APA Annual Meeting Highlights New Research

Floyd R. Sallee, M.D., et al. (NR 563) evaluated the pharmacokinetics and safety of ziprasidone (Zeldox) for treating Tourette's syndrome (TS) in children and adolescents. In a single-dose, open-label study, children and adolescents (boys and girls; 7 to 17 years old) with moderate-to-severe TS or chronic motor or vocal tic disorder received oral ziprasidone (dosage according to body weight) after breakfast. These patients were supervised at an inpatient facility 32 hours after dosing. During this time, venous blood samples were taken and the serum was analyzed for ziprasidone.

Researchers concluded that single oral doses of ziprasidone (5 mg, 10 mg and 20 mg) showed linear pharmacokinetics and were well-tolerated in children and adolescents with TS. In fact, researchers also concluded that the rates of absorption and elimination of ziprasidone are not affected by body weight. This finding was supported by a linear regression analysis that compared data from a study involving adults who received a 40 mg dose of an identical ziprasidone formula to these data involving adolescents.

Eric A. Nofzinger, M.D., et al. tested the hypothesis about whether bupropion (Wellbutrin) sustained release (SR), which typically enhances rapid eye movement (REM) sleep, may also result in a reversal of anterior paralimbic functional deficits in depressed patients (NR 705).

In this study, during waking and REM sleep, 10 unipolar depressed patients had three nights of electroencephalogram sleep, brain magnetic resonance imaging and 18F-Fluordeoxyglucose ([18F]FDG) positron emission tomography studies. Identical evaluations were repeated after the 10-week, open-label treatment with bupropion SR (final total daily dose was 400 mg). State (waking versus REM sleep) by treatment (pre versus post) interactions were analyzed in the anterior paralimbic system. Of the 10 patients, five completed all the studies.

The findings showed that bupropion SR reverses anterior paralimbic functional deficits in depressed patients in this waking to REM sleep brain imaging probe. Further studies are needed to determine if this effect is specific to bupropion SR or if it applies to other effective antidepressants.

This study was designed by Frederick W. Reimherr, M.D., and colleagues to assess the effectiveness of bupropion SR in treating adults diagnosed with attention-deficit/hyperactivity disorder (NR 718). In an acute study followed by an open six-month stimulant extension, 60 subjects were selected using the Utah Criteria and DSM-IV criteria for ADHD. In a double-blind manner, 60% were assigned to bupropion SR and 40% to placebo.

The outcome measures used were Wender Reimherr Attentional Deficit Disorder Scale (WRADDS) and the physician-rated CGI. On the WRADDS (using a 40% decline to define responders), 41% responded to bupropion SR, while 16% responded to placebo. All measures favored bupropion SR, but due to the unequal assignment of patients, the results did not reach p<0.05 level of statistical significance.

James J. Hudziak, M.D., et al. conducted a study to determine the efficacy, tolerability and safety of bupropion SR in adolescents with ADHD (NR 737). In this open-label trial, 16 adolescents (14 male, ages 13 to 17) were screened with a semi-structured DSM-IV interview. Methylphenidate(Drug information on methylphenidate) (Ritalin) was discontinued one day prior to bupropion SR treatment. Dosage was increased from 150 mg once daily to twice daily after one week.

At the end of an eight-week treatment phase, patients were assessed using the Child Behavior Checklist, Teacher Report Form, Youth Self-Report, and Conners Self, Parent and Teacher Rating Scales. Based on all these tools, it was concluded that bupropion SR is an effective and well-tolerated treatment for adolescents with ADHD. In fact, the findings suggest that bupropion SR may be more effective than methylphenidate in treating some symptoms.

David A. Gorelick, M.D., noted that, although many pharmacological treatments for stimulant abuse have been evaluated, none of them have been consistently effective in controlled clinical trials (Symposium 23C). Some medications show promise, but have not been rigorously evaluated, including anticonvulsants such as phenytoin (Dilantin) and vigabatrin (Sabril), the combination of bupropion plus bromocriptine(Drug information on bromocriptine) (Parlodel), and the selective monoamine inhibitor selegiline(Drug information on selegiline) (Eldepryl). Some promising new approaches include compounds that bind to the presynaptic dopamine transporter, a major site of action for cocaine; antibodies that bind cocaine peripherally, thus preventing it from entering the brain; and the enzyme butyrylcholinesterase, which enhances cocaine metabolism. Buprenorphine(Drug information on buprenorphine) (Subutex), a partial µ-opiate agonist, has shown some promise in the treatment of patients who are abusing other drugs in addition to stimulants.

The smoking population is becoming smaller, but those who continue to smoke are often hard-core smokers who find it difficult to stop the habit, according to Alexander H. Glassman, M.D. (Symposium 48A). Thus, finding effective treatments for this group is a challenge. A few current treatments have been effective, such as nicotine(Drug information on nicotine) gum and numerous patch preparations, especially with behavioral support.

The most significant advance in smoking cessation treatments has been the use of non-nicotine preparations. The antidepressant bupropion has been proven to be effective in aiding smoking cessation. Combining available treatments also improves the smoker's chances of success.