Desipramine 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. 

A meta-analysis of placebo-controlled studies by Levin and Lehman (1991) showed that desipramine produced greater cocaine abstinence than placebo. Although a more recent review did not concur (Lima et al. 2001), secondary analyses of studies with imipramine, desipramine, and bupropion suggested that depressed cocaine abusers are more likely to show significant reductions in cocaine abuse than nondepressed cocaine abusers (Margolin et al. 1995 Nunes et al. 1991 Ziedonis and Kosten 1991). Furthermore, recent work with desipramine supported its efficacy in opioid-dependent patients, particularly in combination with contingency management therapies (Kosten et al. 2004 Oliveto et al. 1999). 

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. 

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. 

Depression SSRIs SNRIs Mirtazapine Bupropion Nortriptyline Desipramine ... 

The so-called atypical antidepressants such as venlafaxine and bupropion can be tried, but their safety and efficacy in treating patients with dementia have not been well studied. The older tricyclic antidepressants and monoamine oxidase inhibitors are not tolerated well by demented patients and should be avoided. Two possible exceptions are nortriptyline (Pamelor) and desipramine (Norpramin), but even these should be tried only after the newer antidepressants have proved ineffective. 

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). 

Drugs that might be affected by lopinavir/ritonavir include ergot derivatives, oral contraceptives, antiarrhythmics, HMG-CoA reductase inhibitors, HIV protease inhibitors, atovaquone, calcium channel blockers, ketoconazole, itraconazole, pimozide, cisapride, clarithromycin, disulfiram, metronidazole, immunosuppressants, midazolam, triazolam, narcotic analgesics, rifabutin and rifabutin metabolite, sildenafil, warfarin, bupropion, clozapine, desipramine, piroxicam, quinidine, theophylline, and zolpidem. 

Other alternatives to the stimulants that have been studied for treatment of ADHD in children and adults include the tricyclic antidepressants desipramine and nortriptyline the newer antidepressants bupropion, venlafaxine, and atomoxetine the beta-blocker pindolol and the selective monoamine oxidase inhibitor, deprenyl. Across these agents, the number of controlled studies varies from none (nortriptyline) to four (bupropion). Only deprenyl and desipramine have been studied in children with ADHD and tic disorders. 

Nolen WA, Haffmans PMJ, Bouvy PF, et al Monoamine oxidase inhibitors in resistant major depression. J Affect Disord 28 189-197, 1993 Nomikos GC, Damsma G, Wenkstern D, et al Chronic desipramine enhances amphetamine-induced increases in interstitial concentrations of dopamine in the nucleus accumbens. Eur J Pharmacol 195 63-73, 1991 Nomikos GC, Damsma D, Wenkstern D, et al Effects of chronic bupropion on interstitial concentrations of dopamine in rat nucleus accumbens and striatum. Neuropsychopharmacology 7 7-14, 1992... 

In psychomotorically retarded patients, many clinicians prefer to use a less sedating drug (e.g., an SSRI, venlafaxine, bupropion, or desipramine), but definitive evidence is lacking. 

Those who fail to respond to an SSRI may respond to a TCA, and vice versa. Thus, these two broad-spectrum classes can be used in a sequential strategy to adequately treat the majority of cases. However, many physicians try another newer antidepressant (e.g, venlafaxine, bupropion, nefazodone) in such patients because of the safety and tolerability problems associated with TCAs. Of note, the tolerability profile of secondary amine TCAs such as desipramine is as favorable as any of the newer antidepressants and probably better than nefazodone. Nevertheless, the secondary amine TCAs have a therapeutic index as narrow as tertiary amine TCAs (e.g., amitriptyline, imipramine) in terms of lethality in overdoses resulting from cardiotoxicity. 

As a results of these studies, clinicians have proposed that switching to reboxetine or bupropion might a useful strategy given that these antidepressants share the ability with desipramine and imipramine to block NE uptake. Nevertheless, only one small open label study has been done to test this possibility ( 365). If bupropion is to be used in patients switched from an ineffective trial of fluoxetine, the dose should be kept low for several weeks to allow for the clearance of fluoxetine and norfluoxetine. Case reports indicate that fluoxetine can elevate levels of the active metabolites of bupropion, which, in turn, could mediate an increase risk of adverse effects (366). 

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. 

Desipramine and maprotiline, which are selective NE reuptake inhibitors, should not be combined with an MAOl because of the risk of hypertensive crisis. The combination of an MAOl plus reboxetine and bupropion also blocks the NE uptake pump and thus theoretically should carry the same risk of a hypertensive crisis when combined with an MAOl. Thus, these combinations should also be avoided. 

Consistent with its most potent known mechanism of action, bupropion is an indirect dopamine agonist via its inhibition of the neuronal uptake pump for dopamine (503, 504). Hence, bupropion can potentiate the effects of other dopamine agonists. This interaction does not typically cause serious problems and may even be advantageous in specific instances such as patients with Parkinson s disease plus a depressive disorder. Because of its ability to inhibit NE uptake, bupropion would be prone to the same interactions as NSRIs such as desipramine and reboxetine. 

