📋 Key Information Summary
- Tiredness is one of the most common presenting complaints in Australian general practice, accounting for an estimated 5–10% of all consultations.
- The Murtagh Diagnostic Model provides a systematic framework: consider the most common conditions first, then the most serious, then conditions that are commonly missed (masquerades).
- The Seven Masquerades of Tiredness are: depression, diabetes mellitus, thyroid disease, anaemia, obstructive sleep apnoea, medication adverse effects, and occult malignancy.
- Key investigations in the initial work-up include FBC, ESR, UEC, LFTs, TFTs, fasting glucose/HbA1c, ferritin, vitamin B12, folate, and urinalysis.
- Chronic fatigue syndrome (CFS/ME) is a clinical diagnosis of exclusion, formally defined by the 2015 IOM criteria requiring ≥6 months of profound fatigue with post-exertional malaise, unrefreshing sleep, and cognitive impairment or orthostatic intolerance.
- Post-exertional malaise (PEM) is the hallmark feature distinguishing CFS/ME from other causes of fatigue and must be present for diagnosis.
- Management of CFS/ME is multimodal: activity pacing, sleep hygiene, graded activity (not graded exercise therapy in the traditional sense), symptom-targeted pharmacotherapy, and psychological support.
- In children, tiredness is most commonly caused by inadequate sleep, psychological stress, or viral illness; CFS/ME affects approximately 0.5–1% of Australian adolescents.
- In the elderly, fatigue may indicate serious pathology including malignancy, cardiac failure, depression, polypharmacy, or sarcopenia — do not dismiss as "normal ageing."
- Aboriginal and Torres Strait Islander peoples experience fatigue at significantly higher rates due to chronic disease burden, iron deficiency, renal disease, rheumatic heart disease, and social determinants of health.
- Medication review is essential — common offenders include beta-blockers, statins, SSRIs, antihistamines, opioids, anticonvulsants, and proton pump inhibitors.
- A structured re-assessment at 4–6 weeks with repeat investigation is recommended if no cause is identified at initial presentation.
Introduction & Australian Epidemiology
Tiredness and fatigue represent one of the most prevalent presenting complaints in Australian general practice. The terms are often used interchangeably by patients, though clinicians distinguish between subjective tiredness (a desire to sleep), fatigue (a lack of physical or mental energy), and weakness (objective loss of muscle strength). A systematic diagnostic approach is essential because fatigue may be the presenting feature of a wide range of conditions — from benign lifestyle factors to life-threatening malignancy.
The Royal Australian College of General Practitioners (RACGP) recognises fatigue as a "symptom-based encounter" requiring a structured assessment to avoid premature closure. Australian data from the Bettering the Evaluation and Care of Health (BEACH) study indicated that fatigue or tiredness was the principal reason for approximately 1.6 million GP consultations annually, making it among the top ten reasons for encounter.
Australian Burden of Disease
- Prevalence of persistent fatigue in the Australian adult population is estimated at 10–15%, rising to 20–25% in primary care cohorts.
- Chronic fatigue syndrome (CFS/ME) affects an estimated 0.4–1.0% of the Australian population (approximately 100,000–250,000 people), according to Emerge Australia.
- Fatigue is a major contributor to work productivity loss, with the Australian Institute of Health and Welfare (AIHW) reporting significant economic burden from chronic fatigue-related disability.
- Aboriginal and Torres Strait Islander peoples experience disproportionately higher rates of fatigue, driven by higher prevalence of chronic kidney disease, type 2 diabetes, rheumatic heart disease, iron deficiency, and obstructive sleep apnoea.
Safety netting: Always exclude serious "red flag" causes — malignancy, cardiac failure, temporal arteritis, severe anaemia, Addison's disease — before attributing fatigue to a benign or functional aetiology. Unintentional weight loss, night sweats, lymphadenopathy, new headaches in an older patient, or progressive functional decline warrant urgent investigation.
