Major Depressive Disorder

Major Depressive Disorder Care Protocol will be implemented from January 2026 – HSG GPs may refer to updates from AIC for details on the implementation of these protocols.

Background

Mental health is an important aspect of overall general well-being. Major Depressive Disorder (MDD) is a significant chronic mental health condition of considerable morbidity.¹ The 12-month and lifetime prevalences of MDD in Singapore were 2.3% and 6.3% respectively in 2016.² MDD is a risk factor for suicide, accounting for up to 60% of suicides.³MDD often co-exists with chronic physical health conditions, which can lead to poorer health outcomes.⁴ For example, MDD can result in suboptimal diabetes self-care and has been linked to adverse diabetes, cardiovascular and stroke sequelae.^5-7

This protocol will focus on the management of MDD in persons aged 18 years and older in primary care. This protocol does not cover special populations such as children, adolescents or pregnant women. In addition to this care protocol, GPs should refer to the prevailing MOH ACE Clinical Guidances (ACGs) for clinical management and practices. For support and resources, GPs should refer to the “Practice Guide for Tiered Care Model for Mental Health (Adult)"⁸ and the “Community Mental Health Resource Kit for General Practitioners (GPs)".⁹

Clinical Approach

Overview

1. Figure 1 provides an overview of the recommended approach and management of patients diagnosed with MDD in primary care.

Figure 1. Overview of the Approach and Management of Patients diagnosed with MDD in Primary Care

Detection

Early detection of individuals at risk and do PHQ-2
If PHQ-2 score ≥3, further assessment with PHQ-9 is recommended
If PHQ-9 ≥10, consider MDD

Diagnostic Assessment

Use DSM-5 to diagnose MDD
Consider medical and drug-related factors
Consider other psychiatric conditions, especially anxiety and bipolar disorders
Assess MDD severity based on symptom profile, functional impairment and risk of harm (to self and others)
Assess suicide risk using C-SSRS, incorporating risk factors as well as protective factors, in conjunction with clinical judgement
Classify MDD severity (Figure 3) to guide management (Refer to Clinical Approach Paragraph 12)
Assess social factors (Refer to Clinical Approach Paragraph 14)

Management

Establish goals of care and treatment approach (Refer to Management Paragraph 1 & 2)
Treatment Domains (Table 3)

General lifestyle measures
Psychoeducation
Psychosocial Intervention
Pharmacotherapy (Refer to Management Paragraph 6)
Suicide risk management

Follow-Up (Figure 7)

Review patients regularly during treatment
Frequency of review:

Within 2 to 4 weeks of starting antidepressants to review for side effects, worsening mood symptoms (e.g., suicidal ideation) and potential emergence of hypomania/mania symptoms
Subsequently, 2 to 6 weekly reviews if titrating medications
Thereafter, follow up at 2 to 6 monthly intervals based on clinical need

Monitor response to treatment regularly
Continue treatment after remission to reduce relapse risk
Consider a period of review in patients who are in remission
Advise patients who are discharged when and how to seek help
Consider and refer special groups of patients to psychiatrists for specialist management (Refer to Considerations to Specialist Referral - Management Paragraph 8 and )

Early Detection

When to Assess

2. Routine screening for MDD in asymptomatic adults is not recommended^10,11

3. Be sensitive to clinical cues and dispositions in individuals who may be at increased risk of MDD and consider assessing them for MDD ^3,10,12-14

Assessment Tools

4. Consider administering the Patient Health Questionnaire-2 (PHQ-2) in individuals whose clinical presentation triggers a suspicion of MDD.

5. Individuals whose total score is ≥3 on the PHQ-2 can be further assessed using the PHQ-9 .¹⁵ Note that the two PHQ-2 questions are already in the PHQ-9, so only 7 additional questions need to be asked. Scoring ≥10 on the PHQ-9 suggests possible MDD and warrants further diagnostic assessment.

6. PHQ-2 and PHQ-9 are subjective reports of symptoms by individuals. Clinical judgement should be exercised when interpreting the results.

7. Community partners, schools or social agencies may detect individuals with suspected MDD and refer them to GPs for assessment. These individuals may already have completed the PHQ-2, PHQ-9 and PHQ-9 Functional Question.

Diagnostic Assessment

8. Assess and diagnose individuals for MDD using the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria . Key symptoms of MDD are highlighted in Table 1. Key Symptoms of MDD. (mnemonic: SIGECAPS¹⁶). This should form part of the overall clinical evaluation, which includes history taking, physical examination, mental state examination, relevant investigations and case formulation.

