Evaluation of the effect of long-term use of antidepressants in the SSRI group on bone density with dental volumetric tomography.

AIM: The present study aims to employ dental volumetric tomography to examine bone mineral density among men that used antidepressants in the SSRI group for a long time. METHOD: The present study was conducted through the utilisation of data related to patients that presented to the Faculty of Dentistry of Dicle University and had a dental volumetric tomography (DVT) scan for any reason. The patients were divided into 2 groups based on the use of antidepressants: Group 1 included 68 patients as the control group, and Group 2 consisted of 68 patients that used antidepressants. Radiomorphometric measurements were performed on DVT data: DVT-Mandibular Index (DVT-MI), DVT-Cortical Index (DVT-CI), Hounsfield Unit (HU) CORTICAL, and HU SPONGIOSIS values were calculated. RESULTS: The group of patients that used antidepressants exhibited a significant increase in DVT CI and a significant decrease in HU CORTICAL, HU SPONGIOSIS and DVT MI values. These findings were suggestive of osteoporosis. CONCLUSION: Long-term use of antidepressants should be taken into consideration as a risk factor for osteoporosis in men.

Anxiety-like effects induced by acute fluoxetine, sertraline or m-CPP treatment are reversed by pretreatment with the 5-HT2C receptor antagonist SB-242084 but not the 5-HT1A receptor antagonist WAY-100635.

The possible role of 5-HT1A and 5-HT2C receptors in the anxiety induced by fear, acute treatment with SSRI antidepressants or the 5-HT receptor agonist m-CPP were tested in the social interaction anxiety test in male Sprague-Dawley rats. Fluoxetine (2.5-10 mg/kg, i.p.), sertraline (15 mg/kg, i.p.) and m-CPP (0.5-2.0 mg/kg, i.p.) all had an anxiogenic-like profile (decrease in time of total social interaction and increase in self-grooming compared to vehicle) under low-light, familiar arena test conditions. All these effects were reversed by pretreatment with the highly subtype-selective 5-HT2C receptor antagonist, SB-242084 at doses of either 0.05 or 0.2 mg/kg, i.p. In contrast, the selective 5-HT1A receptor antagonist WAY-100635 (0.05 and 0.2 mg/kg, s.c.) failed to reverse SSRI-induced decrease in time of total social interaction, further, it augmented self-grooming response. SB-242084 (0.2 mg/kg) and WAY-100635 (0.05 and 0.2 mg/kg) reversed hypolocomotion caused by the SSRI antidepressants. SB-242084, tested alone against vehicle under high-light, unfamiliar arena test conditions associated with fear, caused significant anxiolysis at 0.2 mg/kg and higher doses. These results suggest that increased anxiety in rodents, and possibly, also in humans (e.g. agitation or jitteriness after SSRIs and panic after m-CPP), caused by acute administration of SSRI antidepressants or m-CPP, are mediated by activation of 5-HT2C receptors. Blockade of 5-HT1A autoreceptors may exacerbate certain acute adverse effects of SSRI antidepressants. Both 5-HT1A and 5-HT2C receptors are involved in the SSRI-induced decrease in locomotor activity. In addition, our studies confirm data that subtype-selective 5-HT2C receptor antagonists have strong anxiolytic actions.

The effects of grapefruit juice on sertraline metabolism: an in vitro and in vivo study.

Grapefruit juice is an inhibitor of cytochrome P-450 3A4 (CYP3A4). This study was designed to assess the in vitro and in vivo effects of grapefruit juice on sertraline metabolism. The in vitro assay involved analysis of sertraline metabolism by CYP3A4 using CYP3A4-expressed human beta-lymphoblast microsomes. The in vivo study involved high-performance liquid chromatographic analysis of serum trough levels of sertraline and desmethylsertraline in 5 patients who had been taking their usual dose of sertraline for > or =6 weeks, followed by concurrent use of sertraline with grapefruit juice for 1 week. The in vitro assay demonstrated that grapefruit juice inhibited the formation of desmethylsertraline in a dose-dependent manner. In the in vivo study, mean serum sertraline levels were determined in 5 patients with a history of depression (4 males and 1 female). The mean age of the patients was 68.6 years, their mean weight was 69.6 kg, and their mean sertraline dosage was 55 mg/d. The results of the in vivo study appeared to be consistent with the in vitro findings, in that mean (+/- SD) serum sertraline trough levels increased significantly from 13.7+/-4.9 microg/L before to 20.2+/-4.4 microg/L (P = 0.047) after administration of grapefruit juice. Thus the in vitro study demonstrated that grapefruit juice can inhibit the metabolism of sertraline. A larger study is warranted to substantiate the clinical significance of the in vivo findings.