Tiredness Diagnostic Model & Seven Masquerades
John Murtagh's diagnostic model provides the foundational framework for approaching undifferentiated symptoms in Australian general practice. Applied to tiredness, the model requires clinicians to think through five levels of diagnostic possibility in a structured sequence.
Murtagh's Diagnostic Framework Applied to Tiredness
1
Most Common Conditions
Depression and anxiety, lifestyle factors (sleep deprivation, overwork, sedentary behaviour), viral illness (post-viral fatigue), iron deficiency anaemia, thyroid dysfunction, type 2 diabetes mellitus.
2
Most Serious Conditions
Occult malignancy (especially haematological, gastrointestinal, lung), cardiac failure, Addison's disease (adrenal insufficiency), temporal arteritis, chronic infections (HIV, TB, endocarditis), severe anaemia (haematological cause), multiple sclerosis.
3
Conditions Commonly Missed (Masquerades)
See the Seven Masquerades table below — conditions that frequently present as "simple tiredness" but require specific targeted investigation.
4
Is the Patient Trying to Tell Me Something?
Consider psychosocial factors: domestic violence, workplace bullying, financial stress, carer burnout, grief, substance misuse. Fatigue may be a somatic expression of distress.
5
Could This Be a Medication Side Effect?
Comprehensive medication review — prescription, over-the-counter, and complementary medicines. Common fatigue-inducing agents include beta-blockers, statins, antidepressants, antihistamines, opioids, gabapentinoids, and proton pump inhibitors.
The Seven Masquerades of Tiredness
The following seven conditions are the classic "masquerades" — they frequently present with fatigue as the dominant or sole symptom and can be missed if not actively considered.
| Masquerade | Key Clues | First-Line Investigations |
|---|---|---|
| Depression | Low mood ≥2 weeks, anhedonia, early morning waking, appetite change, guilt, poor concentration. Use PHQ-9 or DASS-21. | Clinical diagnosis. Screen with PHQ-9 (MBS item 701–707 for GP Mental Health Treatment Plan). FBC, TFTs to exclude organic causes. |
| Diabetes Mellitus | Polyuria, polydipsia, blurred vision, recurrent infections, family history, central obesity, high-risk ethnicity. | Fasting venous glucose ≥7.0 mmol/L, HbA1c ≥6.5% (48 mmol/mol), or oral glucose tolerance test (OGTT). Point-of-care HbA1c acceptable for screening. |
| Thyroid Disease | Hypothyroidism: weight gain, cold intolerance, constipation, dry skin, bradycardia. Hyperthyroidism: weight loss, heat intolerance, tremor, anxiety, palpitations. | TSH (first-line), free T4, free T3 if TSH abnormal. Thyroid peroxidase antibodies (anti-TPO) if autoimmune thyroiditis suspected. |
| Anaemia | Pallor, dyspnoea on exertion, pica, koilonychia, menorrhagia, GI blood loss, dietary restriction. | FBC with film, ferritin, transferrin saturation, B12, folate. Iron studies essential — ferritin <30 µg/L warrants treatment even if Hb is normal (latent iron deficiency). Reticulocyte count if haemolysis suspected. |
| Obstructive Sleep Apnoea | Snoring, witnessed apnoeas, morning headaches, daytime somnolence (Epworth Sleepiness Scale ≥10), neck circumference >43 cm, BMI >30, retrognathia. | Epworth Sleepiness Scale, STOP-BANG questionnaire. Referral for polysomnography (Medicare-rebatable with specialist referral, MBS item 12203/12250). |
| Medication Effects | Temporal correlation with drug initiation or dose change. Polypharmacy (≥5 medications). Common offenders: beta-blockers, statins, SSRIs/SNRIs, antihistamines (first-generation), opioids, benzodiazepines, gabapentin, pregabalin, PPIs. | Medication review (Home Medicines Review — MBS item 900). Deprescribing trial under supervision where safe. |
| Occult Malignancy | Unintentional weight loss >5%, night sweats, lymphadenopathy, new lumps, haematuria, melaena, change in bowel habit, persistent cough, bone pain. Age >50 with unexplained fatigue. | FBC (lymphoproliferative disorder), ESR/CRP, LDH, serum protein electrophoresis, CT if indicated. Age-appropriate cancer screening (bowel — FOBT; cervix; breast; skin). |
Red flags requiring urgent investigation: Unexplained weight loss >5% in 6 months, lymphadenopathy, temporal tenderness/headache in patient >50 years (giant cell arteritis), new systolic murmur with fatigue (endocarditis/valvular disease), severe fatigue with hypotension and hyperpigmentation (Addison's disease), haematuria, or rectal bleeding.
