The other face of depression, reduced positive affect: The role of catecholamines in causation and cure
ABSTRACT Despite significant advances in pharmacologic therapy of depression over the past two decades, a substantial proportion of patients fail to respond or experience only partial response to serotonin re-uptake inhibitor antidepressants, resulting in chronic functional impairment. There appears to be a pattern of symptoms that are inadequately addressed by serotonergic antidepressants - loss of pleasure, loss of interest, fatigue and loss of energy. These symptoms are key to the maintenance of drive and motivation. Although these symptoms are variously defined, they are consistent with the concept of ;decreased positive affect'. Positive affect subsumes a broad range of positive mood states, including feelings of happiness (joy), interest, energy, enthusiasm, alertness and self-confidence. Although preliminary, there is evidence to suggest that antidepressants that enhance noradrenergic and dopaminergic activity may afford a therapeutic advantage over serotonergic antidepressants in the treatment of symptoms associated with a reduction in positive affect. Dopaminergic and noradrenergic agents, including the dual acting norepinephrine and dopamine re-uptake inhibitors, have demonstrated antidepressant activity in the absence of serotonergic function, showing similar efficacy to both tricyclic and serotonin re-uptake inhibitor antidepressants. Moreover, the norepinephrine and dopamine re-uptake inhibitor bupropion has been shown to significantly improve symptoms of energy, pleasure and interest in patients with depression with predominant baseline symptoms of decreased pleasure, interest and energy. Focusing treatment on the predominant or driving symptomatology for an individual patient with major depression could potentially improve rates of response and remission.
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- "It is of interest then that SRIs (by releasing 5-HT) adversely affect the neural processing of rewarding and aversive stimuli (Alén et al., 2013), possibly resulting in down-regulation of the reward system (Lane, 2014). Clinically, SRIs are less effective in managing the anhedonic symptoms of depression (Nutt et al., 2007; Lane, 2014) and in fact provoke cognitive and emotional blunting (Sansone and Sansone, 2010). These SRI-associated effects have been ascribed to 5-HT 2C -mediated suppression of frontal DA function (Barnhart et al., 2004; Wongpakaran et al., 2007; McCabe et al., 2010; Sansone and Sansone, 2010) (Figure 2). "
ABSTRACT: Objective Antidepressants are at best 50–55% effective. Non-compliance and the antidepressant discontinuation syndrome (ADS) are causally related yet poorly appreciated. While ADS is associated with most antidepressants, agomelatine seems to be devoid of such risk. We review the neurobiology and clinical consequences of antidepressant non-compliance and the ADS. Agomelatine is presented as a counterpoint to learn more on how ADS risk is determined by pharmacokinetics and pharmacology.DesignThe relevant literature is reviewed through a MEDLINE search via PubMed, focusing on agomelatine and clinical and preclinical research on ADS.ResultsAltered serotonergic dysfunction appears central to ADS so that how an antidepressant targets serotonin will determine its relative risk for inducing ADS and thereby affect later treatment outcome. Low ADS risk with agomelatine versus other antidepressants can be ascribed to its unique pharmacokinetic characteristics as well as its distinctive actions on serotonin, including melatonergic, monoaminergic and glutamatergic-nitrergic systems.Conclusions This review raises awareness of the long-term negative aspects of non-compliance and inappropriate antidepressant discontinuation, and suggests possible approaches to “design-out” a risk for ADS. It reveals intuitive and rational ideas for antidepressant drug design, and provides new thoughts on antidepressant pharmacology, ADS risk and how these affect long-term outcome. Copyright © 2014 John Wiley & Sons, Ltd.Human Psychopharmacology Clinical and Experimental 11/2014; 29(6). DOI:10.1002/hup.2429 · 1.85 Impact Factor
- "For example, the noradrenaline and dopamine reuptake inhibitor, bupropion, has been shown to significantly improve symptoms of energy, pleasure and interest in patients with depression with predominant baseline symptoms of decreased pleasure, interest and energy. Thus, there is a pattern of symptoms inadequately addressed by serotonergic antidepressants, suggesting treatments that enhance noradrenergic or dopaminergic activity may be more appropriate to certain types of TRD, such as depression with comorbid anxiety disorders or patients with predominant symptoms of fatigue (Nutt et al., 2007). It is also becoming apparent that inflammatory processes can contribute to the pathogenesis of MDD. "
Dataset: The hidden third
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- "Highly prevalent, this disorder affects about 25% of women and 12% of men and is the leading cause of disability worldwide (Gelenberg, 2011; McIntyre et al., 2011). Depression often manifests through multiple symptoms, including despair, guilt, anhedonia, psychomotor dysfunction, reduced positive affect and memory impairment (Nutt et al., 2007). High co-morbidity rates between depression and anxiety disorders as well as dementia have also been well described (Momartin et al., 2004; Berger et al., 2005). "
ABSTRACT: Cotinine, the predominant metabolite of nicotine, appears to act as an antidepressant. We have previously shown that cotinine reduced immobile postures in Porsolt's forced swim (FS) and tail suspension tests while preserving the synaptic density in the hippocampus as well as prefrontal and entorhinal cortices of mice subjected to chronic restraint stress. In this study, we investigated the effect of daily oral cotinine (5 mg/kg) on depressive-like behavior induced by repeated, FS stress for 6 consecutive days in adult, male C57BL/6J mice. The results support our previous report that cotinine administration reduces depressive-like behavior in mice subjected or not to high salience stress. In addition, cotinine enhanced the expression of the vascular endothelial growth factor (VEGF) in the hippocampus of mice subjected to repetitive FS stress. Altogether, the results suggest that cotinine may be an effective antidepressant positively influencing mood through a mechanism involving the preservation of brain homeostasis and the expression of critical growth factors such as VEGF. (PsycINFO Database Record (c) 2014 APA, all rights reserved).Behavioral Neuroscience 10/2014; DOI:10.1037/bne0000021 · 3.25 Impact Factor