Measurement-Based Care in Mental Health

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Questions and Answers

What is one core component of measurement-based care?

Using patient feedback only

Employing clinician-led decision-making without patient input

Administering validated outcome scales during patient encounters (correct)

Reducing visit frequency to save time

What is a benefit of measurement-based care?

It hinders effective communication with patients.

It eliminates the need for clinical assessments.

It enhances medication adherence and treatment outcomes. (correct)

It focuses solely on pharmacological treatments.

Which type of scales are practical and often used in measurement-based care?

Physician-rated scales only

Patient-rated scales (PROMs) (correct)

Non-validated scales

Generic health questionnaires not specific to conditions

What is one reason measurement-based care is not widely implemented?

Monotonous and mechanical application without patient engagement. Signup and view all the answers

What is a suggested application of measurement-based care?

Across both pharmacological treatments and psychotherapies. Signup and view all the answers

What is the initial screening tool recommended for depression screening?

PHQ-2 Signup and view all the answers

What is the follow-up action if the PHQ-2 score is positive?

Use the PHQ-9 to confirm diagnosis. Signup and view all the answers

Which of the following is NOT a recommended strategy to improve access to mental health care?

In-person therapy only Signup and view all the answers

What is one limitation of depression screening tools such as PHQ-2 and PHQ-9?

They may result in false positives. Signup and view all the answers

What is the typical duration of the acute phase of depression treatment?

8–16 weeks Signup and view all the answers

Which of the following assessments is needed for a comprehensive clinical evaluation?

Incorporating diagnostic frameworks like DSM-5 or ICD-11 Signup and view all the answers

What should be the primary focus during the maintenance phase of treatment?

Improving quality of life and functional improvement Signup and view all the answers

What aspect does the DSM-5 TR specifiers primarily help with?

Describing the overall formulation Signup and view all the answers

What is the primary objective during the maintenance phase of treatment?

Restore functioning and quality of life Signup and view all the answers

Which of the following is a non-remission outcome related to poor functional outcomes?

Higher risk of relapse Signup and view all the answers

What should be monitored closely during the initial weeks of antidepressant treatment?

Risk of suicidal behavior Signup and view all the answers

Which action is essential for preventing recurrence of symptoms post-remission?

Promote early intervention Signup and view all the answers

What is a significant risk associated with discontinuing antidepressants?

Increased risk shortly after discontinuation Signup and view all the answers

Which of the following is NOT a component of psychoeducation in shared decision-making?

Psychoeducation for family members Signup and view all the answers

What is the relationship between symptom remission and the risk of relapse?

Lower risk of relapse with symptom remission Signup and view all the answers

Which type of antidepressants is commonly implicated in suicide risk?

SSRIs and SNRIs Signup and view all the answers

What is a primary challenge of the stepped care model?

Delaying access to intensive treatments Signup and view all the answers

Which care model focuses on tailoring treatment from the outset based on patient complexity?

Stratified Care Signup and view all the answers

In the context of shared decision-making, what is a key component of collaborative care?

Multidisciplinary team approach Signup and view all the answers

What does measurement-based care primarily enable?

Improvement in care quality and outcomes Signup and view all the answers

What is a significant challenge when implementing collaborative care?

Requires strong team coordination Signup and view all the answers

How does stratified care enhance resource utilization?

By directing appropriate treatment from the start Signup and view all the answers

Which tool is suggested for assessing treatment beliefs during history taking?

CHOICE-D Signup and view all the answers

What is one advantage of the stepped care model?

It uses resources efficiently Signup and view all the answers

What is the recommended frequency for the first-line treatment sessions for sustained recovery?

Twice a week Signup and view all the answers

Which class of medications does Fluoxetine belong to?

SSRI Signup and view all the answers

Which medication is classified as a serotonin reuptake inhibitor and also a partial agonist?

Vilazodone Signup and view all the answers

In selecting medications, which factor is NOT typically considered?

Color of the medication Signup and view all the answers

What is a common side effect associated with SSRIs and SNRIs?

Gastrointestinal-related issues Signup and view all the answers

Which medication is classified as a serotonin 2 antagonist and is also an alpha-2 antagonist?

Mianserin Signup and view all the answers

What is the mechanism of action for Quetiapine?

Dopamine, serotonin, alpha-1 and alpha-2 receptor antagonism Signup and view all the answers

Which antidepressant is a level 1 evidence MAOI?

Phenelzine Signup and view all the answers

Which guideline remains the primary resource for special populations in the treatment of depressive disorders?

CANMAT 2016 Signup and view all the answers

What is a critical consideration when interpreting CANMAT recommendations regarding medications?

Recommendations may not match the actual level of evidence. Signup and view all the answers

What type of risk factors are described as dynamic in the treatment of Major Depressive Disorder (MDD)?

Factors that assist in personalized treatment planning Signup and view all the answers

What is a recommended step after a positive depression screening in clinical settings?

Diagnostic assessment and treatment planning Signup and view all the answers

How is the neuroscience-based nomenclature (NBN) significant in depression medication management?

