It should be noted up-front that these drugs are meant for people who are obese — those with a BMI number 30 or greater. While doctors often prescribe drugs for conditions not specifically approved by the FDA (called “off-label” use), doctors are likely to be more conservative in prescribing these two drugs when they first become available because of their unfamiliarity with them.

Both drugs can also be prescribed to people who are overweight, with a BMI of 27 or more and at least one weight-related condition such as type 2 diabetes, high blood pressure, or high cholesterol.

Qsymia (pronounced kyoo-sim-EE-uh and manufactured by Vivus Pharmaceuticals) and Belviq (pronounced bel-VEEK and manufactured by Arena Pharmaceuticals) have been shown to be effective in their clinical trials to help people lose significant amounts of weight.

Qsymia appears to be the more effective weight loss medication. People taking Qsymia for up to one year had an average weight loss of nearly 9 percent over those taking an inactive placebo. Over 70 percent of people taking Qsymia lost at least 5 percent of their body weight (only 20 percent of patients taking an inactive placebo lost this much weight).

People taking Belviq had an average weight loss that was 3 to 3.7 percent greater than people taking placebo. After taking Belviq for one or two years, some 47 percent of people without diabetes lost at least 5% of their body weight (only 23 percent of patients taking an inactive placebo lost this much weight.)

Although likely to be expensive, both weight loss drugs will likely be approved by insurance companies for treatment of obesity or being overweight with other health conditions. Why? Because obesity is a serious chronic health problem affecting more than one-third of U.S. adults (35.7 percent), according to the U.S. Centers for Disease Control and Prevention. As such, it costs insurers a lot of money. In 2008, medical costs associated with obesity were estimated at $147 billion. Anything to bring those costs down is likely to become approved for payment by insurance companies.

How Do Qsymia and Belviq Work?

Qsymia combines two generic drugs in a new formulation. One half the drug is composed of the seizure and migraine medication called topiramate. Topiramate causes weight loss in several ways, including increasing feelings of fullness, making foods taste less appealing, and increasing calorie burning. The other half of Qsymia is the appetite-suppressant called phentermine. Phentermine is thought to suppress appetite by triggering release of a brain chemical that increases blood concentrations of the appetite-regulating hormone leptin.

Belviq, on the other hand, appears to work by turning on a specific chemical “switch” in the brain that increases levels of serotonin. It’s not clear exactly why this helps a person lose weight.

Who Can’t Take These Drugs?

As with all medications, certain people cannot take these medications.

• Pregnant or nursing women should not take either Belviq or Qsymia.
• Qsymia:
  • People with glaucoma
  • People who have been told they have an overactive thyroid
  • People taking a type of antidepressant called a MAOI
  • People allergic to phentermine or topiramate
• Belviq:
  People taking drugs linked to valvular heart disease, such as cabergoline (Dostinex)
  • People taking certain medicines for depression; migraine; the common cold; or mood, anxiety, psychotic, or thought disorders
  • Men with conditions that predispose them to erections lasting more than four hours. These conditions include sickle cell anemia, multiple myeloma, and leukemia
  • Men with a deformed penis

When Can I Get Them?

Qsymia will be available sometime after September 2012, while Belviq won’t be available until early-to-mid 2013.

As with any medication, talk to your doctor to see if this medication may be right for you. Tell your doctor if you are on any other medications, nutritional supplements (including vitamins), pregnant, nursing, or have any other health condition.

These are the top 25 psychiatric medications by number of U.S. prescriptions dispensed in 2011, according to IMS Health. I’ve also provided their 2009 and 2005 ranking (you can view the 2009 list here).

To put the percent changes below into perspective, the U.S. total population rose approximately 1.6 percent from 2009 to 2011. That suggests that anything above 1.6 percent change was driven by other factors — more people seeking treatment, more pharmaceutical advertising and marketing, or some other factor.

The biggest movers and shakers on the list were Celexa — moving up 15 spots to grab the second most-prescribed psychiatric drug in 2011 — and Wellbutrin XL, moving from 22 to 13.

Drugs used to treat attention deficit hyperactivity disorder (ADHD) — generic amphetamine salts and methylphenidate — enjoyed big gains as well.

Notes:

If no percentage change is listed, we did not track it in 2005.