Key History, Examination & Investigations
Structured History Approach
Onset & Temporal Pattern
- Acute (<1 month): consider infection, acute illness, medication change, stressor
- Subacute (1–6 months): consider malignancy, endocrine, autoimmune
- Chronic (>6 months): consider CFS/ME, depression, chronic disease
- Diurnal variation: morning fatigue → depression, hypothyroidism; afternoon/evening → organic disease, overwork
Associated Symptoms
- Weight change (gain: hypothyroid, depression; loss: malignancy, hyperthyroid, diabetes)
- Sleep disturbance (insomnia, hypersomnia, unrefreshing sleep, snoring)
- Pain (widespread: fibromyalgia; joint: autoimmune; headache: GCA)
- Psychological (mood, anxiety, stress, memory)
- Autonomic symptoms (dizziness, palpitations — consider POTS, Addison's)
Red-Flag Screening Questions
- "Have you lost weight without trying?"
- "Do you have any new lumps or bumps?"
- "Have you noticed blood in your urine or stools?"
- "Do you wake up drenched in sweat at night?"
- "Are you finding it harder to exercise, or getting breathless with activities you used to manage?"
- "Do you feel safe at home?"
Physical Examination
| System | Examination Focus | Suggesting |
|---|---|---|
| General | Vital signs (BP, HR, temp, BMI), pallor, jaundice, cachexia, hydration | Orthostatic hypotension (Addison's, autonomic); tachycardia (thyrotoxicosis, anaemia, infection) |
| HEENT | Conjunctival pallor, thyromegaly, lymphadenopathy (cervical/supraclavicular), temporal artery tenderness | Anaemia, thyroid disease, lymphoma, GCA |
| Cardiovascular | Murmurs, gallop rhythm, JVP elevation, peripheral oedema | Heart failure, valvular disease, endocarditis |
| Respiratory | Crackles, wheeze, reduced air entry | COPD, pulmonary fibrosis, pleural effusion (malignancy) |
| Abdominal | Hepatomegaly, splenomegaly, masses, ascites | Malignancy, chronic liver disease, haematological disorder |
| Musculoskeletal | Proximal weakness (stand from chair without arms), temporal artery thickening | Polymyalgia rheumatica, GCA, myopathy (statins) |
| Neurological | Tone, power, reflexes, sensory testing, Romberg's | Multiple sclerosis, B12 deficiency neuropathy, myasthenia |
| Skin | Hyperpigmentation (palmar creases, buccal mucosa), dry skin, brittle nails, hair loss | Addison's disease, hypothyroidism, iron deficiency |
Investigations — Tiered Approach
ESSENTIAL
Full Blood Count (FBC) with film
Detects anaemia, haematological malignancy, infection. PBS-listed, universally available. MBS item 65070.
ESSENTIAL
Urea, Electrolytes, Creatinine (UEC)
Renal function, dehydration, electrolyte disturbance. MBS item 66500.
ESSENTIAL
Liver Function Tests (LFTs)
Hepatic dysfunction, cholestasis, infiltrative disease. MBS item 66515.
ESSENTIAL
Thyroid Function Tests (TSH ± fT4, fT3)
First-line: TSH. If TSH abnormal → fT4 ± fT3. Anti-TPO if autoimmune thyroiditis suspected. MBS item 66716.
