Section: A B C D E F G Resources References

Treatment of Adult Major

Depressive Disorder (MDD) Tool
This tool is designed to support primary care providers in the treatment of adult patients (≥ 18 years) who have major depressive disorder
(MDD). MDD is the most prevalent depressive disorder, and approximately 7% of Canadians meet the diagnostic criteria every year.1,2 The
treatment of MDD involves psychotherapy and/or pharmacotherapy. Providers should work with patients to create a treatment plan
together using providers’ clinical expertise and keeping in mind the patient’s preferences, as well as the practicality, feasibility, availability
and affordability of treatment.

TABLE OF CONTENTS

pg. 1 Section A: Overview of MDD pathway pg. 6 Section E: Complementary and alternative medicine
pg. 2 Section B: Assessing suicidality and managing pg. 7 Section F: Follow-up and monitoring
suicide-related behaviour
pg. 9 Section G: Special patient populations
pg. 3 Section C: Psychotherapy options
pg. 10 Resources
pg.3 Section D: Pharmacotherapy management

SECTION A: Overview of MDD pathway

Patient has suspected depression

Talking Points

It is important to provide your patient with non-judgmental care (e.g. “Being

Consider unexpected life events (e.g. death in the family, diagnosed with depression is nothing to be ashamed of, it is very common and
change in family status, financial crisis). Consider special many adults are diagnosed with it every year”)
patient populations. • Don’t use clinical/psychiatric language (e.g. “mental health,” “psychiatric,”
and/or “maladaptive”) unless the patient uses these terms first

• Use understandable language for cognitive distortions (e.g. “assumption”

Screen the patient using the PHQ-93 for depression which covers many cognitive distortions, “thought trap” instead of rumination)

• Use positive language, and maintain a focus on your patient’s strengths

• Avoid stigmatizing labels (e.g. “abnormal”, “unusual”)

• Talk about symptoms instead of disorders/diagnoses

PHQ-9 Scores of > 5
PHQ-9 (a score of
0-4 does not meet
Mild Moderate Severe
criteria for MDD)
(score 5-9) (score 10-14) (score >14)
Conduct Diagnostic Work-up Treat the cause of secondary
Yes
• Rule out causes of secondary MDD and other disorders
MDD by considering testing
for B-12 deficiency, CBC, folic
Set EMR reminders Conduct Risk Assessment
No acid deficiency, corticosteroid
to follow-up at Is the patient at immediate risk medication, hypothyroidism and
the patient’s next of harm to self and/or others? Use syphilis
appointment to see the CEP’s Keeping Your Patients • Rule out comorbid alcohol5 and Confirm the diagnosis of MDD
if their PHQ-9 score Safe: A Guide to Primary Care No
substance use disorder6 using the DSM-V criteria*
changes. Management of Mental Health • Rule out bipolar disorder7
and Addictions-related Risks and
• Assess if patient has a sleeping
Functional Impairments4 tool to disorder8
assess the patient.
• Rule out other chronic diseases

Yes

Create a safety plan with lower risk patients.

Consult the Asessing suicdality and managing suicide-related behaviour
section. Proceed with the following sections: Psychotherapy options,
Advise your patient, their family, caregivers and friends to
Pharmacotherapy management , Complementary and alternatives medicine.
call 911 or get them to the nearest Emergency Department
Consult the Asessing suicdality and managing suicide-
related behaviour section for more information.

Refer to Follow-up and Monitoring

* A DSM-V score of > 5 with symptoms during the same two week period that are a change from the previous functioning. Depressed Mood (Q1) and/or loss of
interest/pleasure (Q2) must be present9

November 2019 cep.health/major-depressive-disorder Page 1 of 12

 Section: A B C D E F G Resources References

SECTION B: Assessing suicidality and managing suicide-related behaviour

Suicidal thoughts, plans, and attempts are very common among people with MDD.10 Every clinical encounter with a patient that has MDD
should include an assessment of suicide risk.10
Assess if a patient is at risk of suicide or developing suicidal thoughts by using the Columbia-Suicide Severity Rating Scale (C-SSRS)

In case of an emergency: Talking Points

• Advise your patient, their family, caregivers and friends to call 911
or go to the Emergency Department • Use active listening: involves receiving a message,
processing it, and sending it back.
• Consult the CEP’s Keeping Your Patients Safe on how to complete a
• Remember that your patient is the expert on their
Form 1, if you believe that your patient is at immediate risk of harming
own experience.
themselves or others

• Schedule periodic follow-up appointments to track your patient’s progress and assess their well-being
• Monitor the presence and strength of the patients’ protective factors4
• Create a safety plan with lower-risk patients
• Help your patient identify the nearest distress centre11 Basic components of a safety plan
Work with your patient to develop a safety plan that they can use when in crisis.

Safety plan12 1. Recognize warning signs that are proximal to an impending suicidal crisis.

Having a safety plan in place is important for both patients 2. Identify and employ internal coping strategies without needing to contact another person.
and providers as it: 3. Use contacts with people as a means of distraction from suicidal thoughts and
• Facilitates honest communication between patient and urges (e.g. going to healthy social settings without discussing suicidal thoughts).
provider 4. Contact family members or friends who may help to resolve a crisis and with
• Establishes a collaborative relationship between patient whom suicidality can be discussed.
and provider 5. Contact mental health professionals or agencies.
• Facilitate the patient’s active involvement 6. Reduce the potential use of lethal means.
• Enhances patient’s commitment to treatment See Keeping Your Patients Safe and Portico for more information

Click here to access a safety plan template

SECTION C: Psychotherapy options

When selecting a specific type of

psychotherapy consider the patient’s
Talking Points
treatment goals and preferences (e.g.
group or individual therapy), whether the Set realistic expectations when initiating treatment
patient has had a prior positive response to
• “If you stick to your treatment, you should feel better than you do now. It’s also okay if you don’t
psychotherapy treatment and if providers feel better right away. We can help to eventually make your life feel easier.”
skilled in the preferred psychotherapy
• “Recovery will have its ups and downs.”
approach are available.
• “People who stick to their treatment plan are the ones who see the most improvement over
time. So, we are going to work together to make sure that happens.”
The stepped care approach:
Start with the least intrusive form of Provide your patient with adequate support
care and progress to more intensive • “Depression is a common experience, you’re not alone in this. It takes a lot of strength to seek
care if needed. support.”

