Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sertraline is a selective inhibitor of central serotonin reuptake. Thus, it enhances serotoninergic transmission--a property which appears to explain its antidepressant activity. Its elimination half-life (approximately 26 hours) makes it suitable for once daily administration. Although clinical experience with sertraline is limited, it appears to possess antidepressant efficacy similar to that of amitriptyline and dothiepin, marginally better than imipramine, and significantly better than placebo. Additionally, sertraline is the only antidepressant licensed in the UK for the prevention of recurrence of depression, and preliminary findings suggest that the drug may also be effective in the treatment of obsessive-compulsive disorder. Sertraline and other serotonin reuptake inhibitors possess tolerability advantages over tricyclic antidepressants. Sertraline has minimal anticholinergic activity, is essentially devoid of cardiovascular effects, has a wide therapeutic index and may be administered to elderly patients or those with underlying cardiovascular disorders. However, as with other serotonin reuptake inhibitors, sertraline has been associated with gastrointestinal disturbances (nausea, diarrhoea/loose stools) and male sexual dysfunction (primarily ejaculatory disturbance), although each of these effects is usually mild and transient, decreasing in frequency with continued treatment. As a drug class, serotonin reuptake inhibitors such as sertraline appear to provide significant advantages compared with the more established antidepressant agents, particularly in terms of tolerability. Although much broader clinical experience is required before sertraline's full therapeutic potential can be realised, if future studies confirm the encouraging initial findings, sertraline will undoubtedly become an important option in the treatment of depression.
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PMID:Sertraline. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depression and obsessive-compulsive disorder. 128 Oct 75

The pharmacology and pharmacokinetics, adverse effects, drug interactions, efficacy, and dosage and administration of the new selective serotonin reuptake inhibitors paroxetine, sertraline, and fluvoxamine are reviewed. Paroxetine, sertraline, and fluvoxamine all have large volumes of distribution and are highly bound to plasma proteins. In contrast to fluoxetine, these three drugs possess shorter elimination half-lives of approximately one day and are metabolized to clinically inactive compounds. Nausea was the most commonly reported adverse effect for all three agents. Other reported adverse effects are headache, sedation, dry mouth, insomnia, sexual dysfunction, and constipation. Because of their favorable pharmacokinetic profiles, paroxetine, sertraline, and fluvoxaetine are less likely than fluoxamine to interact with other drugs. Paroxetine has been found to be superior to placebo and equivalent to amitriptyline, imipramine, clomipramine, and doxepin in treatment of depression. Sertraline has been found to be superior to placebo and equivalent to amitriptyline in treatment of depression. Fluvoxamine has been found to be superior to placebo and equivalent to imipramine, clomipramine, desipramine, mianserin, and maprotiline in the treatment of depression. Fluvoxamine and sertraline have been shown to be superior to placebo in the treatment of obsessive-compulsive disorder. Clinical experience has demonstrated all three drugs to be effective in treatment of depression. They may be especially useful in elderly patients, in those who cannot tolerate alternative treatments, and in those who do not respond to adequate trials of other antidepressant therapies.
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PMID:Paroxetine, sertraline, and fluvoxamine: new selective serotonin reuptake inhibitors. 146 19

Sertraline is a non-tricyclic, potent and selective serotonin reuptake inhibitor (SSRI) which is currently approved for the treatment of depression in several countries, including the UK and the USA. The role of serotonin in the aetiology of obsessive compulsive disorder (OCD) has been established through considerable indirect evidence. The strongest evidence comes from the fact that drugs known to be SSRIs have been found to be useful in the pharmacotherapy of OCD. Two double-blind, placebo-controlled studies, including a total of 412 patients, were undertaken to evaluate the efficacy and safety of sertraline in OCD. The first of these studies of a flexible dosing design showed that sertraline, given for eight weeks in daily dosages of 50-200 mg, was a safe and effective treatment for OCD, and superior to placebo. The second study of a fixed dose design and 12 weeks duration confirmed the efficacy and safety of sertraline in OCD at fixed dosages of 50, 100, or 200 mg/day and demonstrated that further improvement in OCD symptoms can be achieved through continued treatment with sertraline. A comparison between the results of these two studies and similar studies with clomipramine shows that, while both drugs have significant therapeutic efficacy, their side-effect profiles may be markedly distinct.
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PMID:Sertraline in the treatment of obsessive compulsive disorder: two double-blind, placebo-controlled studies. 148 77

