Pharmacological management options: Tricyclic Antidepressants (TCAs) and Selective Serotonin Reuptake Inhibitors (SSRIs)

AMITRIPTYLINE
It is the most widely used tricyclic antidepressant and has been proven to be safe and effective in the treatment of depression. It 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.

FLUOXETINE
It is a selective inhibitor of serotonin reuptake. It has practically no affinity to other receptors such as α1-, α2-, and β-adrenergic; serotonergic; dopaminergic; histaminergic1; muscarinic; and GABA receptors.
- It is available as an oral solution 20mg/5ml and 10mg, 20mg and 40mg oral capsules/tablets.
- It can be taken as a single daily dose.
- It 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.

Recommendations
- Both TCAs and SSRI 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 and non-selective monoamine reuptake inhibitors (NSMRI), 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 antidepressant 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 psychostimulants, as monotherapy, significantly reduced short term depressive symptoms in comparison with placebo with non significant heterogeneity.
- There is some evidence to suggest that in the short-term, psychostimulants reduce the symptoms of depression and may have a role 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 reuptake inhibitors depression has been associated with an increased risk of suicidal ideation and behavior.
- Antidepressive therapy often requires higher doses of antidepressants. Amitryptiline may be titrated up to 225 mg per day for treatment of depression. The 75 mg tablet facilitates treatment with higher doses in palliative care patients.

See reference for more information.

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 pp. Published June 5, 2013 by IAHPC Press. Available at https://www.amazon.com/Essential-Medicines-Palliative-Care-Application-ebook/dp/B00D7S2D0C