Sustained-release bupropion, and

Hurt RD, Sachs DP, Glover ED, et al A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 337 1195—1202, 1997 Jorenby DE, Leischow SJ, Nides MA, et al A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Eng J Med 340 685— 691, 1999... 

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. 

Hurt RD, Sachs DP, Glover ED, et al. A comparison of sustained release bupropion and placebo for smoking cessation. N Engl J Med 1997 337 1195-1202. 

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. 

Depression Bupropion (immediate release) IR, Wellbutrin (sustained release) SR, and bupropion (extended release) XL are indicated for the treatment of depression. Smoking cessation (Zyban only) Indicated as an aid to smoking-cessation treatment. 

Reimherr FW, Cunningham LA, Batey SR, et al. A multicenter evaluation of the efficacy and safety of 150 and 300 mg/d sustained-release bupropion tablets versus placebo in depressed outpatients. Clin Thei 1998 20 505-516. 

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. 

Numerous pharmacotherapies have been proven to be effective for smoking cessation and should be offered in the absence of contraindications. These include sustained-release bupropion, nicotine gum, nicotine inhaler, nicotine nasal spray, and nicotine patch. 

A randomised, open-label, crossover study in 24 healthy subjects found no evidence of any signiflcant pharmacokinetic interaction between a single 300-mg dose of bupropion (sustained release preparation) and a single 800-mg dose of cimetidine. No special precautions would seem to be necessary on concurrent use. 

Combination studies The combination of immediate-release naltrexone 16, 32, or 48 mg/day-I-sustained-release bupropion 400 mg/day has been investigated in a randomized, controlled study for the treatment of obesity in 419 individuals, of whom 64 took naltrexone 16 mg/day, 63 took 32 mg/day, and 61 took 48 mg/day [211 "]. 

Nicotine replacement therapy in the form of transdermal nicotine preparations combined with sustained-release bupropion (51) has been successfully tried in some hard core nicotine addicts, after the above social and practical measurements have been taken. The combined therapy of transdermal nicotine and bupropion should last for at least 6 months, and in many cases much longer if the crave to smoke still exists. Sustained-release bupropion therapy alone resulted in a 23.1% tobacco use cessation at one year in a placebo-controlled trial (51). Combination therapy of bupropion and high dose transdermal nicotine has been successful for smoking cessation, but the physician should be certain that his or her patient is not prone to coronary spasm. In premenopausal women, nicotine has been identified as the most important risk factor for coronary spasm (52). 

Alcohol Health Res World 22 122-123, 1998 Solhkhah R, Finkel J, Hird S Possible risperidone-induced visual hallucinations. J Am Acad Child Adolesc Psychiatry 39 1074-1073, 2000 Solhkhah R, Wilens TE, Prince JB, et al Bupropion sustained release for substance abuse, ADHD, and mood disorders in adolescents (NR31), in New Research Absrracts, Annual Meeting of the American Psychiatric Associarion. Washington, DC, American Psychiatric Associarion, 2001... 

Briggs G, Freeman R, Yaffe S Drugs in Pregnancy and Lactation A Reference Guide to Maternal and Fetal Risk. Philadelphia, Lippincott, Williams Wilkins, 2002 Chengappa KN, Kambhampati R, Perkins K, et al Bupropion sustained release as a smoking cessation treatment in remitted depressed patients maintained on neatment with selective serotonin reuptake inhibitor antidepressants. J Clin Psychiatry 62 503—508, 2001... 

The STAR D study showed that one in three depressed patients who previously did not achieve remission with an antidepressant became symptom-free with the help of an additional medication (e.g., bupropion sustained release), and one in four achieved remission after switching to a different antidepressant (e.g., venlafaxine XR). 

Bupropion sustained release (SR) is an effective smoking-cessation treatment. It is contraindicated in patients with a seizure disorder, a current or prior diagnosis of bulimia or anorexia nervosa, and use of a monoamine oxidase inhibitor within the previous 14 days. It can be used in combination with NRT. 

The sustained-release (SR) form of bupropion is prescribed at a dose of 150 mg/ day for 3 days and then increased as tolerated to 150 mg twice a day. The XL form of bupropion is administered at a dose of 150mg/day for 3 days and then increased as tolerated to 300mg taken once daily. Bupropion should be taken for 12 weeks and can be used in conjunction with nicotine replacement. Patients should be advised to plan on total smoking cessation after the first week of treatment with bupropion. 

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. 

Bupropion is an aminoketone that exerts its therapeutic effect through the inhibition of norepinephrine and dopamine reuptake. Bupropion s receptor occupancy profile shows an absence of anticholinergic and antihista-minic effects (Cusack et ah, 1994). Bupropion is absorbed rapidly from the gastrointestinal tract, and peak blood levels are achieved within 2 hours for regular release and 3 hours for sustained-release preparations = 10 hours). Bupropion undergoes extensive first-pass metabolism in the liver, yielding three active metabolites hydrobupropion, threohydroxybu-propion, and erythrohydrobupropion. The half-lives of the active metabolites are approximately 20 + hours (Preskorn, 1993). 

Daviss, W.B., Bentivoglio, P., Racusin, R., Brown, K., Bostic, J., and Wiley, L. (2001) Bupropion sustained release in adolescents with comorbid attention deficit hyperactivity. / Am Acad Child Adolesc Psychiatry 40 307—314. 

Davidson (426) found that the risk of seizures with bupropion was higher at doses greater than the recommended maximum (i.e., 450 mg per day). The seizure risk may be as low as one per 1,000 patients with the sustained release formulation when the dose is kept less than 450 mg per day, and the patient has no preexisting seizure history and is not on any medication that also can lower seizure thresholds or interfere with the metabolism of bupropion. 

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. 

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. 

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