NA – Rank not available for this year.

* – This is not a psychiatric medication, but is often prescribed for a mental health issue.

How This Data is Derived

Information in the National Prescription Audit (NPA) is derived from IMS Health’s Xponent service, one of the most complete, national-level prescription databases in the U.S. Xponent captures roughly 70% Market Share of all prescriptions in the U.S. IMS then uses a patented projection methodology from a stratified and geographically balanced sample to represent 100% Market Share coverage of U.S. prescription activity at retail, mail service, long-term care, and managed care outlets.

For decades, the dominant hypothesis of depression has been that low levels of monoamines in the brain cause this debilitating disorder.

In the ‘80s, the selective serotonin reuptake inhibitor (SSRI) fluoxetine (brand name: Prozac) heralded a new era of safer drugs which also target the monoamine system. Since then, various SSRIs and serotonin-norepinephrine reuptake inhibitors (or SNRIs) have been developed as new antidepressants. While these drugs aren’t more effective than older antidepressants, they are less toxic.

But SSRIs and SNRIs don’t work for everyone, so MAOIs and TCAs still are prescribed.

Two out of three patients with depression do not fully recover on an antidepressant medication according to findings from STAR*D, the largest clinical trial study of treatments for major depressive disorder, funded by the National Institute of Mental Health. (One-third of patients do have a remission of their depression symptoms.)

These results “are important because previously it was unclear just how effective (or ineffective) antidepressant medications are in patients seeking treatment in real-world settings,” said James Murrough, M.D., board-certified psychiatrist and a research fellow at the Mount Sinai School of Medicine Mood and Anxiety Disorders Program.

As Murrough explained, depression treatment can be thought of in thirds: “for one third of patients, symptoms remit; another third don’t have as good of an outcome, experiencing residual symptoms and waxing and waning course or chronic course and are at risk for relapse whether they’re on or off medication; and then a third don’t get much benefit at all.”

He added that around “10 to 20 percent have persistent clinically significant symptoms that aren’t decreased by current treatment — these are the patients that we are the most worried about.”

So there’s a real need to find treatments that work for these patients. Since the 1950s and 1980s breakthroughs, researchers haven’t discovered drugs that target chemical systems in the brain other than the monoamine system.

“We haven’t been able to find any new systems, because we don’t understand the underlying biology of depression,” Murrough said.

But researchers are studying other mechanisms of depression and various drugs have recently been approved to treat depression. Below, you’ll learn about these drugs along with several chemical systems research is exploring.

Recently Approved Drugs for Depression

Recently approved drugs for depression are generally “me-too” drugs. A “me-too drug is a drug whose mechanism of action (what it does at the molecular level in the brain) is not meaningfully different than its predecessor,” Dr. Murrough said.

Prime examples of me-too drugs are desvenlafaxine (Pristiq), an SNRI, and escitalopram (Lexapro), an SSRI, he said. Pristiq is simply Effexor’s main metabolite. Lexapro is essentially a close relative derivative of citalopram (Celexa). Interestingly, sales still skyrocketed when Lexapro came out.

As Murrough said, there is value in some me-too drugs. Generally, all drugs within the classes SSRIs and SNRIs are me-too drugs. But the side effect profiles for each drug have slight differences, which can help patients.

For instance, Prozac tends to be more activating, so a doctor may prescribe it for patients with low energy, Murrough said. In contrast, paroxetine (Paxil) makes people more tired, so it’s prescribed to patients who have trouble sleeping, he said.

The drug Oleptro was approved this year for depression. It doesn’t target new mechanisms, and it isn’t even a me-too drug, Murrough said. It’s a reformulation of trazodone, an atypical antidepressant that’s been used as a sleeping aid by psychiatrists and other doctors. Because it’s so sedating, its earlier form would just put patients to sleep. “It is unclear if the new formulation will offer any benefit for patients over the original,” Murrough said.

These recently approved medicines “characterize the state of drugs in psychiatry,” Murrough said, and speak to “what’s wrong with antidepressant drug development today.” Novel treatments just aren’t on the market.

Augmentation of Depression Drugs

Recently, the biggest development in depression treatment has been the use of augmenting agents, said David Marks, M.D., assistant professor at the Department of Psychiatry & Behavioral Sciences at the Duke University Medical Center.