It identifies medications through their pharmacological activities. Signup and view all the answers

What is emphasized regarding the use of validated scales during screening for depressive disorders?

They must be supported by appropriate resources for follow-up. Signup and view all the answers

Which of the following statements about psychopharmacology in depression treatment is correct?

This presentation will only provide limited discussion on psychopharmacology. Signup and view all the answers

What is the purpose of level of evidence visuals in the CANMAT guidelines?

To prioritize medications based on their proven efficacy. Signup and view all the answers

Study Notes

Depressive Disorders Management

Dr. Sanjay Rao, MBBS, MD, FRCPsych, FRCPC, MBA is the Medical Director of the Centre for Mental and Psychological Health & Unified CBT Academy at Ottawa University and an Associate Professor of Psychiatry. He is an additional Professor of Psychiatry at Dalhousie University.

This Presentation

This presentation focuses on CANMAT Guidelines for depression management.
Specifics of basic psychopharmacology and psychotherapeutic approaches won't be covered, as there are separate lectures for those topics. However, understanding the specific model for treatment is important for effective clinical outcomes.
The advances in depression management and critical reviews will be limited to CANMAT recommendations due to time constraints.

CANMAT Update 2023/2024

Questions and answers will focus on the key areas of general treatment for depressive disorders
Refer to tables for clinical exams as the text of the paper contains recent materials relevant for Psychiatry Fellowship examinations
Neuroscience-based nomenclature is used for medications, e.g. serotonin-dopamine activity regulator instead of atypical antipsychotics.
For special populations, CANMAT 2016 guidelines remain the resource.

CANMAT Guidelines Reading Tips

Table A: CANMAT Criteria for Level of Evidence
- Level 2: High-quality meta-analysis with narrow confidence intervals and/or two or more RCTs (randomized controlled trials) with adequate sample size.
- Level 3: Lower-quality meta-analysis with wide confidence intervals and/or one or more RCTs with adequate sample size.
- Level 4: Small-sample RCTs; Non-randomized, controlled prospective studies or high-quality retrospective studies.
- Expert opinion/consensus.
Table B: CANMAT Criteria for Line of Treatment
- First line: Level I or level II evidence plus clinical support
- Second line: Level III evidence or higher plus clinical support.
- Third line: Level IV evidence or higher plus clinical support.

Risk Factors for MDD

Static risk factors:
- Female sex
- Family history of mood disorders,
- History of adverse childhood events/maltreatment
- Death of spouse
Dynamic risk factors:
- Chronic illnesses
- Psychiatric comorbidities (especially anxiety)
- Alcohol and substance use disorders
- Insomnia or hormonal shifts, e.g., puberty, pregnancy, postpartum, perimenopause

Screening

Depression screening is recommended for individuals in primary and secondary care settings with depression risk factors.
Use validated scales for screening. Sufficient resources and systems for diagnostic assessment and treatment should be available.
Screening is most valuable when subsequent care pathways are established.

Screening Tools

Procedure: Use PHQ-2 as an initial screener; if positive, follow up with PHQ-9 to assess symptom severity.
- This two-step process improves specificity without compromising sensitivity compared to using the PHQ-9 alone.
Utility in Measurement Based Care (MBC): PHQ tools are used for ongoing monitoring during treatment to track symptom progression and treatment outcomes.
Limitation: False positives are possible, so clinical interview is necessary for confirmation.

Assessment and Diagnosis

Clinical assessment incorporates diagnostic frameworks like DSM-5 or ICD-11.
Assess vulnerability and resilience factors across the lifespan.
Consider collateral information, cultural sensitivity, and childhood maltreatment
Conduct differential diagnosis for comorbidity.
Includes medical workup, such as CBC and TSH, and specific tests (e.g., ECG for cardiac conditions or neuroimaging for late-life depression).

Using DSM-5 TR Specifiers

Descriptive, not for guiding medication treatment.
Provides information on MDD, dysthymia, and residual symptoms for PDDs.
Focus should be on improving quality of life (QOL) and functional improvement.

Summary of Good Practice

Conduct thorough assessment to include obtaining collateral information.
Provide evidence-based treatments for the patient
Develop a comprehensive safety and management plan for the patient.
Establish a therapeutic alliance with the patient.
Provide support, education, and self-management strategies.

Equity and Diversity

Higher prevalence of depression in equity-deserving groups.
Barriers to access include geography, language, mistrust, stigma, and fragmented healthcare.
Strategies for improving access include screening programs, culturally competent care, collaborative care, and digital health interventions with cultural adaptations.

Recommendations for Screening and Assessment

Develop suspicion for MDD in individuals with potentially modifiable or nonmodifiable risk factors.
Screen for depression using a validated scale (e.g., PHQ-2 followed by PHQ9).
Conduct a comprehensive diagnostic assessment acknowledging biological, psychological, and social factors, and recognizing ethnocultural diversity within a longitudinal framework.
Employ strategies like screening, culturally competent care, collaborative care, and digital health interventions for equity-deserving groups to improve access to and quality of mental health care.

