Sertraline drug administration

The prototypical serotonin reuptake inhibitor (SRI) medication is the non-selective agent clomipramine, a tricyclic antidepressant (TCA). The Selective SRIs (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalo-pram (Celexa). The Food and Drug Administration (FDA) approved clinical indications for these medications are described in Table 22.1. 

A number of SSRIs and SNRIs were tested for their effects on cognitive function in repeated-dose studies in healthy, non-depressed volunteers. Studies with SSRIs before 1999 have been reviewed by Lane and O Hanlon (1999) and some more recent reports deal with nefazodone. paroxetine and sertraline (Furlan et al., 2001 Schmitt et al., 2001 van Laar et al.. 2002). However, considering the populations studied in these trials (non-depressed subjects), the duration of drug administration (1 2 weeks) and the mostly low drug doses used, the relevance of these studies for a clinical situation may be questioned. 

Leber, P. (1991, December 24). Recommendation to approve NDA 19839 (Zoloft sertraline) Memorandum to Robert Temple (Internal Document). Rockville, MD Department of Health and Human Services, Public Health Service, Food and Drug Administration, Center for Drug Evaluation and Research. 

Zoloft Summary Basis of Approval. (1988, April 13). Also includes Memorandum of Thomas P. Laughren, Supervisory Overview of NDA 19839 (sertraline), August 9, 1991. Food and Drug Administration, Rockville, Maryland. Obtained through the Freedom of Information Act. 

The Food and Drug Administration (FDA) has approved five antidepressants for the management of OCD clomipramine, fluoxetine, fluvoxamine, paroxetine, and sertraline. In adolescents with OCD, CBT is generally selected first for mild OCD, but CBT plus an SSRI (e.g., fluoxetine, fluvoxamine, sertraline, or paroxetine) are used for more severe OCD. In adults, CBT is the initial choice for mild OCD, and CBT plus an SSRI or an SSRI alone is selected for more severe OCD. Figure 70-2 is an algorithm for the treatment of OCD. 

A series of DAT selective 3-phenyltropanes have been reported to have potential for treatment of cocaine abuse [33,36,37]. RTI-336,15 (reuptake IC50 — 4.1 nM) was the most potent among these tropane derivatives in locomotor activity and drug discrimination it was less stimulatory than cocaine, and had the slowest onset and longest duration of action. It also reduced self-administration of cocaine in rats and rhesus monkeys. Interestingly, in rhesus monkeys trained to self-administer cocaine, when coadministrated with either citalopram or sertraline, 15 produced significantly more robust reductions in cocaine self-administration compared with 15 alone [38]. 

These drugs increase synaptic serotonin by selectively blocking the serotonin reuptake transporter. In preclinical and human studies acute doses tend to be anxiogenic (Bell and Nutt 1998) but chronic administration has anxiolytic effects, possibly due to downregulation of presynaptic autoreceptors (Blier et al. 1990). There are five SSRIs widely available citalopram, fluoxetine, fluvoxam-ine, paroxetine and sertraline. Escitalopram, the S-enantiomer of citalopram. 

Fluoxetine is a potential drug of abuse.136 Overdose with sertraline causes suicidal tendencies, whereas citalopram causes fatal reactions such as cardiac dysfunction.137 The adverse effects could be treated with stomach wash, administration of activated charcoal, dialysis, and hemoperfusion. 

MAOIs SSRIs t risk of serotonin syndrome >- For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome Additive inhibitory on serotonin reuptake Avoid co-administration. MAOIs should not be started for at least 1 week after stopping SSRIs (2 weeks after sertraline, S weeks after fluoxetine). Conversely, SSRIs should not be started for at least 2 weeks after stopping MAOIs... 

SERTRALINE PIMOZIDE plasma concentrations of these drugs and potential risk of dangerous arrhythmias Sertraline inhibits metabolism of pimozide. Precise site of inhibition uncertain Avoid co-administration... 

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... 

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. ... 

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