Table 1. Key Symptoms of MDD

(a) Depressed mood or loss of interest or pleasure most of the day, nearly every day, for at least 2 consecutive weeks plus 4 or more of the following symptoms:
Sleep	Insomnia or hypersomnia, nearly every day
Interest [if not in (a)]	Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day
Guilt	Feelings of worthlessness or excessive or inappropriate guilt nearly every day
Energy	Fatigue or loss of energy nearly every day
Concentration	Diminished ability to think or concentrate, or indecisiveness, nearly every day
Appetite	Significant weight loss or weight gain, or a decrease or increase in appetite nearly every day
Psychomotor	Psychomotor agitation or retardation nearly every day
Suicide	Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide

9. Evaluate and consider medical or drug-related conditions that may be associated with or contribute to MDD.^13,17-20 These lists are not exhaustive.

10. Evaluate and consider other psychiatric conditions that may manifest with similar symptoms as those of MDD .^17,18,20,21 In particular, the presence of manic and/or hypomanic episodes in the setting of major depressive episodes would suggest a diagnosis of bipolar disorder rather than MDD.

Figure 2. Components of MDD severity. (Source: 2025 MDD ACG)

11. Assess the severity of MDD by evaluating symptom profile, functional impairment and risk of harm (to self and others) to guide holistic management.²² (See Figure 2).

a. Symptom Profile: Assess the intensity, duration and comorbid mental health symptoms. Use of the PHQ-9^a is strongly encouraged to objectively measure MDD symptom severity.

b. Functional Impairment: Assess impairment in areas such as the capacity for self-care, social interactions, and the ability to perform school, workplace, household or caregiver responsibilities. Consider using the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) 12-item version as an initial measure of functional impairment.

c. Risk of Harm (to self and others):

i. Assess overall suicide risk by using the Columbia-Suicide Severity Rating Scale (C-SSRS), incorporating both risk and protective factors, in conjunction with clinical judgement, for patients who meet any of the criteria listed in Table 2.

Table 2. Patients who should be assessed for Suicide Risk

1	Patients reporting suicidal ideation and behaviour
2	Patients with PHQ-9 ≥20 (Severe)
3	Patients who score ≥1 for question 9 of the PHQ-9

Patients with high suicide risk (Red) require urgent psychiatric attention.

Refer here for suicide risk management. 

ii. Assess any intent or risk to harm others, such as family members or caregivers.

^aLocally, the PHQ-9 is commonly used to measure symptom severity, a core dimension of the patient’s overall symptom profile. Patients who score 0–4 on the PHQ-9 are unlikely to have clinically significant MDD. Should there be a strong clinical suspicion of MDD, GPs should consider further evaluation and assessment for MDD and/or other medical conditions.

12. Use Figure 3²² to classify the severity of MDD, which guides management, level of care needs and appropriate siting of care. Refer to PHQ-9 as a starting point for categorising MDD severity, with the other dimensions contributing to the overall holistic assessment. Refer to Table 3 which outlines the reference PHQ-9 scores and recommended care corresponding to each MDD severity level.

Figure 3. Holistic assessment of MDD severity (based on symptom profile, functional impairment, and risk of harm) (Source: 2025 MDD ACG)

‡ The PHQ-9 scores presented are in the context of patients diagnosed with MDD. According to the 2025 MDD ACG, a single PHQ-9 score range of 14 and below is employed for mild to moderate MDD, in recognition that some patients may initially screen with a low PHQ-9 score yet subsequently be diagnosed with MDD upon clinical assessment. In such cases, scores of 5 to 9 may represent mild severity, and accordingly scores of 10 to 14 may represent moderate severity.

13. Consider assessing patients with MDD for concurrent anxiety symptoms as:

a. Anxiety symptoms can manifest in depressive disorders (e.g. Anxiety subtype of MDD)

b. MDD and anxiety disorders can co-exist, which is associated with reduced likelihood of remission in MDD,^50,51 and thus represents a higher severity of illness. More extensive interventions may be warranted.

c. Patients with both MDD and anxiety disorders have an increased risk of suicide^23-26

14. Consider social factors as part of the assessment:

a. Family dynamics and support

b. Financial situation

c. Housing arrangement

d. Work situation

e. Relationships

f. Spiritual beliefs

Management

1. Goals of management are:^{13, 22}

a. Remission of depressive symptoms

b. Restoration of occupational and psychosocial functions

c. Prevention and reduction of relapse

2. General Principles.

a. Treatment for patients with MDD entails both an acute phase (to treat the presenting episode) and a maintenance phase (to prevent relapse) (Figure 4)^22,27,28

Figure 4. Treatment Phases of MDD (adapted) (Source: 2025 MDD ACG)