Objectives and Phases of Treatment

Primary Goals:
- Full symptom remission with optimal quality of life, patient safety, and relapse prevention.
Individualized Goals:
- Patient-centered approach and shared decision-making.
Treatment Phases:
- Acute: 8-16 weeks (or until symptom remission);
- Maintenance: 6-24 months (or longer as indicated clinically).

Treatment Phases: Acute

Objective:
- Ensure patient safety (assess and mitigate risks like suicide).
- Improve symptom severity and functioning.
- Achieve symptom remission assessed by validated scales.
Actions:
- Develop a safety plan.
- Provide psychoeducation for self-management.
- Implement evidence-based treatments, monitoring adherence and side effects.

Treatment Phases: Maintenance

Objectives:
- Maintain symptom remission.
- Achieve premorbid quality of life.
- Prevent recurrence.
Actions:
- Monitor for lasting symptoms and side effects.
- Provide psychoeducation for early relapse detection and prompt intervention.
- Adhere to care plans to include addressing treatment obstacles.
- Use evidence-based approaches to build resilience and discontinue procedures if clinically indicated.

Symptom Remission

Symptom remission=lower risk of relapse
Non-Remission=Poor functional outcomes
Remission + functional outcomes= Patient centred care
Residual Symptoms common even with remission= risk of recurrence
Chronic and Treatment-Resistant Cases may need focus on QOL and functional outcomes

Suicide: Modifiable Risk Factors

Symptoms and life events, suicidal ideation, hopelessness, anxiety, impulsivity, psychotic symptoms,
Stressful life events, comorbid conditions (post-traumatic stress, substance use, personality disorders)
Chronic painful medical conditions, e.g. headaches or arthritis.

Safety Planning

Steps:
- Identify warning signs
- Develop coping strategies
- Connect with supportive people
- Engage with social and community resources
- Identify professional contacts
- Make the environment safe

Antidepressants and Suicide Risk

General Evidence on Risk Reduction: Reduce risk particularly of suicidal thoughts
Age-Specific Risk Variation: Young adults (<25 years) - slight increase, adults (25-65) – no significant change, older adults (>65) – reduced suicidal behavior.
Temporal Relationship with Risk: Risk exists before and after the beginning of antidepressant use, with increased risk after discontinuation.
Medication-Specific Considerations: SSRIs and SNRIs frequently implicated.
Monitoring: Suicide risk monitoring during the initial weeks of treatment is crucial.

Shared Decision Making

Improve patient satisfaction with care.
This strategy (SDM) includes psychoeducation.
Includes components like:
- Pharmacology (treatment)
- Psychotherapy
- Neuromodulation treatments
- Lifestyle changes
- Alternative medicine approaches.

Shared Decision Making: Tools

Use tools like CHOICE-D (for patients and families).
Create high-level summaries from available resources and information.
Use credible resource materials like NICE UK or Patient Info site.

Shared Decision Making: Other Concerns

Accessibility of neuromodulation or treatment modalities.
Provide a comprehensive care plan with other options to help patients with depression.
Keep in mind the cost of care
Explore and include resources to help the patient
Get other professionals involved, e.g., related to employment, finances, legal, education, etc.

Lifestyle Interventions

First line: Supervised exercise for mild depression (30–40 minutes, 3–4 times per week for at least 9 weeks), light therapy (10,000 lux white light for 30 minutes daily) for seasonal (winter) pattern MDE.
Second line: Light therapy for mild severity nonseasonal MDE, Adjunctive exercise for moderate severity MDE and adjunctive light therapy for moderate severity nonseasonal MDE.
Third line: Adjunctive healthy diet (focused on fruits, vegetables, fiber, low in fat and carbohydrates); Mediterranean diet; adjunctive sleep hygiene and CBT-I; and adjunctive sleep deprivation (wake therapy).
Treatments for Probiotics are insufficient.

Stepped Care

Sequentially escalate interventions based on patient response and severity.

Stratified Care

Personalized treatment from the start; unnecessary steps are reduced.

Collaborative Care

Involves primary and mental health specialists; focuses on underserved populations; and seeks to offer comprehensive care that includes reducing symptoms and suicidal ideation, and is especially effective with comorbidity.

Measurement Based Care: Principles

Routine outcome measurement and feedback guide clinical decision-making.
Core components include regularly administering validated outcome scales during clinical encounters, reviewing score results with patients, and using scores, with clinical assessments, to support collaborative decision-making
Offers benefits such as improved medication adherence, better treatment outcomes, stronger therapeutic alliances, and increased likelihood of detecting suicidal ideation.

Measurement Based Care: Application

Applicable to both pharmacological treatments and psychotherapies.
Helps identify and address non-responders with adjustments to treatment strategies.
Incorporates patient-rated and clinician-rated scales (PROMs) that are practical for symptoms, side effects, functioning, and quality of life.
Using scales in the clinical assessment process aids in identifying areas of concern and provides insights that assist with treatment.

Measurement Based Care: Reflections

Experimenting with MBC in most patient encounters reduces bias in overestimating improvement.
Online and automated systems are needed.
Issues with implementation of MBC include not recognizing models of existing clinical practices in training; lack of adequate mental health features in EMRs; and the potential for mechanical application.

