Latanoprost or brimonidine as treatment for elevated intraocular pressure: multicenter trial in the United States.

PURPOSE: To compare the efficacy and tolerability of latanoprost or brimonidine in patients with elevated intraocular pressure (IOP). MATERIALS AND METHODS: This prospective, randomized, masked-evaluator, parallel-group, multicenter study in the United States included patients with primary open angle glaucoma or ocular hypertension. Patients received latanoprost 0.005% once daily (8:00 AM; n = 152) or brimonidine tartrate 0.2% twice daily (8:00 AM and 8:00 PM; n = 151). Patients underwent evaluation at screening, baseline (randomization), and after 0.5, 3, and 6 months of treatment. IOP was measured at 8:00 AM, 10:00 AM, noon, and 4:00 PM at baseline and the months 3 and 6 visits, and at 8:00 AM only at week 2. The main outcome measure was the difference in diurnal IOP change from baseline to month 6 between treatment groups. Adverse events were recorded at each visit. RESULTS: Baseline mean diurnal IOP levels were similar between groups. At month 6, the adjusted mean (+/- SEM) diurnal IOP reduction was 5.7 +/- 0.3 mm Hg in the latanoprost group and 3.1 +/- 0.3 mm Hg in patients receiving brimonidine (P < 0.001). The mean difference in diurnal IOP reduction was 2.5 +/- 0.3 mm Hg (95% CI: 1.9, 3.2; P < 0.001). Five times more patients receiving brimonidine than latanoprost were withdrawn from the study due to adverse events. CONCLUSION: Latanoprost instilled once daily is more effective and better tolerated than brimonidine administered twice daily for the treatment of patients with glaucoma or ocular hypertension. During therapy, the range of daily fluctuation of IOP is less for latanoprost compared with brimonidine.

Comparison of latanoprost with fixed-combination dorzolamide and timolol in adult patients with elevated intraocular pressure: an eight-week, randomized, open-label, parallel-group, multicenter study in Latin America.

BACKGROUND: The newer ocular hypotensive agents available to treat glaucoma and ocular hypertension (OHT) include latanoprost, a prostaglandin F(2alpha) analogue, and the fixed combination of dorzolamide hydrochloride, a carbonic anhydrase inhibitor, and timolol maleate, a beta-blocker. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of latanoprost with that of the fixed combination of dorzolamide and timolol over 8 weeks. METHODS: This interventional, 8-week, randomized, open-label, parallel-group study was conducted at 18 centers in 6 Latin American countries. Patients with unilateral or bilateral primary open-angle, pigmentary, or exfoliative glaucoma or OHT were randomized to receive latanoprost, 1 drop in the affected eye QD (evening), or fixed-combination dorzolamide/timolol, 1 drop in the affected eye BID (morning and evening). Medications were self-administered, 1 drop per affected eye. At baseline and week 8, intraocular pressure (IOP) was measured 3 times each at 8:30 am, 10:00 am, 2:00 pm, and 5:00 pm and after the water-drinking test, which estimates the IOP peak of diurnal tension curve, performed following the 5:00 pm IOP assessment. The primary efficacy outcome was change in diurnal IOP (the mean of IOP measurements) from baseline to week 8. Adverse effect (AE) data were recorded at each visit. RESULTS: A total of 229 patients were randomized (latanoprost, n = 112; dorzolamide/timolol, n = 117). Mean baseline diurnal IOP values were similar between the 2 groups. Mean (SD) diurnal IOP reductions at week 8 before the water-drinking test were 6.9 (3.0) mm Hg for the latanoprost group and 6.4 (3.2) mm Hg for the dorzolamide/timolol group. Mean IOP values were similar at all time points except at 5:00 pm, when levels were significantly lower in latanoprost-treated patients (P = 0.025). After the water-drinking test, the increase in IOP values was similar between groups at baseline but lower in latanoprost-treated patients at week 8 (adjusted difference, 1.08 mm Hg; P = 0.012). Fewer patients treated with latanoprost reported ocular or systemic AEs (P = 0.025 and P < 0.001, respectively). CONCLUSIONS: In this study of patients with unilateral or bilateral primary open-angle, pigmentary, or exfoliative glaucoma or OHT IOP reductions generally were similar between treatment groups, except at 5:00 pm, when the mean IOP level was significantly lower in latanoprost-treated patients. Latanoprost was better tolerated than fixed-combination dorzolamide and timolol.

Efficacy and safety of the fixed combinations latanoprost/timolol versus dorzolamide/timolol in patients with elevated intraocular pressure.

PURPOSE: To compare the efficacy and safety of the fixed combination of latanoprost and timolol with those of the fixed combination of dorzolamide and timolol in patients with elevated intraocular pressure (IOP). DESIGN: Three-month, randomized, parallel group, evaluator-masked, multicenter study. PARTICIPANTS: Patients with primary open-angle glaucoma or ocular hypertension with elevated IOP insufficiently responsive to monotherapy; 253 randomized: 125 to receive a fixed combination of latanoprost 0.005% and timolol 0.5% once daily, and 128 to receive a fixed combination of dorzolamide 2% and timolol 0.5% twice daily. METHODS: Visits were at screening (current ocular hypotensive therapy was discontinued), 2 weeks (if needed for an IOP-safety check), baseline (randomization), and after 1 and 3 months of therapy. Intraocular pressure was measured in triplicate at 8 am, 12 pm, and 4 pm at each study visit, and diurnal IOP was calculated as the mean value of these recordings. Adverse events were recorded at each visit. MAIN OUTCOME MEASURE: The difference between treatment groups in the change in mean diurnal IOP from baseline to month 3. RESULTS: Mean diurnal IOP levels were similar at baseline. Mean (+/- standard error of the mean) reductions in diurnal IOP from baseline to month 3 were 9.4+/-0.27 mmHg in the latanoprost/timolol fixed-combination group, versus 8.4+/-0.26 mmHg in patients receiving the dorzolamide/timolol fixed combination. The mean difference in diurnal IOP reduction between treatments was 1.00 mmHg (95% confidence interval, 0.31-1.69; P = 0.005) in favor of the latanoprost/timolol fixed combination. Both treatments generally were well tolerated. CONCLUSIONS: The fixed combination of latanoprost and timolol was slightly more effective than that of dorzolamide and timolol in reducing mean diurnal IOP, and both treatments were generally well tolerated.

