The utility of the Dementia Severity Rating Scale in differentiating mild cognitive impairment and Alzheimer disease from controls.

The current study investigated the utility of the Dementia Severity Rating Scale (DSRS) total score to identify individuals at the earliest stage of impairment (ie, mild cognitive impairment/MCI). In addition, the authors sought to investigate how well the measure correlates with an expanded battery of cognitive tests and other measures of functional abilities. Of the 320 participants included in this study, 85 were normal controls, 96 had single-domain or multiple-domain amnestic MCI, and 139 had possible or probable Alzheimer disease (AD). Each participant underwent a thorough cognitive, neurological, and physical examination. Results from this study indicated that the DSRS total scores differed significantly between the 3 groups (P<0.001) and accurately identified 81% of the control group, 60% of the MCI group, and 78% of the AD group in a post hoc discriminant analysis. When combined with a brief cognitive measure (ie, Consortium to Establish a Registry for Alzheimer's Disease Word List 5 min recall test), the DSRS accurately identified 98% of the control group, 76% of the MCI group, and 82% of the AD group. Implications for clinical practice and proposed areas of future research are discussed.

Open trial of injectable risperidone for methamphetamine dependence.

We tested acceptability and tolerability of long-acting injectable risperidone for methamphetamine (MA) dependence in an open trial with the hypothesis that participants would reduce MA use. Participants were also evaluated for changes in neurocognitive function and psychiatric symptomology. Participants with MA dependence (n = 34) entered a 7-day open-label run-in with oral risperidone. Participants who tolerated oral risperidone (n = 22) were begun on long-acting injectable risperidone 25 mg intramuscular medication with subsequent injections q 2 weeks to a total of 4 injections. Participants remained on oral risperidone during the first 3 weeks after initial injection. Participants were offered 8 weekly individual sessions of relapse prevention counseling. At baseline, participants reported using MA an average of 4.1 days per week (SD = 1.9). Estimated mean days of MA use per week while on injections was 1.0 (95% confidence interval = 0.6-1.4), with days of use decreasing significantly from baseline through week 8 (ß = -0.27; 95% confidence interval: - 0.38--0.16; P < 0.001). Mean week 6 risperidone + 9-OH risperidone plasma levels for participants abstinent from MA from weeks 5 to 8 (n = 7, 63.6%) were 18.8 ng/mL (SD = 6.6) compared with 12.3 (SD = 4.0) for those not abstinent (n = 4; P = 0.075). No serious adverse events occurred. Verbal memory improved at week 4 compared with baseline (P < 0.05). Participation in this trial of injectable risperidone was associated with reductions in MA use as well as some positive benefits on verbal memory. However, these results are limited by the use of an open trial design with a high dropout rate. Risperidone deserves further study in controlled trials as a pharmacotherapy for MA dependence.

Time to discontinuation and self-discontinuation of olanzapine and risperidone in patients with schizophrenia in a naturalistic outpatient setting.

BACKGROUND: Although efficacy of antipsychotic medications is well documented, their effectiveness in real-world practice is less robust. We examined the effectiveness of olanzapine and risperidone in schizophrenia in a naturalistic setting. METHODS: We used an electronic medical records database at a Veterans Affairs Medical Center to conduct a retrospective study of all new outpatient medication trials of olanzapine (n = 221) and risperidone (n = 274) over a 2-year period beginning January 1999 in patients diagnosed with schizophrenia or schizoaffective disorder. We defined medication discontinuation as a switch between the 2 agents (most switches) or self-discontinuation when a patient is without medication supply for longer than 1 month. RESULTS: Sample mean age (+/-SD) was 48.4 (+/-11.6) years; 91% were men. Discontinuation rates were high (73%), trending lower in olanzapine (70%) than risperidone (76%) (P = 0.12). Median time to discontinuation was 120 days (95% confidence interval [CI], 105-135), longer for olanzapine (150 days; 95% CI, 120-180) than risperidone (90 days; 95% CI, 71-109) (P = 0.04). Self-discontinuation was high (48%), with no significant difference between olanzapine (50%) and risperidone (46%). Switching rate was 25% and more likely to occur in risperidone (30%) than olanzapine (20%) (odds ratio, 1.72; 95% CI, 1.13-2.61). CONCLUSIONS: Effectiveness of antipsychotic medications in schizophrenia may be hampered by high rates of medication self-discontinuation in outpatient practice settings. Time to discontinuation suggests that olanzapine may be more effective than risperidone. Strategies to address causes of poor adherence should be incorporated in medication algorithms to optimize their effectiveness.

Olanzapine-induced weight gain and increased visceral adiposity is blocked by melatonin replacement therapy in rats.

The atypical antipsychotic drug olanzapine increases body weight and visceral adiposity in schizophrenia. In rats, aging-associated increased body weight and visceral adiposity are reversed by administration of the pineal hormone melatonin. We asked if melatonin similarly would reverse olanzapine-induced increased weight and visceral adiposity in rats. Four groups (n=11/group) of female rats (240-250 g) were treated for 8 weeks with olanzapine, melatonin, olanzapine+melatonin, or vehicle alone in drinking water. Body weight and food and water consumption were determined weekly, locomotor activity at weeks 3 and 6, and nocturnal plasma melatonin concentration at week 7. At week 8, the rats were killed and visceral (perirenal, retroperitoneal, omental, and mesenteric) fat pads dissected and weighed. Olanzapine treatment reduced nocturnal plasma melatonin by 55% (p<0.001), which was restored to control levels by olanzapine+melatonin. Body weight increased 18% in rats treated with olanzapine alone, but only 10% with olanzapine+melatonin, 5% with melatonin alone, and 7% with vehicle control. Body weight and visceral fat pad weight increases in rats treated with olanzapine alone were greater than in each of the other three groups (all p<0.01), which were not significantly different. These results suggest that olanzapine-induced increases in body weight and visceral adiposity may be at least in part secondary to olanzapine-induced reduction of plasma melatonin levels, and that melatonin may be useful for the management of olanzapine-induced weight gain in humans.