Deperin Mechanism of Action

Pharmacotherapeutic group: Selective serotonin reuptake inhibitors. ATC Code: N06AB06.
Pharmacology: Pharmacodynamics: Mechanism of action: Sertraline is a potent and specific inhibitor of neuronal serotonin (5-HT) uptake in vitro, which results in the potentiation of the effects of 5-HT in animals. It has only very weak effects on norepinephrine and dopamine neuronal reuptake. At clinical doses, sertraline blocks the uptake of serotonin into human platelets. It is devoid of stimulant, sedative or anticholinergic activity or cardiotoxicity in animals. In controlled studies in normal volunteers, Sertraline did not cause sedation and did not interfere with psychomotor performance. In accord with its selective inhibition of 5-HT uptake, Sertraline does not enhance catecholaminergic activity. Sertraline has no affinity for muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, GABA or benzodiazepine receptors. The chronic administration of Sertraline in animals was associated with down-regulation of brain norepinephrine receptors as observed with other clinically effective antidepressants and antiobsessional drugs.
Clinical efficacy and safety: Major Depressive Disorder: A study was conducted which involved depressed outpatients who had responded by the end of an initial 8-week open treatment phase on Sertraline 50-200 mg/day. These patients (n=295) were randomized to continuation for 44 weeks on double-blind Sertraline 50-200 mg/day or placebo. A statistically significantly lower relapse rate was observed for patients taking Sertraline compared to those on placebo. The mean dose for completers was 70 mg/day. The % of responders (defined as those patients that did not relapse) for Sertraline and placebo arms were 83.4% and 60.8%, respectively.
Post traumatic stress disorder (PTSD): Combined data from the 3 studies of PTSD in the general population found a lower response rate in males compared to females. The results in females are more robust and males were associated with other baseline variables (more substance abuse, longer duration, source of trauma etc) which are correlated with decreased effect.
Paediatric OCD: The safety and efficacy of Sertraline (50-200 mg/day) was examined in the treatment of non-depressed children (6-12 years old) and adolescent (13-17 years old) outpatients with obsessive compulsive disorder (OCD). Patients randomized to sertraline showed significantly greater improvement than those randomised to placebo on the Children's Yale-Brown Obsessive Compulsive Scale CY-BOCS (p=0.005) the NIMH Global Obsessive Compulsive Scale (p=0.019), and the CGI improvement (p=0.002) scales. In addition, a trend toward greater improvement in the sertraline group than the placebo group was also observed on the CGI Severity scale (p=0.089).
Paediatric population: No data is available for children under 6 years of age.
Pharmacokinetics: Sertraline is slowly absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 4.5 to 8.4 hours after ingestion. It undergoes extensive first-pass metabolism in the liver. The main pathway is demethylation to inactive N-desmethylsertraline, a process that appears to involve multiple cytochrome P450 isoenzymes; further metabolism and glucuronide conjugation occurs. Sertraline is widely distributed throughout body tissues and is about 98% bound to plasma proteins. The plasma elimination half-life of sertraline is reported to be about 26 hours; steady-state concentrations are achieved after about one week with regular oral doses. Sertraline is excreted in about equal amounts in the urine and faeces, mainly as metabolites. Sertraline is distributed into breastmilk.