Examples of Validated Rating Scales for Measurement-Based Care

Symptoms/severity: Hamilton Depression Rating Scale, Montgomery-Åsberg Depression Rating Scale, Columbia Suicide Severity Rating Scale, Dimensional Anhedonia Rating Scale, Inventory for Depressive Symptomatology.
Functioning: Multidimensional Scale of Independent Functioning, Work and Social Adjustment Scale, Sheehan Disability Scale, Social and Occupational Functioning Assessment Scale.
Quality of Life: WHO Disability Assessment Scale, Quality of Life Interview, UKU Side Effect Rating Scale, Toronto Side Effect Scale.
Side Effects: Frequency, Intensity and Burden of Side Effects Rating Scale.
Other scales like the Beck Depression Inventory II, Clinically Useful Depression Outcome Scale, Patient-Rated Outcome Measurement Information System (PROMIS), and the Quick Inventory for Depressive Symptomatology are commonly used.

Treatment Choices: Stratified Care

Mild with low safety risk: Psychotherapy (if readily available), exercise or certain CAM treatments or DHls as monotherapy.
Moderate with low-moderate safety risk: Psychotherapy or pharmacotherapy as initial choices; pharmacotherapy has slightly better efficacy for mild to moderate cases; structured psychotherapy (CBT) shows slightly greater effects in the longer term.
Severe with moderate to high safety risk: A combination of psychotherapy and pharmacotherapy, especially if patients prefer this approach.
Severe MDD with psychotic symptoms: A combination of antidepressant and antipsychotic medication.
Severe/life-threatening symptoms: Electroconvulsive therapy (ECT) may be considered.

Combining Medications & Evidence-Based Therapies

Why: Enhanced efficacy for acute treatment; Reduced risk of recurrence; Psychological treatment for residual symptoms; sustained recovery.
How: Planned sequential treatment for high-risk patients; Combined treatment for severe cases; Life-threatening situations.

First Line and Level 1 Evidence: Psychological Treatment

First line: Cognitive-behavioral therapy, interpersonal therapy, Behavioral Activation.
Second line: Cognitive behavioral analysis system of psychotherapy, mindfulness-based cognitive therapy, problem-solving therapy, short-term psychodynamic psychotherapy.
Third line: Acceptance and commitment therapy and long-term psychodynamic therapy, etc.; Evidence is less robust for some therapies compared to CBT and IPT.
Recommendations include 12-16 sessions for first line treatment with a maximum of 20 sessions suggested.

First Line and Level 1 Evidence: Antidepressants

SSRI, SNRI, NDRI, Alpha-2 antagonist, Serotonin reuptake inhibitor, Serotonin receptor modulator, melatonin receptor agonist and antagonist.

Second Line Antidepressants

Tricyclic antidepressants (TCAs).
Reversible inhibitors of monoamine oxidase (RIMAs).

Third Line Antidepressants: Level 1 Evidence

Monoamine oxidase inhibitors (MAOIs)
Noradrenergic and specific serotonergic antidepressants)

Initial Selection of Medications

Factors to consider: Personalization (efficacy, adverse effects, cost, patient preference); Psychoeducation; Adverse effects management (GI, sedation, weight gain, sexual dysfunction); selection based on comorbidities, patient age, and symptom dimensions; and specific recommendations (e.g., SNRIs for elderly, Fluoxetine/agomelatine for young).

New Evidence: Psychotherapies

CBT, BA, and IPT are effective as first-line treatments.
CBT, MBCT, PST, and STPP therapies are relevant for updates in second-line treatments; issues with heterogeneity and bias related to data should be kept in mind when evaluating the validity and impact of the studies.
ACT remains effective for mild to moderate depression.
Emerging treatments such as Transdiagnostic Psychotherapy and Metacognitive Therapy are also mentioned.

New Evidence: Pharmacotherapy

Dextromethorphan-bupropion combination may be an option for second-line treatment for limited evidence and potential safety concerns for longer-term use;
Brexanolone and Zuranolone (allopregnanolone agonists) are now widely available in the US.
Pramipexole may be considered as a third-line adjunctive treatment, demonstrating efficacy in small sampling RCTs for MDD or bipolar depression.

New Evidence: CAMs

St. John's Wort: First- and second-line treatment for mild to moderate depression
Other Herbs: Saffron, lavender, and Rhodiola showed modest benefit; third-line treatment for mild depression.
Nutraceuticals: L-Methyl Folate, S-Adenosyl-L-Methionine, Omega-3 fatty acids are considered third-line.
Other Emerging CAM interventions: The Mediterranean diet is considered third-line, while probiotics do not have sufficient evidence to support recommendation.

DSM-5-TR Specifiers Treatment: No Difference

No significant difference in treatment for anxious distress, atypical features, melancholic features, mixed features, psychotic features, or catatonic features – except for catatonia.
Further research and robust RCTs are needed to justify some of the differences stated.

Symptoms & Medications

Symptom dimensions like cognitive dysfunction, sleep disturbance, and somatic symptoms are linked to specific medications.
A causal link should not be assumed without further investigation and evidence; this relationship may be more complex than some portray.

