Venlafaxine XR demonstrates higher rates of sustained remission compared to fluoxetine, paroxetine or placebo
The combined serotonin-norepinephrine reuptake inhibitor, venlafaxine XR, has demonstrated significant response and remission in patients diagnosed with depression when measured with the Hamilton Depression Rating Scale (HAM-D). This pooled analysis of data from five studies compared the sustained remission of depressive symptoms in patients treated with venlafaxine XR, the selective serotonin reuptake inhibitors (SSRIs) fluoxetine or paroxetine, or placebo. Data from 1391 subjects enrolled in five active and placebo-controlled studies who met the DSM-III-R or DSM-IV criteria for major depressive disorder were analysed. Three treatment groups were compared: venlafaxine XR (n = 560), fluoxetine/paroxetine (n = 298) and placebo (n = 496). Mean treatment duration was 8 weeks. Responders were defined as those patients whose HAM-D-21 score decreased by > or = 50% from baseline. Remission was defined as a HAM-D-17 score < or = 7. Sustained remission was defined as maintenance of remission through week 8 or the end of treatment (if before week 8) and for > or = 2 weeks. Between-group rate comparisons in outcome measures were carried out using Fisher's exact and log-rank tests. Venlafaxine XR produced significantly higher rates of sustained remission in depressed patients compared to fluoxetine/paroxetine or placebo over this 8-week treatment period. As early as week 2, a significantly greater proportion of patients treated with venlafaxine achieved improved depression scores (remission and response). A significantly greater rate of remission and sustained remission occurred with venlafaxine compared to placebo. Remission was achieved earlier with venlafaxine and lasted throughout the remainder of the study. These results demonstrate that venlafaxine XR is more effective than fluoxetine/paroxetine for sustaining remission of depressive symptoms.
Available from: Mauricio P Cunha
- "It is used in the treatment of depression (Detke et al., 2004), anxiety (Carter and McCormack, 2009) and pain (Bellingham and Peng, 2010). It has been proposed that 5-HT and NE reuptake inhibitors may result in higher remission rates of major depressive disorder than therapy with selective inhibitors of 5-HT reuptake (Shelton et al., 2005; Thase et al., 2001; Smith et al., 2002). It has been reported that duloxetine has some advantages over other antidepressants, since it has greater effectiveness than fluoxetine and paroxetine in patients with moderate to severe depression (Thase et al., 2007) and has a better tolerability than venlafaxine (Stahl et al., 2005). "
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ABSTRACT: Duloxetine is a selective serotonin and noradrenaline reuptake inhibitor used as antidepressant. However, its mechanisms of action are not fully understood. This study investigated the effect of duloxetine in the mouse forced swimming test (FST) and in the tail suspension test (TST) and the involvement of the NMDA receptors and the l-arginine-NO-cGMP pathway in its effect in the FST. Duloxetine reduced the immobility time both in the FST and in the TST (dose range of 1-30mg/kg, i.p.), without changing locomotion in an open-field. Duloxetine administered orally (1-30mg/kg) also reduced the immobility time in the FST. The effect of duloxetine (10mg/kg, p.o.) in the FST was prevented by pre-treatment with NMDA (0.1pmol/site, i.c.v.), d-serine (30μg/site, i.c.v.), (l-arginine (750mg/kg, i.p.), S-nitroso-N-acetyl-penicillamine (SNAP, 25μg/site, i.c.v) or sildenafil (5mg/kg, i.p.). The administration of MK-801 (0.001mg/kg, i.p.), 7-nitroindazole (50mg/kg, i.p.), methylene blue (20mg/kg, i.p.) or 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) (30pmol/site i.c.v.) in combination with a sub-effective dose of duloxetine (0.3mg/kg, p.o.) reduced the immobility time in the FST. Moreover, the administration of duloxetine (10mg/kg) produced a reduction in NOx levels in the hippocampus and cerebral cortex. Altogether the results suggest that the effect of duloxetine in the FST is dependent on either a blockade of NMDA receptors or an inhibition of NO. In addition, our results further reinforce the role of NMDA receptors and l-arginine-NO-cGMP pathway, besides the monoaminergic systems, in the mechanism of action of current prescribed antidepressant agents.
