Paroxetine administration

Cooper TA, Valcour VG, Gibbons RB, O Brien-Falls K. Spontaneous ecchymoses due to paroxetine administration. Am J Med 1998 104(2) 197-8. 

The effects of paroxetine 20 mg/day for 4 weeks on steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone have been studied in 10 patients taking risperidone 4-8 mg/day (175). During paroxetine administration, mean plasma risperidone concentrations increased significantly, while... 

TABLE 2. Effects of repeated systemic administration of MDMA on the regional decreases in [ H]paroxetine-labeled serotonin uptake sites... 

The answer is b. (Katzung, p 1130J Fatalities have been reported when fluoxetine and MAO inhibitors (MAOIs) such as tranylcypromine have been given simultaneously The MAOLs should be stopped at least two weeks before the administration of fluoxetine or paroxetine. The mechanism of this interaction is under investigation... 

Concurrent administration of lithium and selective serotonin re-uptake inhibitors, such as paroxetine, results in an increased risk of central nervous system effects and lithium toxicity has been reported. 

Hypersensitivity to SSRIs in combination with a monoamine oxidase inhibitor (MAOl), or within 14 days of discontinuing an MAOl administration of thioridazine with fluoxetine or within a minimum of 5 weeks after fluoxetine has been discontinued coadministration of fluvoxamine with cisapride, thioridazine or pimozide concomitant use of thioridazine with paroxetine concomitant use of pimozide with sertraline coadministration of sertraline oral concentrate and disulfiram. 

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 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. 

Joyce D, Hurwitz HMB Avoidance behaviour in the rat after 5-hydroxytryptophan (5-HTP) administration. Psychopharmacologia 5 424-430, 1964 Joyce EM The neurochemistry of Korsakoff s syndrome, in Cognitive Neurochemistry. Edited by Stahl SM, Iversen SD, Goodman EC. Oxford, England, Oxford Science Publications, 1987, pp 327-345 Judd EK, Chua P, Lynch C, et al Eenfluramine augmentation of clomipramine treatment of obsessive compulsive disorder. Aust N Z J Psychiatry 25 412-414, 1991 Judge R, Steiner M The long-term efficacy and safety of paroxetine in panic disorder. 

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. 

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). 

Hajos M, Gartside SE, Sharp T. Inhibition of median and dorsal raphe neurones following administration of the selective serotonin reuptake inhibitor paroxetine. Naunyn-Schmiedeberqs Arch Pharmacol 1995 351 624-629. 

The 5-HT1B / mice demonstrated augmented increases of 5-HT levels in response to systemic administration of SSRIs, compared to wild-type mice when measured in the ventral hippocampus (41,49,54-56,60). However, when the effects of SSRIs were measured in other regions of 5-HT1B / mice, their effects were not different from wild-type mice. For example, the effects of systemic paroxetine in the prefrontal cortex (54), or systemic fluoxetine in... 

Kirwan JF, Subak-Sharpe I, Teimory M. Bilateral acute angle closure glaucoma after administration of paroxetine. Br J Ophthalmol 1997 81(3) 252. 

FLUOXETINE, PAROXETINE, SERTRALINE, VENLAFAXINE ZOLPIDEM Cases of agitation hallucinations Uncertain Avoid co-administration... 

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