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A statistically significantly lower relapse rate was observed for patients taking sertraline compared to those on placebo. These patients (N=295) were randomized to continuation for 44 weeks on double-blind sertraline 50 mg/day to 200 mg/day or placebo. Sertraline does not function as a positive reinforcer in rhesus monkeys trained to self-administer cocaine, nor does it substitute as a discriminative stimulus for either d-amphetamine or pentobarbital in rhesus monkeys.Ĭlinical Trials: Major Depressive Disorder: A study was conducted that involved depressed outpatients who had responded by the end of an initial 8-week open treatment phase on sertraline 50 mg/day to 200 mg/day. Sertraline did not produce either the stimulation and anxiety associated with d-amphetamine or the sedation and psychomotor impairment associated with alprazolam. In contrast, subjects rated both alprazolam and d-amphetamine significantly greater than placebo on measures of drug liking, euphoria and abuse potential. In a placebo-controlled, double-blind randomized study of the comparative abuse liability of sertraline, alprazolam and d-amphetamine in humans, sertraline did not produce positive subjective effects indicative of abuse potential. Sertraline has not demonstrated potential for abuse. The chronic administration of sertraline in animals was associated with down regulation of brain norepinephrine receptors as observed with other clinically effective antidepressants and anti-obsessional drugs. Sertraline has no affinity for muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, gamma-aminobutyric acid (GABA) or benzodiazepine receptors. In accord with its selective inhibition of 5-HT uptake, sertraline does not enhance catecholaminergic activity. In controlled studies in normal volunteers, sertraline did not cause sedation and did not interfere with psychomotor performance. It is devoid of stimulant, sedative or anticholinergic activity or cardiotoxicity in animals.
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At clinical doses, sertraline blocks the uptake of serotonin into human platelets. It has only very weak effects on norepinephrine and dopamine neuronal reuptake. Pharmacology: Pharmacodynamics: Sertraline is a potent and selective inhibitor of neuronal serotonin (5-HT) reuptake in vitro, which results in the potentiation of the effects of 5-HT in animals.