Potential of levetiracetam in mood disorders: a preliminary review

Levetiracetam is a newer antiepileptic agent that was first approved by the US FDA in 1999 as an adjunctive therapy for the treatment of refractory partial epilepsy in adults. Since then, it has been approved for a wider patient population, i.e. as adjunctive therapy for partial seizures in patients >4 years of age (worldwide) and as first-line monotherapy for partial seizures in patients >16 years of age (in Europe); and as adjunctive therapy for juvenile myoclonic seizures (in Europe and the US). It has a favourable pharmacokinetic profile and appears to act at a specific site in the CNS. Pharmacodynamic evidence indicates that levetiracetam indirectly facilitates GABAergic function, and an increasing body of evidence suggests an important role for GABA in the pathophysiology of mood disorders. Preclinical studies using animal models of depression, anxiety and mania provide evidence for levetiracetam as a mood stabiliser. Preliminary clinical evidence from case reports and open-label pilot studies indicates that the drug, both as add-on therapy and as monotherapy, has efficacy in a wide range of bipolar spectrum disorders. Most recently, a 31% remission rate was reported in patients with bipolar disorder who were in the depressed phase at baseline and who received levetiracetam as add-on therapy for 8 weeks in an open-label trial. While these results are encouraging, placebo-controlled data are needed to further clarify the role of levetiracetam in the treatment of mood disorders.     

Intraoperative floppy iris syndrome (IFIS) in patients receiving tamsulosin or doxazosin—a UK-based comparison of incidence and complication rates

Background

The association between intraoperative floppy iris syndrome (IFIS) and tamsulosin has been well-described. The rate of IFIS in association with other α-1 antagonists needs further clarification. The objective of this study was to determine the incidence of IFIS and associated cataract surgery complications in patients taking tamsulosin or doxazosin.

Methods

Patients receiving tamsulosin or doxazosin, and an equivalent number of controls, were identified using the electronic patient record for cataract surgery performed over 2 years. The presence of IFIS and intraoperative complications were ascertained. Modifications of surgical technique in the form of preoperative 1 % atropine, intraoperative diluted phenylephrine, iris hooks, or highly viscous viscoelastic materials were recorded.

Results

Of the 2,785 cataract operations performed in 2,028 patients, 52 cases (1.9 %) were on tamsulosin and 109 were on doxazosin (3.9 %). In the doxazosin group (excluding three cases with incomplete data), significantly more eyes (17 of 106 eyes, 16 %) showed at least one IFIS characteristic than controls, six eyes (6 %) required adjustment of surgical technique, and intraoperative complications occurred in two eyes (1.9 %). In the tamsulosin group, significantly more eyes (25 of 52 eyes, 48 %) demonstrated at least one IFIS feature than control or doxazosin eyes; 18 eyes (35 %) needed adjustment of surgical technique, and seven (13.5 %) suffered intraoperative complications.

Conclusion

Incidence of IFIS was significantly higher in tamsulosin and doxazosin patients. The presence of IFIS was associated with a significantly higher complication rate. We would advise that all patients receiving α1 antagonists (not only those receiving tamsulosin) should be identified preoperatively, receive appropriate modifications in preparation, and have alternative techniques and a senior surgeon available at the time of surgery.     

Association Between Use of Proton Pump Inhibitors and a Clostridium difficile-Associated Disease Outbreak: Case-Control Study

Background:

The use of proton pump inhibitors (PPIs) has been implicated as a potential contributor to the development of Clostridium difficile–associated disease (CDAD) because of the ability of these drugs to substantially reduce the bactericidal effect of gastric acid. This study focused on the impact of PPIs, among other known risk factors, during an outbreak of CDAD in a hospital setting.

Objectives:

The primary objective was to determine whether there was an association between current use of a PPI and the CDAD outbreak. Secondary objectives were to evaluate any correlations between the CDAD outbreak and past use of PPIs, use of antibiotics, diabetes mellitus, enteral feeding, cancer, gastrointestinal surgery, inflammatory bowel disease, and previous care or residence in an institutional setting.

Methods:

A retrospective case–control study was conducted. One hundred and fifty cases of hospital-acquired Clostridium difficile were identified. Patients were individually matched to controls for age, sex, date of admission to hospital, and hospital unit. The groups were compared with respect to each exposure.

Results:

Eight case patients could not be matched with suitable controls. Therefore, data from 142 cases and 142 controls were analyzed. There was no association between current use of a PPI and the CDAD outbreak (odds ratio [OR] 1.0, 95% confidence interval [CI] 0.99–1.01). Similarly, there was no correlation between the CDAD outbreak and diabetes, enteral feeding, cancer, gastrointestinal surgery, inflammatory bowel disease, or previous care or residence in an institution. However, the development of CDAD was positively associated with use of antibiotics within the 30 days preceding the infection (OR 12.0, 95% CI 4.0–35.7) and with past use of a PPI (OR 2.4, 95% CI 1.4–4.3).

Conclusions:

The development of CDAD during a hospital outbreak was associated with use of antibiotics and with past, not current, use of PPIs.