ESSENTIAL
Fasting Glucose & HbA1c
Screening for diabetes mellitus and pre-diabetes. Venous glucose preferred over point-of-care. MBS item 66555.
ESSENTIAL
Iron Studies (ferritin, iron, transferrin saturation)
Iron deficiency is the most common cause of fatigue in women of reproductive age. Treat if ferritin <30 µg/L regardless of Hb. MBS item 66080.
SECOND-LINE
Vitamin B12 & Folate
Especially in elderly, vegans/vegetarians, patients on metformin or PPIs, or macrocytosis on FBC. MBS item 66820/66830.
SECOND-LINE
ESR & CRP
Inflammatory markers — elevated in GCA, polymyalgia rheumatica, malignancy, chronic infection, autoimmune disease. MBS item 65070.
SECOND-LINE
Urinalysis
Glycosuria, proteinuria, haematuria. May indicate diabetes, renal disease, or urinary tract malignancy. Point-of-care or lab.
IF INDICATED
Cortisol (9 am serum cortisol ± short Synacthen test)
If clinical features of Addison's disease: hyperpigmentation, postural hypotension, hyponatraemia, hyperkalaemia. Specialist test — refer to endocrinology.
IF INDICATED
HIV Serology
Consider in patients with risk factors, unexplained fatigue, weight loss, lymphadenopathy, or recurrent infections. With patient consent.
SPECIALIST
Polysomnography (Sleep Study)
For suspected OSA. Requires specialist referral — Medicare-rebatable (MBS item 12203 for full polysomnography). Bulk-billing availability varies by state.
Chronic Fatigue Syndrome (CFS/ME) — Criteria & Management
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, chronic, multisystem neuroimmune condition characterised by profound fatigue that is not explained by other medical conditions and is not substantially alleviated by rest. The preferred terminology in Australia, endorsed by Emerge Australia, is ME/CFS.
Diagnostic Criteria — 2015 IOM (NAM) Criteria
The 2015 Institute of Medicine (now National Academy of Medicine) criteria are the most widely accepted current diagnostic framework. All three mandatory symptoms must be present for ≥6 months and be of moderate to severe intensity.
Mandatory diagnostic symptoms (all three required):
- Substantial reduction or impairment in the ability to engage in pre-illness levels of activity, persisting >6 months, accompanied by fatigue that is profound, of new onset (not lifelong), not the result of excessive exertion, and not substantially alleviated by rest.
- Post-exertional malaise (PEM) — worsening of symptoms after physical, cognitive, or emotional exertion that would not have caused problems before illness. Often delayed by 12–72 hours and prolonged.
- Unrefreshing sleep.
Plus at least one of:
- Cognitive impairment (impaired memory, concentration, information processing).
- Orthostatic intolerance (worsening of symptoms upon standing, lightheadedness, or syncope).
Conditions to Exclude Before Diagnosis
| Category | Conditions to Exclude | Investigation |
|---|---|---|
| Endocrine | Hypothyroidism, Addison's disease, diabetes mellitus, adrenal insufficiency | TSH, cortisol, HbA1c |
| Haematological | Iron deficiency anaemia, B12 deficiency, haematological malignancy | FBC, iron studies, B12, folate |
| Infectious | HIV, hepatitis B/C, tuberculosis, chronic infection, Lyme disease | Serology, cultures as indicated |
| Autoimmune | SLE, rheumatoid arthritis, Sjögren's syndrome, coeliac disease | ANA, anti-dsDNA, RF, anti-CCP, coeliac serology (tTG-IgA) |
| Neurological | Multiple sclerosis, myasthenia gravis, narcolepsy | MRI brain, nerve conduction studies (specialist) |
| Psychiatric | Major depressive disorder (note: can be comorbid), somatic symptom disorder | PHQ-9, clinical assessment (depression alone does not exclude ME/CFS if PEM is present) |
| Sleep | Obstructive sleep apnoea, restless legs syndrome | Polysomnography if indicated |
| Medication | Drug-induced fatigue (beta-blockers, statins, antidepressants, opioids) | Medication review, deprescribing trial |
Important distinction: Post-exertional malaise (PEM) is the cardinal feature that differentiates ME/CFS from other fatigue states. If a patient reports that physical or mental exertion reliably worsens their symptoms for days afterwards, this should raise strong suspicion for ME/CFS regardless of other comorbidities.
