Sertraline about

A 51-year-old woman took about 8 g of sertraline, about 80 times the usual daily dose. On admission to hospital she was somnolent but reusable. Her electrocardiogram showed a transiently prolonged QTC interval (510 ms falling to 470 ms). On the third day she developed agitation, disorientation, myoclonus, and pyrexia (38.5°C), was treated with supportive measures, and recovered over the next 3 days. 

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

The SSRIs are believed to be more effective for numbing symptoms than other drugs. About 60% of sertraline-treated patients showed improvement in arousal and avoidance/numbing symptoms, but not reexperiencing symptoms. Similar numbers of patients have been shown to improve on paroxetine. Fluoxetine was effective in a placebo-controlled trial, and fluvoxamine was effective in an open trial. 

Elderly Clearance of fluvoxamine is decreased by about 50% in elderly patients. A lower starting dose of paroxetine is recommended. Sertraline plasma clearance may be lower. In 2 pharmacokinetic studies, citalopram AUC was increased by 23% and 30%, respectively, in elderly subjects as compared with younger subjects, and its half-life was increased by 30% and 50%, respectively. In 2 pharmacokinetic studies, escitalopram half-life was increased by approximately 50% in elderly subjects as compared with young subjects and C ax was unchanged. 

Answer Because of sertraline s favorable side effect profile and no need for dietary restrictions, it probably should be chosen over the older agents (TCAs and MAOIs). She should be warned about nausea and possibly loose stools, anorgasmia, and insomnia before she begins therapy. It also should be explained that the medication will take at least 2 weeks to begin working and that a complete trial of the medication to assess its efficacy will take 4 to 6 weeks. Since this is her first episode of depression, she should take the medication for 6 to 12 months after her symptoms have remitted before considering discontinuation of drug therapy. 

In most cases, SSRIs are the first choice for drugs to combat OCD. Clomipramine, fluvoxamine, fluoxetine, paroxetine, sertraline, and citalopram are all SSRIs that have been proven effective in reducing OCD symptoms. However, in about 40 to 60% of patients, these drugs do not completely alleviate all the symptoms. When this is the case, a second type of drug called a neuroleptic is often added. Neuroleptic drugs, such as haloperidol, clozapine, risperidone, and chlorpromazine... 

In a double-blind, parallel-group study, Bondareff et id. (2000) compared the SSRI sertraline and the tricyclic compound nortriptyline with regard to their efficacy and safety in a group of 210 outpatients 60 years and older. The patients met the DSM-DI-R criteria for major depressive episode and had a minimum score of 18 on the Hamilton Rating Scale for Depression. Their mean age was about 68 years, most patients were white and about 60% were female the severity of depression was rated as moderate in more than 70% and as severe in more than 20% of the cases. The daily doses of sertraline were between 50 and 150 mg, and those of nortriptyline were 25 100 mg the treatment lasted 12 weeks. In addition to clinical rating scales and self-assessment instruments, patients took the following tests of cognitive performance ... 

About 70% of the patients in both treatment groups completed the trial, with similar therapeutic efficacy (Hamilton Rating Scale for Depression) shown for both compounds. The pattern of adverse events was different, with more patients reporting diarrhea, nausea and insomnia on sertraline, and more patients on nortriptyline... 

Heimann and March (1996) reported about a 15-year-old with a long history of chronic, low grade depression who became manic after 1 month on sertraline. Her behaviors included physical aggression toward a peer, intoxication with alcohol, and sexual promiscuity. Behaviors such as this can, unfortunately, ruin a child s life. 

When blood and milk were sampled in 22 nursing women taking sertraline (25-200 mg/day), sertraline and its metabolite, desmethylsertraline, were found in all the milk samples (89). The maximum concentration of sertraline and desmethylsertraline in the milk occurred 8-9 hours after maternal ingestion of the daily dose of sertraline. Eleven infants had detectable desmethylsertraline of these, four also had detectable sertraline. No adverse effects were noted in any of the children. The authors calculated that the infants had received on average about 0.5% of the maternal sertraline dose. 

Sertraline hydrochloride has an average half-life of about 26 hours, and mean peak plasma concentrations occur at 4.5-8.4 hours. The dosage is 50-200 mg/day orally. Its major metabolite, /V-desmethylsertraline, is less active than sertraline. Adverse effects are as for the SSRIs in general. 

Level II results showed that patients who failed to benefit from SSRI treatment (citalopram) are good candidates for augmentation (with sustained-release bupropion or with Buspirone) or switching (to sustained-release bupropion or sertraline or sustained-release venlafaxine—three antidepressants with different mechanisms of action). One third of the patients in each group reached remission. Thus, overall, after two well-delivered (robust doses and sufficient duration) medication treatment courses (results for the group who received CBT were not published yet) about 50% of the patients achieved full remission of symptoms. Results from Levels III and IV were not yet available at this time. Once results of all four levels are added up we will have at our disposal an antidepressant roadmap to follow. We will also learn of the percentage of patients who, in spite of these systematic efforts, are still unresponsive to antidepressant treatment and require more drastic or unconventional treatment approaches. 

