Depressive disorders bupropion

Major depressive disorder (bupropion, bupropion SR, and bupropion XL)... 

Jiang, R. H., Shu, L., Zhang, H. Y. et al. (2006). A phase II randomized double blind multi-centers and parallel control clinical trial for bupropion SR in the treatment of depressive disorders. Chinese Journal of New Drugs, 15(2), 128-31. 

Atypical Antidepressants. None of the so-called atypical antidepressants have been tested in the treatment of AN. However, mianserin, an antidepressant available in Europe, has been found to increase body weight in patients with various depressive disorders. Although bupropion (Wellbutrin, Zyban) has not been tested in the treatment of AN, it is effective in the treatment of BN. However, immediate-release bupropion is associated with an especially high risk for seizures in these patients and is therefore contraindicated in those with eating disorders. The seizure risk associated with sustained-release bupropion remains unclear at this time, as the doses studied have not been as high as those for immediate-release bupropion. 

Suicidality in children and adolescents Although Zyban is not indicated for treatment of depression, it contains the same active ingredient as the antidepressant bupropion medications Wellbutrin, Wellbutrin SR, and Wellbutrin XL Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of bupropion or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Closely observe patients who are started on therapy for clinical worsening, suicidality, or unusual changes in behavior. Advice families and caregivers of the need for close observation and communication with the prescriber. Bupropion is not approved for use in pediatric patients. 

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. 

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. 

Dhillon S, Yang LP, Curran MP Bupropion A review of its use in the management of major depressive disorder. Drugs 2008 68(5) 653. [PMID 18370448]... 

Extensive studies on bupropion, including animal models of depression, have demonstrated that the desired inhibition of dopamine and norepinephrine reuptake resides mainly with radafaxine (that is the (S,S)-enantiomer, 2a). Furthermore, these studies confirmed that the (R,R) -enantiomer, 2b, is associated with a number of the known related undesirable side effects. Hence, development of radafaxine hydrochloride was undertaken for the treatment of Major Depressive Disorder (MDD) as a stand-alone New Chemical Entity (NCE). Furthermore, owing to the undesirable side effects associated with the (R,R)-enantiomer 2b, levels of this compound were to be controlled to <0.5% to minimize these effects. 

Triple reuptake inhibitors (TRIs), which inhibit reuptake at all three transporters, have attracted considerable interest in recent years [77]. The involvement of dopamine reuptake in the etiology of depression and other CNS disorders has been recognized [29,30]. As a result, TRIs have been proposed to offer a faster onset of action and improved efficacy for depression over currently prescribed single or dual action monoamine reuptake inhibitors. Historically, the mesocorticolimbic dopamine pathway is thought to mediate the anhedonia and lack of motivation observed in depressed patients [78,79]. In addition, methylphenidate, both immediate release and extended release formula, has been found to be effective as an augmenting agent in treatment-resistant depression [4]. Furthermore, clinical studies using the combination of bupropion and an SSRI or SNRI have showed improved efficacy for the treatment of MDD in patients refractory to the treatment with SSRIs, SNRIs, or bupropion alone [5,80,81]. 

Bupropion is also effective both in the treatment of depression and in smoking cessation. For more information, refer to Chapter 3 (Mood Disorders) and Chapter 6 (Substance Use Disorders). 

Psychosis or mania Antidepressants can precipitate manic episodes in bipolar disorder patients during the depressed phase of their illness and may activate latent psychosis in other susceptible individuals. The sustained-release formulation of bupropion is expected to pose similar risks. There were no reports of activation of psychosis or mania in clinical trials conducted in nondepressed smokers. 

According to the Expert Consensus Panel for Mental Retardation Rush and Frances, (2000), the mainstays of the pharmacological treatment of acute mania or bipolar disorder in adults are anticonvulsant medications (divalproex, valproic acid, or carbamazepine) or lithium. Both divalproex or valproic acid and lithium were preferred treatments for classic, euphoric manic episodes. Divalproex or valproic acid was preferred over lithium and carbamazepine for mixed or dysphoric manic episodes and rapid-cycling mania. For depressive episodes associated with bipolar disorder, the addition of an antidepressant (SSRI, bupropion, or venlafaxine) was recommended. According to the Expert Consensus Panel, the presence of MR does not affect the choice of medication for these psychiatric disorders in adults. 

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... 

