Incidence and duration of antidepressant-induced nausea: duloxetine compared with paroxetine and fluoxetine

OBJECTIVE: This analysis assessed the incidence, severity, onset, and duration of nausea among patients with major depressive disorder (MDD) treated with the new antidepressant duloxetine. METHODS: Data were pooled from 8 double-blind, randomized, placebo- and active comparator-controlled trials employing patients with MDD that were submitted to the US Food and Drug Administration to support duloxetine's new drug application for treatment of MDD. RESULTS: The numbers of patients receiving each regimen were as follows: placebo, n = 777; duloxetine 40 mg/d, n = 177; duloxetine 60 mg/d, n = 251; duloxetine 80 mg/d, n = 363; duloxetine 120 mg/d, n = 348; paroxetine 20 mg/d, n = 359; and fluoxetine 20 mg/d, n = 70. In acute placebo-controlled trials of duloxetine 40 to 120 mg/d, treatment-emergent nausea was reported by more duloxetine-treated patients than those receiving placebo (19.9% [227/1139] vs 6.9% [154/777], respectively; P <0.001). Among duloxetine-treated patients, the median time to onset of nausea was 1 day, and the median duration of nausea was 7 days. The incidence of nausea was similar to placebo rates after 1 week. In paroxetine-controlled studies, the incidence of treatment-emergent nausea in patients receiving duloxetine did not differ significantly from paroxetine (14.4% vs 12.0%, respectively). In head-to-head studies, the incidence of treatment-emergent nausea with duloxetine did not differ significantly from that with fluoxetine (17.1% vs 15.7%, respectively). Most duloxetine-treated patients reported nausea to be mild (52.9%) or moderate (41.4%). Treatment discontinuation secondary to nausea occurred in more duloxetine-treated patients than those receiving placebo (1.4% [16/1139] vs 0.1% [1/777], respectively; P = 0.002). Following abrupt discontinuation after acute treatment, 5.9% of duloxetine-treated patients exhibited nausea compared with 0.3% of patients receiving placebo (P < 0.001). The incidence of treatment-emergent nausea during 6-month continuation of duloxetine treatment (80 mg/d, 2.1%; 120 mg/d, 1.3%) was similar to placebo (1.6%). Following abrupt discontinuation after 8 months of treatment, nausea was reported by 1.6% of patients receiving duloxetine 120 mg/d compared with 0% for those receiving duloxetine 80 mg/d and 0% for placebo. CONCLUSIONS: Duloxetine induced mild to moderate nausea in a subset of patients with MDD during treatment initiation. Nausea resolved rapidly with continued treatment. The incidence of duloxetine-induced nausea resembled that produced by paroxetine and fluoxetine.     

Effect of cystine on the methionine requirement of healthy Indian men determined by using the 24-h indicator amino acid balance approach

BACKGROUND: The 1985 FAO/WHO/UNU requirement for methionine in healthy adults consuming a cystine-free diet is 13 mg.kg(-1).d(-1). It is unclear whether this daily requirement is influenced by dietary cystine. OBJECTIVE: We assessed the effect of 2 intakes of cystine (5 and 12 mg.kg(-1).d(-1)) on methionine requirements in well-nourished Indian men by using 7 test methionine intakes (3, 6, 9, 13, 18, 21 and 24 mg.kg(-1).d(-1)) and the 24-h indicator amino acid oxidation (24-h IAAO) and balance (24-h IAAB) methods. We combined these data with those from an experiment with zero cystine intake and in which the exact same method was used. DESIGN: Two studies were performed in which a diet containing either 5 or 12 mg cystine.kg(-1).d(-1) was fed to 21 well-nourished Indian men over three 7-d periods. The 24-h IAAO and 24-h IAAB values were measured on day 7 with the use of a 24-h intravenous [13C]leucine tracer infusion. The breakpoints in the relation between these values and methionine intake in each study were assessed by two-phase linear regression. RESULTS: Breakpoints in the response curve were obtained at methionine intakes of 20 (95% Fiellers CI: 17, 26) and 10 (95% Fiellers CI: 8, 16) mg.kg(-1).d(-1) with cystine intakes of 5 and 12 mg.kg(-1).d(-1) intakes, respectively, which suggested a sparing effect of cystine. Although the 5- and 12-mg cystine breakpoints differed from one another, they did not differ significantly from that estimated previously with 0 mg cystine. CONCLUSION: Cystine may spare the methionine requirement in healthy men, although the amount of sparing is difficult to quantify.     

