Altered mental status from olanzapine overdose treated with physostigmine.

BACKGROUND: Olanzapine is commonly prescribed to patients with schizophrenia. One retrospective study demonstrates the efficacy of physostigmine in reversing mental status changes induced by olanzapine. We report two patients with delirium due to confirmed olanzapine overdose treated with physostigmine. One patient's mental status transiently returned to normal. The other patient completely recovered. CASE 1: A 25-year-old man ingested 300 mg of olanzapine. On presentation, he was agitated, delirious, tachycardic, had dry skin and mucous membranes, and dilated pupils (6 mm) minimally reactive to light. Physostigmine, 0.5 mg, was given intravenously (IV) without effect. Additional physostigmine doses of 1.5 mg IV administered 5 minutes later and then 1 mg IV resulted in the patient having a clear sensorium and normal mentation. The patient's mental status continued to remain normal for the duration of his hospital stay. Olanzapine was identified in the urine by high performance liquid chromatography. CASE 2: A 20-year-old female ingested 600 mg of olanzapine. On presentation, she was tachycardic, obtunded, and minimally responsive to painful stimuli, with decreased bowel sounds, dry skin and dry mucous membranes. Physostigmine, 2 mg, was given IV. Shortly thereafter she regained full consciousness and began speaking coherently. She remained in this condition for approximately 30 minutes, and then became obtunded. Her serum olanzapine concentration was 1230 ng/mL. No further doses of physostigmine were administered. On day 3 of admission her mental status returned to normal. CONCLUSION: We report two cases of olanzapine-induced mental status changes treated with physostigmine. The utility of physostigmine as a safe or necessary antidote in the setting of olanzapine overdose remains to be determined.

Gaucher disease: the origins of the Ashkenazi Jewish N370S and 84GG acid beta-glucosidase mutations.

Type 1 Gaucher disease (GD), a non-neuronopathic lysosomal storage disorder, results from the deficient activity of acid beta-glucosidase (GBA). Type 1 disease is panethnic but is more prevalent in individuals of Ashkenazi Jewish (AJ) descent. Of the causative GBA mutations, N370S is particularly frequent in the AJ population, (q approximately .03), whereas the 84GG insertion (q approximately .003) occurs exclusively in the Ashkenazim. To investigate the genetic history of these mutations in the AJ population, short tandem repeat (STR) markers were used to map a 9.3-cM region containing the GBA locus and to genotype 261 AJ N370S chromosomes, 60 European non-Jewish N370S chromosomes, and 62 AJ 84GG chromosomes. A highly conserved haplotype at four markers flanking GBA (PKLR, D1S1595, D1S2721, and D1S2777) was observed on both the AJ chromosomes and the non-Jewish N370S chromosomes, suggesting the occurrence of a founder common to both populations. Of note, the presence of different divergent haplotypes suggested the occurrence of de novo, recurrent N370S mutations. In contrast, a different conserved haplotype at these markers was identified on the 84GG chromosomes, which was unique to the AJ population. On the basis of the linkage disequilibrium (LD) delta values, the non-Jewish European N370S chromosomes had greater haplotype diversity and less LD at the markers flanking the conserved haplotype than did the AJ N370S chromosomes. This finding is consistent with the presence of the N370S mutation in the non-Jewish European population prior to the founding of the AJ population. Coalescence analyses for the N370S and 84GG mutations estimated similar coalescence times, of 48 and 55.5 generations ago, respectively. The results of these studies are consistent with a significant bottleneck occurring in the AJ population during the first millennium, when the population became established in Europe.