Specifically, some research has found that adding atypical antipsychotic drugs, like aripiprazole (Abilify) and quetiapine (Seroquel), to an antidepressant can boost its effectiveness.

Atypical antipsychotics are used to treat schizophrenia and bipolar disorder. “Abilify has three strong studies that show how well it works in patients that have partially responded to antidepressants,” Marks said. According to Murrough, augmentation has become a common strategy in depression treatment.

The Glutamate System and Depression

Researchers have looked at the role of the glutamate system in depression. Glutamate is abundant in the brain and is one of the most common neurotransmitters. It’s involved in memory, learning and cognition.

Some research has implicated the dysfunction of the glutamate system in medical conditions, such as Huntington’s chorea and epilepsy, and psychological disorders, such as schizophrenia and anxiety disorders.

Recent research suggests that drugs targeting a specific type of glutamate receptor in the brain — called the NMDA receptor — may have antidepressant effects.

Studies have explored ketamine, an NMDA antagonist, in treating treatment-resistant depression and acute suicidal ideation. Ketamine has a long history in analgesia and anesthesiology.

Currently, when a person is at imminent risk for attempting suicide or has attempted suicide, they’re admitted to a psychiatric hospital and closely monitored. But, as Murrough explained, medically, there’s nothing doctors can do to help with suicidal ideation or intense depressed mood. Antidepressants typically four to six weeks to work.

Ketamine appears to have fast antidepressant effects — within hours or a day. Thus, it may help protect patients from suicidal thinking or acute dysphoria when they’re in the hospital. Unfortunately, its effects only last seven to 10 days.

This research is “highly experimental, and probably less than 100 patients in the country have participated in controlled depression studies of ketamine,” Murrough said. The patients in these studies typically have treatment-resistant depression: They haven’t responded to several antidepressants and have moderate to severe symptoms of depression.

They’re admitted to the hospital and receive ketamine intravenously from an anesthesiologist, while their vital signs are closely monitored.

Ketamine is a drug of abuse, known by such street names as “Special K.” It induces trance-like or hallucination states. It also produces mild to moderate cognitive side effects, like other anesthetics. People report feeling “out of it,” intoxicated and disconnected in general.

These side effects actually “introduce a potential bias to the study design” because participants know they’re getting the treatment (when saline is given in the placebo condition), Murrough said.

To eliminate this bias, Murrough and his team are conducting the first-ever study to compare ketamine to a different anesthetic — the benzodiazepine midazolam (Versed) — which has similar transient effects as ketamine, he said. The study is currently recruiting participants.

Murrough cautioned that ketamine isn’t meant to be a treatment administrated at your doctor’s office. In a recent article in the journal Nature Medicine, he said ketamine treatment may be “akin to electroconvulsive shock treatment.”

Studying ketamine may reveal mechanisms underlying depression and help to find drugs that can be prescribed as antidepressants to a wider patient population.

Pharmaceutical companies have started exploring other NMDA receptor antagonists for treatment-resistant depression. For instance, in July 2010, the pharmaceutical company Evotec Neurosciences began testing a compound in a Phase II study, which evaluates the safety and efficacy of a drug.

The reality is that it is possible to safely discontinue any medication, including psychiatric ones.

Stop your medication for the right reasons.

“Timing is everything,” according to Dr. Michael D. Banov, medical director of Northwest Behavioral Medicine and Research Center in Atlanta, and author of the book Taking Antidepressants: Your Comprehensive Guide to Starting, Staying On, and Safely Quitting. Just because someone wants to stop taking their medicine doesn’t mean they’re actually ready, he said.

There are many reasons individuals decide to stop taking medicine. For instance, they might feel better and think they don’t need treatment anymore. Their family might be pressuring them to stop, they read something about a drug that scares them, or they’re afraid that the drug will affect their personality, Banov said. Sometimes people want to stop after making major changes in their lives, such as getting a divorce, moving or changing jobs. But, according to Dr. Banov, this is actually “the worst time” to stop.