Aim of Acute Phase: To restore function and resolve symptoms (since remission of symptoms is associated with reduced risk of relapse)²⁸

Aim of Maintenance Phase: To sustain remission and reduce risk of relapse^29,30

b. Personalise the treatment approach based on MDD severity and other patient factors (Figure 5)²²

c. The mainstay treatment options for MDD in primary care are pharmacotherapy with antidepressants, psychological treatment (supportive counselling or psychotherapy) and a combination of both²²

d. Adopt a biopsychosocial model to manage MDD

e. Use a patient-centred care approach to set clear treatment goals, duration, and expectations

f. Promote patient empowerment through shared decision-making, psychoeducation and self-help

Figure 5. Patient factors that influence overall treatment approach of MDD (Source: 2025 MDD ACG)

3. Treatment Domains

a. General lifestyle measures

b. Psychoeducation

c. Psychosocial Intervention

d. Pharmacotherapy

e. Suicide risk management

4. The recommended management of MDD in primary care is summarised in Table 3.^1,2 GPs should exercise clinical discretion depending on the medical context, patient preferences and resource availability, when deciding the appropriate escalation of care and referring to suitable interventions.

5. For patients who do not fulfil the diagnostic criteria for MDD or have no significant functional impairment or have no to minimal symptoms of low mood, GPs may refer to for the management and resources available.

Table 3. Summary of Management of MDD in Primary Care^1,22 [Reference: PGTCMMH(Adult) and 2025 MDD ACG]

MDD Severity	Mild to Moderate		Moderate to Severe	Severe
MDD Severity Sub-classification	Mild	Moderate
Reference PHQ-9 Score	5–9	10–14	15–19	20–27
Corresponding Care Level under Tiered Care Model^b	Tier 2	Tier 3	Tier 3	Tier 4
Treatment Domains
General Lifestyle Measures	✅	✅	✅	✅
Psychoeducation	✅	✅	✅	✅
Psychosocial Intervention	Supportive Counselling or Psychotherapy and Social Intervention Refer to paired COMIT		Psychotherapy and Social Intervention Refer to paired COMIT	Refer to hospital Psychiatric services
Pharmacotherapy	For patients with mild to moderate MDD Offer psychological treatment (supportive counselling or psychotherapy) over antidepressants where feasible and acceptable		For patients with moderate-severe to severe MDD a. Offer a combination of a second-generation^c antidepressant with psychotherapy, or psychotherapy alone or b. Consider a second-generation antidepressant when psychotherapy is not feasible or acceptable
Pharmacotherapy			GPs should initiate and monitor, with the option to escalate to hospital psychiatric services	Refer to hospital Psychiatric services GPs to consider initiating with close follow-up while pending hospital psychiatric services
Suicide Risk Management	Assessment Use C-SSRS, incorporating both risk and protective factors, together with clinical judgement, to assess overall suicide risk in patients who: a. Report suicidal ideation and behaviour, or b. Score PHQ-9 ≥20 (Severe), or c. Score ≥1 for question 9 of the PHQ-9
Suicide Risk Management	Management In general: a. High Risk (Red): Refer urgently to hospital psychiatrists or A&E/IMH Emergency Departments (if indicated) for urgent assessment b. Medium Risk (Orange): Exercise clinical discretion based on the following factors to determine if patients can be managed in the community or require urgent assessment by hospital psychiatrists, A&E/IMH Emergency Departments: 1) Patient factors 2) Ability for close monitoring 3) Availability of suicide intervention services c. Low Risk (Yellow): Usually can be managed in the community with monitoring and support
Monitoring
Treatment Response	Assess symptom response (PHQ-9) and functional improvement^d (e.g., WHODAS 2.0) at regular intervals based on clinical needs
Treatment Response				Participate in continued shared care with hospital Psychiatric services.
Detection of Early Relapse	Consider reviewing patients in remission for a period to detect early signs of relapse, especially in those at increased risks

^bTier 1 initiatives are targeted towards healthy individuals who are coping well or have none to minimal symptoms of mental health conditions. The focus will be on promoting mental well-being and building resilience. These include curriculum that builds mental well-being and resilience in schools, digital self-help platforms and parents and community support groups.
^c2nd generation antidepressants refer to newer antidepressants after tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs).
^dThese assessments such as the PHQ-9 and WHODAS 2.0 may not be solely done by GPs and can be administered by other mental healthcare providers (e.g., COMIT) caring for the patients in a multi-disciplinary / multi-agency setting.