First-line psychotherapy options

Mild to Moderate 13,14 Severe 13,14

• Cognitive-behavioral therapy (CBT) It is suggested to offer a combination of both psychotherapy (see Mild
to Moderate for first-line psychotherapy options) and pharmacotherapy
• Interpersonal psychotherapy (IPT)
(see SECTION D: Pharmacotherapy management) for patients with severe
• Behavioral therapy/behavioral activation (BT/BA) forms/presentations of MDD.
• Acceptance and commitment therapy (ACT) For additional help, consult specialists across the province to provide the
• Mindfulness-based cognitive therapy (MBCT) best care possible for patients with complex MDD at OTN eConsult15 and
• Problem-solving therapy (PST) the Collaborative Mental Health Network (CMHN).16

Refer to ConnexOntario for Addiction, Mental Health, and Problem

Gambling Treatment Services.

For more details on psychotherapy options and second-line treatments please see Appendix A
November 2019 cep.health/major-depressive-disorder Page 2 of 12
 Section: A B C D E F G Resources References

SECTION D: Pharmacotherapy management

The medications listed below (organized by drug class), are all equal in efficacy and in evidence.17,18 The selection of a first-line
antidepressant is dependent on the following considerations:

Patient: Medication:
• Clinical features and dimensions (refer to Appendix F) • Comparative efficacy
• Comorbid conditions • Comparative tolerability warnings, contraindications and
precautions
• Response and side effects of previous use of antidepressants
• Potential interactions with other medications (refer to Appendix E)
• Patient preference
• Simplicity of use
• Cost and availability

First-line antidepressants 17,19

Drug Class Antidepressant Formulations Dosage Side Effects Warnings, Contraindications and
Precautions

DAA Bupropion 100 mg and 150 SR formulation (doses >150 • Agitation • Contraindicated in seizure disorders
mg tablet mg/day PO should be given • Insomnia • Contraindications for any patient
Product monograph in divided doses): • Anorexia undergoing abrupt discontinuation of
for SR51 Initial: 150 mg/day PO alcohol49
Usual: 150–300 mg/day PO
Product monograph • There is an increased risk of seizure
High: 375–450 mg/day PO
for XL52 in patients with anorexia nervosa or
XL formulation (given once
bulimia49
daily):
Initial: 150 mg/day PO • Contraindications for any patient
Usual: 150–300 mg/day PO undergoing abrupt discontinuation
High: 450 mg/day PO of alcohol

SM Vortioxetine 5 mg, 10 mg, Initial: 5–10 mg daily PO • Nausea

15 mg, 20 mg Usual: 10–20 mg daily PO • Constipation
Product monograph53 tablet • Vomiting
Transient symptoms associated with abrupt
discontinuation include:
• Headache
• Increased dreaming
• Mood swings
• Muscle tension
• Vertigo
• Rhinorrhea

SNRI Desvenlafaxine 50 and 100 Initial: 50 mg daily PO • Nausea

mg extended- Usual: 50 mg daily PO • Sleep disturbance
Product monograph 54 release tablet High: 100 mg daily PO • Drowsiness
• Nervousness
• Dizziness
• Dry mouth

Duloxetine 30 mg and 60 Initial: 60 mg daily PO • Nausea • Do not use in patients with severe
mg delayed- Usual: 60 mg daily PO • Drowsiness renal impairment (ClCr <30 mL/min)
Product monograph55 release capsule High: 120 mg/day PO • Insomnia • QT interval at doses beyond 120mg
• Dizziness BID is prolonged
If necessary, for tolerability, • Dry mouth
may start with 30 mg/day and
increase to 60 mg in 1–2 wk

Venlafaxine 37.5 mg, 75 mg, Initial: 37.5–75 mg/day PO • Nausea • Can prolong the QTc interval at a dose
150 mg capsule Usual: 112.5–225 mg/day PO • Sleep disturbance of 450 mg/day (given as 225 mg twice
Product monograph56 High: 300–375 mg/day PO • Drowsiness a day)43
• Nervousness
• Dizziness
• Dry mouth
• Dose-related hypertension rarely occurs,
particularly at doses ≥225 mg/day

November 2019 cep.health/major-depressive-disorder Page 3 of 12

 Section: A B C D E F G Resources References

SECTION D: Pharmacotherapy management (continued)

First-line antidepressants 17,19 (continued)

Drug Class Antidepressant Formulations Dosage Side Effects Warnings, Contraindications and
Precautions

SSRI* Citalopram 10 mg, 20 mg, Initial: 10–20 mg/day PO • Nausea • Increased risk of GI bleeding, SIADH
40 mg tablet Usual: 20–40 mg/day PO • Dry mouth • Dose-dependent QT interval
Product monograph57 High: 40 mg/day PO19 • Sleep disturbance prolongation that is clinically
• Somnolence significant with the 60 mg daily dose37
Increase as needed by 20 mg • Sweating
daily, at intervals of ≥1 wk39 • Sexual dysfunction

Escitalopram 10 mg and 20 Initial: 10 mg/day PO • Nausea • Increased risk of GI bleeding, SIADH

mg tablet Usual: 10–20 mg/day PO • Dry mouth • Dose-dependent QTc prolongation
Product monograph58 High: 20 mg/day PO • Sleep disturbance
• Somnolence
Increase as needed by 5–10 • Sweating
mg daily at intervals of ≥1 wk39 • Sexual dysfunction

Fluoxetine 10 mg and 20 Initial: 10–20 mg/day PO • Nausea • Increased risk of GI bleeding

mg capsule Usual: 20–40 mg/day PO • Nervousness
Product monograph59 High: 60–80 mg/day PO • Anorexia
• Insomnia
• Sexual dysfunction

Fluvoxamine 50 mg and 100 Initial: 50–100 mg/day PO • Nausea • Increased risk of GI bleeding
mg tablet Usual: 150–200 mg/day PO • Drowsiness
Product monograph 60
High: 300 mg/day PO • Sweating
• Anorexia
Increase as needed by 50 mg • Sexual dysfunction
daily every 3–4 days39

Paroxetine, 12.5 mg, 25 mg Initial: 12.5–25 mg/day PO • Nausea • Increased risk of GI bleeding
Controlled-Release controlled- Usual: 25–50 mg/day PO • Drowsiness
release tablet High: 75 mg/day PO • Fatigue
Product monograph61 • Sweating
Increase as needed by 12.5 mg • Constipation
daily at intervals of ≥1 wk39 • Dry mouth
• Dizziness
• Sexual dysfunction

Paroxetine, 10 mg, 20 mg, Initial: 10–20 mg/day PO • Nausea • Increased risk of GI bleeding
Immediate-Release 30 mg, 40 mg Usual: 20–40 mg/day PO • Drowsiness
immediate- High: 60 mg/day PO • Fatigue
Product monograph62 release tablet • Sweating
Increase as needed by 10 mg • Constipation
daily at intervals of 1–2 wk39 • Dry mouth
• Dizziness
• Sexual dysfunction