Severity Grading
Mild
~50% reduction in activity
Can still work or study with modifications. Reduced social and leisure activities. Needs rest periods.
Setting: Primary care management
Moderate
~70% reduction in activity
Unable to work or attend school full-time. Significant mobility limitations. Requires assistance with daily tasks on bad days.
Setting: GP + allied health + consider specialist
Severe
>90% reduction in activity
Housebound or bedbound. Unable to perform basic self-care. May be tube-fed, sensitive to light/sound/touch. Often unable to leave the house.
Setting: Specialist care, multidisciplinary, home visits
Management of ME/CFS
There is currently no cure for ME/CFS. Management is focused on symptom relief, functional optimisation, and quality-of-life improvement. A patient-centred, multidisciplinary approach is essential.
Non-Pharmacological Management
1
Activity Pacing
The cornerstone of ME/CFS management. Patients learn to balance activity and rest to avoid triggering PEM. Activities are planned within the patient's "energy envelope." The goal is consistency, not escalation. This is distinct from graded exercise therapy (GET).
2
Sleep Hygiene & Management
Consistent sleep-wake schedule, sleep restriction therapy if hypersomnia present, address sleep disorders (restless legs, OSA), avoid stimulants before bed, dark/quiet environment. Melatonin may assist with circadian rhythm regulation.
3
Cognitive Support
Cognitive aids (lists, diaries, alarms), breaking tasks into manageable segments, avoiding cognitive overexertion during PEM episodes. Occupational therapy referral for adaptive strategies.
4
Psychological Support
Acceptance and commitment therapy (ACT), mindfulness-based stress reduction, counselling for adjustment and grief. Not as a "cure" but for coping with chronic illness. Note: traditional CBT as a treatment for ME/CFS itself is no longer recommended by NICE 2021 guidelines.
Pharmacological Management
No medication is approved specifically for ME/CFS in Australia. Pharmacotherapy targets individual symptoms. Start low, go slow.
Amitriptyline
Endep® · Trypizol® · Tricyclic antidepressant
Indication
Sleep disturbance, pain, comorbid depression
Adult dose
10–25 mg PO nocte, titrate to 50–75 mg nocte as tolerated
Paediatric dose
Not routinely recommended <12 years for ME/CFS; specialist guidance required
Renal adjustment
Use with caution in severe renal impairment; no specific dose adjustment in eTG
Key cautions
Anticholinergic effects, drowsiness, weight gain, QT prolongation. Avoid in significant cardiac disease.
PBS status
✔ PBS General Benefit
Low-Dose Melatonin
Circadin® · Modified-release melatonin
Indication
Circadian rhythm disturbance, unrefreshing sleep
Adult dose
2 mg PO 1–2 hours before bedtime; immediate-release 0.5–3 mg off-label used
Paediatric dose
Modified-release: ≥55 years only (Circadin PBS); immediate-release: 1–3 mg off-label under specialist guidance
Key cautions
Generally well tolerated. Drowsiness, headache. Avoid driving after dose.
PBS status
🔶 PBS Authority Required (≥55 years, insomnia ≥4 weeks)
Duloxetine
Cymbalta® · SNRI antidepressant
Indication
Comorbid depression, widespread pain, neuropathic pain
Adult dose
30 mg PO daily for 1 week, then 60 mg PO daily
Renal adjustment
Avoid if eGFR <30 mL/min/1.73 m²
Hepatic adjustment
Avoid in hepatic impairment
Key cautions
Nausea (common initially), serotonin syndrome risk with other serotonergic agents, discontinuation syndrome.
