Depression | January 25, 2015 | Author: The Super Pharmacist
Criteria to diagnose depression involve identifying negative symptoms (e.g. sadness, helplessness). Recent studies have identified that core differences exist between GP goals and patient goals. GP goals are to reduce negative symptoms; patient goals are to increase positive symptoms (e.g. happiness, fulfilment). SSRI's are effective at reducing negative symptoms, but have limited effects on increasing positive symptoms (emotional numbing). The newly available agomelatine is suggesting a potential to increase positive symptoms, thus achieving patient goals. Current available research suggests many ways in which agomelatine enhances positive symptoms, especially in comparison to SSRIs and SNRIs.
Depression is a major health concern worldwide. In Australia, almost a million adults suffer the condition in any one year and 1 out of every 7 persons will experience an episode during a lifetime.
For the individual, depression means a daily struggle against feelings of hopelessness and helplessness.
If you are diagnosed with depression, it means that you match particular clinical criteria; but it also means that you are experiencing more of certain negative emotions and less of some positive emotions.
Let’s list some of these criteria and emotions:
Sometimes GPs and patients will differ in the goals that they have in mind respectively for the treatment of depression. While GPs are more focused on managing the clinical criteria and negative emotions of depression, patients are looking to get out of the doldrums with a remedy that can boost their positive emotions. One study concludes that GPs require increased awareness of the extent to which their treatment goals are considered relevant or achievable by patients.
Patients often question the reasoning behind GPs’ distinction of depression from “normal” sadness. While some GPs may feel frustrated when a patient’s depression is resistant to cure, the patient may be more focused on getting by from day to day. In another study, the treatment goals that were most frequently expressed by patients included improving social and family relationships, finding a job, and getting more organised at home.
Although all classes of antidepressants are comparable in efficacy, SSRIs are the ones most commonly prescribed due to their favourable overall profile. Venlafaxine, which is an SNRI, is also popular. While these medicines have proven effectiveness when ameliorating the negative symptoms of depression, they have not been as successful in augmenting positive emotions. In fact, in certain cases the outcome has been to the contrary as SSRIs are known to cause “emotional blunting”. Emotional blunting, also known as emotional numbing, is a dulling of emotional reactivity as well as a reduced ability to feel and express emotions. Such a person will smile, laugh, or cry less, and may feel emotionally flat. Emotional blunting not only dampens experience of personal emotional states, it can hamper a person’s ability to fully and correctly perceive emotional responses and cues of friends and family. Despite the fact that some emotional blunting will inevitably arise from the depression itself, it is now well-known and backed by clinical evidence that SSRIs do numb emotions.
Closely linked to the emotional blunting effect of SSRIs is their tendency to cause sexual dysfunction, which can be construed as arising from numbing of the perception and expression of sexual emotions. The scientific mechanism behind these outcomes is serotonin’s (a neurotransmitter) effect on the emotional pathways in the brain and SSRIs ability to raise serotonin levels.
Since SNRIs, the major antidepressant in use in this category being venlafaxine, also raise brain serotonin levels, they are associated with emotional numbing and sexual dysfunction as well.
Agomelatine is a new antidepressant with a novel mechanism of action. It acts on melatonin receptors in the brain to bring about its effects, which is quite different from the mechanisms of any of the antidepressants in current use (it does not increase brain serotonin levels). Agomelatine was developed by Servier Laboratories Ltd., and has been approved for use in the European Union and Australia.
Because of its unique mechanism of action, agomelatine avoids many of the negative effects associated with most of the antidepressants in current use. When compared to SSRIs and SNRIs, there are at least 5 ways by which agomelatine seems better at improving positive symptoms and emotions, and thereby realising patient goals and expectations:
1. No Emotional Numbing and more Positive Emotions6 Agomelatine has not been associated with emotional numbness, which has so frequently been the case with SSRIs. Emotional blunting impedes one’s ability to experience positive emotions. Many a time, this has been the reason why patients discontinue therapy or want to switch from SSRIs. By not causing emotional dullness, agomelatine allows patients to experience positive emotions. This not only assures them that their treatment is working, it achieves a basic goal of depression therapy.