Sertraline 25 mg, 50 mg, Initial: 25–50 mg/day PO • Nausea • Increased risk of GI bleeding
100 mg capsule Usual: 50–100 mg/day PO • Tremors
Product monograph 63
High: 150–200 mg/day PO • Diarrhea
• Dry mouth
Increase as needed by 25 mg • Sexual dysfunction
daily at intervals of ≥1 wk39

Tetracyclic Mirtazapine 15 mg, 30 mg, Initial: 15–30 mg/day PO • Weight gain • The risk of QT prolongation and/or
antidepressant 45 mg tablet Usual: 30–45 mg/day PO • Sedation ventricular arrhythmias (e.g. Torsades
Product monograph 64
High: 60 mg/day PO de Pointes) may be increased with
concomitant use of medicines that
prolong the QTc interval42

Bolded = covered by Ontario Drug Benefit18

Legend
PO = oral administration
DAA=Dual Action Antidepressants
SSRI=Selective Serotonin Reuptake Inhibitors
SNRI=Serotonin-Norepinephrine Reuptake Inhibitors
SM = Serotonin Modulators

* Avoid combined use with drugs associated with prolonged QTc interval19
For details on drug interactions, please see Appendix E
For more details on second-line pharmacotherapy options please see Appendix B

November 2019 cep.health/major-depressive-disorder Page 4 of 12

 Section: A B C D E F G Resources References

SECTION E: Complementary and alternative medicine

Complementary and alternative medicine (CAM) treatments are a group of diverse medical and health care systems, practices and
products that are not generally considered part of conventional medicine.20 Patients may prefer CAM treatments due to fewer side effects,
lower costs, precived efficacy and empowerment. CAM treatments may be appropriate for patients with mild MDD while pharmacological
and psychological treatments remain the first-line interventions for moderate to severe MDD. The following is presented as guidance for
clinicians when considering CAM treatments in the context of individual patients and not as standards of care.20

Exercise St. John’s wort

Monotherapy Monotherapy
First-line for Mild and Moderate First-line for Mild and
MDD Moderate MDD
Second-line for Severe MDD Second-line for Severe MDD
Administration: Administration:
30 minutes of moderate- Formulations of SJW have
intensity exercise at least 3 varied widely, as has the dose
times weekly for a minimum of range (500 to 1800 mg/day),
9 weeks is considered effective. while treatment duration has
spanned 4 to 12 weeks.

Light therapy Omega-3 SAM-e Yoga

Monotherapy or adjunctive Monotherapy or adjunctive Adjunctive Adjunctive
Second-line for Mild, Moderate Second-line for Mild, Moderate Second-line for Mild, Moderate Second-line for Mild, Moderate
and Severe MDD and Severe MDD and Severe MDD and Severe MDD
Administration: Administration: Administration: Administration:
The standard protocol is 10,000 The typical dose range is 3 to Oral (over-the-counter): 800 – Duration varies, averaging 2-4
lux (light intensity) for 30 9 g/day of 0-3 or 1 to 2 g of EPA 1600 mg/day given in divided sessions a week over a course
minutes per day during the plus 1 to 2 g of DHA per day. doses with meals over 4-12 of 2-3 months.
early morning for up to 6 weeks. Duration of treatment ranges weeks.
from 4 to 16 weeks.
Intravenous and intramuscular
formulations: SAM-e, at doses
of 200 to 400 mg/day across
2 to 8 weeks, which may
be more effective than oral
supplements.

Table adapted from the Canadian Network for Mood and Anxiety Treatments (CANMAT). 2016 Clinical Guidelines for the Management of Adults with Major
Depressive Disorder: Section 5. Complementary and Alternative Medicine Treatments. 2016. 20

Caution: St. John’s wort 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. 20

November 2019 cep.health/major-depressive-disorder Page 5 of 12

 Section: A B C D E F G Resources References

SECTION F: Follow-up and monitoring

Functional outcomes of treatment

Recovery from depression includes both symptom relief and improved functioning.17 After achieving symptom remission, treatment is
recommended to be maintained for 6-9 months. Use clinical expertise and consider patient’s life events before determining tapering and/
or stopping treatments. Unless there are clinical reasons otherwise, it is recommended to slowly taper patients off antidepressants over
several weeks to avoid discontinuation syndrome. It is helpful to explain to patients what to watch out for once they have discontinued
antidepressants (e.g. flu-like symptoms, insomnia, nausea and imbalance). If symptoms persist or are worrisome the patient should contact
their providers.

Inadequate treatment response pathway

In patients who have not achieved remission on the highest tolerated dose after two weeks of confirmed adherence, it is recommended to
switch to another monotherapy (medication or psychotherapy) or augment with a second medication or psychotherapy. Use the pathway
below to determine next steps.

Response

Use the PHQ-9 to

assess severity of
depression

Improved PHQ-9
score after 2 weeks
of confirmed
adherence to
antidepressant? Risk factors for recurrence:
• Frequent, recurrent
No Yes episodes
Continue treatment
• Severe episodes
for 6-8 weeks Maintain treatment
No (psychosis, severe
for 6-9 months impairment, suicidality)
• Chronic episodes
• Presence of comorbid
Yes
Risk factors for Yes
Maintain treatment psychiatric or other
Symptom remission?
recurrence? for 2 years or longer medical conditions
• Presence of residual
symptoms
No
• Difficult-to-treat episodes
If symptoms do not improve, add
Partial an adjunctive medication.
response (>25% Refer to first-line adjunctive
improvement)* medications for options.
Optimize by
increasing
dose if not
at maximum
dosage (every 2 If symptoms do not improve,
weeks) switch medications.
No response
(<25% For early treatment resistance,
improvement)* consider adjunctive use
of psychological and
neurostimulation treatments.
Refer to switching antidepressants
for options.

