Antidepressant drugs bupropion

Figure 9.9 The antidepressant drug bupropion used as an antismoking agent and astemizole to treat allergy that also has some antimalarial activities.

Guidelines agree that when antidepressants must be used, they should be combined with a mood-stabilizing drug to reduce the risk of mood switch to hypomania or mania.17,41 The question of which antidepressant drugs are less likely to cause a mood switch is not resolved. Anecdotal reports suggested bupropion may be less likely to cause this effect, but systematic reviews have not supported this conclusion. Prevailing evidence recommends that tricyclic antidepressants be avoided.41,43... 

Hesse LM, Venkatakrishnan K, Court MH, et al. CYP2B6 mediates the in vitro hydroxyla-tion of bupropion potential drug interactions with other antidepressants. Drug Metab Dispos... 

Bupropion is another alternative pharmacological approach to tobacco abstinence. It is an antidepressant drug that blocks reuptake of norepinephrine and dopamine, and also blocks nicotinic receptors in the low to intermediate micromolar range (Fryer and Lukas 1999). Thus, the effects of bupropion on nicotine addiction may be through dual effects on dopaminergic and nicotinic systems. Further, it has been an effective treatment in controlled studies, both alone and in combination with the nicotine patch. Bupropion alone or in combination with a nicotine patch was more effective than placebo or the nicotine patch alone. 

Bupropion is an atypical antidepressant drug that is the only nonnicotine-based prescription medicine approved for smoking cessation by the FDA. Its mechanism of action is presumed to be mediated by its capacity to block neuronal reuptake of dopamine and/or norepinephrine (Fiore et al. 2000). Relative to other antidepressants, bupropion has a relatively high affinity for the dopamine transporter (Baldessarini 2001). There is also evidence that bupropion acts as a functional nicotine antagonist, suggesting another potential mechanism by which bupropion could reduce smoking rates (Slemmer et al. 2000). 

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). 

Answer Several options are available for the pharmacological approach, including nicotine replacement and antidepressant drugs (e.g., bupropion). 

Dassa D, Kaladjian A, Azorin JM, et al Clozapine in the treatment of psychotic refractory depression. Br J Psychiatry 163 822-824, 1993 Dauge V, Steimes P, Derrien M, et al CCK8 effects on motivational and emotional states of rats involve CCKA receptors of the postero-median part of the nucleus accumbens. Pharmacol Biochem Behav 34 157-163, 1989 Davidson J Seizures and bupropion a review. J Clin Psychiatry 50 256-261, 1989 Davidson J, Pelton S Eorms of atypical depression and their response to antidepressant drugs. Psychiatry Res 17 87-95, 1986 Davidson JR, Miller R, Turnbull CD, et al Atypical depression. Arch Gen Psychiatry 39 527-534, 1982... 

The depressive phase of manic-depressive disorder often requires concurrent use of an antidepressant drug (see Chapter 30). Tricyclic antidepressant agents have been linked to precipitation of mania, with more rapid cycling of mood swings, although most patients do not show this effect. Selective serotonin reuptake inhibitors are less likely to induce mania but may have limited efficacy. Bupropion has shown some promise but—like tricyclic antidepressants—may induce mania at higher doses. As shown in recent controlled trials, the anticonvulsant lamotrigine is effective for many patients with bipolar depression. For some patients, however, one of the older monoamine oxidase inhibitors may be the antidepressant of choice. Quetiapine and the combination of olanzapine and fluoxetine has been approved for use in bipolar depression. 

While the amine hypothesis is undoubtedly too simplistic, it has provided the major experimental models for the discovery of new antidepressant drugs. As a result, all the currently available antidepressant drugs—except bupropion—are classified as having their primary actions on the metabolism, reuptake, or selective receptor antagonism of serotonin, norepinephrine, or both. 

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. 

Peck AW, Stern WC, Watkinson C. Incidence of seizures during treatment with tricyclic antidepressant drugs and bupropion. J Clin Psychiatry 1983 44(5 Part 2) 197-201. 

The drug bupropion, sold as Wellbutrin SR and Zyban, is a prescription-only antidepressant that has been successfully used to help smokers quit. It targets the pleasure centers of the brain. Again, talk with your doctor about possibly getting a prescription to help you cope with the emotional components of quitting. 

Hesse, L. M., Venkatakrishnan, K., Court, M. H., von Moltke, L. L., Duan, S. X., Shader, R. I., and Greenblatt, D. J. (2000) CYP2B6 mediates the in vitro hydroxylation of bupropion potential drug interactions with other antidepressants. Drug Metab. Dispos. 28, 1176-1183. 

Antidepressant drugs A major class of psychotropic drugs with diverse chemical configurations including the monoamine oxidase inhibitors (MAOIs), the heterocyclic drugs (composed of mono-, di-, tri-, and hetero-cyclics), the serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline, trazodone, and venlafaxine), and bupropion are more recent innovations. Antidepressants usually must be taken for several weeks to have the desired effect and they often have a low therapeutic index, so they must be closely monitored. 

Bupropion (brand name Wellbutrin) An antidepressant drug known to induce seizures and therefore administered with specific recommendations on dosage ranges. It should not be administered concurrently with MAOIs. 

The amine hypothesis of mood postulates that brain amines, particularly norepinephrine (NE) and serotonin (5-HT), are neurotransmitters in pathways that function in the expression of mood. According to the amine hypothesis, a functional decrease in the activity of such amines would result in depression a functional increase of activity would result in mood elevation. Difficulties with this hypothesis include the facts that (1) antidepressant drugs cause changes in amine activity within hours, but weeks may be required for them to achieve clinical effects (2) most antidepressants ultimately cause a down-regulation of amine receptors and (3) at least one antidepressant, bupropion, has minimal effects on brain NE or 5-HT. 

After ingestion of a meal that included sardines, cheese, and red wine, a patient taking an antidepressant drug experiences a hypertensive crisis. The drug most likely to be responsible is (A) Bupropion Fluoxetine Imipramine Phenelzine Trazodone... 

The mechanism of action of most of the miscellaneous antidepressants is not clearly understood. Examples of this group of drugs include fluoxetine (Prozac) and bupropion (Wellbutrin). 

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