and may not be safe for you.
  • A rule of thumb is to find a product with only one ingredient and “NPN” or Natural Product Number. Having one ingredient makes the product less likely to interfere with other medications or include things that are not safe for you. The Natural Product Number means that the company has proven to Health Canada that the product has passed safety standards and is what it claims to be.
  • Talk to your pharmacist to confirm that the natural product is a good fit for you.
  • St. John’s Wort 
    • First-line monotherapy for mild to moderate depression.
    • Typical or studied dose and duration: formulations of SJW have varied widely, as has the dose range (500 to 1800 mg/day), while treatment duration has spanned 4 to 12 weeks
    • Use caution when recommending St. John’s Wort. It can cause many side effects, including gastrointestinal issues, headaches, skin irritation, photosensitivity and dry mouth. There is a concern that higher potency extracts may interfere with the metabolism of various medications, including antidepressants. St. John’s Wort should not be used in pregnant or breastfeeding individuals
  • Omega-3  (e.g. eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA]) 
    • Second-line monotherapy or adjunctive therapy for mild to moderate depression
    • Typical or studied dose and duration: 3 to 9 g/day of o-3 or 1 to 2 g of EPA plus 1 to 2 g of DHA per day. Duration of treatment ranges from 4 to 16 weeks
  • SAM-e (s-adenosyl-L-methionine) 
    • Second-line adjunctive therapy for mild to severe depression
    • Typical or studied dose and duration: dose range of 800 to 1600 mg/day given in divided doses with meals over 4 to 12 weeks
  • Acetyl-L-carnitine
    • Third-line monotherapy for mild to moderate depression
    • Typical or studied dose and duration: N/A
  • Crocus sativus (saffron)
    • Third-line monotherapy or adjunctive therapy for mild to moderate depression
    • Typical or studied dose and duration: 20 to 30 mg/day over 6 to 8 weeks
  • DHEA
    • Third-line monotherapy for mild to moderate depression
    • Typical or studied dose and duration: doses ranges from 30 to 450 mg/day, with treatment lasting 6 to 8 weeks
  • Folate
    • Third-line adjunctive for mild to moderate depression
    • Typical or studied dose and duration: 1,000 mcg (typical upper limit for ages 19+)37
  • Lavandula (lavender)
    • Third-line adjunctive mild to moderate depression
    • Typical or studied dose and/or duration: 2 to 4.5 mL/day (alcoholic tincture 1:2) or 6 to 12 mL/day (alcoholic tincture 1:5). It has only been studied as a short-term acute intervention in the short term (4-8 weeks).
    • Adverse effects of Lavandula include nausea, confusion and mild headaches

NHPs not recommended:1

  • Inositol
  • Tryptophan 
  • Rhodiola rosea (roseroot)

References New

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    NICE. Generalised anxiety disorder and panic disorder in adults: management | Guidance | NICE [Internet]. NICE; 2011 [cited 2023 Feb 10]. Available from: https://www.nice.org.uk/guidance/cg113

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