Fluvoxamine Desipramine

Drug therapies include tricyclic antidepressants and SSRIs. Treatment should be continued for at least 29 weeks. Nortriptyline, amitriptyline, clomipramine, desipramine, fluvoxamine, and bupropion have been used successfully. 

Extracted metabolites, desipramine, fluvoxamine, imipramine, maprotiline, nortriptyline Noninterfering chlordiazepoxide, clobazam, clozapine, diazepam, flurazepam, fluspiri-lene, haloperidol, nitrazepam, oxazepam, perazine, pimozide, spiroperidol, trifluperidol Interfering clomipramine, doxepin... 

Values were back calculated from actual in vivo DDI data for fluconazole and S-warfarin (fee, CYP2C9 = 0.91), fluvoxamine and theophylline (fcL,CYPiA2 = 0.8), fluvoxamine and S-mephenytoin (fcL,CYP2C9 = 1). ketoconazole and midazolam fcL,CYP3A,hepatic = 0.93), and quinidine and desipramine (fcL,CYP2D6 = 0.9). 

Amitriptyline, clomipramine, imipramine, desipramine, nortriptyline, trimipramine, AT-desmethylclomipramine, fluvoxamine, norfluoxetine, paroxetine, venlafaxine, sertraline Neuroleptics... 

FIGURE 39.2 Treatment algorithm for pediatric obsessive-compulsive disorder (OCD). In adjusting cognitive behavior therapy (CBT), increase frequency or intensity, or alter the setting or format, e.g., have it be home based or day treatment. CMI, clomipramine DMI, desipramine NT, nortriptyline SSRI, selective serotonin reuptake inhibitor (fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram). 

P450 IID6 -fin women Inhibited by OCs Hydroxylation of nortriptyline and desipramine, haloperidol, clozapine, risperidone, venlafaxine Fluoxetine, fluvoxamine, paroxetine, sertraline... 

Basic pharmacology. Fluvoxamine is an effective serotonin reuptake inhibitor with an ICjg value of 0.3 pmol/L comparable ICjg values for desipramine and fluoxetine are 0.8 jmol/L and 1.3 omol/L, respectively [Bradford 1984]. The ICjo values for NA and dopamine were 100 times higher than those for serotonin [Bradford 1984]. In vitro data indicate that fluvoxamine has little or no affinity for Oj, a, Pi, P2, Dj, S-HTj, muscarinic, or histaminergic receptors [Benfield and Ward 1986]. Fluvoxamine has a total of 11 metabolites, and the 2 principal ones have little or no pharmacological activity [Claassen 1983]. 

Goodman WK, Price LH, Delgado PL, et al Specificity of serotonin reuptake inhibitors in the treatment of obsessive compulsive disorder comparison of fluvoxamine and desipramine. Arch Gen Psychiatry 47 577-585, 1990b Goodman WK, Rasmussen SA, Foa EB, et al Obsessive compulsive disorder, in Clinical Evaluation of Psychotropic Drugs Principles and Guidance. Edited by Prien RF, Robinson DS. New York, Raven, 1994, pp 431-466 Goodnick P Effects of lithium on indices of 5HT and catecholamines in the clinical content a review. Lithium 1 65-73, 1990... 

Kupfer DJ, Perel JM, Pollock BG, et al Fluvoxamine versus desipramine comparative polysomnographic effects. Biol Psychiatry 29 23-40, 1991... 

Because reboxetine and bupropion share with desipramine the ability to block the NE uptake pump, some clinician may want to combine them with an SSRI. Bupropion, however, should be used cautiously with fluvoxamine, fluoxetine, and paroxetine because these three antidepressants inhibit one or more CYP enzymes to a substantial degree at their lowest, usually effective antidepressant dose. Therefore, the dose of bupropion should be kept low and TDM could be used to ensure that unusually high levels of bupropion or its active metabolites do not develop. 

Selective serotonin reuptake inhibitors (SSRIs) [P] Fluoxetine and paroxetine inhibit CYP2D6 and decrease metabolism of antidepressants metabolized by this enzyme (eg, desipramine). Citalopram, sertraline, and fluvoxamine are only weak inhibitors of CYP2D6, but fluvoxamine inhibits CYP1A2 and CYP3A4 and thus can inhibit the metabolism of antidepressants metabolized by these enzymes. 

It has been known since the mid-1980s that clomipramine, a potent but nonse-lective serotonin reuptake inhibitor, is effective in reducing OCD symptoms. Since then, numerous studies have confirmed the superiority of clomipramine over placebo in OCD patients, whereas other antidepressant medications with less potent inhibitory effects on serotonin reuptake (e.g., nortripytline, desipramine) seem to be ineffective in OCD. Demonstration of the anti-OCD actions of all five SSRIs, namely, fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram, also supports the hypothesis that the antiobsessional effects of these various pharmacologic agents is due to their potent serotonergic reuptake blocking activity. 

