Sertraline Bupropion

Bipolar patients with so-called breakthrough major depressive episodes, despite adequate treatment, were placed in a randomized doubleblind 10-week study and treated with bupropion, sertraline, or venlafaxine augmentation (Post et al., 2001). Switches to hypomania or mania occurred in 14% of the patients. Those who responded positively to the treatment were continued for 1 year in a blinded maintenance trial, and 33% switched into hypomania or mania. In a second phase of their antidepressant augmentation studies, 18.2% switched into hypomania or... 

B6 S-Mephenytoin (N-desmethyl metabolite) Bupropion Sertraline (but also inhibits 2D6)... 

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

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. 

Stewart, Andrew A. Nierenberg, Michael E. Thase, Louise Ritz, Melanie M. Biggs, Diane Warden, James F. Luther, Kathy Shores-Wilson, George Niederehe and Maurizio Fava, Bupropion-Sr, Sertraline, or Venlafaxine-Xr after Failure of SSRIs for Depression , New England Journal of Medicine 354 (2006b) 1231-42... 

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. 

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),... 

Kavoussi RJ, Segraves RT, Hughes AR, et al. Double-blind comparison of bupropion sustained release and sertraline in depressed outpatients. J Clin Psychiatry 1997 58 532-537. 

No information in product labeling, but low plausibility of grapefruit juice interaction bupropion, doxazosin, gabapentin, lisinopril, risperidone, sertraline, and sibutramine. 

B6 Artemisinin, bupropion, cyclophosphamide, efavirenz, ifosfamide, ketamine, S-mephobarbital, S-mephenytoin (/V-demethylation to nirvanol), methadone, nevirapine, propofol, selegiline, sertraline, ticlopidine Phenobarbital, cyclophosphamide Ticlopidine, clopidogrel... 

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. 

Coleman CC, Cunningham LA, Foster VJ, Batey SR, Donahue RM, Houser TL, Ascher JA. Sexual dysfunction associated with the treatment of depression a placebo-con-trolled comparison of bupropion sustained release and sertraline treatment. Ann Clin Psychiatry 1999 11(4) 205-15. 

Croft H, Settle E Jr, Houser T, Batey SR, Donahue RM, Ascher JA. A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. Clin Ther 1999 21(4) 643—58. 

FIGURE 3.2. Protocol for thr STARED project, (a) Level 1 (b) level 2 (c) level 3 (d) level 4. CIT, citalopram SER, sertraline BUP, bupropion VEN, venlafaxine CT, cognitive-behavioral therapy BUS, Buspirone MIRT, mirtazpine NTP, nortriptyline LI, lithium THY, thyroid hormone TCP, tranylcypromine. 

Level II results showed that patients who failed to benefit from SSRI treatment (citalopram) are good candidates for augmentation (with sustained-release bupropion or with Buspirone) or switching (to sustained-release bupropion or sertraline or sustained-release venlafaxine—three antidepressants with different mechanisms of action). One third of the patients in each group reached remission. Thus, overall, after two well-delivered (robust doses and sufficient duration) medication treatment courses (results for the group who received CBT were not published yet) about 50% of the patients achieved full remission of symptoms. Results from Levels III and IV were not yet available at this time. Once results of all four levels are added up we will have at our disposal an antidepressant roadmap to follow. We will also learn of the percentage of patients who, in spite of these systematic efforts, are still unresponsive to antidepressant treatment and require more drastic or unconventional treatment approaches. 

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... 

Preskorn SH. Comparison of fhe folerabilify of bupropion, fluoxetine, imipramine, nefazodone, paroxefine, sertraline, and venlafaxine. J Clin Psychiafry f 995 56(Suppl 6) f2-2f. 

In the U.S., sertraline (Zoloft) is commonly augmented with bupropion (Wellbutrin) with good results in a combination anecdotally called Well-loft (use combinations of antidepressants with caution as this may activate bipolar disorder and suicidal ideation)... 

Case Conclusion Given her favorable response to an SSRI in the past, sertraline would appear to be a logical choice for treatment of her latest episode, but her complaint of sexual dysfunction should be taken seriously, as this commonly leads to medication noncompliance. As all SSRI and venlafaxine are capable of inducing this side effect, bupropion is initiated and slowly titrated to effect. The activating properties of bupropion proved to be a notable benefit for this patient as her symptoms resolved within the first 3 weeks of receiving a therapeutic dose. 

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)... 

Clinically important, potentially hazardous interactions with alfentanil, aminophylline, amisulpride, amoxicillin, ampicillin, anticonvulsants, astemizole, atorvastatin, benzodiazepines, bromocriptine, buprenorphine, bupropion, carbamazepine, cilostazol, ciprofloxacin, cisapride, clindamycin, colchicine, cyclosporine, dasatinib, digoxin, dihydroergotamine, diltiazem, disopyramide, enoxacin, eplerenone, ergotamine, eszopiclone, everolimus, fluconazole, fluoxetine, fluvastatin, gatifloxacin, HMG-CoA reductase inhibitors, imatinib, itraconazole, ketoconazole, lomefloxacin, lorazepam, lovastatin, methadone, methylprednisolone, methysergide, midazolam, mizolastine, moxifloxacin, nitrazepam, norfloxacin, ofloxacin, paroxetine, pimozide, pravastatin, quinolones, ranolazine, repaglinide, rupatadine, sertraline, sildenafil, simvastatin, sparfloxacin, sulpiride, tacrolimus, terfenadine, triazolam, troleandomycin, vardenafil, verapamil, vinblastine, warfarin, zaleplon, zolpidem, zuclopenthixol... 

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... 

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