PBS status
✔ PBS General Benefit
Low-Dose Naltrexone (off-label)
Naltrexone compounding · Opioid antagonist (off-label)
Indication
Pain, fatigue, brain fog in ME/CFS — emerging evidence, used off-label
Adult dose
1.5–4.5 mg PO nocte (compounded); start at 0.5 mg, titrate weekly
Key cautions
Must not be used concurrently with opioid analgesics. Vivid dreams, nausea. Limited RCT evidence — primarily observational and small trials.
PBS status
✘ Not PBS listed (compounded, private prescription)
Australian Resources & Support
- Emerge Australia — the peak body for ME/CFS in Australia (emerge.org.au). Provides patient resources, GP education, and advocacy.
- NICE Guidelines 2021 (UK) — the most current evidence-based clinical guideline, which de-emphasised GET and CBT as treatments and centred pacing and energy management.
- Disability Support — patients with severe ME/CFS may be eligible for the National Disability Insurance Scheme (NDIS) or Disability Support Pension (DSP).
- Centrelink/Medicare — Chronic Disease Management (CDM) items (MBS items 721, 723) enable GP Management Plans and Team Care Arrangements with allied health (up to 5 allied health visits per calendar year).
Do not recommend: Unsupervised graded exercise therapy (GET) for ME/CFS. The 2021 NICE guidelines removed GET as a recommended treatment due to evidence of harm. Activity must be guided by the patient's energy envelope, with the goal of avoiding PEM. Pushing through fatigue is counterproductive and may cause prolonged relapse.
Tiredness in Children & Elderly
Tiredness in Children & Adolescents
Fatigue is a common presenting complaint in paediatric practice. The differential diagnosis varies significantly by age group, and a careful developmental and psychosocial history is essential.
Common Causes by Age
| Age Group | Common Causes | Key Considerations |
|---|---|---|
| Infants (0–12 months) | Inadequate feeds, iron deficiency, congenital heart disease, infection, sleep fragmentation | Assess growth, feeding history, sleep diary. FBC, ferritin if poor diet or prolonged breastfeeding without solids. |
| Toddlers & Pre-school (1–5 years) | Inadequate sleep, screen time, iron deficiency, coeliac disease, recurrent viral illness, obstructive sleep apnoea (adenotonsillar hypertrophy) | Sleep requirements: 10–13 hours/day (1–3 years), 10–12 hours/day (3–5 years). Snoring and mouth breathing warrant ENT assessment. |
| School-age (5–12 years) | Insufficient sleep, bullying, academic stress, iron deficiency, coeliac disease, ME/CFS, depression, post-viral fatigue | Screen time and social media use a significant contributor. FBC, iron studies, coeliac serology (tTG-IgA), TFTs. |
| Adolescents (12–18 years) | Delayed sleep phase disorder, academic/social stress, depression, anxiety, iron deficiency (menstruating females), ME/CFS, substance use | Australian adolescents average 6.5 hours sleep (recommended: 8–10 hours). Assess for self-harm risk, substance use. ME/CFS prevalence ~0.5–1% in this age group. |
Sleep requirements in Australian children: The Australian 24-Hour Movement Guidelines recommend: infants 12–16 hours (including naps), toddlers 11–14 hours, pre-schoolers 10–13 hours, school-age 9–11 hours, and adolescents 8–10 hours per 24-hour period.
Paediatric ME/CFS
- Affects 0.5–1.0% of Australian adolescents; more common in girls post-puberty.
- Often triggered by Epstein-Barr virus (glandular fever) or other acute infections.
- Diagnosis criteria are the same as adults (2015 IOM) but adapted: ≥6 months of fatigue with PEM, unrefreshing sleep, and cognitive impairment.
- School avoidance and reduced attendance is a key functional marker. Liaise with school for modified attendance and workload.
