Desipramine Fluoxetine

Codeine, dextromethorphan, haloperidol, thioridazine, perphenazine, nortriptyline, desipramine, fluoxetine, norfluoxetine, TCAs (hydroxylation), beta-blockers such as timolol and metoprolol, type 1C antiarrhythmics encainide, flecainide TCAs (desmethylation), triazolam, alprazolam, midazolam, carbamazepine, terfenadine, quinidine, lidocaine, erythromycin, cyclosporin... 

An isolated report describes a woman who developed marked and acute hypotension and weakness when desipramine, fluoxetine and venlafaxine were replaced by nefazodone. Isolated cases describe the serotonin syndrome in patients given nefazodone together, or sequentially, with another serotonei c drug (amitriptyline, paroxetine, St John s wort, or trazodone). The manufacturer recommended that nefazodone should not be used with an MAOI or within 14 days of discontinuing an MAOL Note that, due to adverse hepatic effects nefazodone was widely withdrawn from the market. 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

Antidepressants Desipramine, imipramine, sertraline, fluoxetine, paroxetine, venlafaxine, bupropion, nefazodone, mirtazapine, gepirone, amineptine Mixed findings suggest that better designed studies may find a niche for some of these drugs. Amineptine was effective for withdrawal symptoms. 

Decision analytic models have been constmcted to compare the costs of TCAs with those of SSRIs and other compounds. These comparisons have included imipramine or amitriptyline versus paroxetine or sertraline (Stewart, 1994) imipramine versus paroxetine Qonsson and Bebbington, 1994 McFarland, 1994 Lapierre et al, 1995) fluoxetine versus amitriptyline, clomipramine, doxepin and imipramine (Le Pen et al, 1994) venlafaxine versus amitriptyline, desipramine. 

The answer is c. (Hardman, p 436.) The tricyclics and second-generation antidepressants act by blocking serotonin or norepinephrine uptake into the presynaptic terminal. Fluoxetine selectively inhibits serotonin uptake with minimal effects on norepinephrine uptake. Protriptyline, maprotiline, desipramine, and amoxapine have greater effect on norepinephrine uptake... 

It has been known for over 25 years that many of the tricyclic antidepressants (TCAs), e.g. imipramine and amitriptyline, are potent inhibitors of both norepinephrine and 5-HT reuptake. Some tricyclic antidepressants, e.g. desipramine, inhibit the uptake of norepinephrine much more potently than the uptake of 5-HT. Thus, it was unclear for some time whether the inhibition of 5-HT uptake played any role in the antidepressant action of those TCAs that possessed this pharmacological property. Recently, however, effective antidepressants such as fluoxetine, paroxetine and sertraline have been marketed and these SSRIs are much more potent inhibitors of the uptake of 5-HT than that of norepinephrine (Fig. 13-8). Thus, selective inhibition of the uptake of either norepinephrine or 5-HT can result in an antidepressant effect (Ch. 55). 

Additional ADRs linked to diet pills include psychosis myocardial ischemia drug interactions, such as the interaction of fenfluramine with imipramine, fenfluramine with amitriptyline or desipramine, or the toxic reaction between fluoxetine and phentermine and the release of serotonin while inhibiting its reuptake, contributing to hyperserotonin reactions. When the next craze takes hold of patients and their physicians, hopefully physicians and pharmacists will take a more vocal position and recommend restraint, xmtil some proof of efficacy and lack of toxicity is shown for new faddish off-label combinations. 

Solid phase extraction (SPE) has been used to efficiently extract several types of antidepressants, which can then be conveniently analyzed on GC-NPD. One assay extracted and analyzed viloxazine, venlafaxine, imipramine, desipramine, sertraline, and amoxapine from whole blood in one procedure (Martinez et al., 2002). The same laboratory analyzed fluoxetine, amitriptyline, nortriptyline, trimipramine, maprotiUne, clomipramine, and trazodone in whole blood in one assay (Martinez et al., 2003). SPE has also been used for the simultaneous analysis of TCAs and their metabolites by de la Torre et al. (1998). 

Aspeslet LJ, Baker GB, Coutts RT, Torok-Both GA. 1994. The effects of desipramine and iprindole on levels of enantiomers of fluoxetine in rat brain and urine. Ghirality 6 86. 

Goodnough DB, Baker GB, Coutts RT. 1995. Simultaneous quantification of fluoxetine, norfluoxetine and desipramine using gas chromatography with nitrogen—phosphorus detection. J Pharmacol Toxicol Methods 34 143. 

Antidepressants. In the early 1980s, the recognition that depression is a frequent comorbid feature of BN coupled with the observation that appetite changes are a common feature of depression led researchers to evaluate antidepressant treatment for BN. Since that time, a series of controlled studies have demonstrated efficacy for a wide assortment of antidepressants including the TCAs imipramine (Tofranil) and desipramine (Norpramin), the MAOl phenelzine (Nardil), the SSRl fluoxetine (Prozac), and the atypical antidepressants trazodone (Desyrel) and bupropion (Wellbutrin). Overall, approximately two-thirds of antidepressant-treated patients with bulimia experience symptomatic improvement while nearly one-third achieves complete remission of binging and purging. In addition, the improvement in the symptoms of BN is not dependent on the presence of comorbid depression. 

Antidepressants. Short-term studies of desipramine and fluoxetine indicate that both medications reduce binging in patients with BED. In addition, fluoxetine-treated patients may also experience a modest reduction in weight during short-term treatment. However, this early weight loss with fluoxetine may not be sustained despite continued treatment. 