Fluvoxamine increases the systemic availability of oral melatonin, probably by reducing its first-pass clearance (34). In a crossover study in seven healthy subjects, serum melatonin concentrations were increased by fluvoxamine but not citalopram (35). In another study fluoxetine, paroxetine, citalopram, imipramine, and desipramine did not affect the biotransformation of melatonin at therapeutic concentrations in vitro (36). 

Imipramine, desipramine, amitriptyline, nortriptyline, trimipramine, clomipramine, lofepramine, amoxapine, dosulepin, maprotiline, mianserin, setiptiline, trazodone, fluvoxamine, paroxetine, milnacipram, sulpiride, tandspirone, methylpheni-date, melitracen Amitriptyline, imipramine, trimipramine, clomipramine, citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, reboxetine, viloxazine, doxepin, maprotiline, mianserine, mirtazapine, moclobemide, trazodone, opipramol (and some metabolites)... 

Spina E, Campo GM, Avenoso A, Polhcino MA, Caputi AP. Interaction between Fluvoxamine and imipra-mine/desipramine in four patients. Ther Drug Monit 1992 14(3) 194-6. 

ANTIDEPRESSANTS-duloxetine, modobemide, SSRIs - escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, TCAs - amitriptyline, clomipramine, desipramine, doxepin, imipramine... 

Fluoxetine, paroxetine, bupropion, duloxetine, and other CYP450 2D6 inhibitors may increase TCA concentrations Fluvoxamine, a CYP450 1A2 inhibitor, can decrease the conversion of imipramine to desmethylimipramine (desipramine) and increase imipramine plasma concentrations Cimetidine may increase plasma concentrations of TCAs and cause anticholinergic symptoms Phenothiazines or haloperidol may raise TCA blood concentrations May alter effects of antihypertensive drugs may inhibit hypotensive effects of clonidine... 

The older tricyclic agents show less than a ten-fold selectivity in inhibiting noradrenaline over that for 5-HT (e.g. desipramine, imipramine, nortriptyline) through amitryptyline. which shows virtually no selectivity, to trazodone, zimelidine and clomipramine, which are somewhat 5-HT selective. The newer Serotonin-Selective Reuptake Inhibitors (SSRIs) show a higher selectivity for inhibition of 5-HT reuptake in the brain, and have a different pharmacology. Examples clinically used include citalopram, fluoxetine, fluvoxamine, nefazodone, paroxetine, sertraline, trazodone and venlafaxine. Experimental agents include 6-nitroquipazine, alaproclate, litoxetine, indatraline and p-CIT. 

The future of psychopharmacotherapy may include creative dietary or other pharmacological manipulations of the CYP enzyme system to achieve a positive treatment response. Recently, it was demonstrated that levels of cyclosporine (an expensive immunosuppressive agent) were dramatically increased in patients who were concomitantly administered grapefruit juice (Hollander et al. 1995). In other studies, paroxetine and fluoxetine were used to raise desipramine levels in superextensive me-tabolizers who were nonresponsive to standard doses (Kraus et al. 1996). Also, the authors used fluvoxamine to augment olanzapine and clozapine concentrations when a lack of response was obtained at standard or upper-level doses. Because per-pill costs of many of today s newer-generation psychoactive compounds often prove prohibitive, use of dietary and pharmacological CYP inhibitors could have significant pharmacoeconomic implications. 

Clinically important, potentially hazardous interactions with amitriptyline, amoxapine, bupropion, citalopram, clomipramine, desipramine, doxepin, fluoxetine, fluvoxamine, imipramine, meperidine, nefazodone, nortriptyline, paroxetine, pizotifen, protriptyline, rizatriptan, sertraline, sibutramine, sumatriptan, trimipramine, tryptophan, venlafaxine, zolmitriptan... 

Coadministration of cimetidine reduced citalopram oral clearance by 29%, whereas the addition of fluvoxamine caused a significant increase in plasma concentrations of citalopram. At this time, esci-talopram is considered unbkely to be involved in cbnically important pharmacokinetic interactions, althongh coadministration of escitalo-pram and desipramine resnlted in a donbling of the area nnder the cnrve for desipramine. ... 

Clomipramine, fluvoxamine, sertraline, and fluoxetine are approved by the FDA for treatment of OCD in children and adolescents. Childhood and adult OCD appear to respond similarly to drug therapy. The SSRIs appear to be effective and well tolerated in treatment of OCD in children and are generally considered first-line agents. Treatment with an SSRI produces a favorable response in 75% of children and adolescents with OCD. A combination of SSRIs and CBT is preferred in most cases. In children, the most commonly described side effects of SSRI therapy include nausea, headache, tremor, gastrointestinal complaints, drowsiness, akathisia, insomnia, disinhibition, and agitation. Clomipramine was significantly better than placebo in the treatment of OCD in children and adolescents, with 75% of patients having a moderate to marked improvement. Clomipramine was also more effective than desipramine in children and adolescents. ... 

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