Effect

*For chronic (characterized as MDD with duration greater than two years)13 and resistant (treated with, but failed to respond to, at least
four adequate medication and/or ECT treatment regimens)13 depressions, consider: (1) a chronic disease approach, with less emphasis
on symptom remission and more emphasis on improvement in functioning and quality of life; and, (2) larger evaluation periods for
improvement.
For early treatment-resistant patients, consider switching to an antidepressant with superior efficacy or use other medications adjunctively.17

November 2019 cep.health/major-depressive-disorder Page 6 of 12

 Section: A B C D E F G Resources References

SECTION F: Follow-up and monitoring (continued)

Switching antidepressants
Considering switching to another antidepressants when:
• It is the first antidepressant trial (in subsequent trials lack of response may not be a factor for choosing between switching and adding
adjunctive medications)
• There is failure of one or more antidepressants (in this case, consider switching to a second- or third-line antidepressant)
• There are poorly tolerated side effects to the initial antidepressant. Work with your patient to see if they can try to tolerate the side
effects for one to two weeks to see if they disappear or are no longer problematic before switching
• There is more time to wait for a response (less severe, less functional impairment)
• Patient prefers to switch to another antidepressant

Options Antidepressants with

Level of Evidence
When considering switching to another antidepressant, there is not enough Superior Efficacy
of a difference in efficacy between antidepressants to make a decision on this Escitalopram ••••
factor alone. When initially selecting an antidepressant base it on tolerability
first but if there is no improvement, consider switching to a different Mirtazapine ••••

antidepressant. There has been some Meta-analysis on a few antidepressants Sertraline ••••
that suggest there may be a very slight difference in efficacy. When switching,
Venlafaxine ••••
you may want to consider these medications with a slightly better efficacy.
Citalopram •••

Recommendations for adjunctive medications17

Consider adding an adjunctive medication to your patient’s treatment when:
• There have been two or more antidepressant trials
• The initial antidepressant is well-tolerated
• There are specific residual symptoms or side effects to the initial antidepressant that can be targeted
• There is less time to wait for a response (more severe, more functional impairment)
• Patient prefers to add on another medication

First-line adjunctive medications

Adjunctive Level of
Dosing Adverse Effects
Agent Evidence

Aripiprazole •••• 2-15 mg EPS (akathisia, parkinsonism), dizziness, orthostatic hypotension, headache, GI complaints, nasopharyngitis, tremor,
sedation, insomnia19

Quetiapine •••• 150-300 mg Sedation, dizziness, weight gain, orthostatic hypotension, hepatic transaminase elevation, headache,
anticholinergic effects, increased risk of diabetes and dyslipidemia, possible increased risk of cataracts. May reduce
thyroid hormone levels19

Risperidone •••• 1-3 mg Sedation, headaches, weight gain, orthostatic hypotension, rhinitis, anxiety, dose-related hyperprolactinemia, EPS.
Risk of intraoperative floppy iris syndrome in patients undergoing cataract surgery who have been exposed to
risperidone19

Consider consulting with a pharmacist before initiating adjunctive medication.

For second-line adjunctive medications, see Appendix C

Level of evidence:
• • • • = Meta-analysis with narrow confidence intervals and/or 2 or more RCTs with adequate sample size, preferably placebo-controlled,
• • • = Meta-analysis with wide confidence intervals and/or 1 or more RCTs with adequate sample size,
• • = Small-sample RCTs or nonrandomized, controlled prospective studies or case series or high-quality retrospective studies,
• = Expert opinion/consensus

November 2019 cep.health/major-depressive-disorder Page 7 of 12

 Section: A B C D E F G Resources References

SECTION G: Special patient populations

Antenatal and postpartum MDD

For pregnant and postpartum women use the Edinburgh Postnatal Depression Scale (EPDS)35 to screen for depression.

Although postpartum psychosis is rare, women with this disorder may have homicidal impulses toward the newborn. Careful
assessment of homicidal and suicidal ideation, as well as intention and plans are important. Postpartum psychosis must always
be treated as a psychiatric emergency, with hospitalization considered for the safety of the mother and baby.14

For women who wish to become pregnant, are pregnant, or are breastfeeding, depression-focused psychotherapy alone is recommended.
Depending on the severity of symptoms, depression-focused psychotherapy should be considered as the first option.14 Most medications can be
safely used by breastfeeding mothers. Consider all risks and benefits of pharmacotherapy for both mother and baby before prescribing medication.

First-line treatment options for antenatal MDD

Mild to Moderate21 Severe*

• CBT (individual or group) • Pharmacotherapy is the first-line treatment, either

alone or in combination with CBT or IPT 21
• IPT (individual or group)
Specialists are available across the province to
provide the best care possible for your patients at
OTN eConsult15 and the Collaborative Mental Health
Network (CMHN)16

First-line treatment options for postpartum MDD

Mild to Moderate21 Severe*

• CBT (individual or group) • Pharmacotherapy should be used first-line, with or

without psychotherapy21
• IPT (individual or group)
• Citalopram

• Escitalopram

• Setraline21

Specialists are available across the province to provide

the best care possible for your patients at OTN eConsult15
and the Collaborative Mental Health Network (CMHN).16

For second-line treatment options for antenatal and for postpartum MDD please see Appendix D

*Electroconvulsive therapy (ECT) can be an effective treatment for severe MDD in pregnant
and postpartum patients who:
1) have psychotic features;
2) treatment-resistant patients; and,
3) who elect to use this modality as a matter of preference.14,21
Weigh the risks and benefits of ECT with pregnant patients before recommending treatment.

• Valproate and paroxetine must not be used in pregnant women13,22

• St John’s Wort must not be used in pregnant or breastfeeding women13

Consult Resources for antenatal and postpartum MDD at the end of this tool

November 2019 cep.health/major-depressive-disorder Page 8 of 12

 Section: A B C D E F G Resources References

SECTION G: Special patient populations (continued)

Older Adults
Late-life depression (LLD) can be defined as MDD occuring in adults 60 years and older. It is important to differentiate early adult-onset
(MDD) depression recurring in late life from late-onset depression21. For older adults use the Geriatric Depression Scale (GDS) to screen for
depression.
• Check the patient’s family history, consult patient’s family or caregiver to provide input on their cognition and conduct assessments
to rule out dementia

• Use the Montreal Cognitive Assessment (MoCA) or Mini-Mental State Exam (MMSE) to asses the patient

• The MoCA Clinic and Institute recommends to complete the MoCA Training & Certification Program46 before providers administer,
interpret and score test results to avoid misdiagnosis and liability.25

• Start at the lowest possible dose of an antidepressant and increase dose as needed (See Section D: Pharmacotherapy management for
first-line antidpressants and Appendix B: Pharmacotherapy options for second-line antidepressants tables for recommended dosages)

• Monitor sodium level closely when starting or changing dosages in older adults 25

According to the 2019 American Geriatric’s Society Beers Criteria: antipsychotics, mirtazapine,
SNRIs, SSRIs and TCA are to be used with caution in the older adult population because it may
exacerbate or cause SIADH or hyponatremia.25

Mild to Moderate13,21 Severe21

• ACT • Bupropion
• BT/BA • Citalopram/escitalopram
• Bupropion • Desvenlafaxine
• Citalopram/escitalopram • Mirtazapine*
• CBT • Sertraline
• Desvenlafaxine • Venlafaxine
• IPT • Vortioxetine
• MBCT Specialists are available across the province
• Mirtazapine* to provide the best care possible for your
patients at OTN eConsult15 and the Collaborative
• PST Mental Health Network (CMHN).16
• Sertraline
• Venlafaxine
• Vortioxetine