Switching to reboxetine: an efficacy and safety study in patients with major depressive disorder unresponsive to fluoxetine.

The aim of the present study was to evaluate the efficacy and safety of an immediate switch to reboxetine, a selective noradrenaline reuptake inhibitor (selective NRI), in patients with depression unresponsive to the selective serotonin reuptake inhibitor (SSRI) fluoxetine. The study included 128 adult outpatients with DSM-IV major depressive disorder (MDD) who had not responded to at least 6 to 12 weeks of fluoxetine treatment, with at least 3 weeks of treatment on a minimum dose of 40 mg/d. Patients were switched, without a washout period, to reboxetine 4 mg twice daily, with the possibility of increasing the dose to 10 mg/d (given in divided doses) after 4 weeks of treatment. Efficacy was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and the Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales. Safety was evaluated by recording spontaneously reported adverse events.A statistically significant (P < 0.001) improvement in the mean total HAM-D-17 score was seen from baseline by week 1 of treatment with reboxetine, and the improvement continue to week 8. CGI-I and CGI-S scores were similarly improved. The switch to reboxetine was well tolerated; the most common treatment-emergent adverse events were insomnia, headache, dry mouth, diaphoresis, and constipation, all of which were mild to moderate in severity and decreased in frequency as the study progressed.Immediate switching to reboxetine appears to be a safe and effective treatment for patients with depression who have failed to respond to an adequate dose of fluoxetine.

A comparison of latanoprost, bimatoprost, and travoprost in patients with elevated intraocular pressure: a 12-week, randomized, masked-evaluator multicenter study.

PURPOSE: To Internet Advance publication at ajo.com Feb 13, 2003. compare the intraocular pressure (IOP)-lowering effect and safety of latanoprost, bimatoprost, and travoprost in patients with open-angle glaucoma (OAG) or ocular hypertension (OH). DESIGN: Interventional study. METHODS: This 12-week, randomized, parallel-group study was conducted at 45 US sites. Previously treated patients with OAG or OH and an IOP > or =23 mm Hg in one or both eyes after washout received either latanoprost 0.005%, bimatoprost 0.03%, or travoprost 0.004% once daily in the evening. At baseline and after 6 and 12 weeks of therapy, masked evaluators measured IOP in triplicate at 8:00 AM, 12 noon, 4:00 PM, and 8:00 PM, and masked investigators graded conjunctival hyperemia before the 8:00 AM IOP measurement. The primary efficacy outcome measure was change between baseline and Week 12 in the 8:00 AM IOP (time of peak drug effect). RESULTS: In all, 410 of 411 randomized patients were included in intent-to-treat analyses (latanoprost, 136; bimatoprost, 136; travoprost, 138). Baseline mean 8:00 AM IOP levels were similar (P =.772); by week 12, reductions were observed in all 3 groups (P <.001 for each). Adjusted (ANCOVA) reductions in mean IOP at 8:00 AM were similar (P =.128) as were those at 12 noon, 4:00 PM, and 8:00 PM. Fewer latanoprost-treated patients reported ocular adverse events (P <.001, latanoprost vs bimatoprost), fewer reported hyperemia (P =.001, latanoprost vs bimatoprost), and average hyperemia scores were lower at week 12 (P =.001, latanoprost vs bimatoprost). CONCLUSIONS: Latanoprost, bimatoprost, and travoprost were comparable in their ability to reduce IOP in OAG and OH patients. Latanoprost exhibited greater ocular tolerability.

Randomized clinical trial of latanoprost and unoprostone in patients with elevated intraocular pressure.

PURPOSE: To compare the intraocular pressure (IOP)-lowering effect and safety of latanoprost 0.005% once daily with that of unoprostone 0.15% twice daily for patients with primary open-angle glaucoma or ocular hypertension. DESIGN: Randomized clinical trial. METHODS: In a prospective, 8-week, investigator-masked, parallel-group study conducted at numerous centers in the United States, 165 previously treated patients with IOP >or= 25 mm Hg in one or both eyes after washout were randomly assigned to receive either latanoprost 0.005% once daily in the evening or unoprostone 0.15% twice daily. Observations procedures were Goldmann applanation tonometry, best-corrected visual acuity, slit lamp biomicroscopy, and ophthalmoscopy. The main outcome measure was change in the mean of the IOPs measured at 8:00 AM, 12 noon, and 4:00 PM between baseline (before treatment) and after 8 weeks of treatment. RESULTS: The change in the mean +/- SD of the IOPs measured at 8:00 AM, 12 noon, and 4:00 PM was -7.2 +/- 3.2 mm Hg (28%) for latanoprost (25.3 +/- 2.8 mm Hg at baseline to 18.2 +/- 2.8 mm Hg at 8 weeks) and -3.9 +/- 2.6 mm Hg (15%) for unoprostone (25.5 +/- 3.3 mm Hg at baseline to 21.6 +/- 4.0 mm Hg; P