6. Psychosocial Intervention is a critical component of care in patients with MDD. Within the Tiered Care Model, GPs can collaborate with COMITs, which are allied health-led teams operated by Social Service Agencies, to deliver comprehensive, non-pharmacological mental health services to patients in the community. These services include mental health assessments and psychosocial interventions. The partnering COMIT to the GPs will be referred to as “paired COMIT” in this Care Protocol. For patients with chronic physical conditions and mild MDD under Tier 2, GPs may consider referring them to PCN nurses for counselling as an alternative approach.

7. Pharmacotherapy^{13,18,21,22,31-33}

a. Antidepressants are the mainstay of pharmacotherapy. Refer to Table 4 on the common classes of antidepressants.

b. Second generation antidepressants (e.g., SSRIs, SNRIs and other newer agents) are preferred over first-generation antidepressants (i.e., TCAs, MAOIs^e) due to their more favourable safety profiles, lower risk of toxicity and adverse effects.

c. Refer to Table 1 for key prescribing information to support the selection of commonly used antidepressants in primary care.

^e Monoamine oxidase inhibitors (MAOIs) are not recommended as the 1st line treatment of MDD due to its potentially serious adverse effect profile, drug-drug and drug-food interactions. MAOIs have a potent hypotensive effect. Use of MAOIs is contraindicated with other antidepressants and medications, such as tramadol and dextromethorphan, due to the risk of serotonin syndrome. MAOIs should be avoided with sympathomimetic agents as its combined use can provoke a hypertensive crisis. MAOIs prevent the breakdown of tyramine, and should not be taken with tyramine-rich containing food (e.g., aged cheeses, meat, fish and poultry) as this can trigger a hypertensive crisis (tyramine pressor response).^52,53

Table 4. Common Classes of Antidepressants

S/N	Class	Examples
1.	Selective serotonin reuptake inhibitor (SSRI)	Fluoxetine, fluvoxamine, escitalopram, sertraline
2.	Noradrenergic and specific serotonergic antidepressant (NaSSA)	Mirtazapine
3.	Serotonin-norepinephrine reuptake inhibitor (SNRI)	Venlafaxine, duloxetine
4.	Tricyclic antidepressant (TCA)	Amitriptyline, nortriptyline, imipramine, clomipramine

d. Refer to Figure 6 for starting and managing antidepressants in primary care

Figure 6. Starting and Managing Antidepressants in Primary Care

Starting Antidepressants

Select antidepressant

Consider desired drug characteristics, safety, side effect profile, drug-drug interactions, comorbid health conditions, ease of use, patient preference, drug availability and cost
Engage in shared decision-making with patient when selecting antidepressants
Refer Table 1 for a summary of antidepressants and their characteristics to guide drug selection

Start antidepressant at a low dose

To reduce the risk of adverse effects and facilitate adherence³⁴
Refer to Figure 1 on the advice to provide patients when starting them on antidepressants

Review response

Symptom improvement may occur as early as 2 weeks
Allow 4 to 12 weeks for full effect before making adjustments^37,38

Close monitoring during initiation

Monitor for transient worsening of mood symptoms, anxiety, and potential increased suicide ideation, especially in younger patients under 25 years of age or with pre-existing suicide risk^13,39-41
Risk of suicidal behaviour and self-harm highest during the initial 1 to 3 months after starting an antidepressant and 1 month after stopping an antidepressant42 (Refer to Suicide Risk Assessment and Suicide Risk Management)
Provide appropriate guidance on seeking medical attention and safety planning where necessary

Adjust treatment

If patients respond poorly to antidepressants or experience intolerable side effects, consider one or more of the following strategies listed in Figure 8
Should there be a need to switch antidepressants, refer to Table 4 and Table 5 and related text in the section for guidelines on switching

Managing Antidepressant Therapy

Divide antidepressant therapy into 2 treatment phases: acute and maintenance phases (Table 2)
Acute Phase

Continue antidepressants until remission of symptoms
Usually takes 6 to 16 weeks

Maintenance Phase

Continue antidepressants for at least 6 months after the acute phase to reduce occurrence of relapse
Patients with risk factors for relapse (Table 3) should be considered for a longer duration of treatment, up to 2 years or longer^22,28,35,36

Discontinuing antidepressants

Do not stop antidepressants abruptly to avoid discontinuation syndrome
Taper off antidepressants gradually^35,43 to minimise discontinuation symptoms^12,34
Slower tapering may be required in patients on antidepressants for longer duration

7. Follow-Up (Figure 7)

Figure 7. Follow-up of Patients with MDD in Primary Care

Monitoring Treatment

Aim

Review treatment goals and duration to promote adherence and compliance (Refer to Management Paragraph 1)
Discuss and address patients' concerns and expectations
Monitor for treatment response and side effects