Sertraline is slowly absorbed after oral administration, with peak plasma concentrations at 6-8 h. Plasma concentrations are linearly related to dose. The elimination half-life is about 32 h; metabolism is by demethylation to an inactive metabolite. Once-daily dosing is recommended, with steady state being reached after about 7 days. The kinetics of sertraline in the elderly and in patients with renal impairment are similar to those in young healthy female volunteers. In young male volunteers, peak plasma concentrations were lower, and elimination half-life shorter, than in elderly men or both groups of women. Nevertheless, no reduction in dosage is recommended for these groups. Sertraline is highly active in animal models of depression, and administration of the drug to healthy human beings causes a selective, dose-related inhibition of 5-hydroxytryptamine (5-HT) uptake into blood platelets. Single doses of sertraline in volunteers caused changes in the quantitative pharmaco-electroencephalogram suggesting antidepressant and anxiolytic actions, with sedative potential evident only at doses of 200 mg or more. Sertraline does not impair psychomotor performance, including simulated car driving, and overall seems neither stimulating nor sedating: an increase in critical flicker fusion threshold suggests a slight alerting effect, whereas subjective tests indicate an increase in perceived sedation at doses of 100 mg or more. No potentiation of the effects of ethanol has been noted in either young or elderly subjects. No adverse effects on the electrocardiogram, blood pressure, or systolic time intervals have been detected, and sertraline lacks anticholinergic action. These studies imply a low probability of adverse central nervous and cardiovascular effects. Sertraline is probably a weak inducer of hepatic microsomal enzyme activity. Sertraline does not affect the clearance of lithium but there may be a pharmacodynamic interaction which leads to increased tremor when the drugs are given together. No clinically relevant effects were noted in the interaction studies with digoxin, atenolol and diazepam. The pharmacokinetics and pharmacodynamics of sertraline are generally favourable. However, caution is needed when sertraline is given to patients receiving lithium or drugs with a low therapeutic ratio, such as corticosteroids, oral hypoglycaemic agents, and warfarin.
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PMID:Clinical implications of the pharmacology of sertraline. 180 26

Three 6-8 week comparative studies have shown sertraline to be an effective, safe and well-tolerated treatment for acute depressive illness. The first, a double-blind fixed-dose study, demonstrated the efficacy of sertraline over placebo; the second, a forced upward titration, active- and placebo-controlled, double-blind study, showed that sertraline was of equal efficacy to amitriptyline. The third was a double-blind comparison of sertraline and amitriptyline in elderly depressives, with the dose being increased as necessary and as tolerated. The overall results showed sertraline to be consistently superior to placebo and equivalent in therapeutic effect to amitriptyline on a number of measures including depression, anxiety, insomnia and suicidal ideation. Efficacy was found in both moderately and severely depressed patients whose primary psychiatric diagnoses included single-episode and recurrent major depression, with and without melancholia. Sertraline was also found to be effective in patients with a high baseline anxiety score on the Hamilton Rating Scale for Depression.
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PMID:Controlling acute episodes of depression. 180 27

Sertraline, administered i.p. in single doses or as three injections in 24 h, significantly reduced the immobility of rats in the forced swimming test at 64 and 100 mumol/kg. The effect of three doses of 64 mumol/kg in 24 h was not modified in animals treated i.p. with metergoline (5 mg/kg) 3 h before testing. I.c.v. administration of 150 micrograms 5,7-dihydroxytryptamine, which depleted brain serotonin, or infusion of 6 micrograms 6-hydroxydopamine in the locus coeruleus, which markedly depleted noradrenaline in terminal regions, was also ineffective. The effect of 64 mumol/kg sertraline, once daily for 7 days, was not modified by i.c.v. 5,7-dihydroxytryptamine. The effect of three doses of 64 mumol/kg sertraline in 24 h was instead completely antagonized by 100 mg/kg sulpiride given 90 min before testing. The exact mechanism of this effect and its relevance for the favourable effects of sertraline in human depression remain to be clarified.
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PMID:Role of central serotonergic neurons in the effect of sertraline in rats in the forced swimming test. 190 56

Sertraline hydrochloride is a new naphthylamino compound that specifically blocks neuronal reuptake of serotonin. It is currently available in the United Kingdom and under review in the US. Sertraline follows first-order kinetics, with a plasma elimination half-life of 24-26 hours. It is highly bound to plasma proteins and has a large volume of distribution. Multicenter studies conducted by the manufacturer have shown sertraline to be efficacious in the treatment of depression and obsessive-compulsive disorder. The daily dose will range from 50 to 200 mg/d for the treatment of depression. The adverse-effect profile differs greatly from the tricyclic antidepressants, but is similar to that of fluoxetine. The most prominent adverse effects are gastrointestinal (nausea, diarrhea/loose stools, dyspepsia).
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PMID:Sertraline: a new specific serotonin reuptake blocker. 194 75