Orbital apex syndrome secondary to Pseudallescheria boydii fungal sinusitis in an immunocompetent patient

Orbital apex syndrome secondary to mucormycosis in immuno-compromised patients is well described; however, few reports exist of a paranasal sinus mycetoma resulting in this presentation in the immuno-competent patient. The case is reported of a 92-year-old man who developed orbital apex syndrome secondary to a sphenoidal sinus mycetoma of Pseudallescheria boydii.     

Intrinsic regenerative ability of mature CNS neurons.

A prevailing view in neuroscience is that the mature CNS has relatively little capacity to respond adaptively to injury. Recent data indicating a high degree of structural plasticity in the adult brain provides an impetus to reexamine how central neurons react to trauma. An analysis of both in vivo and in vitro experimental studies demonstrates that certain brain neurons may have an intrinsic ability to respond to structural injury by an attempt at regenerative sprouting. Indeed, aberrant sprouting following neuronal injury may be the cause of epilepsy following brain trauma and may underlie the neuronal changes stimulated by plaque formation in Alzheimer's disease. An understanding of the stereotypical reaction to injury of different CNS neurons, as well as the role of nonneuronal cells, may provide new avenues for therapeutic intervention for a range of neurodegenerative diseases and "acquired" forms of CNS injury.     

Detecting protein losing enteropathy by Tc-99m dextran scintigraphy: a novel experience

OBJECTIVE: To evaluate protien using enteropathy by Tc-99m dextran scintigraphy. METHODS: Methods for detecting protein loss from the intestine revolve around fecal nitrogen excretion, the clearance of alpha-1 antitrypsin in stools and by endoscopic biopsy. RESULT: The diagnosis of protein-losing enteropathy (PLE) can also be established by a scintigraphic method that is noninvasive, simple and requires no patient preparation or motivation. This diagnostic modality can also delineate the site of protein loss, thereby offering a targeted approach, and if need be, surgery. Radiolabelling of a non-protein, noncolloidal, nonparticulate and biofriendly molecule like dextran with Technetium-99m for imaging enteric protein loss was utilized in imaging eight children with PLE. CONCLUSION: The results were encouraging. The authors advocate the use of this diagnostic tool in identifying patients with PLE, particularly in the pediatric age group.     

Long-acting GnRH analogue triptorelin therapy in central isosexual precocious puberty

OBJECTIVE: To evaluate the efficacy of long acting GnRH analogue in improving the auxological outcome of patients with central isosexual precocious puberty (CIPP) and to determine the factors influencing the response. METHODS: Thirty-five patients (30 girls, 5 boys) with CIPP were treated with a long acting GnRH analogue, triptorelin. Final height outcomes and factors affecting treatment were analyzed. RESULTS: Treatment was started at the chronological age (CA) of 6.5 1.8 years in girls and 4.4 1.5 years in boys and continued for a period of 3.7 1.8 years in girls and 6 1.8 years in boys. Follow-up period after discontinuation of treatment was 2.2 0.5 years in girls and 2.6 0.3 years in boys. Treatment led to regression of precocious puberty and reversal of secondary sexual characteristics. There was decline in growth rate reflected by a fall in heightSD of 0.8 0.8 in girls and 2.3 0.9 in boys (p = 0.014), an even greater retardation in bone age (BA) advancement with a decrease in BA-CA of 1.7 1 years in girls and 2.7 1 years in boys and a fall in heightSDBA of 1.5 1.1 in girls and 2.1 1.6 in boys. Final height (149.8 6.9 cm in girls and 161.9 3.9 cm in boys) exceeded projected height at the onset of treatment (143.4 8.3 cm in girls and 154.3 2.7 cm in boys) by 6.4 2.4 cm in girls and 7.6 1.5 cm in boys ( p < 0.001 in both the groups). Factors influencing height gain included age at start of therapy (r = 0.715), BA-CA at the time of initiation of treatment (r = 0.734), heightSDBA at the onset of treatment ( r = 0.566) and the duration of treatment (r = 0.711). Girls treated at an age of less than 6 years (n = 9) had a greater height gain (8.7 1.6 cm versus 5.3 1.9 cm, p < 0.001) and achieved similar final height (148.7 8 cm versus 150.2 6.6 cm) in those treated after this age (n = 21). No side effects of GnRH therapy were observed in the study. CONCLUSION: Long acting GnRH therapy is effective in improving the auxological outcome of patients with CIPP. Maximum benefit is observed in girls with greater bone age advancement treated at a younger age and for a longer duration of treatment. These girls had lower bone age advance at discontinuation of treatment.