Antipsychotic switching versus augmentation among early non-responders to risperidone or olanzapine in acute-phase schizophrenia.

PURPOSE: We examined whether augmentation with olanzapine would be superior to switching to olanzapine among early non-responders (ENRs) to risperidone, and whether augmentation with risperidone would be superior to switching to risperidone among ENRs to olanzapine. We performed a rater-blinded, randomized clinical trial at psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. ENRs to the initial antipsychotic (Clinical Global Impressions-Improvement Scale: ≥ 4 at 2 weeks) were allocated to receive either augmentation with or switching to the other antipsychotic (RIS+OLZ vs. RIS-OLZ; OLZ+RIS vs. OLZ-RIS) RESULTS: Sixty patients who completed 2 weeks of risperidone treatment were divided into 33 early responders (RIS-ER) and 27 ENRs (RIS+OLZ, n=14; RIS-OLZ, n=13). Although time to treatment discontinuation for any cause was significantly shorter in RIS+OLZ group (54.1 days [95% confidence interval, 41.3-67.0]) than in RIS-ER group (68.7 [61.2-76.2]; P=0.050), it was not significantly shorter in RIS-OLZ group (58.5 [43.1-73.9]) than in RIS-ER group (P=0.19). Sixty patients who completed 2 weeks of olanzapine treatment were divided into 36 early responders (OLZ-ER) and 24 ENRs (OLZ+RIS, n=11; OLZ-RIS, n=13). Although time to treatment discontinuation for any cause was significantly shorter in OLZ-RIS group (56.1days [40.7-71.5]) than in OLZ-ER group (74.9 [68.5-81.3]; P=0.008), it was not significantly shorter in OLZ+RIS group (64.6 [49.6-79.6]) than in OLZ-ER group (P=0.20). CONCLUSION: Despite the lack of pharmacokinetic investigation of dose adequacy in this study, it is possible that switching to olanzapine among ENRs to risperidone might have a small advantage over augmentation with olanzapine, while augmentation with risperidone might have a small advantage over switching to risperidone among ENRs to olanzapine. Further research is required before it would be appropriate to modify routine practice in the direction of these findings.

The possibility that requiring high-dose olanzapine cannot be explained by pharmacokinetics in the treatment of acute-phase schizophrenia.

We examined clinical characteristics including serum olanzapine concentrations for acute schizophrenia patients who required above conventional doses. We performed a rater-blinded, randomized clinical trial in 12 psychiatric emergency sites. Eligible patients were 18-64 years old and met diagnostic criteria for schizophrenia, acute schizophrenia-like psychotic disorder, or schizoaffective disorder. A total of 42 patients were randomly assigned by means of sealed envelopes to receive risperidone (3-12 mg/day; n=20) and olanzapine (10-40 mg/day; n=22), with follow-up at 8 weeks. The Negative score of the Positive and Negative Syndrome Scale was significantly higher in patients who required high doses than in patients who responded to conventional doses. Serum olanzapine concentrations at the time of oral 20mg/day could be obtained from 5 out of 7 patients who subsequently required high-dose olanzapine. All values were more than 30 ng/mL after 11-16 h from dosing to sample collection, and the mean value was 47.876 (S.D. 21.546) ng/mL. Such concentrations are appropriate with respect to a therapeutic range of 20-50 ng/mL. The present study has shown evidence that the reason for requiring high-dose olanzapine cannot be explained by pharmacokinetics in the treatment of acute-phase schizophrenia.

A comparison between augmentation with olanzapine and increased risperidone dose in acute schizophrenia patients showing early non-response to risperidone.

We examined whether augmentation with olanzapine would be superior to increased risperidone dose among acute schizophrenia patients showing early non-response to risperidone. We performed a rater-blinded, randomized controlled trial at psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. Early response was defined as Clinical Global Impressions-Improvement Scale score ≤3 following 2 weeks of treatment. Early non-responders were allocated to receive either augmentation with olanzapine (RIS+OLZ group) or increased risperidone dose (RIS+RIS group). The 78 patients who completed 2 weeks of treatment were divided into 52 early responders to risperidone and 26 early non-responders to risperidone (RIS+OLZ group, n=13; RIS+RIS group, n=13). No difference in the achievement of ≥50% improvement in Positive and Negative Syndrome Scale total score was observed between RIS+OLZ and RIS+RIS groups. Although time to treatment discontinuation for any cause was significantly shorter in the RIS+RIS group (6.8 weeks [95% confidence interval, 5.2-8.4]) than in early responders to risperidone (8.6 weeks [7.9-9.3]; P=0.018), there was no significant difference between the RIS+OLZ group (7.9 weeks [6.3-9.5]) and early responders to risperidone. Secondary outcomes justify the inclusion of augmentation arms in additional, larger studies comparing strategies for early non-responders.