There are four classes of antidepressants tricyclic antidepressants (imipramine, trimipramine, amitriptyline, doxepin, desipramine, protriptyline, nortriptyline, amoxapine, maprotiline) monoaminooxidase (MAO) inhibitors (phenelzine, isocarboxazid, tranylcypromine) second-generation antidepressants or atypical antidepressants, which are a chemically dissimilar group of recently proposed drugs (bupropion, trazodone, fluoxetine) and amphetamines and other stimulators of the CNS (dextroamphetamine, methylphenidate). 

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). 

Relapse prevention with medication has been studied in BN as well as AN. In 1991 Walsh et al. placed bulimics who had a 50% or more reduction in binge eating on desipramine in maintenance treatment. About half of the patients relapsed below the 50% reduction within 4 months, despite continued use of the medication. In a second multicenter collaborative study examining the efficacy of fluoxetine maintenance in bulimic patients who had responded to the drug with a 50% reduction of symptoms, the patients who were maintained on the active drug were significantly less likely to relapse than those who were switched to placebo at the end of the acute treatment phase (Romano, 1999). 

In a five-cell design study, Walsh et al. (1997) compared CBT, supportive therapy (a time and contact control), each combined with medication (involving desipramine followed by fluoxetine in those who did not achieve abstinence on desipramine, or placebo), and medication management alone. The CBT was superior to supportive therapy and active drug was superior to placebo. The best results were achieved with a combination of CBT plus active drug. Results from CBT plus placebo were roughly equivalent to those with medication management alone. 

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

The addition of a nonselective noradrenaline reuptake inhibitor, desipramine, to an SSRl, fluoxetine, has been reported to be associated with a more rapid downregulation of P-adrenoceptors in rats than seen with either treatment on its own [B. M. Baron et al. 1988). This observation suggests that the addition of desipramine to fluoxetine might be associated with more rapid response and therefore possibly improved response. 

The only current evidence to support this view is the finding that the addition of desipramine to fluoxetine was better than desipramine alone in the treatment of patients with depression (J. C. Nelson et al. 1991). Desipramine alone resulted in the expected improvement of approximately 20% at week 1 and 40% at 2 weeks in 52 patients. In patients treated with the combination of fluoxetine and desipramine, the response was greatly accelerated, and a response of 42% was seen at the first week of treatment. At the end of 4 weeks of treatment, 71 % of the 14 patients on combined treatment were in complete remission compared with only 14% of those receiving desipramine alone. This study provides some evidence of the better efficacy seen with a double action on both noradrenaline and serotonin, but firm conclusions cannot be drawn because of the open nature of the investigation. 

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]. 

Barnes NM, Costall B, Naylor RJ, et al Normal densities of 5-HT3 receptor recognition sites in Alzheimer s disease. Neuroreport 1 253-254, 1990 Barnes R, Veith R, Okimoto J, et al Efficacy of antipsychotic medications in behaviorally disturbed dementia patients. Am J Psychiatry 139 1170-1174, 1982 Baron BM, Ogden AM, Siegel BW, et al Rapid down regulation of beta-adrenoceptors by co-administration of desipramine and fluoxetine. Eur J Pharmacol 154 25-134, 1988... 

Nelson JC, Mazure CM, Bowers MB, et al Aprehminary, open study of the combination of fluoxetine and desipramine for rapid treatment of major depression. Arch Gen Psychiatry 48 303-307, 1991... 

Results of crossover studies indicate that lithium is efficacious in treating acute depression in bipolar subjects unequivocally (36%, 29/80) and partially (43%. 34/80). respectively (Xomberg and Pope, 1993 Keck and McElroy, 2002). Various antidepressants have shown variable rates of efficacy in the treatment of acute bipolar depression, i.e. desipramine (50%), maprotiline (67%), imipra-mine (40 60%), tranylcypromine (87%), moclobemide (53%) and fluoxetine (60%) (Keck and McElroy, 2002). Among the anticonvulsants, valproic add and lamotrigine appear to have some potential efficacy in the treatment of acute bipolar depression (Calabrese et al., 1992, 1999 Fatemi et al., 1997). 

Levkovitz. Y., Caftori, R., Avital, A., Richter-Levin. G. The SSRI drug fluoxetine, but not the noradrenergic tricyclic drug desipramine, improves memory performance during acute major depression. Brain Res. Bull. 58, 345-350, 2002. 

Pharmacological treatments were used by nearly half of the 149 services which offered any treatment, with a wide range of medications directed at various features of cocaine usage. Fluoxetine and desipramine were the most frequently prescribed antidepressants, with benzodiazepines used to aid sleep and reduce distress in withdrawal states. Sedative antipsychotics were used, apparently in states of severe agitation as well as more directly for psychotic complications. 

Preskorn SH, Alderman J, Chung M, et al. Pharmacokinetics of desipramine coadministered with sertraline or fluoxetine. J Clin Psychopharmacol 1994 14 90-98. 

With this caveat in mind, each side of the debate has evidence to support its position. The evidence is first summarized supporting the position that SSRIs are less effective than are some other antidepressants (particularly those with dual effects on both serotonin and NE CNS systems) in patients with more severe depression or who are hospitalized. Danish investigators in two double-blind, active-controlled studies found that clomipramine produced a superior response with either paroxetine or citalopram in the treatment of patients hospitalized for major depression (116, 117). Two double-blind studies also have shown that venlafaxine and mirtazapine were more effective than fluoxetine in patients hospitalized with depression ( 114,118). Finally, there are studies showing that the addition of desipramine (one of the most selective NE reuptake inhibitors) to an SSRI can convert nonresponders or pamal responders to full response ( 119, 119a, 120). 

---