Key Principles

Advise patients against abruptly stopping treatment as this can lead to relapses, worsening of existing symptoms or discontinuation symptoms (if patients are on antidepressants)
Continue treatment after remission to reduce relapse risk. The following treatments are effective:

Continuation of antidepressant treatment (Table 2)
Provision of psychological treatment (even with tapering of antidepressants)
Combination of psychological treatment and antidepressants

Frequency

Depends on the severity, type of treatment, phase of treatment and patient response
Review at regular intervals, especially at the initiation of antidepressants and step-down/discharge
General guide on monitoring intervals^31,44

Within 2 to 4 weeks of starting antidepressants to review for side effects, worsening mood symptoms (e.g., suicidal ideation) and the potential emergence of hypomania/mania symptoms
Subsequently, 2 to 6 weekly reviews of titrating antidepressants
Thereafter, follow-up at 2 to 6 monthly intervals based on clinical need

Tools

Symptom Response: Consider using PHQ-9
Functional Improvement: Consider using WHODAS 2.0 12-item version

Adjusting Treatment

Patients with Suboptimal Response

Assess and address possible reasons if treatment response remains suboptimal after an adequate treatment trial (about 4 to 12 weeks of antidepressant at the appropriate therapeutic dose and/or about 8 to 9 sessions of psychotherapy), such as:²²

Ongoing psychosocial stressors and poor coping mechanism
Suboptimal treatment adherence
Diagnostic inaccuracy or presence of other mental health conditions
Comorbid conditions that may limit response to treatment or mimic depression symptoms such as fatigue

If above is ineffective, adjust management by referring to Figure 8 for recommended strategies²²

Patients who default Treatment

Reassess and restart treatment at the appropriate intensity and duration
Evaluate and address barriers to treatment compliance

Patients in Remission

Consider a period of review for patients who have completed treatment and are in remission, especially those who may be at increased risk of relapses (Table 3)^22,28,35,36
Rate of relapse is highest in the first several months after stopping treatment, with one-third to half occurring within one year^45-48
Suggested frequency and duration of review can be as follows:

1 month after completion
Subsequently, at 3 to 6 months
Thereafter, may discharge from care (or consider review at 6 to 12 months before discharge)

Advise patients who are well and discharged from care on when and how to seek help should they experience a relapse

Figure 8. Changes in management strategy when initial response is suboptimal (Source: 2025 MDD ACG)

9. Considerations for Specialist Referral

a. Consider referring special groups of individuals diagnosed with MDD for specialist psychiatric care

b. Consider referring individuals urgently to hospital psychiatric services or A&E/IMH Emergency Departments for same-day management (if indicated) if the individual has:

i. Severe functional impairment
ii. Severe psychotic symptoms (e.g., hallucinations, delusions, disorganized speech/behaviour and apathy)
iii. High risk of harm to self (e.g., High suicide risk). Refer to Suicide Risk management
iv. High risk of harm to others

c. In general, GPs can manage up to moderate-severe MDD with training

d. While patients with severe MDD should be referred to hospital psychiatric services, GPs participating in the Mental Health GP Partnership Programme (MHGPP) may manage patients up to severe MDD, if deemed appropriate and are adequately resourced

e. GPs involved in shared care can manage MDD of greater severity and complexity, depending on the care pathways, support and resources provided by the shared care programmes.

10. Recommended Care Components⁴⁹ (Table 5)

Recommended Care Components	Minimum Frequency*	Remarks
PHQ-9 score	At the intake assessment, prior to step-down/discharge and 6-monthly
WHODAS 2.0	Annually	Administer at first consultation, and at 6-monthly or at discharge whichever is earlier

*More frequently if clinically indicated

Data Submission

The following data fields should be documented in GPs' case notes as part of good clinical practice for all patients enrolled to their practice.

Submission of data fields marked with asterisks* is mandatory and required for the Healthier SG Annual Service Fee payments.

Diagnosis

1. Diagnosis*

2. CDMP Condition(s)*

3. Diagnosis Year

Symptom Severity/ Response Assessment

1. PHQ-9 at initial diagnosis, and 6-monthly intervals or at step-down/discharge (whichever earlier)*

2. Date of administering PHQ-9*

3. Date of patients' attendance at psychosocial counselling*

Financing

CHAS/PG/MG cardholders who are Healthier SG enrollees will be eligible for the Healthier SG Chronic Tier, which provides percentage-based subsidies for a whitelist of drug products sold within the MOH price caps. When making claims, GPs will need to submit the quantities and selling prices for each whitelisted drug product prescribed.

Details on the GP Annual Service Fee for enrollees with MDD can be found in the Healthier SG Enrolment Programme Agreement.

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