“Because children and teens, who are developing social, emotional and learning skills, can suffer devastating effects from GAD, appropriate and effective counseling and medical treatment of the illness is essential,” says co-author Arifulla Khan, M.D., medical director of the Northwest Clinical Research Center (NWCRC) in Bellevue, WA and adjunct associate professor of psychiatry at Duke University School of Medicine. “It is welcome news that our study revealed that one medication, venlafaxine, which is effective in helping adults with depression and GAD achieve remission -- virtual elimination -- of symptoms, also is significantly effective in reducing the symptoms of GAD in children and teens.”
About 2.8 percent of U.S. adults and five percent of U.S. children suffer from GAD, excessive anxiety and worry that are difficult to control. These are the children who miss school because of headaches, stomachaches, vomiting, etc. Further, they are constantly going to see the school nurse, cannot function well in school, are shy, and withdrawn. GAD differs from normal feelings of nervousness because the symptoms are chronic and include alarming reactions that can occur for no apparent reason. If left untreated, children with GAD may have social difficulties, school problems, low self-esteem and increased risk for other serious conditions including substance abuse, depression, and suicide.
In the study of children and adolescents aged six to 17 years with GAD, the venlafaxine extended release formulation produced a significant decrease in GAD symptoms, averaging 18.6 points, on a standard GAD measurement scale, compared to an average 12.4 point decrease among those receiving a placebo (p <0.001). The scale used was based on nine delineated items of the Columbia KIDDIE Schedule of Affective Disorders and Schizophrenia Sub-section GAD (C KIDDIE-SADS GAD). At the study beginning, all the participants’ scores averaged about 40.4.
Also, 64 percent of the venlafaxine group responded to the therapy, compared to 40 percent of those on placebo (p =0.004), as measured by a rating of “very much improved” or “much improved” on the standard Clinical Global Impression-Improvement (CGI-I) scale. To qualify for study participation, pediatric patients were required to have a CGI Severity of Illness (CGI-S) rating of at least “moderately ill.”
During the screening phase of the study, Khan and his co-investigators provided placebo for four to 10 days to 156 pediatric patients with GAD, 83 aged six to 11 years and 73 aged 12 to 17 years. Then, the researchers randomly assigned the children and teens to receive either venlafaxine or a placebo for up to eight weeks, followed by an optional one or more weeks in which the doses of drug or placebo were gradually reduced. All of the participants’ parents or guardians consented to the children’s enrollment, and the children and teens gave their assent. However, neither the investigators, the parents nor the children knew whether a participant received venlafaxine or a placebo during the double-blind phase of the study.
During the double-blind phase, 77 children and teens received 37.5 to 225 milligrams (mg) of the extended release formulation of venlafaxine once a day, with doses adjusted for their body weight. The participants were not allowed to take any psychopharmacologic or herbal drugs during the study. However, they could take non-psychopharmacologic drugs with psychotropic effects if taken for one or more months before study start. The participants also could continue undergoing psychotherapy if it was well established before study start.
In addition to the nine delineated items of the C-KIDDIE-SADS GAD and CGI-I rating scales, the investigators also used the entire C-KIDDIE-SADS GAD, the CGI-S, the Pediatric Anxiety Rating Scale (PARS), the Hamilton Rating Scale for Anxiety (HAM-A) and the Screen for Child Anxiety Related Emotional Disorders (SCARED) to evaluate treatment.
The participants tolerated venlafaxine well, Khan notes, and the adverse events observed were similar to those observed in studies among adults treated with venlafaxine for depression or GAD. Only two of the 77 -- three percent -- of those on venlafaxine discontinued the study because of adverse events, while seven of the 79 -- nine percent -- in the placebo group withdrew. The most common adverse events included weakness (asthenia), aversion to food (anorexia), weight loss, excessive muscular activity (hyperkinesias), sleepiness (somnolence) and profuse nosebleeds (epistaxis). Overall, 19 of the venlafaxine group and 25 of the placebo group did not complete the study.
To determine if a child or teen met the diagnostic criteria for GAD required to enroll in the study, investigators evaluated all prospective participants using the C-KIDDIE-SADS GAD and the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria. The anxiety symptoms had to be present for at least six months and the participants could not be depressed as measured by the Childhood Depression Rating Scale-Revised (CDRS-R). Moreover, no concurrent psychiatric disorders were allowed except simple phobia, as confirmed by KIDDIE-SADS-PL.
Khan’s co-authors are Nadia R. Kunz, Pharm.D., Elizabeth Nicolacopoulos, B.S.N., Lisa Jenkins, Ph.D., Paul P. Yeung, M.D., M.PH., of Wyeth Research, Collegeville, Pa., which supported the study.
About Venlafaxine and GAD
Venlafaxine extended-release, a once-daily formulation of venlafaxine, is approved in 33 countries worldwide to treat adults with depression or GAD. Although GAD is a chronic disorder, symptoms can fluctuate and often worsen during stressful events. The anxiety and worry are associated with three or more of the following symptoms, some of which must be present for more days than not for six months: restlessness or feeling keyed up or on edge; fatigue; difficulty concentrating or mind going blank; irritability; muscle tension; or sleep disturbances, such as difficulty falling or staying asleep or restless, unsatisfying sleep. Clinically, they present as children given to superficial illnesses; miss school for headaches or stomachaches. These are the kids constantly going to school nurse for minor symptoms, are shy, withdrawn and function well below their capacity.
Children and teens with GAD often have problems with peers, schoolwork and participating in family routines and events. They often seek reassurance for their worries and may try to avoid situations that may trigger or worsen their anxiety.
Venlafaxine is a structurally novel antidepressant chemically unrelated to any other available antidepressant. Venlafaxine inhibits noradrenaline and serotonin, two brain chemicals involved in depression. Serotonin (5-hydroxytryptamine or 5-HT) enhances mood, thus affecting, for example, impulse, appetite and feelings of aggression. Norepinephrine affects motivation.
About NWCRC
NWCRC is a medical research facility dedicated to conducting the highest quality, patient-oriented clinical research. NWCRC specializes in clinical studies for patients with psychiatric indications such as depression, bipolar mood disorder, psychotic disorders, generalized anxiety and panic attacks, as well as with diabetes or elevated cholesterol.
Arif Khan, MD
Christine Khan, Psychiatric Nurse
1900 116th Avenue NE
Bellevue, WA 98004
Phone: (425) 453-0404
Fax: (425) 453-1033
akhan@nwcrc.net