Anhedonia

70% of MDD patients report anhedonia.
Potential treatments include monoaminergic, methylphenidate, ketamine, and psilocybin.
Anhedonia may improve as depression improves.

Drug Formulations

Extended-release formulations may be more convenient.
Brand and generic medications generally show no difference.
CANMAT recommends based on what works best, in terms of brand, generic, IR, or XR formulations.

Antidepressant Risks

SSRI Risk:
- Elderly: Fractures, falls, hyponatremia, GI bleed (especially with NSAIDs)
- Younger: Suicidal ideation, akathisia, agitation, aggression
- CYP2D6: Paroxetine & Fluoxetine, CYP3A4: Fluvoxamine, Serotonin syndrome
SNRI Risk:
- Elderly: Fractures, falls, hyponatremia, GI bleed (especially with NSAIDs)
- Younger: Suicidal ideation, akathisia, agitation, aggression
- CYP2D6: Paroxetine & Fluoxetine, CYP3A4: Fluvoxamine, Serotonin syndrome
TCA Risk:
- Overdose, Anticholinergic effects (e.g., dry mouth, constipation, blurred vision), weight gain, sedation
- Higher risk in overdose, anticholinergic effects, and sedation.
Additional risks: Rare risks like liver injury associated with various medications including some antidepressants

Antidepressants and Weight Gain

Several antidepressants are associated with weight gain, with some having greater risks than others.

Must Talk About Sexual Side Effects

Decrease in libido, ejaculatory dysfunction, and anorgasmia
5-HT2 and 5-HT3 receptor activation is relevant.

Treatment Options

Consider switching to Bupropion or a Phosphodiesterase inhibitor (additional cost), or Buspirone (less effective) if there are other issues with the current treatment.

Emotional Blunting

Antidepressants can cause emotional blunting.
SSRIs are associated with a high risk of emotional blunting (20–92% dependent on dosage).
Strategies include changing antidepressants (e.g., bupropion or ketamine) and combining antidepressants with evidence-based psychotherapies.

Pharmacogenomic Testing

Rationale: Improving treatment response and reducing side effects.
Relevant Genes: Drug metabolism (e.g., CYP450 enzymes) and serotonin transporters and receptors.
Clinical Evidence: Modest improvement in response and remission rates with pharmacogenomic testing; Absolute improvements are usually small, and some studies may lack blinding and are therefore prone to bias.
CANMAT does not recommend routine pharmacogenomic testing.

Biomarkers for Treatment Selection

Biomarkers are objective measures of substances, structures, or processes in the body.
Potential depression biomarkers include inflammatory markers (e.g., interleukin-8, C-reactive protein), electrophysiological measures (e.g., loudness dependence of auditory evoked potentials), but robust evidence supporting routine use in antidepressant treatment selection is lacking, and further research is required before routine use can be supported.

Complementary and Alternative Medications (CAMs)

First Line: St. John's wort for mild depression, Acupuncture for mild depression.
Second Line: St. John's wort for moderate depression, Adjunctive acupuncture for moderate severity MDEs, Adjunctive L-methyl folate for mild to moderate severity MDEs, Adjunctive SAM-e for mild to moderate severity MDEs, DHEA for mild severity MDE, Omega-3 fatty acids, Saffron, Lavender, and rose root for mild MDEs.

Managing Comorbidity

Common comorbidities include anxiety, substance use disorders, ADHD, personality disorders, diabetes, cardiovascular disease, cancer, and chronic pain.
Depression is more challenging to treat with comorbidities due to symptom overlap and increased side effects from treatments.

Comorbid Conditions: Pharmacotherapy

Outcomes may be worse with comorbidities.
Antidepressants remain effective though, even with medical comorbidities.
Manage medication side effects and interactions carefully to prevent worsening of comorbid conditions.
Reduce polypharmacy.

Comorbid Conditions: Psychotherapy

CBT and BA are generally effective for depression with medical comorbidities.
Adjustments to therapy or an increase in sessions may be necessary to address comorbidity complications and specific needs.
Some studies reported limited benefit of CBT for personality disorder conditions; current evidence does not support this in line with the most recent CANMAT updates.

Cultural Adaptations in Psychotherapy

Evidence suggests that CBT for Arabic-speaking adults and mindfulness for Black Americans are effective.
Adaptations may include incorporating cultural idioms, appropriate matching of therapists with their clients, and culturally relevant elements like spirituality or traditional practices to enhance acceptance, relevance, and efficacy.

DHIs: CANMAT Recommendations

First line: guided iCBT for mild to moderate severity depression.
Second line: self-directed DHIs for mild to moderate severity depression, supported by clinician guidance; guided iBA DHI for mild to moderate severity depression.
Third line: self-directed DHIs when other interventions are unavailable; chatbots and conversational agents.

Guided Digital Interventions Examples

A variety of guided and unguided digital interventions, e.g. apps and websites, are available and may be suitable for depression treatment.

