Disease relevance of Cymbalta

• Duloxetine treatment improved fibromyalgia symptoms and pain severity regardless of baseline status of major depressive disorder [1].
• Short-term duloxetine treatment resulted in mean weight loss (-1.03 kg; P < 0.001 vs. placebo), whereas slight, nonsignificant weight gain was seen in both duloxetine and routine care groups with longer treatment [2].
• Duloxetine: in stress urinary incontinence [3].
• Duloxetine vs. placebo in patients with painful diabetic neuropathy [4].
• RESULTS: Duloxetine-treated patients demonstrated significantly greater improvement in overall pain (p =.016), back pain (p =.002), and shoulder pain (p =.021) at week 9 compared with patients receiving placebo [5].

Psychiatry related information on Cymbalta

• Duloxetine-induced ultrarapid cycling in an adolescent with bipolar depression [6].
• Exacerbation of PTSD symptoms with use of duloxetine [7].
• More importantly, duloxetine appears to have better response rates and remission from depressive symptoms, perhaps due to its ability to treat a wider range of symptoms [8].
• In acute pain models, duloxetine had no significant effect on response latency in the mouse tail-flick test but produced modest increases in response latencies in the mouse hot plate test [9].
• We provide the first reports on duloxetine treatment of MDEs in the course of psychotic disorders [10].

High impact information on Cymbalta

• A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder [1].
• Effect of chronic administration of duloxetine on serotonin and norepinephrine transporter binding sites in rat brain [11].
• Duloxetine may be a dual serotonin/norepinephrine reuptake inhibitor, as it is only a slightly more potent inhibitor of serotonin than norepinephrine uptake in vitro [11].
• Metabolic changes did not appear to impact improvement in pain severity seen with duloxetine, and nerve conduction was also not significantly impacted by treatment [2].
• The results of these 2 studies suggest that caution should be used when CYP2D6 substrates and inhibitors are coadministered with duloxetine [12].

Chemical compound and disease context of Cymbalta

• The dual serotonin and noradrenaline reuptake inhibitor duloxetine for the treatment of interstitial cystitis: results of an observational study [13].
• Duloxetine (1-30mg/kg, i.p.), a balanced serotonergic-noradrenergic reuptake inhibitor (SNRI), was equiefficacious and more potent than the SNRI venlafaxine (3-100mg/kg, i.p.) in reversing both thermal hyperalgesia and mechanical allodynia induced by carrageenan [14].
• In the hot plate test, duloxetine and mirtazapine significantly increased (P<0.05) the nociceptive response latency, whereas amitriptyline and citalopram were ineffective [15].
• OBJECTIVE: Duloxetine, a serotonin/norepinephrine reuptake inhibitor, has been effective in the treatment of mild and moderate stress urinary incontinence [16].
• Overall, paroxetine and escitalopram exhibited the least sleep disruptive profiles, whereas duloxetine, venlafaxine, and reboxetine increased the time spent awake and suppressed paradoxical sleep [17].

Biological context of Cymbalta

• In study 2, steady-state pharmacokinetics of duloxetine 40 mg once daily were determined in the presence and absence of steady-state paroxetine 20 mg once daily [12].
• Consequently, we hypothesized that chronic duloxetine treatment, at doses producing serum levels within its therapeutic range, would affect both monoamine transporters dose-dependently, with a higher dose causing greater reductions of binding sites for both transporters [11].
• Nevertheless, given that the highest dose of duloxetine increased supine systolic blood pressure, it is possible that it represents the threshold regimen for NE reuptake inhibition [18].
• There was a significant increase for duloxetine compared with placebo for heart rate (1.6 vs. -0.6 beats per minute) and for systolic BP (1.0 vs. -1.2 mm Hg); the difference for diastolic BP (1.1 vs. 0.3) was not significant [19].
• 4. Venlafaxine (100 and 300 mg kg-1, p.o.) and duloxetine (30 mg kg-1, p.o.) also significantly decreased food intake in the 2 and 8 h following drug administration [20].

