8th January 2024

Neurological Symptoms

Depression

The prevalence of depressive disorder in the UK general population is around 7.5%, but around 15% of palliative patients meet the diagnostic criteria for major depressive disorder, and many others exhibit depressive symptoms. For a diagnosis of depression, at least one of the core symptoms must be present for at least two weeks. Other associated symptoms, as shown below, should also be considered.

Palliative patients have additional risk factors for depression. This is especially true for those who are young, have advanced disease at diagnosis, are socially isolated, have poor symptom control, have had a decline in performance status, have a previous personal or family history of depression, and those with additional life stresses such as a recent bereavement or relationship breakdown.

The associated symptoms used to diagnose depression, as shown above, can be less useful in palliative patients who may have fatigue, appetite changes or sleep disturbances because of their disease or treatment.

Screening tools to help diagnose depression includes the PHQ-9, which is used in primary care. The Hospital Anxiety and Depression (HAD) questionnaire is largely focused on physical symptoms, so it may not be useful in a palliative setting, whilst the Brief Edinburgh Depression Scale (BEDS) has been shown to be more valuable in a palliative context.

Differentials for Depression in Palliative Patients

• Dementia
• Poorly controlled physical symptoms
• Medication side-effects, e.g., steroids, methyldopa, propranolol
• Brain metastases
• Metabolic – hypothyroidism, hypercalcaemia, B12/ folate deficiency

Management of Depression

Non-Pharmacological:

• Adequate symptom control and referral to palliative services if necessary
• Guided self-help programmes
• Cognitive Behavioural Therapy (CBT)
• Counselling

Pharmacological:

There is currently insufficient evidence to recommend one antidepressant over another, so choice should be based on the patient’s previous experience with antidepressants, likelihood of interactions with other medications and consideration of side effects. It is important to remember that antidepressants can take several weeks to work, so if someone is approaching end-of-life, there will be insufficient time for the medication to work.

• SSRIs e.g., sertraline, fluoxetine, citalopram
  • Side effects include nausea, vomiting, anorexia, diarrhoea, increased risk of gastrointestinal (GI) bleeding, insomnia, agitation and increased risk of serotonin syndrome if used with other serotonergic medications
  • Serotonin syndrome is a group of symptoms that can happen with use of serotonergic medications, e.g. SSRIs, MAOIs, St John’s Wort, ecstasy, and amphetamines. Symptoms include confusion, sweating, hyperthermia, hyperreflexia, myoclonus and rigidity. Management is supportive, including IV fluids and benzodiazepines may be used. In more severe cases, serotonin antagonists such as cyproheptadine or chlorpromazine may be necessary
• Mirtazapine
  • Generally, well tolerated and can have beneficial effects on appetite, weight gain and management of insomnia
• Tricyclics, e.g., amitriptyline
  • Antimuscarinics can cause dry mouth, constipation, blurred vision and urinary retention. It can have a role in palliative patients with neuropathic pain but would generally not be started as first line for depression

Pruritus

Pruritis or itch is an unpleasant sensation of the skin or mucous membranes that elicits the urge to rub or scratch the area.

It is not as common in palliative patients as pain or breathlessness but can significantly affect quality of life.

The pathophysiology of pruritus is dependent on the cause and is often independent of histamine, e.g., uraemic pruritus, meaning antihistamines can have a limited role.

Assessment

Palliative patients may have multiple reasons for pruritus, so should be assessed for skin conditions like eczema and contact dermatitis, and infectious causes such as candidiasis or fungal infection should be excluded.

Medications should be reviewed as opioids, Penicillins, and cephalosporins can all contribute to pruritus. If any new medications have been started, drug reaction should be excluded.

Blood tests should be considered, and possible conditions contributing to pruritus are listed below:

• Full blood count – Polycythaemia, leukaemia, lymphoma, multiple myeloma
• Ferritin (If anaemic) – Iron deficiency
• Urea and electrolytes – Uraemia in renal failure
• Liver function tests – hepatic failure, cholestatic jaundice
• Bone profile – Hyperphosphatemia, hypercalcaemia
• Thyroid function – Hyperthyroidism
• HIV test – Pruritus can occur in up to 30% of those with HIV

Management of Pruritus

Conservative

• Ensure skin is not dry
• Soap substitutes and emollients
• Short fingernails
• Psychological support to help break cycle of itching and scratching

Pharmacological and Non-Pharmacological Management by Diagnosis

Sedating antihistamines like chlorphenamine, benzodiazepines or doxepin given at night can help with sleep. Other strategies may be appropriate depending on the cause, as shown in Table 1.