- Management: pacing, sleep hygiene, graded return to school activity (within energy envelope), psychological support. Avoid GET.
- Referral: paediatrician, paediatric rheumatologist, or specialist ME/CFS clinic where available.
Tiredness in the Elderly (≥65 years)
Fatigue in older Australians is common but should never be dismissed as a normal consequence of ageing. Up to 30% of community-dwelling adults over 65 report persistent fatigue, and it is an independent predictor of falls, disability, hospitalisation, and mortality.
Common Causes in the Elderly
| Category | Conditions |
|---|---|
| Cardiac | Heart failure (especially HFpEF), atrial fibrillation, valvular disease, ischaemic heart disease |
| Endocrine | Hypothyroidism, type 2 diabetes, adrenal insufficiency, vitamin D deficiency |
| Haematological | Iron deficiency (GI blood loss, poor intake), B12/folate deficiency, myelodysplastic syndrome, chronic disease anaemia |
| Malignancy | Colorectal, lung, prostate, haematological (myeloma, lymphoma, leukaemia) |
| Metabolic | Chronic kidney disease, electrolyte disturbance (hyponatraemia, hypercalcaemia) |
| Psychiatric | Depression (prevalence 10–15% in elderly), anxiety, grief, social isolation |
| Medications | Polypharmacy is the single most modifiable cause — average Australian aged ≥75 takes 7 medications |
| Frailty & Sarcopenia | Age-related muscle loss, deconditioning, nutritional insufficiency, reduced physical activity |
| Sleep | Obstructive sleep apnoea, nocturia, chronic pain, restless legs syndrome |
Investigation Approach in the Elderly
- Essential: FBC, UEC, LFTs, TFTs, HbA1c, iron studies, B12, folate, calcium, phosphate, vitamin D (25-OH), ESR/CRP, urinalysis, ECG.
- Consider: serum protein electrophoresis (myeloma screen — especially if raised ESR, anaemia, renal impairment), cortisol if clinical suspicion, chest X-ray, faecal occult blood test.
- Medicine review — arrange a Home Medicines Review (HMR; MBS item 900) or Residential Medication Management Review (RMMR; MBS item 903). Deprescribing is a key intervention.
- Assess nutritional status — Mini Nutritional Assessment (MNA), unintentional weight loss, albumin (limited utility as acute-phase reactant).
- Screen for frailty — Clinical Frailty Scale (CFS), FRAIL questionnaire, or gait speed assessment.
Do not normalise fatigue in older patients. Fature in an older person is a symptom that warrants investigation, not acceptance. It may be the presenting feature of heart failure, occult malignancy, giant cell arteritis, or adrenal insufficiency — all treatable and some life-threatening if missed.
Special Populations
Pregnancy
Physiological fatigue
Fatigue is extremely common, especially in the first trimester and third trimester. Rule out pathological causes: iron deficiency (check ferritin — target >30 µg/L), thyroid dysfunction (TSH changes in pregnancy — trimester-specific reference ranges), gestational diabetes, UTI, depression.
Iron supplementation
Ferrous sulfate 325 mg PO daily (elemental iron ~105 mg) if ferritin <30 µg/L. PBS General Benefit. If oral intolerant, IV iron (ferric carboxymaltose) may be indicated under obstetric supervision.
Medication caution
Amitriptyline and duloxetine require careful risk-benefit assessment in pregnancy. Melatonin: insufficient safety data. Refer to obstetric medicine specialist if CFS/ME management needed during pregnancy.
Paediatrics
Sleep is king
Inadequate sleep is the most common cause of tiredness in children. Screen time, late bedtimes, and delayed sleep phase disorder are major contributors. Enforce Australian 24-Hour Movement Guidelines.
Coeliac disease
Prevalence ~1:70 in Australian children. May present with fatigue, growth faltering, iron deficiency. Screen with tTG-IgA + total IgA. Confirm with small bowel biopsy. Refer to paediatric gastroenterology.