Defining Outcomes

Early improvement: 20%+ reduction of symptom scale scores within 2-4 weeks from baseline.
Response: 50%+ symptoms reduction from baseline
Remission: Specific scale threshold scores (e.g., HAM-D, MADRS, PHQ-9; ≤7, ≤10, ≤ 4, respectively) and often require sustained symptom absence for at least 2 months.

Laboratory Tests

Routine Testing: Standard lab tests are not usually required to manage MDD, unless there is a pre-existing liver condition.
Liver Function Tests (LFTs): Baseline and ongoing LFTs are recommended for patients with pre-existing liver conditions.
Electrolyte Monitoring: Recommended for older patients (≥ 60 years) due to risk of induced hyponatremia from antidepressants.
Weight, Glucose, and Lipid Monitoring: Regular monitoring is recommended for patients on medications related to weight gain.
Specific Agent Tests: Lithium (serum level monitoring), Atypical Antipsychotics (weight, glucose, and lipid monitoring), Ketamine/esketamine (periodic urinalysis).

Risk Factors for Recurrence

Persistent residual symptoms (anhedonia, sleep problems)
History of childhood maltreatment.
Higher severity/frequency of depressive episodes.
Presence of medical comorbidities (psychiatric or physical conditions).
Previous number of depressive episodes .
Poor social support .
Persistent stressful life events.

Maintaining Remission

Prevent recurrence is crucial with progressive risk as episodes increase.
Implement booster sessions in conjunction with existing psychological approaches.
Continue the lowest effective dose of medication associated with remission.
Optimize treatment adherence to minimize side effects, and maximize efficacy. Monitor emerging symptoms and side effects regularly via MBC.
Promote lifestyle factors including exercise, nutrition, quality sleep, and substance avoidance.
Foster engagement in peer support groups.

Relapse Prevention: For Sustained Remission

Maintenance pharmacotherapy and psychotherapy effectively reduce recurrence rates (50% reduction).
Antidepressants should be continued for at least 6-12 months after remission (previous recommendations were 6-9 months).
Patients with risk factors such as residual symptoms, childhood maltreatment, or recurrent depression may benefit from treatment duration extending to 2 years or longer.

Relapse Prevention: Psychotherapy

CBT, MBCT, IPT, and CBASP, and PST are superior to no intervention controls
Booster psychotherapy sessions over 12 months can significantly reduce risk of relapse
Psychotherapy is often the first-choice approach for mild to moderate MDD

Sequential Treatment Strategies for Relapse Prevention

Switching to psychotherapy after initial pharmacotherapy response can help manage residual symptoms, improve psychological well-being and increase resilience.
This sequential combination approach to treatment is recommended for individuals with recurrent or severe depressive episodes.

Discontinuing Antidepressants

Carefully scheduled and gradual tapering of medications is recommended; exceptions include using fluoxetine
Reductions should be gradual in percentage points vs fixed doses, validated through receptor PET studies, avoiding RCTs
Support with psychological therapies, and monitoring for discontinuation symptoms (FINISH).
High-risk medications like paroxetine and venlafaxine are frequently associated with discontinuation symptoms.

Antidepressant Discontinuation

High-risk antidepressants include paroxetine and venlafaxine.
- Moderate-risk antidepressants include citalopram, desvenlafaxine, duloxetine, escitalopram, fluvoxamine, levomilnacipran, milnacipran, sertraline, and vilazodone.
- Low- or minimal-risk antidepressants include agomelatine, bupropion, fluoxetine, mirtazapine, and vortioxetine.

If Patients Are Not Better

Review clinical findings for possible incorrect diagnosis, demographic factors, comorbid conditions (psychiatric or medical), and acute/chronic stressors.
Review treatment factors for possible inadequate dose, duration, side effects, non-adherence to treatment regimens, pharmacogenetic factors related to drug metabolism, and other considerations.

Non-Response: DTD vs TRD

TRD: Defined as failure to respond to two or more adequate antidepressant trials.
- DTD encompasses treatment non-response for standard depression treatments in general- including or excluding medications and psychotherapies or neuromodulations.
Limitations of TRD include a focus on medication failure excluding other therapeutic approaches, a lack of specific failure definitions (possibly discouraging persistence), with a negative tone.

Difficult to Treat Depression

The framework provides comprehensive and detailed care plans of depression to include considerations of improving functioning and quality of life (QOL).
Treatment pathways are individualized.

Assessing Factors That Interfere with Treatment Response

Assess psychiatric and non-psychiatric comorbidities, adherence to treatment, other biological and psychological factors that may affect response and consider pharmacogenetic factors.

Switching or Adding Adjunctive Medication

Consider switching to another antidepressant with a distinct mechanism of action or an antidepressant with superior efficacy shown in previous studies.
Consider adding adjunctive medications if there is a partial response with initial medication, and it is well tolerated..
First-line additions may be aripiprazole, brexpiprazole; Second-line options might include bupropion, esketamine, ketamine, additional classes and/or strategies.
Third-line options are broad in category and include a wide variety of additional agents.

Switching Antidepressants

Recommendations for switching: When to switch between antidepressants (e.g., inadequate response or intolerable side effects), Consider changing to a different class of antidepressant if no response to the current class or if co-morbidities are present and the symptom profile warrants a change in class.
Switching within the same class is an option if there are tolerability issues with the primary antidepressant, with 4-6 weeks being suggested but with no clear evidence to fully support or reject this window of time.