Source: Watson M, Campbell R, Vallath N, Ward S, Wells J. Oxford Handbook of Palliative Care. 3rd ed. Oxford University Press; 2019.

Fatigue

Fatigue is a sustained, subjective feeling of weakness, tiredness, or low energy. It is reported in up to 80% of patients with cancer, and this increases following treatments like radiotherapy. It is also prevalent in people with non-malignant diseases, including COPD, CCF and multiple sclerosis.

In malignancy, inflammatory cytokines can contribute to fatigue, but secondary causes are common and should be excluded.

Causes of Fatigue

• Organ dysfunction – Renal/ cardiac/ hepatic failure
• Hypothyroidism
• Adrenal insufficiency
• Anaemia
• Infection
• Nutrition – Poor diet/ malabsorption
• Sleep pattern
• Physical exertion or deconditioning
• Depression/ anxiety

Management

Non-Pharmacological:

• Diary – Identifying any triggers for symptoms
• Conserving energy – Prioritising tasks, pace activities, schedule tasks for the time with most energy, occupational therapy input
• Physical activity – Exercise can reduce fatigue, and physiotherapy input may be beneficial
• Stress and anxiety management
• Complementary therapy

Pharmacological:

• Dexamethasone 2-4mg OD may improve appetite, nausea, and subjective feelings of weakness but is more appropriate in those with anorexia/cachexia

References

• Radbruch L, Strasser F, Elsner F, Gonçalves JF, Løge J, Kaasa S, Nauck F, Stone P; Research Steering Committee of the European Association for Palliative Care (EAPC). Fatigue in palliative care patients — an EAPC approach. Palliat Med. 2008 Jan;22(1):13-32. doi: 10.1177/0269216307085183. PMID: 18216074.
• Scottish Palliative Care Guidelines. 2022. [online] Available at: <https://www.palliativecareguidelines.scot.nhs.uk/guidelines/symptom-control/weakness-fatigue.aspx> [Accessed 5 April 2022].
• Blanes M, Belinchón I, Portilla J, Betlloch I, Reus S, Sánchez-Payá J. Pruritus in HIV-infected patients in the era of combination antiretroviral therapy: a study of its prevalence and causes. International Journal of STD & AIDS. 2012;23(4):255-257.
• Scottish Palliative Care Guidelines. 2022. [online] Available at: <https://www.palliativecareguidelines.scot.nhs.uk/guidelines/symptom-control/Pruritis.aspx> [Accessed 5 April 2022].
• Arias De La Torre, J. et al. 2021. Prevalence and age patterns of depression in the United Kingdom. A population-based study. Journal of Affective Disorders 279, pp. 164–172.
• 2022. The Management of Depression in Palliative Care EUROPEAN CLINICAL GUIDELINES. [eBook] Available at: <https://www.kcl.ac.uk/cicelysaunders/attachments/depression-guidlines/the-management-of-depression-in-palliative-care.pdf> [Accessed 20 April 2022].
• Scottish Palliative Care Guidelines. 2022. [online] Available at: <https://www.palliativecareguidelines.scot.nhs.uk/guidelines/symptom-control/weakness-fatigue.aspx> [Accessed 5 April 2022].
• Lloyd-Williams M, Shiels C, Dowrick C. The development of the Brief Edinburgh Depression Scale (BEDS) to screen for depression in patients with advanced cancer. J Affect Disord. 2007 Apr;99(1-3):259-64. doi: 10.1016/j.jad.2006.09.015. Epub 2006 Oct 20. PMID: 17055588.
• Volpi-Abadie, Jacqueline et al. “Serotonin syndrome.” The Ochsner journal vol. 13,4 (2013): 533-40.
• Watson M, Campbell R, Vallath N, Ward S, Wells J. Oxford Handbook of Palliative Care. 3rd ed. Oxford University Press; 2019.