Fluoxetine 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. 

The selective serotonin reuptake inhibitors (SSRls) have received increased attention in the treatment of anxiety disorders. With the recent Food and Drug Administration (FDA) approval of fluoxetine and fluvoxamine in the treatment of obsessive-compulsive disorder, it has been made clear that this... 

Public Citizen s Health Research Group. (1991, May 23). Re Citizen s petition for revision of fluoxetine (Prozac) labeling Letter to David Kessler, Commissioner, Food and Drug Administration. Washington, DC Author. 

Temple, R. (1987, December 28). Memorandum Fluoxetine label (Internal Document). Rockville, MD Department of Health and Human Services, Public Health Service, Food and Drug Administration, Center for Drug Evaluation and Research. 

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 review initiated by the US Food and Drug Administration and the manufacturers of fluoxetine briefly describes another 23 anecdotal observations of suspected phenytoin/fluoxetine interactions (most of them incompletely documented). These suggest that a marked 1.5-fold increase in serum phenytoin levels, with accompanying toxicity, can occur within 1 to 42 days (mean onset time of 2 weeks) after starting fluoxetine. Another case describes raised phenytoin levels with improved efficacy when fluoxetine was started, and reduced levels and possible loss of efficacy when fluoxetine was stopped. Conversely, a retrospective review of 7 patients taking phenytoin and fluoxetine found no cases of an interaction. ... 

There is a decreased effectiveness of fluoxetine in patients who smoke cigarettes during administration of die drug. Fluoxetine is not administered witii lithium because this combination can increase lithium levels. The SSRIs are not administered witii herbal preparations containing St. Jbhn s wort because tiiere is an increased risk for severe reactions. 

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. 

The most common interactions with SSRIs are pharmacokinetic interactions. For example, paroxetine and fluoxetine are potent CYP2D6 inhibitors (Table 30-4). Thus, administration with 2D6 substrates such as TCAs can lead to dramatic and sometimes unpredictable elevations in the tricyclic drug concentration. The result may be toxicity from the TCA. Similarly, fluvoxamine, a CYP3A4 inhibitor, may elevate the levels of concurrently administered substrates for this enzyme such as diltiazem and induce bradycardia or hypotension. Other SSRIs, such as citalopram and escitalopram, are relatively free of pharmacokinetic interactions. The most serious interaction with the SSRIs are pharmacodynamic interactions with MAOIs that produce a serotonin syndrome (see below). 

Several other classes of medications have been tried in this disorder. Examples are amantadine, a dopaminergic drug that has been reported to aid in detoxification, fluoxetine, a selective serotonin reuptake antagonist that has been reported to reduce cocaine use, and buprenorphine, a partial opioid agonist that has been found to reduce cocaine self-administration in monkeys. Thus far, all of the studies of medications to help prevent relapse to cocaine dependence have revealed modest benefits at best. Reports of success in uncontrolled trials have not been replicated in carefully controlled, double-blind studies. At present, there is general agreement that no medication is yet available that can be used reliably in the treatment of cocaine addiction. 

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