For second-line treatment options see Appendix D

Patients on Tamoxifen
Patients with MDD that are being treated for breast cancer with Tamoxifen should Moderate inhibitors that impart lesser degrees of inhibi-
not be prescribed antidepressants that inhibit CYP2D6 (buproprion, duloxetine, tion and are reasonable alternatives:26,28
fluoxetine, paroxetine) because it will decrease the efficacy of the breast cancer
• Sertraline • Doxepin
treatment.26
• Citalopram • Venlafaxine
• Escitalopram
For women already taking tamoxifen and other medications (e.g. aromatase
inhibitors)27 with a known CYP2D6 inhibitor, any change in antidepressant
treatment should be gradual to minimize the risks of SSRI withdrawal and
adverse effects commonly seen on initiation of treatment.26

November 2019 cep.health/major-depressive-disorder Page 9 of 12

 Section: A B C D E F G Resources References

RESOURCES

Resources for providers

[I] Columbia-Suicide Severity Rating Scale - Provides suggested probes to understand the presence and severity of an individual’s suicidal ideation.
Ultimately, the determination of the presence of suicidal ideation or behavior depends on the judgment of the individual administering the scale:
https://www.integration.samhsa.gov/clinical-practice/Columbia_Suicide_Severity_Rating_Scale.pdf
[II] Centre for Effective Practice - Keeping Your Patients Safe: A Guide to Primary Care Management of Mental Health and Addictions-related Risks and
Functional Impairments tool https://cep.health/clinical-products/adult-mental-health/
[III] Provides mindfulness-based cognitive therapy (MBCT), mindfulness-based stress reduction (MBSR), mindful selfcompassion (MSC) and specialized
mindfulness training to the general public https://www.mindfulnessstudies.com/
[IV] Medical calculators, equations, scores, and guidelines at MDCalc https://www.mdcalc.com/
[V] Ontario College of Family Physician’s (OCFP) Collaborative Mental Health Network (CMHN): https://www.ontariofamilyphysicians.ca/education/
collaborative-mentoring-networks/collaborative-mental-health-network
[VI] Ontario Drug Benefit formulary search: https://www.formulary.health.gov.on.ca/formulary/
[VII] OTN eConsult: https://otn.ca/providers/
[VIII] SwitchRx - aims to provide healthcare professionals with the most current and useful information to guide their clinical practice when adjusting their
patient’s psychotropic treatment regimens: https://switchrx.ca/
[IX] RxFiles - antidepressant comparison chart: https://www.rxfiles.ca/RxFiles/uploads/documents/members/cht-Psyc-Antidepressant.pdf

Resources for patients, their family, caregivers and friends

Information on depression
[X] Greenspace - Connects people with therapists across Ontario: https://www.greenspacehealth.ca/patients/
[XI] Canadian Mental Health Association brochure on depression: https://cmha.ca/wp-content/uploads/2015/12/Depression-and-Bipolar-NTNL-brochure-2014-web.pdf
[XII] Here - Resource on helping patients manage their depression: https://www.heretohelp.bc.ca/managing-depression
[XIII] Informed Choices About Depression: Information about depression and treatments for depression: https://depression.informedchoices.ca/fact-sheets/
[XIV] Centre for Clinical Intervention resource on helping patients understand and work through their depression: https://www.cci.health.wa.gov.au/Resources/
Looking-After-Yourself/Depression
Online therapy
[XV] BounceBack Ontario - Guided self-help program grounded in cognitive behavioural therapy designed to help adults manage symptoms depression.
Involves 6 telephone sessions with trained coaches who lead the patient through a series of workbooks. Cost is free. Patient is contacted within 5 business
days of referral to schedule first appointment. Referral or patient self-referral is required: https://bouncebackontario.ca
[XVI] Centre for Mindfulness Studies: Provides mindfulness-based cognitive therapy (MBCT), mindfulness-based stress reduction (MBSR), mindful self-
compassion (MSC) and specialized mindfulness training to the general public. Available from: https://www.mindfulnessstudies.com/
[XVII] Headspace - An online site for meditation: https://www.headspace.com/
[XVIII] Mindshift app - This app uses scientifically proven strategies based on Cognitive Behavioural Therapy (CBT) to help you learn to relax and be mindful,
develop more effective ways of thinking, and use active steps to take charge of your anxiety. Available on the App Store and Google Play
[XIX] Moodgym - A 5-module online cognitive behavioural therapy program for depression. Cost is $39 AUD for 12 month access: https://moodgym.com.au/
Support groups and wellness services
[XX] Canadian Mental Health Association (CMHA) - Locate your local CMHA for mental health support services and programs: https://cmha.ca/find-your-cmha
[XXI] Mood Disorders Association of Ontario - Provides free support programs to people across Ontario, and their families, who are living with depression:
https://www.mooddisorders.ca/
[XXII] Thought Spot app - Provides a live map for easily identifying and accessing health, mental health and wellness services in the Greater Toronto Area.
Available on the App Store and Google Play
Suicide prevention
[XXIII] Canadian Association for Suicide Prevention - Tips on how to identify suicidal thoughts and tips for the patient’s loved ones or caregivers: https://
suicideprevention.ca/im-concerned-about-someone
[XXIV] Distress and Crisis Ontario (DCO) - DCO have distress centres that provide a listening ear for lonely, depressed, and/or suicidal people, usually 24 hours a
day, 7 days a week. Many centres also have Suicide Survivor programs, support services for youth, telephone call out programs for seniors and vulnerable
people, mental health Crisis Lines services and much more: http://www.dcontario.org/about.html
[XXV] ReMinder Suicide Safety Plan app - Helps you to create a simple suicide safety plan, that can be accessed at any time on your phone. Available on the App
Store and Google Play
[XXVI] Portico Network - This toolkit includes information, resource and tools to support clinicians in providing comprehensive care to clients and patients who
demonstrate suicide-related behaviour: https://www.porticonetwork.ca/web/opop/tools/suicide-risk-assessment-toolkit

Resources for antenatal and postpartum MDD

[XXVII] e-lactancia - Is a resource to check the compatibility of medications whilst breastfeeding: http://e-lactancia.org/
[XXVIII] LactMed - Is a database that contains information on drugs and other chemicals to which breastfeeding mothers may be exposed: https://toxnet.nlm.
nih.gov/newtoxnet/lactmed.htm
[XXIX] Infant Risk Centre - Is a leading resource on the safety of medications during pregnancy and lactation: https://www.infantrisk.com/
[XXX] Medications and Mother’s Milk - Online reference for evaluating medication use in breastfeeding mothers. Cost is $59.99 USD for 12 month access:
https://medsmilk.com/
[XXXI] SickKids - Is accepting referrals to the Motherisk Clinic from health-care providers. The Motherisk Clinic is a specialized referral-only service that assesses
the safety of medications and/or substances consumed by pregnant or nursing women and the potential effects on their babies. Health-care providers can
continue to send referrals through EpicCareLink: http://www.sickkids.ca/HealthcareProfessionalsandStudents/Referring-a-Patient/index.html

