Paroxetine Bupropion

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. 

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

C. Nortriptyline (Pamelor) is a TCA, and as a class these drugs require at least one steady-state blood level to safely and effectively use the medication. Paroxetine, venlafaxine, and bupropion have not had blood levels correlated to response, and their relatively low toxicity does not require therapeutic blood monitoring. Nardil is a MAOI, which can be... 

Reports are on hand relating to more recent antidepressants such as bupropion, citalopram (Fairweather ei ul., 1997), fluoxetine (Gelfin et ul.. 1998). moclobemide (Dingemanse et ul., 1998) and paroxetine (Brauer et ul.. 1995). These products, in agreement with their clinical profiles, produce fewer subjective effects and generally less sedation in healthy subjects than the older... 

Although the efficacy of tricyclic antidepressants in the treatment of unipolar depression is beyond reproach, the side-effect profile of these agents makes them less desirable as first-line therapeutic agents. Introduction of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine in the past decade has revolutionized the treatment of depression universally. The side-effect profile of SSRIs, such as nausea, diarrhea and sexual dysfunction, is considerably more benign than that of tricyclic drugs. Multiple controlled trials have proven the efficacy of SSRIs vs. placebo (Nemeroff, 1994). Recently, a number of SNRIs (serotonin and noradrenaline reuptake inhibitors) and so-called atypical antidepressants have been marketed that may have additional advantages over SSRIs, such as more rapid onset of action (venlafaxine. mirtazapine) and low sexual side-effect potential ( bupropion, nefazodone). Additionally, it appears that venlafaxine may be more efficacious in cases of treatment-refractory depression (Clerc et al., 1994 Fatemi et al., 1999). Finally, in a recent report (Thase et al., 2001),... 

In contrast to anticonvulsants and alcohol, drugs such as bupropion, fluoxetine, fluvoxamine, nefazodone, quinidine, paroxetine, and some antipsychotics can inhibit specific CYP enzymes (7, 11, 36, 37, 41, 42, 43 and 44). Thus, TCAs, certain BZDs, bupropion, some steroids, and antipsychotics can all have their metabolism inhibited by drugs such as fluoxetine. For example, fluoxetine at 20 mg/day produces on average a 500% increase in the levels of coprescribed drugs which are principally dependent on CYP 2D6 for their clearance. That can lead to serious or even life-threatening toxicity if the drug has a narrow therapeutic index and the dose is not adjusted for the change in clearance caused by the coadministration of fluoxetine. 

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. 

There is a great disparity of current knowledge regarding the effects of antidepressants on GYP enzymes. There have been almost no studies to test the potential effects of TCAs, MAOIs, and trazodone on GYP enzymes. There has only been one study with bupropion but it demonstrated that bupropion produces substantial inhibition of GYP 2D6 comparable with the effect of fluoxetine and paroxetine. In contrast to studies in these antidepressants, there have been extensive in vitro and in vivo studies of SSRIs, nefazodone, and venlafaxine. 

D6 Tricyclic antidepressants (TCAs), benztropine, perphenazine, clozapine, haloperidol, codeine/oxycodone, risperidone, class Ic antiarrhythmics, 3 blockers, trazodone, paroxetine, maprotiline, amoxapine, duloxetine, mirtazapine (partly), venlafaxine, bupropion Fluoxetine, paroxetine, duloxetine, hydroxybupropion, methadone, cimetidine, haloperidol, quinidine, ritonavir Phenobarbital, rifampin... 

Newer antidepressants (eg, fluoxetine, paroxetine, citalopram, venlafaxine) are mostly SSRIs and are generally safer than the tricyclic antidepressants and monoamine oxidase inhibitors, although they can cause seizures. Bupropion (not an SSRI) has caused seizures even in therapeutic doses. Some antidepressants have been associated with QT prolongation and torsade de pointes arrhythmia. SSRIs may interact with each other or especially with monoamine oxidase inhibitors to cause the serotonin syndrome, characterized by agitation, muscle hyperactivity, and hyperthermia (see Chapter 16). 

OFFICIAL NAMES Amitriptyline (Elavil), amoxapine (Asendin), bupropion (Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), fluoxetine (Prozac), imipramine (Norfranil, Tofranil), isocarboxazid (Marplan), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Aventyl, Pamelor), paroxetine (Paxil), phenelzine (Nardil), protriptyline (Vivactil), sertraline (Zoloft), thioridazine (Mellaril), tranylcypromine (Parnate), trazodone (Desyrel), trimipramine (Sur-montil), venlafaxine (Effexor) the herb St. John s wort (Hypericum perforatum) is sold over-the-counter without prescription STREET NAMES Happy pills... 

Several LC-MS and LC-MS/MS methods were developed in plasma for only one antidepressant and, sometimes, its major metabolite(s) to perform pharmacokinetic, bioavailability, or bioequivalence studies. Analytical methods developed for these purposes require very low LLOQ values and, usually, narrow linear ranges covering the low range of the therapeutic concentrations are validated. In this context, several methodologies were described for the determination of fluoxetine [94, 95, 98-100], paroxetine [44, 71, 85, 101, 102], venlafaxine [48, 61, 64, 86, 103,104], sertraline [62, 68, 83], citalopram [46, 89] and escitalopram [105], mianserine [106, 107], mirtazapine [42], trazodone [84], nefazodone [51, 81], duloxetine [47, 50, 73], and bupropion [43], Deuterated analogues of the analyte of interest or of other drugs were employed by few authors as IS [43, 61, 73, 81, 85, 99] however, in most of these methods, another antidepressant or other therapeutic drug was used for this purpose. 

However, the agency s conclusions were based on a limited number of new antidepressants, including bupropion, citalopram, fluoxetine, flu-voxamine, mirtazapine, nefazodone, paroxetine, sertraline, escitalopram, and venlafaxine, according to an FDA Talk Paper (2004a). These were the drugs most often cited by the public at the two FDA hearings. 

Kennedy SH, McCann SM, Masellis M, McIntyre RS, Raskin J, McKay G, Baker GB. Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects. J Clin Psychiatry 2002 63(3) 181-6. 

FLUOXETINE, FLUVOXAMINE, PAROXETINE, SERTRALINE BUPROPION t plasma concentrations of bupropion and risk of adverse effects Inhibition of CYP2B6 Warn patients about adverse effects, and use alternatives when possible... 

ESCITALOPRAM, FLUOXETINE, FLUVOXAMINE, PAROXETINE, SERTRALINE BUPROPION T plasma concentrations of these SSRIs, with risk of toxic effects Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 Initiate therapy of these drugs at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. paroxetine)... 

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... 

Fluoxetine, paroxetine, bupropion, duloxetine, and other CYP450 2D6 inhibitors may increase TCA concentrations... 

Fluoxetine, paroxetine, bupropion, duloxetine, and other CYP450 2D6 inhibitors may increase TCA 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 Use of TCAs with sympathomimetic agents may increase sympathetic activity Methylphenidate may inhibit metabolism of TCAs... 

CYP450 2D6 inhibitors including paroxetine, fluoxetine, duloxetine, bupropion, sertraline, citalopram, and others can raise thioridazine to dangerous levels... 

Because this group as a whole engages in frequent suicidal acting out, it is advisable to treat borderline patients with medications that have been found to have a low degree of toxicity when taken in overdose. These include antipsychotics and the following antidepressants fluoxetine, paroxetine, bupropion (note above caution), trazodone, and sertraline. Most other antidepressants are quite toxic when taken in overdose. 

High suicide risk Less toxic antidepressants (fluoxetine, trazodone, paroxetine, sertraline, bupropion, venlafaxine, nefazodone)... 

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