Insomnia and the effect of zolpidem-extended-release on the sleep items of the Hamilton Rating Scale for Depression in outpatients with depression, insomnia, and suicidal ideation: Relationship to patient age.

BACKGROUND: There are limited data regarding gamma-aminobutyric acid (GABA) allosteric modulator sleep-aid medications in persons with depression, insomnia, and suicidal ideation (SI). AIMS: This secondary analysis examined the relationship of age to insomnia and the impact of age on the treatment of insomnia with zolpidem extended-release (zolpidem-ER) in depressed suicidal patients. A prior report found that the addition of zolpidem-ER promoted significantly superior reductions in global severity of insomnia in depressed outpatients with insomnia and SI over 8 weeks, but here we report the differences among early, middle, and late insomnia. METHODS: This secondary analysis examined the three early, middle, and late insomnia items of the Hamilton Rating Scale for Depression (HRSD) and their relationship to age and responsiveness to treatment with zolpidem-ER. One hundred and three patients with major depression, SI, and insomnia received open-label serotonin reuptake inhibitors and were randomly allocated 1:1 to receive zolpidem-ER or placebo at bedtime. Results: Older age at baseline was associated with worse middle and late insomnia, but not with early insomnia. Subsequent treatment with zolpidem-ER produced superior improvement in early and middle insomnia, but not late insomnia. CONCLUSIONS: These findings are consistent with the known age-related advancement of sleep timing in the general population and depressed outpatients and with the expected effects of a short half-life GABA allosteric modulator sleep aid. By implication, prescribers of pharmacologic treatment of insomnia in depressed patients should consider an alternative to zolpidem-ER when late insomnia is a concern.Trial registration number: ClinicalTrials.gov Identifier: NCT01689909.

The effect of zolpidem-CR on the suicide item of the Hamilton Rating Scale for Depression in outpatients with depression, insomnia and suicidal ideation: Lessons learned.

The REST-IT study found the addition of zolpidem-controlled release (CR) provided a significant reduction in observer-rated measurement of suicidal ideation (the Columbia Suicide Severity Rating Scale) in 103 depressed outpatients with insomnia and suicidal ideation, but without significant change in a self-report measure of suicidal ideation (the Scale for Suicide Ideation). This secondary analysis of the REST-IT data examined the suicide item of another observer-rated scale, the Hamilton Rating Scale for Depression (HRSD), further clarifying the impact of insomnia-focused treatment on suicidal ideation. This analysis established a significant advantage for zolpidem-CR compared with placebo on the HRSD suicide item.

Characterization of the gut microbiome in an osteosarcoma mouse model.

Compelling evidence has mounted surrounding the relationship between the gut microbiome and many intestinal and extraintestinal cancers. Few studies exist investigating the relationship between the gut microbiome and sarcoma. We hypothesize that the presence of distant osteosarcoma induces change to the profile of flora within the mouse. Twelve mice were used for this experiment: six were sedated and received an injection of human osteosarcoma cells into the flank, while six served as controls. Baseline stool and weight were collected. Tumor size and mouse weight were recorded weekly, and stool samples were collected and stored. Fecal microbiomes of the mice were profiled by 16S rRNA gene sequencing and analyzed for alpha diversity, relative abundances of microbial taxa, and abundance of specific bacteria at different time points. Alpha diversity was increased in the osteosarcoma group compared with the control group. The family Lachnospiraceae had the second strongest negative net average change in relative abundance over time in the osteosarcoma group whereas it had a positive net average change in the control group. An increased Firmicutes/Bacteroidota (F/B) ratio was observed in the osteosarcoma group relative to the control mice. These differences suggest that there may be an interplay between the gut microbiome and osteosarcoma. Clinical significance: Due to the paucity of literature available, our work can support novel research on this relationship and the development of new, personalized treatments for osteosarcoma.