Difference in early prediction of antipsychotic non-response between risperidone and olanzapine in the treatment of acute-phase schizophrenia.

PURPOSE: We examined whether early response/non-response to risperidone according to the Clinical Global Impressions-improvement scale (CGI-I) at 2 weeks could predict subsequent response. This prediction was also applied to olanzapine. We then investigated whether early non-responders (ENRs) to risperidone or olanzapine who switched to the other showed significantly greater improvement, compared with those staying on the initial antipsychotic. We performed a rater-blinded, randomized controlled trial in 18 psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. Early response was defined as CGI-I ≤ 3 following 2 weeks of treatment. The primary outcome measure was achievement of remission and ≥ 50% improvement in the Positive and Negative Syndrome Scale at 4 weeks. RESULTS: At 4 weeks, 53% of risperidone early responders (ERs) went into remission, whereas only 9% of ENRs staying on risperidone (n=11) did (P=0.016). Similarly, at 4 weeks, 81% of risperidone ERs achieved ≥ 50% response, whereas only 9% of ENRs staying on risperidone achieved ≥ 50% response (P < 0.0001). In contrast, 58% of olanzapine ERs (n=33) went into remission, whereas 38% of ENRs staying on olanzapine (n=8) did at 4 weeks (P=0.44). Similarly, 61% of olanzapine ERs achieved ≥ 50% response, whereas 25% of ENRs staying on olanzapine achieved ≥ 50% response (P=0.12). The negative likelihood ratio for the prediction of ≥ 50% response at 4 weeks by early response status to risperidone at 2 weeks was 0.057. CONCLUSION: In newly admitted patients with acute schizophrenia, non-response to risperidone using CGI-I at 2 weeks can predict subsequent response. It looks like there is significant response to olanzapine that doesn't occur until 4 weeks. Thus, clinicians may want to switch to another drug earlier when risperidone is the first drug, and later when olanzapine is the first drug.

Effectiveness of second-generation antipsychotics with acute-phase schizophrenia.

PURPOSE: Although olanzapine may have advantages over other second-generation antipsychotics (SGAs) regarding longer time to treatment discontinuation among chronically ill patients, little evidence has been provided for the comparative effectiveness of SGAs in the acute phase. We aimed to determine if any of four SGAs were more effective in treating newly admitted acute schizophrenic patients. We performed a rater-blinded, randomized controlled trial of four SGAs in 15 psychiatric emergency sites. Eligible patients were 18-64 years old and met diagnostic criteria for schizophrenia, acute schizophrenia-like psychotic disorder, or schizoaffective disorder. A final total of 78 patients were randomly assigned by means of sealed envelopes to receive risperidone (3-12 mg/day; n=20), olanzapine (10-20 mg/day; n=17), quetiapine (300-750 mg/day; n=20), or aripiprazole (12-30 mg/day; n=21), with follow-up at 8 weeks. The primary outcome measure was all-cause treatment discontinuation. RESULTS: Overall, 37% (29/78) of patients discontinued the study medication before 8 weeks: 25% for risperidone; 12% for olanzapine; 55% for quetiapine; and 52% for aripiprazole. Time to treatment discontinuation for any cause was significantly longer in the olanzapine group than in the quetiapine (p=0.006) or aripiprazole (p=0.008) groups, but not compared to the risperidone group (p=0.32). Time to treatment discontinuation was significantly longer in the risperidone group than in the quetiapine group (p=0.048), but not compared to the aripiprazole group (p=0.062). However, the rate of p.r.n. intramuscular haloperidol use was significantly higher in the aripiprazole group than in other groups (p=0.029). CONCLUSION: Olanzapine and risperidone are superior to quetiapine and aripiprazole for the acute treatment of psychosis in hospitalized patients.

Two cases of severe degeneration of the macula following vitrectomy with indocyanine green-assisted internal limiting membrane peeling for idiopathic macular hole.

We describe three eyes of two cases of severe degeneration of the macula following vitrectomy with indocyanine green-assisted internal limiting membrane peeling for idiopathic macular hole. We need to remember the possibility of these complications and have to select the procedures that are safest to use for macular hole surgery.

Relation between stage of endogenous fungal endophthalmitis and prognosis.