2. No Sexual Dysfunction Agomelatine does not cause sexual dysfunction. For people on SSRIs and SNRIs, sexual dysfunction can become a real issue. The good news is, an alternative is now available: agomelatine.
3. Improved Sleep and Circadian Rhythms. Melatonin is a substance secreted by the brain to regulate circadian rhythms. Sleep-wake cycles are an essential component of circadian rhythms.
Agomelatine acts on melatonin receptors in the brain (as an agonist), and therefore improves circadian rhythms.
From the patient’s perspective, this means that sleep is improved: falling and staying asleep at night is easier and you feel more refreshed and energetic during the day.
It is common knowledge and scientifically proven that sleep deprivation can adversely affect your mood, irrespective of underlying depression.
When this is considered in conjunction with the fact that depressive disorders often bring along sleep disturbances, it is easy to see how both will augment each other’s negative effects. Agomelatine, an antidepressant that improves sleep, works on the depression and sleep disturbances simultaneously, greatly enhancing its effectiveness. Both these effects help agomelatine ameliorate negative symptoms of patients and provide them with positive energy.
4. Safer, Less Adverse Effects. As agomelatine has nothing to do with many of the receptors that conventional antidepressants act on, it stays away from many of their adverse effects. When compared to SSRIs and SNRIs, it seems to have a safer overall profile. However, like any other prescription medication, agomelatine is to be used only under medical supervision. Your doctor will help you decide if it is recommended for you and rule out any contraindications.
5. No Discontinuation Symptoms. Another way in which agomelatine is different and better than most of the antidepressants currently available is that it does not have to be tapered off. You can stop using it at any time, without the fear of any discontinuation symptoms. You can see that agomelatine offers some real advantages over SSRIs and SNRIs. However, to balance the argument a bit, SSRIs and SNRIs have a slightly greater effect size than agomelatine. Nonetheless, agomelatine has emerged as a solid alternative for resistant form of depression, and could be considered as a first choice when depression is associated with sleep disturbances. It has also been more effective in cases where depression has been accompanied with symptoms of anxiety.
DSM-5 Criteria for Major Depressive Disorder (MDD).
Geschwind N, Nicolson NA, Peeters F, van Os J, Barge-Schaapveld D, et al. (2011) Early improvement in positive rather than negative emotion predicts remission from depression after pharmacotherapy. Eur Neuropsychopharmacol 21:241–247.
Johnston O, Kumar S, Kendall K, et al. Qualitative study of depression management in primary care: GP and patient goals, and the value of listening. British Journal of General Practice. 2007;57:872–879.
Battle CL, Uebelacker L, Friedman MA, Cardemil EV, Beevers CG, Miller IW. Treatment goals of depressed outpatients: a qualitative investigation of goals identified by participants in a depression treatment trial. Journal of Psychiatric Practice. 2010;16:425–430.
Hickie IB, Rogers NL. Novel melatonin-based therapies: potential advances in the treatment of major depression. Lancet. 2011;378(9791):621–631.
Kennedy SH, Cyriac A. A Dimensional Approach to Measuring Antidepressant Response: Implications for Agomelatine. Psychology. 2012;3:864–869.
Harmer CJ, de Bodinat C, Dawson GR, Dourish CT, Waldenmaier L, Adams S, et al. Agomelatine facilitates positive versus negative affective processing in healthy volunteer models. J Psychopharmacol. 2011;25:1159–1167.
Srinivasan V, Zakaria R, Othman Z, Lauterbach EC, Acuña-Castroviejo D. Agomelatine in depressive disorders: its novel mechanisms of action. J Neuropsychiatry Clin Neurosci. 2012;24(3):290–308.