November 2019 cep.health/major-depressive-disorder Page 10 of 12

 Section: A B C D E F G Resources References

References
[1] American College of Phsyicians. Nonpharmacologic Versus Pharmacologic [29] Centre for Addiction and Mental Health. Cognitive behavioural therapy
Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice an information guide. 2010. [cited 2019 June 13]. Available from: https://
Guideline From the American College of Physicians. 2016. [cited 2019 May 24]. www.camh.ca/-/media/files/guides-and-publications/cbt-guide-en.
Available from https://annals. org/aim/fullarticle/2490527/nonpharmacologic-versus- pdf?la=en&hash=BDA5FF472AA16E82C6AAE307EBCD3BE50347FBFE
pharmacologic-treatment-adult- patients-major-depressive-disorder-clinical [30] Canadian Network for Mood and Anxiety Treatments (CANMAT). 2016 Clinical
[2] Health Quality Ontario. Quality Standards Major Depression: Care for Adults and Guidelines for the Management of Adults with Major Depressive Disorder: Section 2.
Adolescents. [cited 2019 April 26]. Available from: https://www.hqontario.ca/portals/0/ Psychological Treatments. 2016. [cited 2019 April 26]. Available from: https://www.ncbi.
documents/evidence/quality-standards/qs-depression-clinical-guide-1609-en.pdf nlm.nih.gov/pmc/ articles/PMC4994791/pdf/10.1177_0706743716659418.pdf
[3] MD Calc. PHQ-9 (Patient Health Questionnaire-9). [cited 2019 July 3]. Available from: [31] Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe
https:// www.mdcalc.com/phq-9-patient-health-questionnaire-9 G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer
[4] Centre for Effective Practice. Keeping Your Patients Safe: A Guide to Primary DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients
Care Management of Mental Health and Addictions-related Risks and Functional requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006
Impairments. 2017. [cited 2019 August 10]. Available from: https://cep.health/media/ Nov;163(11):1905-17. [cited 2019 September 26]
uploaded/CEP_MHA_ V1.pdf [32] RxTx. Lithium. 2014. [cited 2019 August 17].
[5] Alcohol Use Disorders Identification Test (AUDIT)-C. [cited 2019 September 26]. [33] RxTx. Alertec. 2015. [cited 2019 August 15].
Available from: https://www.integration.samhsa.gov/images/res/tool_auditc.pdf [34] National Institute for Health and Care Excellence (NICE). Depression in adults:
[6] National Institute on Drug Abuse (NIDA). Substance Use—Adult (adapted from the recognition and management. 2009; partially updated 2018. [cited 2019 May 30].
NIDA- Modified ASSIST). [cited 2019 September 26]. Available from: https://www. Available from: https:// www.nice.org.uk/guidance/cg90
psychiatry.org/ psychiatrists/practice/dsm/educational-resources/assessment- [35] Edinburgh Postnatal Depression Scale (EPDS). [cited 2019 August 20]. Available from:
measures#Disorder https://www.fresno.ucsf.edu/pediatrics/downloads/edinburghscale.pdf
[7] The Standards for Bipolar Excellence (STABLE) National Coordinating Council Resource [36] Mayo Clinic. Depression Medication Choice. [cited 2019 June 1]. Available from: https://
Toolkit Workgroup. Stable Resource Toolkit. [cited 2019 September 26]. Available from: shareddecisions.mayoclinic.org/decision-aid-information/decision-aids-for-chronic-
https://www.integration.samhsa.gov/images/res/STABLE_toolkit.pdf disease/depression-medication-choice/
[8] PROMIS Health Organization (PHO) and PROMIS Cooperative Group. Sleep [37] U.S. Food and Drug Administration (FDA). FDA Drug Safety Communication: Revised
Disturbance— Adult (PROMIS—Sleep Disturbance— Short Form). [cited 2019 recommendations for Celexa (citalopram hydrobromide) related to a potential risk of
September 26]. Available from: https://www.psychiatry.org/psychiatrists/practice/dsm/ abnormal heart rhythms with high doses. 2017. [cited 2019 September 10]. Available
educational-resources/ assessment-measures#Disorder from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-
[9] MD Calc. DSM-5 Criteria for Major Depressive Disorder. [cited 2019 May 1]. Available communication- revised-recommendations-celexa-citalopram-hydrobromide-related
from: https://www.mdcalc.com/dsm-5-criteria-major-depressive-disorder [38] MD Calc. Columbia Suicide Severity Rating Scale (C-SSRS Screener). [cited 2019 July 10].
[10] Canadian Network for Mood and Anxiety Treatments (CANMAT). 2016 Clinical Available from: https://www.mdcalc.com/columbia-suicide-severity-rating-scale-c-ssrs
Guidelines for the Management of Adults with Major Depressive Disorder: Section 1. [39] RxTx. Selective Serotonin Reuptake Inhibitors (SSRIs). 2014. [cited 2019 August 12].
Disease Burden and Principles of Care. 2016. [cited 2019 April 26]. Available from: https://
[40] RxTx. Bupropion. 2017. [cited 2019 June 20].
www.ncbi.nlm.nih. gov/pmc/articles/PMC4994789/pdf/10.1177_0706743716659416.pdf
[41] RxTx. Cymbalta. 2019. [cited 2019 August 11].
[11] Government of Ontario. Health Care Options. [cited 2019 September 10]. Available from:
https://www.ontario.ca/locations/health/ [42] RxTx. Remeron. 2019. [cited 2019 August 30].
[12] Rudd MD, Mandrusiak M, Joiner Jr. TE. The case against no-suicide contracts: The [43] RxTx. Effexor. 2018. [cited 2019 September 1].
commitment to treatment statement as a practice alternative. Journal of Clinical [44] RxTx. Tricyclic Antidepressants. 2018. [cited 2019 August 18].
Psychology. 2006 Feb;62(2):243–51. [45] Canadian Association for Suicide Prevention. Directory. [cited 2019 September 24].
[13] U.S. Department of Veterans Affairs and Department of Defense (VA/DoD). Available from: https://suicideprevention.ca/need-help/
Management of Major Depressive Disorder (MDD). 2016. [cited 2019 May 1]. Available [46] Montreal Cognitive Assessment (MOCA). Training & Certification. [cited 2019 September
from: https://www. healthquality.va.gov/guidelines/MH/mdd/ 24]. Available from: https://www.mocatest.org/training-certification/
[14] American Psychiatric Association (APA). Practice guideline for the treatment of [47] BMJ Best Practice. Depression in adults. 2019. [cited 2019 September 26].
patients with major depressive disorder, third edition. 2015. [cited 2019 May 28].
[48] National Institute of Mental Health. Suicide Prevention. [cited 2019 September 26].
Available from: https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/
Available from: https://www.psychiatry.org/File%20Library/Psychiatrists/Practice/DSM/
guidelines/mdd.pdf
APA_DSM5_Level-2-Sleep-Disturbance-Adult.pdf
[15] Ontario Telemedicine Network. eConsult. [cited 2019 June 10]. Available from: https://
[49] DynaMed. Naltrexone/Bupropion. [cited 2019 September 26].
otn. ca/providers/
[50] UpToDate. Tricyclic and tetracyclic drugs: Pharmacology, administration, and side
[16] Ontario College of Family Physicians. Collaborative Mental Health Network. [cited
effects. 2019. [cited 2019 September 26].
2019 August 3]. Available from: https://www.ontariofamilyphysicians.ca/education/
collaborative- mentoring-networks/collaborative-mental-health-network [51] Valeant Canada LP. Wellbutrin® SR Product Monograph. [cited 2019 October 13].
Available from: https://pdf.hres.ca/dpd_pm/00038603.PDF
[17] Canadian Network for Mood and Anxiety Treatments (CANMAT). 2016 Clinical
Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. [52] Valeant Canada LP. Wellbutrin® XL Product Monograph. [cited 2019 October 13].
Pharmacological Treatments. 2016. [cited 2019 April 26]. Available from: https://www. Available from: https://pdf.hres.ca/dpd_pm/00039160.PDF
ncbi.nlm.nih.gov/pmc/ articles/PMC4994790/pdf/10.1177_0706743716659417.pdf [53] Food and Drug Administration. Brintellix (vortioxetine) tablets, for oral use. [cited
[18] Ontario Drug Benefit Formulary. [cited 2019 August 20]. Available from: https://www. 2019 November 25]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/
formulary.health.gov.on.ca/formulary/ label/2013/204447s000lbl.pdf