FLUOXETINE, FLUVOXAMINE, PAROXETINE BZDs - ALPRAZOLAM, DIAZEPAM, MIDAZOLAM t in plasma concentrations of these BZDs. Likely t sedation and interference with psychomotor activity Alprazolam, diazepam and midazolam are subject to metabolism by CYP3A4. Fluvoxamine, fluoxetine and possibly paroxetine are inhibitors of CYP3A4 sertraline is a weak inhibitor. SSRIs are relatively weak compared with ketoconazole, which is possibly 100 times more potent as an inhibitor Warn patients about risks associated with activities that require alertness. Consider use of alternatives such as oxazepam, lorazepam and temazepam, which are metabolized by glucuronidation >- For signs and symptoms of CNS depression, see Clinical Features of Some Adverse Drug Interactions, Central nervous system depression... 

FLUOXETINE, FLUVOXAMINE, PAROXETINE, SERTRALINE BUPROPION t plasma concentrations of bupropion and risk of adverse effects Inhibition of CYP2B6 Warn patients about adverse effects, and use alternatives when possible... 

BUPROPION 1. ANTICANCER DRUGS - thiotepa 2. ANTIDEPRESSANTS-fluoxetine, fluvoxamine, paroxetine, sertraline 3. ANTIVIRALS - efavirenz, protease inhibitors t plasma concentrations of bupropion and risk of adverse effects Inhibition of CYP2B6 Warn patients about adverse effects and use alternatives when possible. Avoid co-administration of bupropion with protease inhibitors. Co-adminis-ter efavirenz and bupropion with caution. A retrospective study showed that two patients received a combination without reported adverse effects. Potential T risk of seizures... 

CYP2D6, usually described as the second most relevant CYP enzyme responsible for about 20% of drugs on the market. It is particularly relevant for drug classes like serotonin re-uptake inhibitors (i.e. fluoxetine, fluvoxamine, paroxetine or sertraline). 

The SSRIs are eliminated mainly through hepatic metabolism. Their half-lives are about 1 day for fluvoxamine, paroxetine, and sertraline (2-5), 1.5 days for citalopram (6), and 2-3 days for fluoxetine (7). Norfluoxetine, the main metabolite of fluoxetine, is a potent and selective serotonin re-uptake inhibitor, and since this metabolite also has a very long half-hfe (7-15 days) it contributes significantly to the clinical effect. Norsertraline, the desmethylated metabolite of sertraline, is also an inhibitor of serotonin re-uptake, but... 

The 1 allele occurs at a frequency of 20% to 26% in Asian populations and about 53% to 55% in Caucasians [83-86]. In Caucasians and Chinese, the 1/1 genotype has been associated with a significantly better and faster SSRI response, while the s/s allele is associated with poor response [83,84,87-97]. In two studies in Japanese and Korean patients, one found that neither the 1 nor s allele had an effect on treatment response the other observed only a slight improved response among s allele carriers [98,99]. The 1 allele has been associated with improved response to paroxetine, fluoxetine, sertraline, and tricyclic antidepressants in depressed patients, while the s allele has been associated with both poorer response and greater incidence... 

The diversity of the SSRIs is evident not only in their chemical structures, but also in their pharmacokinetic profiles. Fluoxetine has an elimination half-fife of 2 to 3 days (4 to 5 days with multiple dosing). The single-dose hah-hfe of norfluoxetine, the active metabolite, is 7 to 9 days. Paroxetine and sertrahne have half-lives of approximately 24 hours. Unlike paroxetine, sertraline has an active metabolite, but the metabohte contributes minimally to the pharmacologic effects. Escitalopram has a half-life of approximately 30 hours. Peak plasma concentrations of citalopram are observed within 2 to 4 hours after dosing, and the elimination half-life is about 30 hours. The SSRIs, with the exception of fluvoxamine, escitalopram, and citalopram, are extensively bound to plasma proteins (94% to 99%). The SSRIs are extensively distributed to the tissues, and aU, with the possible exception of citalopram, may have a nonlinear pattern of drug accumulation with long-term administration. ... 

This can increase sertraline serum levels by about 25%. The data are limited and the clinical significance of such findings is currently questionable. 

Few data are available about sertraline interactions with MAOIs, even though they are expected to be similar to those of the other SSRIs. However, serotonin syndrome has been reported with the combined tranylcypromine-sertraline (and clonazepam also) regimen. At present, only this specific combination should be avoided. 

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