Research has outlined three antidepressants as the most preferred option when it comes to acceptability within patients receiving an initial treatment for depression. However none of these drugs are routinely used as first line treatments when treating an initial major depressive episode. The recent systematic review and network meta-analysis of antidepressant clinical trials by Cipriani et al, revealed that one of agomelatine, escitalopram and vortrioxene should be the initial treatment choice, owing to their favourable acceptability results.

Patients that stop using their antidepressants prematurely, have a greater risk of relapse and a lower chance of maintaining a stable mental health. The decision to choose the most appropriate fist line option in patients is incredibly important with regards to achieving the best possible clinical outcome in patients with depression, with it being much more difficult to achieve a responsive with subsequent treatment options.

When treating depression with antidepressants, the biggest issue that effects course length and remission is the acceptability of that drug within the patient. Antidepressant are associated with a high risk of adverse effects that will range in severity between users, patients will also discontinue treatment if they believe they are not working. 

The study suggests maintaining a patient on the same therapy was the key to accomplishing a stable mental health, with fewer acute episodes of depression and relapse.

Nice advises that prescribers should try and maintain patients on their antidepressants for at least 6 months following the remission of a major depressive episode. This duration can be even longer depending on the severity of previous depressive episodes and the likelihood of residual symptoms and reoccurrence. However, it is found that only 1 in 3 patients on selective serotonin re-uptake inhibitors (SSRIs) receive an effective dose for the suggested 4-month minimum course period.

The trial revealed seven drugs that were most superior to placebo with regards to efficacy: agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine and vortioxetine, of these amitriptyline had the greatest separation from placebo. However, amitriptyline was found to be one of the most inferior in terms of acceptability to patients. There is also the well-known risk of adverse cardiovascular effects and high risk of accidental overdose.

The study highlighted 3 drugs out of the seven most effective, as the most acceptable to patients: agomealatine, escitalopram and vortioxetine. This suggests that these three drugs should be used first line, when it comes to selecting an appropriate and effective antidepressant in patients.

Yet, these 3 drugs are very rarely used in practice, prescribing data reveals citalopram, fluoxetine and sertraline to be the most commonly used antidepressants in community prescribing, with a combined number of over 34 million dispensing items in 2018. This is a dramatic contrast to the level of prescribing for vortioxetine (80,000), agomelatine (20,000) and escitalopram (1,000,00).

This may be due to the high cost associated with two of the most acceptable options: agomelatine (£30), Vortioxetine (£27), compared with the £0.99 unit price of citalopram. Yet, escitalopram proves to be of a much lower cost at £1.28 unit price.

Restricting patients to drugs that have a lower cost profile may not be cost effective in the long-term, when considering the chance of relapse and the high disease burden associated with depression. The wider economic costs of mental illness in England has been estimated at £105.2 billion a year. In the developed world, the single greatest burden of disease is caused by unipolar depression, further to this, depression is the leading cause of disability worldwide, contributing to 22.8% of the total burden, compared to 15.9% for cancer and 16.2% for cardiovascular disease

It is important that prescribers consider the overall cost of ineffective pharmacological management, in the face of an initial increased cost of first line treatment. A slight investment in escitalopram for example may produce better clinical and financial outcomes in the long-term.