Potential paradigm shift in treatment of depression

(Image: Wikimedia Commons)

This discovery and new perspective on the treatment of depression offers hope to the thousands of patients worldwide who suffer from major depression and fail to respond or respond only partially to current treatment options.

Agomelatine - the first antidepressant of its kind, works by resynchronising the body's circadian rhythms.[1] "This treatment signifies a paradigm shift from the way depression has been viewed and treated over the past 60 years, and has the potential to establish a new approach to the treatment of the condition over the next 20-30 years," says psychiatrist, Dr Franco Colin.

A new option

"For decades, antidepressant treatments have followed a particular 'theme' in that they tend to target imbalances of one or more chemicals in the brain. The discovery of a treatment approach based on the link between depression and circadian rhythms is therefore adding a new therapeutic option for the treatment of depression," he says.

Circadian rhythms are physical, mental and behavioural changes that follow a 24-hour cycle[2]. Our master biological clock in the brain governs our circadian rhythms or biorhythms, which are produced by natural factors within the body and are affected by environmental signals such as light, eating and drinking patterns, social interactions and stress, among others[2][3]. These biorhythms are responsible for the regulation of many physiological, biological and behavioural functions from body temperature, hormone release, variations in mood, energy and alertness.[3]

Recent research has linked circadian rhythm dysfunction to symptoms of depression, including disturbed sleep/wake cycles, daytime mood swings and changes throughout the day in the intensity of the depressed mood. In fact, research has shown that the more 'out of synch' a patient's circadian rhythms are, the more severe their depression[4][5]. "Evidence would suggest that the new drug's mode of action helps restore normal circadian rhythm function in depressed patients and effectively treats depression,[3]" says Dr Colin.

More complicated than previously thought

A large body of evidence now suggests that depression is a much more complicated condition than was previously thought, requiring more nuanced treatments and an extension of available options. Current therapeutic treatments generally tend to work by controlling the brain's chemical pathways and increasing the activity and availability of these chemicals or neurotransmitters.[5]

"Agomelatine focuses on more than individual neurotransmitters. Because it has the ability to reset biorhythms, it may mark a new era of treatments that take into account a view of depression that includes biorhythms and their restoration. Evidence shows that patients on agomelatine experience fewer side effects. In clinical trials, the new drug was found to be weight neutral (so patients didn't put on weight); also, no sexual dysfunction was experienced,[1]" says Dr Colin.

Numerous challenges

The treatment of depression is currently associated with numerous challenges. Many patients do not respond to available treatments, while some who do respond often only do so partially and may still experience residual symptoms.[5]

"Scientific data indicate that agomelatine offers new hope to patients who have not responded to treatments thus far. In addition, the treatment promises to reduce some of the unmet needs and side-effects associated with current treatments," says Dr Colin.

Clinical data also suggest that the new drug effectively treats the core symptoms of depression such as depressed mood, anxiety, feelings of guilt and daytime fatigue.[6] Furthermore, the treatment has also been shown to improve aspects of depression that often remain poorly treated with current options. For example, the new treatment may potentially improve daytime alertness, quality of sleep and enable patients to achieve an emotional recovery without the blunting effects observed with some treatments.[7][8]

This new approach and resulting potential to improve depression symptoms in a unique way, coupled with the beneficial side effect profile, translates into better patient adherence (patients take their medications as prescribed). This, in turn, has the potential to produce better long-term outcomes.[5][9]

"For the first time in years, we have a drug which offers us new therapeutic mechanisms and improved tolerability that addresses the bigger picture of depression and has the potential to change how we manage the condition," says Dr Colin.

About major depression:

Major depressive disorder is a psychological condition characterised by an overwhelming sense of sadness and/or hopelessness and is usually accompanied by low self-esteem and loss of interest or pleasure in normally enjoyable activities.

It is estimated that 14% of the global burden of disease worldwide is attributable to depression, while the South African lifetime prevalence of major depression is 9.7%.
(Tomlinson M, et al. S Afr Med J 2009; 99: 368-373.)

References

1. De Bodinat C, et al. Nature Reviews 2010; 9 (8): 628-642.
2. http://www.nigms.nih.gov/Education/Factsheet_CircadianRhythms.htm
3. Hajak G. Depression in clinical practice 2010; 16: No 43
4. Cardinali DP. In: Goodwin GM, ed. Time to Enter a New Era in Depression Management. Paris: Elsevier, 2010. page 37
5. Gorwood P. J Clin Pharmacol 2010; 24 (8 suppl) 15-19.
6. Kennedy SH. Oral presentation delivered at ECNP Congress 2009, Istanbul.
7. Lemoine P, et al. J Clin Psychiatry 2007; 68: 1723-1732.
8. Corruble E, et al. Poster presentation P02-24, EPA, 2011.
9. Goodwin GM, et al. J Clin Psychiatry 2009; 70 (8): 1128-1137.