Recommended medication: AMITRIPTYLINE and FLUOXETINE
: Tablet: 10 mg; 25 mg
: tablet 75 mg
solid oral dosage form 20 mg (as hydrochloride)
Depression is characterized by persistent feelings of extreme sadness and low mood associated with loss of interest in activities and inability to experience pleasure. There are often associated biological features of significant changes in appetite and weight, disturbed sleep, fatigue and poor concentration.
Diagnosing and providing treatment for a major depressive episode in patients with a terminal illness can improve quality of life.
Diagnosis of major depression in a terminally ill patient often relies more on the psychological or cognitive symptoms (worthlessness, hopelessness, excessive guilt, and suicidal ideation) than the physical/somatic signs (weight loss, sleep disturbance) described in depression in patients who are not terminally ill.
The key indicators of depression in the terminally ill are persistent feelings of hopelessness and worthless and/or suicidal ideation.
Depression in palliative care is likely to be significantly under-recognized and undertreated as the symptoms overlap with symptoms of the underlying condition.
Treatment of pain and other reversible physical symptoms should be instituted before or concurrently with initiation of specific depressive treatment.
Psychological approaches to depression in palliative care, particularly cognitive behavioural therapy are important.
Management of depression includes the use of pharmacological and non pharmacological treatment approaches.
This application considers only the pharmacological management of depression.
Anxiety commonly exists as co-morbidity with depression in palliative care.
Pharmacological management options: Tricyclic Antidepressants (TCAs) and Selective Serotonin Reuptake Inhibitors (SSRIs)
is the most widely used tricyclic antidepressant and has been proven to be safe and effective in the treatment of depression.
acts primarily as a serotonin-norepinephrine reuptake inhibitor, with strong actions on the serotonin transporter and moderate effects on the norepinephrine transporter. It has negligible influence on the dopamine transporter and therefore does not affect dopamine reuptake, being nearly 1,000 times weaker on it than on serotonin.
is a selective inhibitor of serotonin reuptake. Fluoxetine has practically no affinity to other receptors such as α1-, α2-, and β-adrenergic; serotonergic; dopaminergic; histaminergic1; muscarinic; and GABA receptors.
is available as an oral solution 20mg/5ml and 10mg, 20mg and 40mg oral capsules/tablets.
can be taken as a single daily dose.
does however have a prolonged time before a therapeutic effect is established and this may be a limiting factor to its use in patients in the terminal stages.
Both tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) were shown to be more effective than a placebo. Improvement of depressive symptoms took several weeks of therapy. The therapeutic benefit persisted after 18 weeks, though side effects such as dry mouth or sexual dysfunction caused patients to stop their medication with prolonged treatment duration. However, patients taking an antidepressant were more likely to experience sexual dysfunction. There is insufficient evidence to support the use of one antidepressant in preference to another.
A recent systematic review found moderate evidence of efficacy of antidepressants (SSRI: selective serotonin reuptake inhibitors and NSMRI: non-selective monoamine reuptake inhibitors), though the evidence was not conclusive for some diseases and medication classes. Some studies showed superior efficacy of NSMRI compared to SSRI.
There is less evidence on antidepressive therapy in palliative care patients, but moderate evidence of efficacy is supported by expert opinion.
Although derived from fewer studies, RCTs consistently support tricyclic antidepressants and selective serotonin reuptake inhibitors for treating depression in cancer when treatment lasts 6 weeks or longer. .
3 trials demonstrated that oral pyschostimulants, as monotherapy, significantly reduced short term depressive symptoms in comparison with placebo with nonsignificant heterogeneity.
There is some evidence to suggest that in the short-term, psychostimulants reduce the symptoms of depression and may have a role in when rapid onset therapy is required for short-term use, such as in end of life care.
No evidence addressed depression management in advanced heart failure or dementia.
Use of selective serotonin re-uptake inhibitors depression has been associated with an increased risk of suicidal ideation and behaviour.
Antidepressive therapy often requires higher dosages of antidepressants. Amitryptiline
may be titrated up to 225 mg per day for treatment of depression. The 75 mg tablet facilitates treatment with higher dosages in palliative care patients.
Adapted from Radbruch L et al. Essential medicines in palliative care - An application for the 19th WHO Expert committee on the selection and use of essential medicines. Kindle Edition, 135 pages. Published June 5th 2013 by IAHPC Press. Available at https://www.amazon.com/Essential-Medicines-Palliative-Care-Application-ebook/dp/B00D7S2D0C