Bupropion is metabolized primarily by CYP2B6, and its metabolism may be altered by drugs such as cyclophosphamide, which is a substrate of 2B6. The major metabolite of bupropion, hydroxybupropion, is a moderate inhibitor of CYP2D6 and so can raise desipramine levels. Bupropion should be avoided in patients taking MAOIs. 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

FIGURE 7—40. Adrenergic combo 1 Bupropion plus norepinephrine reuptake inhibitor (NRI). Here the NE actions of bupropion are double-boosted by the NRI (either selective reboxetine or nonselective desipramine, maprotilene, nortriptyline, or protriptyline). Dopamine is single-boosted by bupropion only. 

By the 1990s antidepressants from the serotonin selective reuptake inhibitor (SSRI) class became recognized as preferred first-line treatments for anxiety disorder subtypes, ranging from obsessive-compulsive disorder, to panic disorder, and now to social phobia and posttraumatic stress disorder (Fig. 8—9). Not all antidepressants, however, are afficacious anxiolytics. For example, desipramine and bupropion seem to be of little help in several anxiety disorder subtypes. Documentation of efficacy... 

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... 

Clinical reports, prescription databases, and a few trials support the use of selective serotonin reuptake inhibitors in combination with the older tricyclics, especially desipramine with bupropion and, most recently, with mirtazapine in patients who do not show an adequate response to a single agent. 

The beneficial effect of mirtazapine in the treatment of depression might be explained by its a2-adrenoceptor antagonistic property. Bupropion and desipramine might be also beneficial in depression because of their ability to increase extracellular NE levels (Femandez-Pastor et al., 2005 Li et al., 2002 Parini et al., 2005 Sacchetti et al., 1999). The beneficial effect of NE in depression can be explained by the excitatory effect of NE on 5-HT neurotransmission and by the direct involvement of NE transmission in anxiety, energy feeling and motivation (Guiard et al., 2008 Stahl, 2000). 

TCAs DRUG DEPENDENCE THERAPIES-BUPROPION 1. t risk of seizures This risk is marked in elderly people, in patients with a history of seizures, addiction to opiates/cocaine/ stimulants, and in diabetics treated with oral hypoglycaemics or insulin 2. t plasma concentrations of amitriptyline, clomipramine, desipramine, doxepin and imipramine, with risk of toxic effects 1. Bupropion is associated with a dose-related risk of seizures. TCAs lower the seizure threshold. Additive effects when combined 2. Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 1. Extreme caution. The dose of bupropion should not exceed 450 mg/day (or 150 mg/day in those with severe hepatic cirrhosis) 2. Initiate therapy of these drugs at the lowest effective dose... 

CINACALCET BUPROPION T plasma concentrations of these substrates, with risk of toxic effects Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 Initiate therapy of these drugs, particularly those with a narrow therapeutic index, at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. hydrocodone, oxycodone, desipramine, paroxetine, chlorpheniramine, mesoridazine, alprenolol, amphetamines, atomoxetine)... 

Add or switch to or from pro-noradrenergic agents (e.g., atomoxetine, reboxetine, other SNRIs, mirtazapine, maprotiline, nortriptyline, desipramine, bupropion) with caution... 

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... 

Bupropion, reboxetine, nortriptyline, desipramine, maprotiline, atomoxetine (all potentially po A/erful enhancers of noradrenergic action, but observe for activation of bipolar disorder and suicidal ideation)... 

Medications play an important part in the treatment of ADD. Stimulants are the mainstay of the treatment of ADD methylphenidate (Ritalin), dextroamphetamine (Dexedrine), and pemoline (Cylert). These differ in their half-lives, with Ritalin having the shortest and Cylert the longest. A warning has recently been issued about Cylert because of reports of sometimes fatal liver toxicity. Thus, it is recommended that it be used only if methylphenidate and dextroamphetamine are ineffective. There is individual variability in resporise, so that a person who does not respond to one may respond well to another. Other medications can also be effective in the treatment of ADD and may be useful, especially in residual ADD, where substance abuse may be an issue. These include tricyclic antidepressants (especially desipramine and imi-pramine) SSRIs, bupropion, venlafaxine, and clonidine. There are reports of antipsy-chotics and lithium being helpful in selected cases, as well. 

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... 

Simultaneous amoxapine, clovoxamine, desipramine, fenfluramine, fluvoxamine, nor-fluoxetine, nortriptyline, propranolol, protriptyline, sertraline Noninterfering amitriptyline, atenolol, bupropion, carbamazepine, chlordiazepoxide, ci-talopram, clomipramine, clozapine, cyclobenzaprine, doxepin, imipramine, loxapine, me-toprolol, mianserin, moclobemide, nomifensine, pindolol, thioridazine, tranyl[Pg.626]

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