Kaplan + Sadock's Synopsis of Psychiatry, 11e

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Chapter 29: Psychopharmacological Treatment

Smoking Cessation As the brand name Zyban, bupropion is indicated for use in combination with behavioral modification programs for smok- ing cessation. It is intended to be used in patients who are highly motivated and who receive some form of structured behavioral support. Bupropion is most effective when combined with nico- tine substitutes (Nico-Derm, Nicotrol). Bipolar Disorders Bupropion is less likely than tricyclic antidepressants to pre- cipitate mania in persons with bipolar I disorder and less likely than other antidepressants to exacerbate or induce rapid-cycling bipolar II disorder; however, the evidence about use of bupro- pion in the treatment of patients with bipolar disorder is limited. Attention-Deficit/Hyperactivity Disorder Bupropion is used as a second-line agent, after the sympatho- mimetics, for treatment of attention-deficit/hyperactivity dis- order (ADHD). It has not been compared with proven ADHD medications such as methylphenidate (Ritalin) or atomox- etine (Strattera) for childhood and adult ADHD. Bupropion is an appropriate choice for persons with comorbid ADHD and depression or persons with comorbid ADHD, conduct disorder, or substance abuse. It may also be considered for use in patients who develop tics when treated with psychostimulants. Cocaine Detoxification Bupropion may be associated with a euphoric feeling; thus, it may be contraindicated in persons with histories of substance abuse. However, because of its dopaminergic effects, bupro- pion has been explored as a treatment to reduce the cravings for cocaine in persons who have withdrawn from the substance. Results have been inconclusive, with some patients showing a reduction in drug craving and others finding their cravings increased. Hypoactive Sexual Desire Disorder Bupropion is often added to drugs such as SSRIs to counteract sexual side effects and may be helpful as a treatment for non- depressed individuals with hypoactive sexual desire disorder. Bupropion may improve sexual arousal, orgasm completion, and sexual satisfaction. Precautions and Adverse Reactions Headache, insomnia, dry mouth, tremor, and nausea are the most common side effects. Restlessness, agitation, and irritabil- ity may also occur. Patients with severe anxiety or panic disor- der should not be prescribed bupropion. Most likely because of its potentiating effects on dopaminergic neurotransmission, bupropion can cause psychotic symptoms, including hallucina- tions, delusions, and catatonia, as well as delirium. Most nota- ble about bupropion is the absence of significant drug-induced orthostatic hypotension, weight gain, daytime drowsiness, and anticholinergic effects. Some persons, however, may experience

▲▲ 29.10 Bupropion Bupropion (Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban) is an antidepressant drug that inhibits the reuptake of norepi- nephrine and, possibly, dopamine. Most significantly, it does not act on the serotonin system like SSRI antidepressants. This results in a side effect profile characterized by a low risk of sexual dysfunction and sedation and with modest weight loss during acute and long-term treatment. No withdrawal syndrome has been linked to discontinuation of bupropion. Although increasingly used as first-line monotherapy, a significant per- centage of bupropion use occurs as add-on therapy to other antidepressants, usually SSRIs. Bupropion has been marketed under the name Zyban for use in smoking cessation regimens. Pharmacologic Actions Three formulations of bupropion are available: immediate release (taken three times daily), sustained release (taken twice daily), and extended release (taken once daily). The different versions of the drug contain the same active ingredient but differ in their pharmacokinetics and dosing. There have been reports of inconsistencies in bioequivalence between various branded and generic versions of bupropion. Any changes with this drug in tolerability or clinical efficacy in a patient who had been doing well should prompt an inquiry about whether these changes correspond to a switch to a new formulation. Immediate-release bupropion is well absorbed from the GI tract. Peak plasma concentrations of bupropion are usually reached within 2 hours of oral administration, and peak levels of the sustained-release version are seen after 3 hours. The mean half-life of the compound is 12 hours, ranging from 8 to 40 hours. Peak levels of extended-release bupropion occur 5 hours after ingestion. This provides a longer time to maximum plasma con- centration (t max ) but comparable peak and trough plasma concen- trations. The 24-hour exposure occurring after administration of the extended-release version of 300 mg once daily is equivalent to that provided by sustained release of 150 mg twice daily. Clini- cally, this permits the drug to be taken once a day in the morn- ing. Plasma levels are also reduced in the evening, making it less likely for some patients to experience treatment-related insomnia. The mechanism of action for the antidepressant effects of bupropion is presumed to involve the inhibition of dopamine and norepinephrine reuptake. Bupropion binds to the dopamine transporter in the brain. The effects of bupropion on smoking cessation may be related to its effects on dopamine reward path- ways or to inhibition of nicotinic acetylcholine receptors.

Therapeutic Indications Depression

Although overshadowed by the SSRIs as first-line treatment for major depression, the therapeutic efficacy of bupropion in depression is well established in both outpatient and inpatient settings. Observed rates of response and remission are compa- rable to those seen with the SSRIs. Bupropion has been found to prevent seasonal major depressive episodes in patients with a history of seasonal pattern or affective disorder.