Two hundred forty-one elderly depressed patients entered the 8-week, double-blind phase of this parallel-group, multicenter study; 161 patients were randomized to receive sertraline (50-200 mg/day) and 80 were randomized to receive amitriptyline (50-150 mg/day). Among evaluable patients, there were no statistically significant differences between treatments in any of the primary efficacy variables: change in total Hamilton Rating Scale for Depression (HAM-D) score (17 items), percentage change in HAM-D score, change in HAM-D Item 1, change in Clinical Global Impressions (CGI) Severity score, change in the Depression Factor of the 56-item Hopkins Symptom Checklist, and the CGI Improvement score at the last visit. Similar results were obtained using data from all patients (intention-to-treat analysis), except that amitriptyline was superior in HAM-D Total score (p = .044). The two drugs produced a similar degree of response: on the basis of the HAM-D criterion, 69.4% of sertraline patients and 62.5% of amitriptyline patients responded, and, on the basis of CGI criterion, 79.5% of sertraline and 73.4% of amitriptyline patients responded. Twenty-eight percent of the sertraline patients withdrew from the study because of a treatment-related side effect and 2.5% (4) because of a laboratory abnormality. In comparison, 35% of the amitriptyline patients withdrew because of treatment-related side effects. Sertraline was associated with a statistically lower frequency of somnolence, dry mouth, constipation, ataxia, and pain and a higher frequency of nausea, anorexia, diarrhea/loose stools, and insomnia; thus, anticholinergic effects were less common and gastrointestinal effects were more common with sertraline than with amitriptyline.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients. 225 79

Sertaline [1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1- naphthalenamine] is a potent and selective inhibitor of neuronal serotonin uptake and is currently under development for the treatment of depression and of obesity. The drug is greater than 97% bound to plasma proteins, yet extensively distributes into tissues. The whole brain concentration of sertraline in the rat is more than 40-fold higher than that in plasma, and the volume of distribution is about 25 liters/kg in the rat and dog. Sertraline is extensively metabolized by the rat and dog prior to excretion. The metabolic clearance of sertraline is greater than 35 ml of blood/min/kg in each species, and first-pass metabolism occurs with oral administration. Initial metabolic steps include N-demethylation, N-hydroxylation, oxidative deamination, and glucuronidation of sertraline carbamic acid, which in solution is in equilibrium with sertraline and carbon dioxide. The N-desmethyl metabolite, which is 10-fold less potent as an inhibitor of serotonin uptake, is formed in both species. Plasma AUC for desmethyl-sertraline is 66 to 270% of that for sertraline, and is dependent on the species examined and route of drug administration. Sertraline and desmethyl-sertraline undergo oxidative deamination to the corresponding ketone, which is subsequently hydroxylated at the alpha-carbon, forming a diastereomeric metabolite pair. The glucuronides of sertraline carbamic acid, N-hydroxy sertraline, and the alpha-hydroxy ketone diastereomers comprise 45% and 82% of the total radiolabel excreted in urine and bile of bile duct-cannulated rats and dogs, respectively. Bile is the major route of elimination in both species.
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PMID:Metabolism and disposition of the 5-hydroxytryptamine uptake blocker sertraline in the rat and dog. 257 98

The authors review preclinical data; clinical pharmacology data; and efficacy data of sertraline, a novel serotonin uptake inhibitor. Both in vitro and in vivo, sertraline is a potent and specific serotonin uptake inhibitor (possessing up to 10 times the activity of similar agents). Chronic dosing produces down-regulation of beta-adrenergic receptors. In man, sertraline inhibits platelet serotonin uptake and is devoid of obvious cardiac effects. The plasma half-life of sertraline is 25 hours. Studies on psychomotor performance show little or no effect at doses up to 100 mg, whereas 200 and 400 mg appear to possess some sedating action. Sertraline exhibits acute antidepressant effects in the dose range 50 to 200 mg/day; in addition, in the same dose range it prevents recurrence of depression. Its side-effect profile is similar to that of drugs of the same class (dry mouth, nausea, and diarrhea being the most prominent); it lacks the obvious anticholinergic and sedating effects of amitriptyline.
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PMID:Sertraline: a new antidepressant. 284 21


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