MAOIs

Indications: For atypical depression symptoms and after multiple first-line antidepressants do not help.
Safety: Low-tyramine diet is needed due to the possibility of hypertensive crisis from interactions with tyramine-containing foods; minimum washout periods of 14 days are necessary between medication treatments to prevent potential dangerous interactions.
Clinical use: Side effects, blood pressure, and patient adherence to the diet must be carefully monitored.
Types: Traditional irreversible (phenelzine, tranylcypromine, isocarboxazid), newer reversible (moclobemide) MAOIs with fewer dietary restrictions.

TCAs

Role: Not first-line for depression treatment, specifically used for treatment-resistant depression, or in chronic pain or insomnia.
Efficacy: Similar to other antidepressants
Safety: Cardiotoxicity in overdose, anticholinergic effects (dry mouth, constipation, blurred vision), weight gain, sedation
Monitoring: Regular monitoring of plasma drug levels and EKG monitoring are important.

Adjunctive Medications: 1st/2nd Line

Table of summary information on adjunctive agents, lines of treatment relevant for the 1st/2nd line treatment and target doses for the agents.

Adjunctive Medications: 3rd Line

The adjunctive treatment recommendations in this table for the 3rd line include considerations for other antidepressants, stimulants, lamotrigine, non-IV racemic ketamine, pramipexole, ziprasidone, and psychedelic-assisted psychotherapy/Cannabis (insufficient evidence of efficacy available, some risk of harm with this approach recommended but there is no supporting evidence).

How to Select Adjunctive Medications

Consider the effectiveness and tolerability of adjunctive agents, side effect profiles, and potential drug interactions.
Evaluate the availability of pharmacogenetic testing to guide treatment selection.
Target specific residual symptoms/side effects via adjunctive medications.

Serotonin-Dopamine Agonists

Best evidence as adjunctive agents for depressive disorders or bipolar disorder types.
Lower doses used in comparison to psychosis or bipolar disorder.
Common side effects: Aripiprazole/brexpiprazole (akathisia, weight gain), Olanzapine (sedation, weight gain, metabolic effects), Quetiapine (sedation, weight gain, metabolic effects), Risperidone (hyperprolactinemia, sexual dysfunction, extrapyramidal symptoms).
Longer-term risks: Tardive dyskinesia, increased mortality in older adults, risk of breast cancer with prolactin-increasing agents.

Glutamate Modulators: Ketamine

NMDA receptor antagonism, reducing inhibition in neurons, with additional effects from AMPA receptor activation and Mu opioid receptor activation
Used often to treat treatment-resistant depression.
High efficacy for rapid reduction of suicidal ideation.
Rapid onset, max effect in 2-3 days, maintenance may require 1-4 weeks.
Common side effects include elevated blood pressure and dissociative symptoms.

Glutamate Modulators: Lamotrigine

A glutamate modulator primarily used in bipolar disorder.
Evidence supports use in unipolar treatment-resistant depression, with higher response rates in meta-analyses in comparison to monotherapy.
Use is associated with high risk of Stevens-Johnson syndrome (potentially fatal allergic reaction).
Requires low-dose initiation and controlled titration.
Considered a third-line treatment.

Stimulants

Mixed evidence regarding their effectiveness in MDD, whether for monotherapy or adjunctive treatment.
Potential effects include anxiety, irritability, jitteriness, tremors, headache, insomnia, and appetite/weight loss.
Tolerance toward stimulants may occur, resulting in less improvements in energy, motivation, and cognition over time.

Modafinil

Evidence consistently supports the use of modafinil as an adjunctive, second-line treatment, particularly compared to other stimulants.
Positive cognitive benefits are often documented, usually in executive functioning.

Lithium and Triiodothyronine

Both medications show supported evidence for efficacy.
Monitoring for lithium requires serum level monitoring; Triiodothyronine requires thyroid level monitoring.
CANMAT recommends them as second-line adjunctive treatment choices.

Pramipexole

A dopamine agonist demonstrated to have acute and longer-term antidepressant effects for MDD and bipolar depression
Superior efficacy (similar to SSRIs) is observed in small sampling RCTs.
Side effects: Nausea is the most common side effect.
Third-line adjunctive treatment choice.

Cannabis

No RCT supports use for MDD treatment, and evidence indicates cannabis worsens depression outcomes.
CANMAT does not recommend cannabis as a treatment approach.

Psychotherapy as Adjunct Treatment in DTD

First line:
- CBT
- IPT
- BA
Second line:
- MBCT
- PST
Other Evidence-Based Therapies/Third line:
- ACT
- STPP (short-term psychodynamic psychotherapy; evidence is less robust)
Combining medication with psychotherapy

Neuromodulation Treatments

Broad range of neuromodulation treatments are available for patients with treatment resistant depression, including:
- non-invasive e.g
- invasive
  - ECT
  - TMS
  - tDCS
  - VNS
  - DBS
  - MST

ECT Protocols

Recommended protocols for ECT and a table of guidelines for the various modalities for ECT.