Also, some mental health conditions require taking medicine indefinitely. Ultimately, how long a person takes a psychotropic drug depends on his or her individual illness, its responses to treatment and their personal situation, according to Dr. Ross J. Baldessarini, professor of psychiatry and neuroscience at Harvard Medical School and director of the psychopharmacology program at the McLean Division of Massachusetts General Hospital. For instance, some individuals struggling with depression may take an antidepressant for nine months to a year and get better; others may need two to five years; and still others, may be “so genetically loaded for depression, that they may need to stay on them indefinitely,” Dr. Banov said.

Don’t stop your medication abruptly.

“Stopping abruptly is especially dangerous,” Baldessarini said.

Depending on the medicine, stopping abruptly or “cold turkey” can cause a variety of distressing reactions, ranging from mild to moderate early discontinuation symptoms with antidepressants, rapid return of the illness being treated, or even potentially life-threatening seizures with a high dose of benzodiazepines.

Consult your doctor before stopping any medicine, and never attempt to do it on your own.

Consider if you’ve received a thorough assessment.

A comprehensive assessment is required prior to stopping medicine. Among other indicators, your doctor needs to consider “your current clinical condition and life circumstances, your past clinical history, reasons to consider stopping versus continuing treatment, side effects and the presence of stressors and supports, as well as the dose and the length of time you’ve been taking a medicine,” Baldessarini said. You and your doctor should talk about these indicators along with how he or she plans to discontinue the drug.

There are no firm, established rules for discontinuing psychiatric medicines. However, there is one major rule of thumb: Reduce the dosage gradually whenever possible. “We still do not know for sure how long is long enough to reduce doses safely,” Baldessarini said. Still, the “slower the dose-reduction, the greater the chances of preventing return of symptoms of the illness for which treatment was started. Very slow discontinuation is especially important when a person has been taking high doses of a medicine over a long time,” he said.

Discontinuing multiple drugs is like peeling an onion, Baldessarini said. He usually leaves the most essential medicine for last. He then reduces doses of one or more optional or supplemental drugs slowly and gradually. Stopping all medicines at once is not safe.

Dealing with small final doses is tricky when dropping from a low dose to nothing. Sometimes doctors decrease the dose to one pill a day or one every two days or split the pill in half, he said. Pill-splitting can be very helpful. You can find pill splitters at your pharmacy.

Don’t expect stopping medication to be a quick process.

Gradually and safely discontinuing a drug doesn’t happen in a few days. Some drugs, including antidepressants, don’t show benefits for several weeks when they’re started; it seems best to avoid discontinuing faster than over several weeks, Banov said.

If you’ve been taking a medicine for years, Banov recommended reducing the dose, stepwise, over at least six weeks. While this may be a conservative practice, he said that “sometimes, you might not detect a change for a few weeks, but later, problems may arise.” Discontinuation symptoms usually occur within days of stopping a medicine, but relapse of the illness being treated can be delayed for weeks after initially feeling well.

In bipolar disorder, Baldessarini and his research team found years ago that the rate of discontinuing ongoing treatment determines the risk and timing of relapse, he said. Initially, their research found that risk for relapse after discontinuing lithium was reduced by one half or more when slow dose-reduction over several weeks was compared to abrupt discontinuation (Baldessarini et al., 2006). Gradual discontinuation of antipsychotic drugs also resulted in lower risk of relapse in schizophrenia (Viguera et al., 1997). In a recent study, he and his colleagues found that stopping an antidepressant abruptly or only over several days resulted in a much greater risk for depression or panic than gradual discontinuation over two weeks or more (Baldessarini et al., 2010).

If you’re switching from one medicine to another, you can be more aggressive than when discontinuing altogether, Banov said. Usually you switch drugs because of ineffectiveness or side effects, and commonly a new drug is introduced as the previous one is gradually removed. This way, there’s little concern about either withdrawal symptoms or relapse, assuming that both drugs have similar effects or belong to the same class, he said. If you’re switching classes, it’s usual to “cross-taper” the medicines: You take both drugs for a while, and then, the doctor reduces the dose of one and ups the dose of the other.

Your doctor may prescribe another medication.

If you’re taking a relatively short-acting antidepressant, such as paroxetine (Paxil) or venlafaxine (Effexor), and you experience bothersome symptoms, “your doctor may prescribe a long-acting antidepressant such as Prozac for a time, and then gradually discontinue the long-acting drug to limit risk of discomfort of withdrawing,” Baldessarini said. “The principal byproduct of the metabolism of fluoxetine has an extraordinarily long half-life or duration of action,” he said, and can take weeks to leave your system.