Anatomical context of Cymbalta

• Duloxetine or duloxetine plus pelvic floor muscle training (PFMT) were more effective in reducing the median IEF than PFMT alone or no treatment in women with SUI [3].
• Antagonism of serotonin 5-HT1A receptors potentiates the increases in extracellular monoamines induced by duloxetine in rat hypothalamus [21].
• In in vitro uptake experiments, duloxetine inhibited [3H]5-hydroxytryptamine (5-HT) and [3H]norepinephrine (NE) uptake in hippocampus slices of control rats with IC50 values of 28 and 46 nM, respectively [22].
• Therefore, this study demonstrates that duloxetine increases serotonergic tone in a limbic forebrain structure and may therefore be effective in the treatment of depression [23].
• Furthermore, when administered initially under irritated bladder conditions, duloxetine produced dose-dependent increases in bladder capacity (by 5-fold) and increased periurethral striated muscle EMG activity (by 8-fold) [24].

Associations of Cymbalta with other chemical compounds

• The blockade of serotonin (5-HT) and norepinephrine (NE) transporters in vitro and in vivo by the dual 5-HT/NE reuptake inhibitors duloxetine and venlafaxine was compared [25].
• Single-dose pharmacokinetics of metoprolol were measured before and after 17 days of treatment with escitalopram 20 mg/d, duloxetine 60 mg/d, or sertraline 100 mg/d in young healthy male and female participants [26].
• METHOD: In an 8-week multicenter, double-blind, placebo-controlled study, 173 patients (aged 18-65 years) with DSM-IV major depressive disorder were randomly allocated to receive placebo (N = 70), duloxetine (N = 70), or fluoxetine, 20 mg q.d. (N = 33) [27].
• METHODS: PET scans with [11C]DASB were performed before and after a single administration of duloxetine (5-60 mg), and three consecutive scans were performed after a single dose or repeated doses of 60 mg of duloxetine [28].
• However, duloxetine (25-200 mg/kg p.o.) did not affect salivation and lacrimation induced by oxotremorine (1 mg/kg s.c.), a cholinergic agonist, whereas it (25-50 mg/kg) reduced the oxotremorine-induced tremor in part [29].

Gene context of Cymbalta

• Duloxetine is metabolized by CYP2D6 and CYP1A2, with moderate potential for interactions at CYP2D6 [30].
• The next few years will determine whether CYP2D6 genotyping is beneficial for patients taking the new drugs aripiprazole, duloxetine, and atomoxetine [31].
• Duloxetine reduced SERT density in the cortex by approximately 75% compared to control, with no effect on NET density in the hippocampus [32].
• The lack of a detectable impact of duloxetine on TYR PD30 suggests that this may not be the most sensitive indirect measure of NE reuptake when assessing dual reuptake inhibitors [33].
• CONCLUSIONS: The two dose regimens of duloxetine (80 mg QD and 60 mg BID) produced a REM sleep pattern comparable to that of most antidepressant medications [34].

Analytical, diagnostic and therapeutic context of Cymbalta

• OBJECTIVE: We examined changes in metabolic parameters in clinical trials of duloxetine for diabetic peripheral neuropathic pain (DPNP) [2].
• In a 12-week, multicenter, double-blind study, 457 patients experiencing pain due to polyneuropathy caused by Type 1 or Type 2 diabetes mellitus were randomly assigned to treatment with duloxetine 20 mg/d (20 mg QD), 60 mg/d (60 mg QD), 120 mg/d (60 mg BID), or placebo [4].
• Placebo, desipramine 50 mg b.i.d., and duloxetine (80 mg q.d. or 60 mg b.i.d.) were compared in a randomized, double-blind, three-period crossover study in 12 healthy male subjects [33].
• The aim of this study was to assess the effects of duloxetine on the 5-HT and NE reuptake processes in healthy human volunteers [18].
• In this review, we highlight the preclinical pharmacology, pharmacokinetic profile, and effects of duloxetine in the pharmacotherapy of depression [8].

References