Available from: Philip Ninan
- "Surprisingly, few randomized trials have evaluated the efficacy of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in long-term prevention of recurrence. Venlafaxine extended release (ER), the first drug classified as a serotoninnorepinephrine reuptake inhibitor, was shown in a randomized, placebo-controlled trial to be effective for recurrent MDD over 2.5 years at doses ranging from 75 to 300 mg/day (Keller et al., 2007a; Montgomery et al., 2004; Shelton et al., 2005). In many countries, however, the approved dosage of venlafaxine ER is ≤225 mg/day, which creates uncertainty about the generalizability of the findings from the whole data set to those settings where venlafaxine ER is not approved up to 300 mg/day. "
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ABSTRACT: The objective of this study was to evaluate the long-term efficacy of venlafaxine extended release (ER) < or =225 mg/day in patients with recurrent major depressive disorder (MDD). In this double-blind trial, outpatients with recurrent MDD (N=1096) were randomized to 10 weeks of acute-phase treatment with venlafaxine ER (75-300 mg/day) or fluoxetine (20-60 mg/day) followed by a 6-month continuation phase and two consecutive 12-month maintenance phases. At the start of each maintenance period, venlafaxine ER responders were randomized to double-blind venlafaxine ER or placebo. In this analysis, data from responders to acute and continuation treatment were analyzed during the combined maintenance phases while receiving venlafaxine ER < or =225 mg/day. Failure to maintain response was defined as an increase in maintenance dose to 300 mg/day or recurrence. Differences were calculated using Kaplan-Meier methods and compared using log-rank tests. Continuation-phase responders (n=114) receiving venlafaxine ER < or =225 mg/day comprised the analysis population (venlafaxine ER: n=55; placebo: n=59). The estimated probability for remaining well across 24 months of maintenance treatment was 67% for venlafaxine ER and 41% for placebo (P=0.007). Venlafaxine ER effectively maintained response at doses < or =225 mg/day for up to 2.5 years in patients with recurrent MDD. The findings are consistent with those of the full data set.
Available from: Xenia Gonda
- "Because SSRIs were only effective in a subpopulation of depressed patients, the question was raised whether the manipulation of other neurotransmitter systems is also required to treat depression successfully. Subsequently attention turned to inhibitors of both serotonin and noradrenalin (SNRI), including venlafaxine, duloxetine and milnacipran , because of their more favourable spectrum of therapeutic effects and increased therapeutic efficiency (Shelton et al., 2005, Thase et al., 2001). There are, however, other subgroups of patients, who do not respond adequately either to SSRIs or to SNRIs, which suggest that other, non-aminergic neurotransmitter systems should also be taken into account in the treatment of depression (Rosenzweig-Lipson et al., 2007). "
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ABSTRACT: The 5-HTTLPR polymorphism plays a key role in the background of affective disorders and the neuroticism trait as well. The aim of our study was to investigate the association of the 5-HTTLPR and such components of the neuroticism trait as depression, anxiety and affective lability in a psychiatrically healthy population. The participants completed the State-Trait Anxiety Inventory (STAI), the Zung Self-rating Depression Scale (ZSDS) and the TEMPS-A questionnaire. 5-HTTLPR genotype was established using PCR. Test scores were compared using ANOVA. Subjects carrying the s allele had a significantly higher score on the ZSDS, on the state anxiety scale of the STAI and on those affective temperament scales which carry a depressive component. Our results indicate that components of the neuroticism trait are also independently associated with 5-HTTLPR suggesting that it is a unified and solid construct. Our results point to the importance of future research aimed at delineating the genetic background of personality traits observable in the healthy population, as these can serve as endophenotypes for neuropsychiatric disorders and can play a crucial role in future research.
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