Specific factors to consider are both psychiatric and physical contraindications. For example, bupropion is contraindicated in a depressed patient with a history of seizures due to the increased risk of recurrence while on this agent. Conversely, it may be an appropriate choice for a bipolar disorder with intermittent depressive episodes that is otherwise under good control with standard mood stabilizers. This consideration is based on the limited data suggesting that bupropion is less likely to induce a manic switch in comparison with standard heterocyclic antidepressants. Another example is the avoidance of benzodiazepines for the treatment of panic disorder in a patient with a history of alcohol or sedative-hypnotic abuse due to the increased risk of misuse or dependency. In this situation, a selective serotonin reuptake inhibitor (SSRI) may be more appropriate. 

Depressed patients with an eating disorder (i.e., anorexia or bulimia) or a history of seizures should not take bupropion or maprotiline because of an increased risk of seizures. 

Grossman F, Potter WZ, Brown EA, Maislin G (1999) A double-blind study comparing idazoxan and bupropion in bipolar depressed patients. J Affect Disord 56 237 13 Hamed AT, Jandhyala BS, Ginos JZ, Lockhandwala MF (1981) Presynaptic dopamine receptors and a-adrenoceptors as mediators of the bradychardic action of N-n-propyl-N-n-butyl dopamine. Eur J Pharmacol 74 83-90... 

Mirtazapine, modafinil, atomoxetine (add A/ith caution and at lower doses since bupropion could theoretically raise atomoxetine levels) both for residual symptoms of depression and attention deficit disorder... 

Bupropion is another second-line agent, particularly for patients who are wary of the SSRIs negative impact on sexual dysfunction. Because it appears to relieve depression through a completely different mechanism than SSRIs, enhancing norepinephrine or dopamine, it is often administered to patients who fail SSRIs or exhibit a partial response. The most common side effects encountered with bupropion are insomnia, jitteriness, and nausea. Bupropion is contraindicated in patients with a history of seizures or eating disorders. 

Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed medications. Their therapeutic actions are diverse, ranging from efficacy in depression to obsessive-compulsive disorder, panic disorder, bulimia, and other conditions. They include bupropion, fluoxetine, nefazodone, paroxetine, and miscellaneous other drugs. 

Daviss WB, Bentivoglio P, Racusn R, et al. Bupropion sustained release in adolescents with comorbid attention-deficit/hyperactivity disorder and depression. J Am Acad Child Adolesc Psychiatry 2001 40 307-314. 

Weilbutrin (Bupropino hydrochloride) A medication that has been successfully used to treat depression in adults. One type of this medication Zyban (bupropion hydrochloride) has been used for smoking cessation. Both of these medications contain bupropin and should not be used together. This medication is not recommended for eating disorders such as bulimia or anorexia nervosa because of the potential for the incidence of seizures. 

Bupropion (100 mg p.o. b.i.d.) is indicated in the treatment of depression. It is reserved for patients who cannot tolerate or have not responded to other medications. Bupropion does not alter the uptake of serotonin, has an equivocal effect on the uptake of norepinephrine, but blocks the uptake of dopamine. Bupropion has no affinity for alpha-1 and alpha-2-adrenergic receptors, H,-histamine receptors, muscarinic cholinergic receptors, or D2-dopaminergic receptors. It does not cause sedation or orthostatic hypotension. However, because it is structurally related to amphetamine, it may cause insomnia, agitation, and anxiety shortly after initiation of therapy. Bupropion lowers the seizure threshold and hence is contraindicated in patients with a history of seizure disorder (see also Tables 5 through 7). 

Another risk of antidepressants in vulnerable patients (particularly those with unrecognized bipolar depression) is switching, sometimes suddenly, from depression to hypomanic or manic excitement, or mixed, dysphoric-agitated, manic-depressive states. To some extent this effect is dose-related and is somewhat more likely in adults treated with tricyclic antidepressants than with serotonin reuptake inhibitors, bupropion, and perhaps with MAO inhibitors. Risk of mania with newer sedating antidepressants, including nefazodone and mirtazapine, also may be relatively low, but some risk of inducing mania can be expected with any treatment that elevates mood, including in children with unsuspected bipolar disorder. 

A 19-year-old white male with a history of multiple drug abuse, psychosis, depression and attention-deficit hyperactivity disorder used an unknown quantity of MXE IV for abuse shortly before he was discharged from an inpatient detoxification facility. He was on bupropion, aripiprazole and chlorprothixene. About 30 min after the injection, he presented to the ER of the hospital with extreme agitation, ataxia and semistuporous state. 

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