Bupropion is presumed to be a dopamine-noradrenaline (norepinephrine) reuptake inhibitor and is an effective antidepressant. It is available as three oral formulations: (i) bupropion immediate release (IR) [Wellbutrin] administered three times daily; (ii) bupropion sustained release (SR) [Wellbutrin SR] administered twice daily; and (iii) bupropion extended/modified release (XR) [Wellbutrin XL/Wellbutrin XR] administered once daily. All three formulations are bioequivalent in terms of systemic exposure to bupropion. Oral three-times-daily bupropion IR was effective and generally well tolerated in the treatment of major depressive disorder (MDD). It was as efficacious and as well tolerated as some TCAs and the SSRI fluoxetine. Moreover, it was associated with less somnolence and weight gain than some TCAs. Twice-daily bupropion SR was also efficacious and generally well tolerated in the treatment of MDD. It was as effective as and had a generally similar tolerability profile to some SSRIs, but had the advantage of less somnolence and sexual dysfunction. The efficacy of bupropion XR in terms of primary efficacy measures was established in two of six well designed placebo-controlled studies. Bupropion XR also demonstrated efficacy in terms of some secondary outcomes in five of these studies. Additionally, bupropion XR was similar, in terms of the primary efficacy outcomes, to the SSRI escitalopram in two placebo-controlled trials and to the serotonin-noradrenaline reuptake inhibitor (SNRI) venlafaxine extended release (XR) in two trials (one of which was placebo-controlled), but not in a third placebo-controlled trial where venlafaxine XR was better than bupropion XR. It was generally as well tolerated as escitalopram and venlafaxine XR, but was associated with less sexual dysfunction than escitalopram. Available clinical data suggest that bupropion is an effective and generally well tolerated option in the treatment of MDD, with the newer formulations having the advantage of reduced frequency of daily administration.
"The monoamine systems show multiple interactions with the HPA axis, and lack of dopamine has been postulated particularly for melancholic depression and psychomotor symptoms (Martinot et al., 2001; Schrijvers et al., 2008). Dopaminergic agents have antidepressant properties both in PD (Yamamoto and Schapira, 2008) and depression (Dhillon et al., 2008). One tentative explanation of the negative cognitive bias in melancholic depression may thus be that it reflects an underlying dopaminergic deficit. "
[Show abstract][Hide abstract] ABSTRACT: Emotion biases feature prominently in cognitive theories of depression and are a focus of psychological interventions. However, there is presently no stable neurocognitive marker of altered emotion-cognition interactions in depression. One reason may be the heterogeneity of major depressive disorder. Our aim in the present study was to find an emotional bias that differentiates patients with melancholic depression from controls, and patients with melancholic from those with non-melancholic depression. We used a working memory paradigm for emotional faces, where two faces with angry, happy, neutral, sad or fearful expression had to be retained over one second. Twenty patients with melancholic depression, 20 age-, education- and gender-matched control participants and 20 patients with non-melancholic depression participated in the study. We analysed performance on the working memory task using signal detection measures. We found an interaction between group and emotion on working memory performance that was driven by the higher performance for sad faces compared to other categories in the melancholic group. We computed a measure of "sad benefit", which distinguished melancholic and non-melancholic patients with good sensitivity and specificity. However, replication studies and formal discriminant analysis will be needed in order to assess whether emotion bias in working memory may become a useful diagnostic tool to distinguish these two syndromes.