ECT is Effective

Highly successful in treatment resistant depression (TRD)
Effective for older patients, those with psychosis or catatonia, and patients with severe depression
Relapse is common.

ECT: Protocol and Delivery

Acute course typically involves 6–12 sessions delivered twice or thrice per week.
Electrode placement and stimulus energy are commonly adjusted for optimal treatment effectiveness.
Specific procedural recommendations exist for optimal results, e.g. right unilateral pulse being slightly less effective but with fewer cognitive side effects as compared to bilateral approaches or bitemporal brief pulses (more effective but with higher cognitive burden)

ECT + Medications

Continuing antidepressants during ECT can enhance positive treatment outcomes.
Ketamine does not improve ECT outcomes.
Some medications such as benzodiazepines and anticonvulsants may interfere with ECT, while others (e.g., lithium and cannabis) worsen cognitive effects.

Safety and Side Effects

Generally, low risk of cardiac events and mortality (similar/comparable to risks with general anesthesia).
Transient side effects include confusion, disorientation, and anterograde amnesia, which are typically short-lasting.
While Cognitive outcomes after ECT are frequently positively observed; subjective cognitive dysfunction may remain, with variability and some controversy.

Relapse & Maintenance

High recurrence rates are common (60-80% within six months).
Maintenance strategies such as continuation ECT (gradual, increased interval) can be more effective for relapse prevention and are useful in comparison with pharmacotherapy (e.g., Lithium with nortriptyline or venlafaxine-XR being frequently superior to antidepressants alone).
Cognitive outcomes are similar between maintenance-ECT and pharmacotherapy, which means choice largely depends on prior success/failure, severity of episode, adverse effects, and patient preferences.

rTMS

rTMS stimulation of cortical neurons with focused magnetic pulses.
Sessions usually last 20–40 minutes, conducted daily for 4–6 weeks, delivered without anesthesia.
Protocols vary based on coil type, stimulation frequency, and number/duration of pulses (trains).
Several types such as high frequency, low-frequency and Theta-burst stimulations (TBS) have their specific uses (increasing verses decreasing excitability and thus targeting cortical networks).

rTMS Outcomes

Response rates range from 40-50% especially effective in treating treatment-resistant depression (TRD).
Specific stimulation (high vs low frequency) over specific areas of the brain (e.g., left dorsolateral prefrontal cortex [DLPFC] verses right DLPFC) are most effective.
Bilateral rTMS may be suitable in first-line treatment for treatment-resistant depression (TRD), particularly for patients with late-life depression.
Predictors of a reduced response may include prior failed treatment responses, elevated baseline severity and difficulty with managing depression or anxiety during the baseline tests.

rTMS for Treatment-Resistant Depression

FDA approved Stanford protocol.
Utilizes fMRI of the DLPFC (dorsolateral prefrontal cortex) for treatment-targeting
The protocol demonstrated a 86.4% remission rate within a 5-day open trial.
A recent RCT also yielded high remission rates (84.6%) within 3 weeks vs 7.1% for the sham treatment protocols.

rTMS: Summary Recommendations

Specific protocols for rTMS are outlined, based on varying types of stimulation, frequencies, and locations in the brain, e.g. ITBS and High-frequency rTMS to left DLPFC; low-frequency rTMS to right DLPFC; and Bilateral rTMS.

rTMS + Medication

Frequently combined with pharmacotherapy.
Antidepressants can positively influence outcomes, but benzodiazepines may decrease the efficacy of rTMS.

Transcranial Direct Current Stimulation (tDCS)

Delivers a constant, weak electrical current to the scalp to modulate cortical excitability.
Usually effective treatment for treating mild to moderate depression (particularly when combined with an anti-depressant medication).
Evidence is limited, resulting from issues with negative trials and flaws in study designs

Magnetic Seizure Therapy (MST)

An alternative to electroconvulsive therapy (ECT).
Induces generalized seizures using focused magnetic stimulation with high intensity and frequency to the vertex or frontal areas.
Showed similar efficacy to unilateral ultra brief-ECT in small studies.

Invasive NM: Vagus Nerve Stimulation (VNS)

Stimulates the left vagal nerve via implanted electrodes in the neck and pulse generator implanted near the chest wall, targeting the nucleus tractus solitarius.
Effective for treatment-resistant depression (TRD).
Generally well tolerated, but further large-scale/controlled studies are needed.
Side effects include pain and voice issues related to implantation.

Deep Brain Stimulation (DBS)

Neurosurgery involving the implantation of electrodes into specific brain areas (e.g., subcallosal cingulate cortex).
Subclavicular pulse generator delivers constant or intermittent electrical stimulation.
Studies suggest relatively limited evidence in the treatment of highly refractory cases.
Adverse effects are reported to be correlated with the surgery itself.

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This quiz explores key concepts of measurement-based care in mental health, including its components, benefits, and tools used for assessment. Questions cover screening tools like PHQ-2, implementation challenges, and treatment phases. Test your knowledge on how measurement-based care can improve mental health outcomes.