Tolerability and safety of fluvoxamine and other antidepressants

Selective serotonin [5-hydroxytryptamine (5-HT)] reuptake inhibitors (SSRIs) and the 5-HT noradrenaline reuptake inhibitor, venlafaxine, are mainstays in treatment for depression. The highly specific actions of SSRIs of enhancing serotonergic neurotransmission appears to explain their benefit, while lack of direct actions on other neurotransmitter systems is responsible for their superior safety profile compared with tricyclic antidepressants. Although SSRIs (and venlafaxine) have similar adverse effects, certain differences are emerging. Fluvoxamine may have fewer effects on sexual dysfunction and sleep pattern. SSRIs have a cardiovascular safety profile superior to that of tricyclic antidepressants for patients with cardiovascular disease; fluvoxamine is safe in patients with cardiovascular disease and in the elderly. A discontinuation syndrome may develop upon abrupt SSRI cessation. SSRIs are more tolerable than tricyclic antidepressants in overdose, and there is no conclusive evidence to suggest that they are associated with an increased risk of suicide. Although the literature suggests that there are no clinically significant differences in efficacy amongst SSRIs, treatment decisions need to be based on considerations such as patient acceptability, response history and toxicity

Chronic Citalopram Administration Causes a Sustained Suppression of Serotonin Synthesis in the Mouse Forebrain

BACKGROUND:Serotonin (5-HT) is a neurotransmitter with important roles in the regulation of neurobehavioral processes, particularly those regulating affect in humans. Drugs that potentiate serotonergic neurotransmission by selectively inhibiting the reuptake of serotonin (SSRIs) are widely used for the treatment of psychiatric disorders. Although the regulation of serotonin synthesis may be an factor in SSRI efficacy, the effect of chronic SSRI administration on 5-HT synthesis is not well understood. Here, we describe effects of chronic administration of the SSRI citalopram (CIT) on 5-HT synthesis and content in the mouse forebrain. METHODOLOGY/PRINCIPAL FINDINGS:Citalopram was administered continuously to adult male C57BL/6J mice via osmotic minipump for 2 days, 14 days or 28 days. Plasma citalopram levels were found to be within the clinical range. 5-HT synthesis was assessed using the decarboxylase inhibition method. Citalopram administration caused a suppression of 5-HT synthesis at all time points. CIT treatment also caused a reduction in forebrain 5-HIAA content. Following chronic CIT treatment, forebrain 5-HT stores were more sensitive to the depleting effects of acute decarboxylase inhibition. CONCLUSIONS/SIGNIFICANCE:Taken together, these results demonstrate that chronic citalopram administration causes a sustained suppression of serotonin synthesis in the mouse forebrain. Furthermore, our results indicate that chronic 5-HT reuptake inhibition renders 5-HT brain stores more sensitive to alterations in serotonin synthesis. These results suggest that the regulation of 5-HT synthesis warrants consideration in efforts to develop novel antidepressant strategies

Sulphate Induced Strength Loss Index Optimisation of Periwinkle and Clam Shell Ash Hybrid Pozzolana Concrete

The globe yearns for sustainability in meeting the present and future needs of man. Hence, research into a more sustainable modes of harvesting, processing and use of nature’s raw resources is evidently timely. Cement replacement is opined on the need to reduce the environmental as well as economical limitations associated with its production, while been configured to allow for adequate strength and durability. This paper introduces the mechanical behaviour of ternary blended cement composed of Portland limestone cement, calcined periwinkle and clamshell ashes in concrete exposed to a sulphated medium. Combined I-optimal mixture design was used to statistically develop and diagnose models from laboratory-analysed data and used to optimize calcination temperature and synergistic ratio, as well as the compressive strength and sulphate induced strength loss index (SISLI). For a constant sulphate medium of 5% sodium sulphate solution, the volatile calcination temperature range (25oC – 200oC) was separated from the placid (335oC – 800oC) during optimization. In comparison to a 28-day control SISLI of 16.47%, the optimal calcination temperature for SISLI was restricted at 606.7oC, yielding a respective SISLI of -0.078%. With respect to synergistic ratio, the developed model suggests that increasing the concentration of clamshell ash lowers the calcination temperature needed to improve concrete's resistance to sulphate attack, however, a balance needed for other mechanical and durability variables provided a ternary configuration of 54.6%PLC:25.1%PSA:20.3%CSA at a calcination temperature of 606.7%. The developed model can hence be integrated into the engineering society in decision making and policies associated with the adequate use of periwinkle and clamshell ashes as components of a ternary blended cement in concrete exposed to a sulphated environment.