"In contrast to the potential blockade of possible high dopamine activity in patients with mania and GAD, the lower tolerability to quetiapine-XR in bipolar depression and MDD may be due to a decreased dopamine function. This assumption is supported by findings that pramipexole, a dopamine D 2/3 receptor agonist and bupropion, a dopamine reuptake inhibitor, may improve depressive symptoms in bipolar depression (Goldberg et al. 2004; Zarate et al. 2004) and MDD (Dhillon et al. 2008; Stahl et al. 2003). A further blockade of dopamine activity with quetiapine-XR may increase somnolence and lower the tolerability to the adverse events. "
[Show abstract][Hide abstract] ABSTRACT: Quetiapine extended-release (quetiapine-XR) has been studied in patients with schizophrenia, bipolar mania, bipolar depression, major depressive disorder (MDD), and generalized anxiety disorder (GAD). The purpose of this study was to compare the tolerability and sensitivity of quetiapine-XR among these psychiatric conditions. The discontinuation due to adverse events (DAEs) and reported somnolence in randomized, double-blind, placebo-controlled studies of quetiapine-XR in these psychiatric conditions were examined. The absolute risk reduction or increase and the number needed to treat to benefit (NNTB) or harm (NNTH) for DAEs and reported somnolence of quetiapine-XR ≥ 300 mg/d relative to placebo were estimated. Data from one study in schizophrenia (n=465), one in mania (n=316), one in bipolar depression (n=280), two in refractory MDD (n=624), two in MDD (n=669) and three in GAD (n=1109) were available. The risk for DAEs of quetiapine-XR relative to placebo was significantly increased in bipolar depression (NNTH=9), refractory MDD (NNTH=8), MDD (NNTH=9), and GAD (NNTH=5), but not in schizophrenia and mania. The risk for reported somnolence of quetiapine-XR relative to placebo was significantly increased in schizophrenia (600 mg/d NNTH=15 and 800 mg/d NNTH=11), mania (NNTH=8), bipolar depression (NNTH=4), refractory MDD (NNTH=5), MDD (NNTH=5) and GAD (NNTH=5). These results suggest that patients with GAD had the poorest tolerability during treatment with quetiapine-XR, but they had a similar sensitivity as those with bipolar depression and MDD. Patients with schizophrenia or mania had a higher tolerability and a lower sensitivity than those with bipolar depression, MDD, or GAD.
The International Journal of Neuropsychopharmacology 02/2011; 14(1):131-42. DOI:10.1017/S146114571000101X · 4.01 Impact Factor
"Notably, without directly affecting extracellular levels of dopamine, sustained administration of antidepressants and electroconvulsive therapy (ECT) enhances transmission at dopaminergic receptors in the nucleus accumbens (Nestler and Carlezon, 2006). Besides the widely use of serotonergic and/or noradrenergic agents for treating depression, a strengthening of dopaminergic transmission could otherwise be achieved by direct blockade of dopamine transporters, such as the antidepressant bupropion (Dhillon et al., 2008). Since dopamine is the main neurotransmitter involved in the mesolimbic reward pathways, it has been proposed that an increase in dopaminergic neurotransmission might counteract the anhedonia (D'Aquila et al., 2000) that is considered a core feature of major depressive disorder (Gorwood, 2008). "
[Show abstract][Hide abstract] ABSTRACT: Melatonin was previously shown to produce an antidepressant-like effect in the tail suspension test. In this work the mechanisms underlying its antidepressant-like effect were further studied by investigating the involvement of the dopaminergic system in its antidepressant-like effect in the tail suspension test. The effect of melatonin (1mg/kg, i.p.) was prevented by the pretreatment of mice with haloperidol (0.2mg/kg, i.p., a nonselective dopaminergic receptor antagonist), SCH23390 (0.05 mg/kg, s.c., a selective dopamine D1 receptor antagonist), and sulpiride (50mg/kg, i.p., a selective dopamine D2 receptor antagonist). The i.p. administration of melatonin (0.01 mg/kg) or fluoxetine (1mg/kg, a serotonin reuptake inhibitor) in combination with SFK38393 (0.1mg/kg, s.c., a dopamine D1 receptor agonist) reduced the immobility time in the tail suspension test as compared with either drug alone. Moreover, the pretreatment with melatonin (0.01 mg/kg, i.p.) produced a synergistic effect with apomorphine (0.5 microg/kg, i.p., a dopamine D2 receptor agonist), but the pretreatment with fluoxetine (1mg/kg, i.p.) was ineffective to potentiate the effect of apomorphine. Dopamine receptor antagonists or agonists alone or in combination with melatonin did not affect locomotor activity. These results indicate that the antidepressant-like effect of melatonin in the tail suspension test is likely mediated by an interaction with the dopaminergic system, through an activation of dopamine D1 and D2 receptors. Our data confirm the previous notion on the role exerted by melatonin in depression, suggesting that it might be further investigated as an alternative for the management of depression associated with anhedonia.
European journal of pharmacology 07/2010; 638(1-3):78-83. DOI:10.1016/j.ejphar.2010.04.011 · 2.53 Impact Factor
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