[19] RxTx. Depression. 2017. [cited 2019 April 28]. [54] Food and Drug Administration. Pristiq® (desvenlafaxine) Extended-Release Tablets,
oral. [cited 2019 October 13]. Available from: https://www.accessdata.fda.gov/
[20] Canadian Network for Mood and Anxiety Treatments (CANMAT). 2016 Clinical
drugsatfda_docs/label/2012/021992s030lbl.pdf
Guidelines for the Management of Adults with Major Depressive Disorder: Section
5. Complementary and Alternative Medicine Treatments. 2016. [cited 2019 April [55] Food and Drug Administration. Cymbalta (duloxetine hydrochloride) Delayed-Release
26]. Available from: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC4994794/ Capsules for Oral Use. [cited 2019 October 13]. Available from: https://www.accessdata.
pdf/10.1177_0706743716660290.pdf fda.gov/drugsatfda_docs/label/2010/022516lbl.pdf

[21] Canadian Network for Mood and Anxiety Treatments (CANMAT). 2016 Clinical [56] Food and Drug Administration. Effexor - venlafaxine hydrochloride. [cited 2019
Guidelines for the Management of Adults with Major Depressive Disorder: Section October 13]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/
6. Special Populations: Youth, Women, and the Elderly. 2016. [cited 2019 April label/2008/020151s051lbl.pdf
26]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994788/ [57] Food and Drug Administration. Celexa® (citalopram hydrobromide). [cited 2019
pdf/10.1177_0706743716659276.pdf October 13]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/
[22] Kurlowicz L. The Mini Mental State Examination (MMSE). 1999. [cited 2019 September 1]. label/2009/020822s037,021046s015lbl.pdf
Available from: https://cgatoolkit.ca/Uploads/ContentDocuments/MMSE.pdf [58] Food and Drug Administration. Lexapro® (escitalopram oxalate) Tablets Lexapro®
[23] Sherry A. The Geriatric Depression Scale (GDS). 2019. [cited 2019 May 28]. Available from: (escitalopram oxalate) Oral Solution. [cited 2019 October 13]. Available from: https://
https://consultgeri.org/try-this/general-assessment/issue-4.pdf www.accessdata.fda.gov/drugsatfda_docs/label/2017/021323s047lbl.pdf

[24] Montreal Cognitive Assessment (MOCA). [cited 2019 September 1]. Available from: [59] Food and Drug Administration. Prozac®. [cited 2019 October 13]. Available from: https://
https:// www.mocatest.org/ www.accessdata.fda.gov/drugsatfda_docs/label/2011/018936s091lbl.pdf

[25] 2019 American Geriatrics Society (AGS) Beers Criteria Update Expert Panel. American [60] Food and Drug Administration. Luvox® (Fluvoxamine Maleate) Tablets. [cited 2019
Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate October 13]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/
medication use in older adults. J Am Geriatr Soc. 2019;67:674-694. label/2007/021519lbl.pdf

[26] Juurlink D. Revisiting the drug interaction between tamoxifen and SSRI [61] Food and Drug Administration. Paxil® (paroxetine hydrochloride). [cited 2019
antidepressants. BMJ. 2016 Sep 30;354:i5309. October 13]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/
label/2008/020031s060,020936s037,020710s024lbl.pdf
[27] Expert opinion
[62] Food and Drug Administration. Paxil® (paroxetine hydrochloride). [cited 2019
[28] Women’s Mental Health. Choice of Antidepressant May Affect Survival in Women
October 13]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/
on Tamoxifen for Breast Cancer. 2011. [cited 2019 May 18]. Available from: https://
label/2011/020031s058s066,020710s022s030lbl.pdf
womensmentalhealth.org/posts/choice-of-antidepressant-may-affect-survival-in-
women- on-tamoxifen-for-breast-cancer/

