Andre Tapp

Schizophrenia, narcolepsy, and HLA-DR15, DQ6

A strong association between HLA-DR2, DQ1 and narcolepsy-cataplexy has been known since 1986. In 1990 a subdivision (HLA-DR15, DQ6) was shown to be equally associated. Narcolepsy symptoms include rapid eye movement (REM)-sleep intrusion hallucinations during the day. Some narcoleptics may be so hallucinated that they become delusional and receive a diagnosis of schizophrenia. Fifty-six inpatient schizophrenics and 56 normal controls were compared to see if there was an excess of the narcolepsy-associated antigens (NAA) among schizophrenics. Patients had frequency of the NAA 3.89 times higher than controls. After a subset was studied by night (n = 9) and day (n = 7) polysomnography, two patients were found to be true narcoleptics. Their psychosis improved with treatment for narcolepsy. When NAA(+) and NAA(-) schizophrenics were compared, the NAA(+) subgroup had significantly higher Brief Psychiatric Rating Scale (BPRS) scores and more hospitalizations. There were no effects attributable only to gender or race. We conclude that narcolepsy can simulate schizophrenia in some cases, and that even in nonnarcoleptic patients, the HLA-DR15,DQ6 antigens mark a group of severe schizophrenics that merits further study.

Quetiapine for the treatment of cocaine dependence: an open-label trial.

The monaminergic properties of second generation antipsychotics are prompting research on their use to treat cocaine dependence, with inconclusive results to date. In preliminary reports, the atypical antipsychotic quetiapine has shown promise for the treatment of substance abuse disorders. The primary objective of the current study was to assess the efficacy of quetiapine in reducing cocaine cravings and use in nonpsychotic subjects with cocaine dependence over 6 weeks of open-label treatment. Twenty-two cocaine-dependent, nonpsychotic men were initiated to open-label treatment with quetiapine (300-600 mg/d). The primary outcome measure was weekly self-report of cocaine cravings as assessed with the Brief Substance Craving Scale. Cocaine use was captured with a self-report Timeline Follow-back calendar, administered every 2 weeks. Side effect monitoring was conducted weekly, and movement disorders were assessed every 2 weeks. Intent-to-treat regression analyses (n = 22) indicated that the Brief Substance Craving Scale total score decreased significantly overtime (P < 0.001). Self-reports also suggested decreased cocaine use. There was no treatment-related increase in movement disorders, and most side effects were mild. However, all subjects did experience sedation, and several subjects dropped out because of it. What is more, weight increased significantly over time (P < 0.001). Open-label quetiapine treatment reduced cravings and improved some aspects of cocaine dependence in nonpsychotic individuals. Additional research is needed to confirm the current findings and to further delineate the role quetiapine may play in the treatment of cocaine use disorders.

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.

Age Disorientation in Kraepelinian Schizophrenia: Frequency and Clinical Correlates

Many schizophrenic patients exhibit significant neuropsychological impairment, and age disorientation is considered to be one of the more extreme manifestations. To evaluate clinical correlates of age disorientation with reference to the course of schizophrenic illness, we compared 39 deteriorated chronic Kraepelinian schizophrenic patients and 39 nondeteriorated schizophrenic patients early in the course of illness. Age disorientation was observed in 36% of patients in the Kraepelinian group, but in no patient in the non-Kraepelinian group. In the Kraepelinian group, age disorientation was unrelated to positive/negative symptoms or illness duration. Our data suggest that age disorientation may be a function of aging in schizophrenia, but is not merely a function of chronicity.

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.