At the EPA congress in Munich, the focus was on advances in the therapy of depressive patients. It is the early improvement in positive mental health that is critical for response and remission. New agents show promise in counteracting the reduction of positive affect in depression.
(ag) The symptomatology of depression includes negative affects such as depressed mood, guilt, anger, sadness, anxiety and fatigue, according to Prof. Guy Goodwin, MD, Oxford. Quite crucially, however, symptoms are also based on the loss of positive affects such as joy, interest, self-confidence, optimism, energy and motivation. Improving mental health in particular by restoring positive affect is essential for complete remission, according to Prof. Goodwin. The expert sees limitations of current treatment primarily in efficacy (no global response/untreated components of the clinical syndrome) and long-term tolerability (impaired sexual function, weight gain). Anhedonia, in which the capacity for positive emotional experience is lowered, has been neglected as a therapeutic goal until now.
New therapeutic paths
Agomelatine (Valdoxan®), a melatonergic (MT1 and MT2 receptor) agonist and 5-HT2C antagonist, is approved in Switzerland for the treatment of adult depressive episodes according to ICD-10 (“major depression” according to DSM IV). In those patients who responded well to agomelatine in acute treatment, it is also indicated for maintenance therapy for six to 12 months [1]. It resynchronizes circadian rhythms in animal models and also increases the release of norepinephrine and dopamine (especially in the frontal cortex), which is related to the regulation of mood and emotions. It has no influence on extracellular serotonin levels. “Furthermore, it leads to a decrease in stress-induced glutamate release and an increase in BDNF (“brain-derived neurotrophic factor”), whose crucial role in mood disorders is confirmed by several studies,” said Prof. Giorgio A. med. Racagni, Milan. Thus, agomelatine has a negative effect on depressed mood and a positive effect on interest and pleasure, which in turn optimizes functioning in everyday life. Unlike other antidepressants, the antidepressant effect does not require the release of serotonin and other monoamines.
Effect on positive affects decisive
“From the point of view of depressed patients, therapy must particularly restore positive mental health (optimism, energy, self-confidence) [2],” explained Prof. Pierre-Michel Llorca, MD, Clermont-Ferrand. “In the hypothetical model of Nutt et al, those antidepressants that increase the release of norepinephrine and dopamine are better at counteracting the reduction of positive affect than serotonergic antidepressants [3].” Does this assumption hold true for agomelatine? New data from Gorwood et al. on 1565 depressed patients show that, for example, motivation, an important positive affect with best predictive value for response, can be improved early and substantially by agomelatine [4]. Likewise, under agomelatine, an improvement in the MAThyS score was detectable in the “joy” domain. The influence of agomelatine on anhedonia was investigated two years ago by Martinotti et al: they concluded that the drug showed a significantly better effect on this disorder than the SSNRI venlafaxine with the same antidepressant efficacy [5].
“Agomelatine actually restores positive affect more quickly with equally good improvement in negative affect compared with other antidepressants. This is important because early change in positive affect (after one week) is a predictor of remission after six weeks [6]. Gorwood et al. also consider an early improvement in positive affect (after two weeks on agomelatine) to be a more specific predictor of subsequent response than attenuation of negative affect [7]. Furthermore, agomelatine counteracts psychomotor retardation and plays a central role in functional remission, the assessment of which is becoming increasingly important in the treatment of major depression [8],” Prof. Llorca concluded.
Source: “Understanding biological and clinical features of depression to achieve better treatment,” Satellite Symposium at the 22nd European Congress of Psychiatry, March 1-4, 2014, Munich, Germany.
Literature:
- Specialized information Valdoxan®: www.kompendium.ch
- Zimmerman M, et al: How should remission from depression be defined? The depressed patient’s perspective. Am J Psychiatry 2006 Jan; 163(1): 148-150.
- Nutt D, et al: The other face of depression, reduced positive affect: the role of catecholamines in causation and cure. J Psychopharmacol 2007 Jul; 21(5): 461-471. epub 2006 Oct 18.
- Gorwood P, et al: Beyond depressive symptoms, how agomelatine modifies emotional reactivity, cognitive speed, motivation, psychomotor function and sensory perception? European Psychiatry 2014; Article: EPA-0762.
- Martinotti G, et al: Agomelatine versus venlafaxine XR in the treatment of anhedonia in major depressive disorder. Journal of Clinical Psychopharmacology 2012; 32(4): 487-491.
- Geschwind N, et al: Early improvement in positive rather than negative emotion predicts remission from depression after pharmacotherapy. Eur Neuropsychopharmacol 2011 Mar; 21(3): 241-247. doi: 10.1016/j.euroneuro.2010.11.004. Epub 2010 Dec 13.
- Gorwood P, et al: The increase of positive emotions after two weeks of agomelatine is more specific to predict later treatment response than the decrease of negative emotions. European Psychiatry 2014; Article: EPA-0601.
- Mouchabac S, Lemoine P, Baylé FJ: Functional remission in depression and patient satisfaction index: results of the diapason study. European Psychiatry 2013; 28 (S1): 1.
InFo NEUROLOGY & PSYCHIATRY 2014; 12(3): 41-42.