BACKGROUND: Although many studies have been published on the risk factors and therapies for endogenous fungal endophthalmitis (EFE), only a few have been published on the relationship between the stage of EFE at the initial examination and the prognosis. Thus, the purpose of this study was to determine the relation between the stage of EFE at the initial examination and the prognosis. METHODS: A total of 103 eyes of 58 patients (40 men, 18 women) with EFE, examined over a 20-year period (1984-2004), were studied. The severity of the EFE at the initial examination was classified into four stages. In addition, the type of fungus, general status, initial and final visual acuity, findings of the anterior and posterior segments, latent fungal infection, duration from initial symptoms to initial visit, history of intravenous hyperalimentation (IVH), results of the Candida Detection System, and beta-D-glucan levels were analyzed. RESULTS: More than 95% of the patients had some type of underlying disorder. Candida albicans was detected initially in the blood in 40 patients. The stage of the EFE advanced as the time from the initial symptoms to the beginning of therapy increased. The final visual acuity was significantly correlated with the stage of EFE at the initial examination. In 20 of 21 patients, blood beta-D-glucan was positive, and 42 patients (90%) were receiving IVH. CONCLUSIONS: Because the stage of EFE advanced with the time between the initial symptoms and the beginning of therapy, and because of the high correlation between the stage of EFE and the final visual acuity, it is very important that treatment be begun as soon as possible. Thus, in patients with visual symptoms and susceptible to opportunistic infections, an early consultation with an ophthalmologist is highly recommended.

Retinal vessel changes in a patient with primary systemic nonfamilial amyloidosis.

A case is described that demonstrates retinal vessel changes and suggests the favorable effects of hemodialysis to treat pathology in a patient with primary systemic nonfamilial amyloidosis. A 47-year-old woman diagnosed as having primary systemic nonfamilial amyloidosis at the age of 30 years had linear and dot hemorrhage, venous dilatation, and tortuosity in the right eye. Fluorescein angiography revealed low-density amorphous areas in the walls of dilated veins near the optic disc. These findings diminished with hemodialysis.

Penetrating keratoplasty surgery combined with vitrectomy after failing previous corneal surgery.

PURPOSE: The preoperative and postoperative factors influencing visual outcome were analyzed in 15 eyes of 15 patients with graft opacity after keratoplasty associated with vitreoretinal disease who underwent combined surgery of fresh corneal retransplantation and vitrectomy. MATERIALS AND METHODS: The data obtained consisted of diagnosis, preoperative visual acuity, corneal and vitreoretinal findings at the time of surgery, interval between the first visit and surgery, intraocular pressure before surgery, gonioscopic findings, results of bacterial culture of surgical specimens, surgical procedure for vitrectomy, corneal and vitreous findings after surgery, visual acuity 6 months after surgery, intraocular pressure after surgery, and additional surgical techniques. RESULTS: The cause of corneal opacity was graft rejection in all patients, who had been treated with high-dose administrations of steroids and cyclosporin. The preoperative diagnosis was proliferative vitreoretinopathy (PVR) in eight eyes and fungal endophthalmitis in seven eyes. Corneal transparency was achieved in 7 eyes (46.6%) 6 months after surgery. Vitreoretinal findings improved in 9 eyes (60%) and PVR recurred in 6 eyes (40%). Visual acuity improved in 7 eyes (46.6%), did not change in 2 eyes (13.3%), and deteriorated in 6 eyes (40%). The six eyes with decreased visual acuity developed phthisis bulbi. Preoperative intraocular pressure was 2.1 mmHg on average in the phthisis bulbi group, significantly lower than in the group with superior prognosis. Goniosynechia was noted before surgery and did not improve after surgery in all six eyes. CONCLUSIONS: The outcome was poor in eyes with goniosynechia and ocular hypotony, and combined surgery is not indicated for either anatomic or visual preservation in such cases. Care should be taken not to overlook intraocular infection in patients undergoing immunosuppressive therapy against graft rejection. The early detection of retinal detachment is also important in eyes exhibiting hypotony after surgery.

Multifunction vitreous forceps (maculorrhexis forceps).

We developed novel multifunction vitreous forceps to decrease the frequency of forceps insertion and enable the removal of the internal limiting membrane and other intravitreal membranes for better surgical results. The basic forceps were conventional continuous curvelinear capsulorrhexis (CCC) forceps. The size of the shaft is 23G and its pointed end measures 500 microm in diameter. Additionally, there is a platform in its tip. The pointed end with platform helps to hold the membrane because the outer sheath can be moved while the tip of the forceps is fixed in position, and its pen hold type grip helps to reduce hand movement. The most advantageous thing is that the sharp point enables us to make an initial flap easily and the desired area of internal limiting membrane can be peeled off by firmly holding the platform.