Med Check

Shire Pharmaceuticals' mixed amphetamine salts–extended release product possesses “unique plasma time concentration and pharmacokinetic profiles,” says a citizen petition that the company filed with the FDA on October 12. The petition asks the FDA to require that drug companies seeking to market a generic version of Shire's Adderall XR must“ establish bioequivalence through a study producing identical or superimposable” profiles between the new generic and the brand-name product.

The petition notes that the “FDA has previously determined when reviewing [the original Adderall XR drug application] that this is the only way that is sufficiently predictive of desired attention-deficit/hyperactivity disorder clinical patient outcomes being substitutable for a clinical efficacy trial.”

Generally, the FDA requires only that supplemental applications for a generic version of an approved proprietary product show a“ similar”—not “superimposable” (implying identical)—pharmacokinetic profile. The FDA had no public comment on the petition at press time.

Solvay Pharmaceuticals gained approval to market fluvoxamine in Japan for the treatment of social anxiety disorder. Fluvoxamine was the first SSRI launched in the Japanese market in 1999. It was initially approved by Japan's Ministry of Health, Labour, and Welfare for the treatment of “depression and depressive state” and for “obsessive compulsive disorder.” This is the first drug in Japan to win approval for the treatment of social anxiety disorder.

Methylphenidate–extended release improves symptom control and compliance when children taking immediate-release formulations of methylphenidate (IR-MPH) are switched to the OROS formulation (OROS-MPH).

In a 21-day acute study, 101 youngsters aged 6 to 16 were switched from immediate-release methylphenidate to the OROS formulation. At the study's end, 88 percent of the parents/caregivers wanted their children to continue taking the study drug and participate in a 12-month extension study. Of those children, 56 (63 percent) completed the one-year trial.

The parent/caregiver global assessment of satisfaction with treatment increased from 49 percent to 69 percent over the year. Study investigator ratings of treatment as “adequate” rose from 49 percent to 71 percent over the year. Efficacy and satisfaction measures were more likely to be higher for patients aged 10 to 16 compared with those younger than 10. Both measures were also more likely to be achieved at daily doses above 36 mg compared with doses of 18 mg. Adverse events were uncommon and represented those known to be associated with stimulant therapy, such as insomnia.

Eur Child Adol Psychiatr 2005; 14:305-309

Clozapine therapy appears to be associated with an increased risk of death from cardiovascular disease, secondary to clozapine-associated medical disorders such as obesity, diabetes, hypertension, and hyperlipidemia. A retrospective review of medical records of 96 patients who had taken the drug over a 10-year period from January 1992 to December 2003 showed the Kaplan-Meier estimate for 10-year mortality from cardiovascular disease to be 9 percent.

Patients taking clozapine who were African American or Hispanic American were significantly more likely to die of cardiovascular disease (odds ratios 7.2 and 11.3, respectively) compared with Caucasian patients taking clozapine. In addition, an estimated 43 percent of the 96 patients developed diabetes mellitus over the 10-year period. Again, Hispanic Americans (odds ratio 4.3) and African Americans (odds ratio 11.5) were more likely than Caucasians to develop diabetes.

J Clin Psychiatry 2005; 66:1116-1121

Valproate does not appear to be effective at reducing aggression in children and adolescents with pervasive developmental disorders. A prospective, double-blind, placebo-controlled study with 30 children aged 6 to 20 tracked aggressive behaviors over eight weeks of valproate therapy. No statistically significant effect of treatment was seen on the primary outcome measure, the Aberrant Behavior Checklist-Community Scale, Irritability Subscale. Secondary measures also showed no significant difference between aggression in those taking valproate compared with those taking placebo. Both rash and increased appetite were statistically significantly higher in those on valproate and included one patient who discontinued the study due to a spreading skin rash that had initially appeared to improve. J Child Adol Psychopharmacol 2005; 15:682-692

Buprenorphine may be more effective than clonidine at reducing heroin and/or opiate drug dependence in adolescents. A study prospectively followed 36 adolescents who met DSM-IV criteria for opiate dependence. Patients were randomly assigned to receive buprenorphine plus behavioral therapy or clonidine plus behavioral therapy for 28 days in an outpatient setting.

Nearly three-quarters (71 percent) of the subjects on buprenorphine completed the trial, while only 39 percent of those on clonidine did. A significantly higher percentage of those taking buprenorphine (72 percent) tested negative for opiates through urine toxicology compared with those taking clonidine (39 percent). Subjects taking buprenorphine generally reported more positive effects of the medication than those who took clonidine.

At the end of the 28 days of therapy, 61 percent of the buprenorphine subjects opted to continue maintenance therapy including naltrexone, compared with 5 percent of the clonidine subjects.

Arch Gen Psychiatry 2005;62:1157-1164

Venlafaxine–extended release may be more effective than other antidepressants for patients who have depression and do not respond to adequate treatment with another antidepressant.

A randomized, open-label study compared nearly 3,100 patients who were referred to outpatient psychiatric care for treatment after failing to respond or tolerate at least four weeks of treatment with an antidepressant other than venlafaxine. A total of 1,632 patients were assigned to take venlafaxine-ER, and 1,465 patients took another antidepressant: paroxetine (21.3 percent), citalopram (20.1 percent), sertraline (19.1 percent), fluoxetine (17.0 percent), or mirtazapine (7.9 percent).

After 24 weeks, 59.3 percent of those taking venlafaxine-ER met criteria for remission (a score of 7 or less on the Hamilton Depression Rating Scale) compared with 51.5 percent of those taking all other antidepressants (a statistically significant difference).

Dep Anxiety 2005; 22:68-76