November 2019 cep.health/major-depressive-disorder Page 11 of 12

 Section: A B C D E F G Resources References

References
[63] Food and Drug Administration. Zoloft® (sertraline hydrochloride). [cited 2019 [74] Food and Drug Administration. Imipramine Hydrochloride. [cited 2019 October 13].
October 13]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/ Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040903lbl.pdf
label/2009/019839s070,020990s032lbl.pdf [75] Food and Drug Administration. Pamelor™. [cited 2019 October 13]. Available from:
[64] Food and Drug Administration. Remeron® (mirtazapine) Tablets. [cited 2019 https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/018012s029,018013s061lbl.pdf
October 13]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/ [76] Food and Drug Administration. Surmontil® (Trimipramine Maleate). [cited 2019
label/2007/020415s019,021208s010lbl.pdf October 13]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/
[65] Food and Drug Administration. Seroquel (quetiapine fumarate) TABLETS. [cited label/2014/016792s037lbl.pdf
2019 October 13]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/ [77] Lexicomp. BuPROPion (Lexi-Drugs). [cited 2019 November 25].
label/2004/20639se1-017,016_seroquel_lbl.pdf
[78] Lexicomp. Citalopram (Lexi-Drugs). [cited 2019 November 25].
[66] Valeant Canada LP. Manerix® (moclobemide) Product Monograph. [cited 2019 October
[79] Lexicomp. Desvenlafaxine (Lexi-Drugs). [cited 2019 November 25].
13]. Available from: https://pdf.hres.ca/dpd_pm/00032713.PDF
[80] Lexicomp. DULoxetine (Lexi-Drugs). [cited 2019 November 25].
[67] Food and Drug Administration. Desyrel® (trazodone hydrochloride) tablets, for oral use.
[cited 2019 October 13]. Available from: https://www.accessdata.fda.gov/drugsatfda_ [81] Lexicomp. Escitalopram (Lexi-Drugs). [cited 2019 November 25].
docs/label/2017/018207s032lbl.pdf [82] Lexicomp. FLUoxetine (Lexi-Drugs). [cited 2019 November 25].
[68] Food and Drug Administration. Viibryd™ (vilazodone hydrochloride) Tablets. [cited [83] Lexicomp. FluvoxaMINE (Lexi-Drugs). [cited 2019 November 25].
2019 October 13]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/ [84] Lexicomp. Mirtazapine (Lexi-Drugs). [cited 2019 November 25].
label/2011/022567s000lbl.pdf
[85] Lexicomp. PARoxetine (Lexi-Drugs). [cited 2019 November 25].
[69] Food and Drug Administration. Fetzimatm (levomilnacipran) extended-release
[86] Lexicomp. Sertraline (Lexi-Drugs). [cited 2019 November 25].
capsules, for oral use. [cited 2019 October 13]. Available from: https://www.accessdata.
fda.gov/drugsatfda_docs/label/2013/204168s000lbl.pdf [87] Lexicomp. Venlafaxine (Lexi-Drugs). [cited 2019 November 25].

[70] Food and Drug Administration. Amitriptyline Hydrochloride Tablets, USP. [cited [88] Lexicomp. Vortioxetine (Lexi-Drugs). [cited 2019 November 25].
2019 October 13]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/ [89] Lexicomp. Levomilnacipran (Lexi-Drugs). [cited 2019 November 25].
label/2014/085966s095,085969s084,085968s096,085971s075,085967s076,0 [90] Lexicomp. Moclobemide (Lexi-Drugs). [cited 2019 November 25].
85970s072lbl.pdf [91] Lexicomp. Vilazodone (Lexi-Drugs). [cited 2019 November 25].
[71] Food and Drug Administration. Anafranil™ (clomipramine hydrochloride) Capsules [92] Lexicomp. Amitriptyline (Lexi-Drugs). [cited 2019 November 25].
USP. [cited 2019 October 13]. Available from: https://www.accessdata.fda.gov/
[93] Lexicomp. ClomiPRAMINE (Lexi-Drugs). [cited 2019 November 25].
drugsatfda_docs/label/2012/019906s037lbl.pdf
[94] Lexicomp. Desipramine (Lexi-Drugs). [cited 2019 November 25].
[72] Food and Drug Administration. Norpramin® (desipramine hydrochloride tablets USP).
[cited 2019 October 13]. Available from: https://www.accessdata.fda.gov/drugsatfda_ [95] Lexicomp. Doxepin (Systemic) (Lexi-Drugs). [cited 2019 November 25].
docs/label/2014/014399s069lbl.pdf [96] Lexicomp. Imipramine (Lexi-Drugs). [cited 2019 November 25].
[73] Food and Drug Administration. Sinequan® (doxepin HCl). [cited 2019 October [97] Lexicomp. Nortriptyline (Lexi-Drugs). [cited 2019 November 25].
13]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/ [98] Lexicomp. Trimipramine (Lexi-Drugs). [cited 2019 November 25].
label/2007/016798s054,017516s023lbl.pdf

This Tool was developed as part of the Knowledge Translation in Primary Care Initiative, led by the Centre for Effective Practice in collaboration with the Ontario College of Family Physicians and the
Nurse Practitioners’ Association of Ontario. Clinical leadership for the development of the Tool was provided by Dr. Mark Silverman CCFP and was subject to external review by health care providers and
other relevant stakeholders. This Tool was funded by the Government of Ontario as part of the Knowledge Translation in Primary Care Initiative.

This Tool was developed for licensed health care professionals in Ontario as a guide only and does not constitute medical or other professional advice. Health care professionals are required
to exercise their own clinical judgement in using this Tool. Neither the Centre for Effective Practice (“CEP”), Ontario College of Family Physicians, Nurse Practitioners’ Association of Ontario,
Government of Ontario, nor any of their respective agents, appointees, directors, officers, employees, contractors, members or volunteers: (i) are providing medical, diagnostic or treatment services
through this Tool; (ii) to the extent permitted by applicable law, accept any responsibility for the use or misuse of this Tool by any individual including, but not limited to, primary care providers
or entity, including for any loss, damage or injury (including death) arising from or in connection with the use of this Tool, in whole or in part; or (iii) give or make any representation, warranty or
endorsement of any external sources referenced in this Tool (whether specifically named or not) that are owned or operated by third parties, including any information or advice contained therein.

The Adult Major Depressive Disorder tool is a product of the Centre for Effective Practice. Permission to use, copy, and distribute this material is for all non-commercial and
research purposes is granted, provided the above disclaimer, this paragraph and the following paragraphs, and appropriate citations appear in all copies, modifications, and
distributions. Use of the Adult Major Depressive Disorder Tool for commercial purposes or any modifications of the Tool are subject to charge and must be negotiated with the
Centre for Effective Practice (Email: [email protected]).

For statistical and bibliographic purposes, please notify the Centre for Effective Practice ([email protected]) of any use or reprinting of the Tool.
Please use the below citation when referencing the Tool:
Reprinted with Permission from Centre for Effective Practice. (November 2019). Treatment of Adult Major Depressive Disorder: Ontario. Toronto: Centre for Effective Practice.
Developed by: In collaboration with:

November 2019 cep.health/major-depressive-disorder Page 12 of 12