ABSTRACT
Despite the introduction of several new classes of antidepressants, tricyclic antidepressants [TCA] have remained as a prominent choice for management of depressive disorders in the geriatrics due to wealth of evidence in relevant literature and the feasibility of their therapeutic drug monitoring in clinical practice. TCAs with tertiary amine structure are associated with much more frequent and severe adverse reactions compared to those with secondary amine structure. Regarding its effectiveness against a wide range of late-life depressive disorders along with favorable safety profile and specified as well as defined therapeutic window, nortriptyline has been considered as a gold standard TCA in the elderly by most researchers and clinicians. Although the overall clinical efficacy of TCA in geriatrics is believed to be comparable to that observed in younger subjects, but their onset of response appear to be somewhat slower in the elderly compare to younger adults [9-12 versus 6 weeks, respectively]. Geriatrics is generally more vulnerable to adverse reactions of TCA due to age-related physiologic alterations in pharmacodynamics and pharmacokinetics. Therefore, the elderly in comparison to young adults usually need lower doses of TCAs to achieve favorable response and minimize adverse reactions. Treatment with TCAs in geriatrics should be initiated with the least tolerable dose and dose increments should be made gradually based on the patient tolerability. To avoid withdrawal syndrome, TCAs should be tapered by 10%-25% every 1-2 weeks. A comprehensive medical assessment such as the presence of cardiac diseases [especially conduction defects], glaucoma, and prostate hypertrophy is crucial before starting TCAs in geriatrics. During the TCA treatment, the elderly should be closely monitored regarding orthostatic blood pressure, electrocardiogram, electrolytes, serum creatinine, liver function tests, and its blood level after any dose change or adding a new medication with potential pharmacokinetics interactions. Due to the plausible aggravation of their co-morbid diseases, administration of TCAs is considered contraindicated in geriatric patients with Alzheimer's disease, ischemic heart disease, cardiac conduction abnormality, congestive heart failure, and angle-closure glaucoma
ABSTRACT
Metabolic side effects of the second generation [atypical] antipsychotics have been a forefront of attention since their availability. One common concern is the development of hyperglycemia and insulin resistance. The aim of this study was to evaluate the effect of early initiation of omega-3 fatty acids supplementation on glucose-insulin homeostasis in a group of psychiatric patients under treatment with olanzapine and sodium valproate or lithium combination. In a double-blind design, eligible participants with schizophrenia, bipolar I, and schizoaffective disorders who were initiated on olanzapine combination with sodium valproate or lithium were randomly assigned to receive omega-3 or identical placebo capsules for 6 weeks. Fasting blood sugar [FBS], insulin and HbA1c were measured at the baseline and at the end of the 6th week. Homeostatic model assessment of insulin resistance [HOMA-IR], as a measure of insulin resistance, was also determined at the same times. At the end of the study, no significant difference was observed between the two arms in terms of FBS, fasting insulin, HbA1c and HOMA-IR. However, trends toward decreasing both fasting insulin levels [p= 0.06] and HOMA-IR [p= 0.07] were noted in the group receiving omega-3. No significant changes in the outcome variables were observed from the baseline to the final measurements in both groups. This study noted that adding omega-3 fatty acids at the commencement of olanzapine combination therapy with valproate or lithium could not favorably influence glucose-insulin homeostasis. However, trends toward a decrease in insulin levels [p= 0.06] and HOMA-IR [p= 0.07] observed in patients receiving omega-3 suggest a possible beneficial role of this supplement in this population and, therefore, warrant further evaluation
ABSTRACT
The aim of this study was to investigate the in vitro cytotoxic activity of total extract of MeOH (70 percent) and partition fractions of hexan, chloroform (CHCL3), ethylacetate (EtOAc) and MeOH-H2O of brown algae species (Sargassum swartzii, Cystoseira myrica, Colpomenia sinuosa) found in the Persian Gulf against in different cell lines including HT-29, Caco-2, T47D, MDA-MB468 and NIH 3T3 cell lines by MTT and AnnexinV-PI assay. The hexan fraction of S. swartzii and C. myrica showed selective cytotoxicity against proliferation of Caco-2 cells (IC50<100 μg/ml) T47D cell line (IC50<100 μg/ml), respectively. S. swartzii and C. myrica were also observed for increasing apoptosis in Caco-2 and T47D cells. Total extract and fractions of C. sinuosa did not show any significant cytotoxicity against the studied cell lines. MDA-MB468 cells were more sensitive to C. myrica than was T47D (IC50 99.9±8.11 vs. 56.50± 0.88). This reflects an estrogen receptor independent mechanism for cytotoxicity of the extract. The IC50 of the hexan fraction of C. myrica on T47D parent cells was lower than it was on T47D-TR cells (IC50 99.9±8.11 vs. 143.15 ± 7.80). This finding suggests a role for the MDR-1 in the development of possible future tolerance to the extract.