Over the last several years the U.S. Food and Drug Administration (FDA) has attempted to tighten its scrutiny of the labeling it approves for psychotropic medications, which has led to a wave of new approvals for drugs already on the market with additional and more specific indications. Recently venlafaxine and paroxetine gained FDA approval for additional indications, and methylphenidate was approved in a new extended-release form.

The approval of new indications for previously approved medications is part of the FDA’s Division of Neuropharmacological Drug Products’ stated efforts to "adequately inform clinicians through labeling as to the specific appropriate use of proposed drug treatments." Pharmaceutical companies are required to show efficacy of the previously approved medication by submitting as few as two clinical trials of the drug in the specific diagnostic population (the regulation simply calls for "more than one clinical trial").

For supplemental drug applications, the FDA generally bases decisions on the safety of the drug in its prior uses on the market. The pharmaceutical company is required, however, to address any safety concerns unique to the drug’s use with the new category of patients being proposed for approval.

The extended release formulation of venlafaxine (Effexor XR) was originally approved for the treatment of depression in 1997. In 1999 it received FDA approval for short-term use in generalized anxiety disorder (GAD) for up to eight weeks. Last month, FDA gave approval for the drug’s long-term use in treating GAD (up to six months). Clinical trials are currently underway for the use of venlafaxine in premenstrual dysphoric disorder as well.

A powerful inhibitor of the reuptake of both serotonin and norepinephrine, venlafaxine can have significant adverse events. Side effects reported with incidence greater than 10 percent and/or twice that of placebo, include nausea, anorexia, dry mouth, insomnia, sexual dysfunction, constipation, and sweating. In addition, treatment with venlafaxine has been associated with sustained elevations of blood pressure. The FDA’s approved labeling recommends regular blood pressure monitoring while on venlafaxine.

Paroxetine (Paxil) is currently approved for the treatment of depression, panic disorder, obsessive-compulsive disorder, and social anxiety disorder. The FDA is assessing whether to add the indication of generalized anxiety disorder. Last month the drug’s manufacturer, SmithKline Beecham, submitted another supplemental new drug application to have paroxetine approved for post-traumatic stress disorder (PTSD).

According to the application, PTSD is commonly comorbid with other psychiatric conditions. The National Comorbidity Survey indicates that nearly 50 percent of patients with PTSD also meet the criteria for depression, and 28 percent also have social anxiety disorder. In addition, PTSD patients are two to three times more likely than the general population to have a substance abuse disorder.

Significant side effects observed with paroxetine include asthenia, sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, and sexual dysfunction.

The FDA approved last month an extended release formulation of methylphenidate (Concerta) for the treatment of attention deficit/hyperactivity disorder (ADHD) in patients aged six and older. The new formulation will allow once-daily dosing, eliminating the need for children to take the medication during school hours.

The most common side effects noted in clinical trials of the extended-release formulation of methylphenidate were headache, upper respiratory tract infection, stomach ache, vomiting, anorexia, insomnia, increased cough, sore throat, and dizziness.

The new formulation should improve compliance for children who experienced difficulty taking the controlled substance through a school nurse and thus sometimes skipped doses so they would not have to go to the nurse’s office.