Psychosocial screening
Bullying (including cyberbullying), academic pressure, family dysfunction, and social isolation are common causes. Use HEADSS assessment in adolescents.
Renal Impairment
CKD-related fatigue
Fatigue is the most commonly reported symptom in CKD stages 3–5. Mechanisms include anaemia (EPO deficiency), uraemia, metabolic acidosis, electrolyte disturbance, and depression. Check eGFR, FBC, iron studies, EPO level if anaemia present.
Drug dosing
Adjust doses of gabapentin, pregabalin, duloxetine (avoid if eGFR <30), and many analgesics. Avoid NSAIDs. Refer to renal guidelines or Therapeutic Guidelines for renal dosing.
Hepatic Impairment
Chronic liver disease
Fatigue is a prominent symptom in chronic hepatitis B/C, autoimmune hepatitis, non-alcoholic fatty liver disease (NAFLD), and cirrhosis. Check LFTs, hepatitis serology, hepatic ultrasound. Consider FibroScan or APRI score for fibrosis staging.
Drug metabolism
Reduce doses of hepatically cleared drugs (duloxetine, amitriptyline) in significant hepatic impairment. Avoid duloxetine in hepatic insufficiency.
Immunocompromised
HIV-related fatigue
Fatigue affects up to 60% of people living with HIV. Causes include the virus itself, ART side effects, opportunistic infection, depression, and hormonal deficiency (testosterone, thyroid). Screen with FBC, viral load, CD4 count, TFTs, testosterone (if male), cortisol.
Post-transplant and immunosuppressant fatigue
Tacrolimus, ciclosporin, mycophenolate, and corticosteroids can all cause fatigue. Monitor drug levels and screen for infections. Refer to transplant team for medication adjustment.
Post-COVID fatigue
Persistent fatigue following SARS-CoV-2 infection (long COVID) is increasingly recognised. Overlaps significantly with ME/CFS if PEM present. Australian Long COVID clinics exist in most states. See NHMRC guidance on post-COVID conditions.
Aboriginal and Torres Strait Islander Health Considerations
Aboriginal and Torres Strait Islander Health
Aboriginal and Torres Strait Islander peoples experience a significantly higher burden of fatigue-related conditions compared to non-Indigenous Australians. Fatigue in this population must be understood within a holistic framework that encompasses physical, social, emotional, cultural, and spiritual wellbeing — consistent with the Aboriginal definition of health in the National Aboriginal Health Strategy.
Key Contributors to Fatigue
Culturally Safe Practice
- Use a holistic, strengths-based approach. Acknowledge the social, emotional, and cultural determinants of health.
- Engage with local Aboriginal Health Workers and Aboriginal Liaison Officers for culturally appropriate history-taking and health education.
- Recognise that "sorry business" (bereavement and cultural obligations) can contribute significantly to fatigue and may require extended time away from work or school.
- Consider yarning-based approaches to clinical consultation where culturally appropriate.
- Ensure follow-up and recall systems are in place — Aboriginal and Torres Strait Islander peoples are eligible for Indigenous-specific Medicare items (MBS item 715 — Aboriginal and Torres Strait Islander health check) which facilitate comprehensive assessment including fatigue screening.
MBS Item 715 — Aboriginal and Torres Strait Islander Health Check: Available annually with no out-of-pocket cost. Provides a comprehensive health assessment that includes screening for chronic disease risk factors, mental health, and lifestyle factors contributing to fatigue. This item facilitates the initial assessment and is an ideal entry point for fatigue work-up. Up to 10 allied health services can follow under MBS item 715-related referrals.
📚 References
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- 2. Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Board on the Health of Select Populations; Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington (DC): National Academies Press; 2015.
- 3. National Institute for Health and Care Excellence (NICE). Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. NICE guideline [NG206]. London: NICE; 2021.
- 4. Emerge Australia. ME/CFS: A guide for GPs. Melbourne: Emerge Australia; 2023. Available from: emerge.org.au.
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