This method is not well established for discontinuing other classes of psychotropic drugs, including antipsychotics and mood stabilizers, so the best option usually is to “discontinue such drugs gradually, with close clinical monitoring by your doctor,” Dr. Baldessarini said.

There are many benefits to this type of drug distribution: Disabled or homebound patients can have their medications conveniently delivered to their homes. Shoppers enjoy a certain level of discretion and anonymity. The selection of products is vast. Medications can be easily researched and compared, and computers can quickly catch potentially dangerous interactions.

But there are also drawbacks to buying medications online. A study released July 9th by the National Center on Addiction and Substance Abuse at Columbia University found that most websites selling prescription opioids, stimulants, and depressants do not require a legal prescription. This rise in illegitimate drug activity also has been linked to the growing abuse of prescription drugs especially among adolescents. There are hundreds of sites devoted to selling powerful drugs such as Oxycontin, Vicodin, methadone and Xanax without a prescription.

According to a 2005 study completed by Christopher Littlejohn and his associates, online merchants can be categorized into four basic types: legitimate, subscription, lifestyle and no-prescription.

Legitimate online pharmacies operate similar to traditional brick-and-mortar pharmacies. Customers must have a prescription from a licensed medical practitioner, and in general these websites do not offer the types of controlled prescription drugs that are most commonly obtained illegally and abused.

Users of subscription pharmacies are granted access to a full range of drugs without a prescription once they sign up for a program and pay a membership fee. These subscription websites often are maintained in countries where prescription regulation is more lax than it is in the United States.

Lifestyle pharmacies ask customers to fill out a medical questionnaire instead of a prescription. They commonly provide more elective or luxury drugs that treat conditions such as alopecia, obesity, and impotence.

No-prescription pharmacies are just that — sites that are willing to mail controlled drugs to online customers without a prescription.

Littlejohn’s study also contended that the people who most commonly ordered drugs illegally from these websites were literate, credit card owning individuals with Internet access. These three factors also lead to the inference that the abusers of online pharmacies are of a relatively high socioeconomic status.

Unlike conventional pharmacies, there is little to no consumer protection over the Internet. Products can be advertised with false claims and the sale of unapproved trial drugs goes unchecked. The administrators of illegal websites often remain anonymous and can quickly disable and create new sites that make it difficult for any regulatory agency to keep track of their activities. Operations are also commonly run outside of the U.S. making law enforcement officials scramble to put together international cooperation efforts.

This lack of effective online pharmacy regulation can lead to disastrous consequences. Francine Haight of La Mesa, Calif. lost her son Ryan to an overdose of the generic form of Vicodin, which he ordered without her permission online with a debit card. “The Internet made it easy for the drug dealers to sneak into your living room,” she said.

The sale of online drugs has led to drug and substance abuse, death related to drug interactions, incorrect dosage or administration, and impure drugs. Illegal prescriptions can end up in the hands of children or others who are incapable of using them responsibly. According to the Drug Enforcement Agency, 85 percent of Internet drug sales are controlled drugs while only 11 percent of those same drugs are being sold at traditional pharmacies.

These statistics display the obvious potential for drug abuse and need for greater online pharmaceutical quality control. The Food and Drug Administration has vowed to increase public outreach and awareness, expand enforcement, and develop tighter bonds of international cooperation. In April the “Ryan Haight Online Pharmacy Consumer Protection Act” was approved by the Senate and is currently being reviewed in House committee meetings. If passed, the legislation would require online pharmacies to be properly certified and for doctors to meet in person with patients before giving out a prescription for a controlled drug. Some state governments have already passed laws that regulate the online drug trade but many advocates are pushing for stricter federal regulation. Some search engine companies have begun to fight back against online sellers by employing a program called “Pharmacy Checker.” The device filters out unlawful advertisers and forces them to provide verification.

References:

Eckholm, Erik. (2008, July 9). Abuses Found in Online Sales of Medication. New York Times, Retrieved July 10th, 2008.

Henney, Jane. (2001). Cyberpharmacies and the role of the US Food and Drug Administration. Journal of Medical Internet Research, 3(1), Retrieved July 10, 2008 from the PubMed database.

Littlejohn,C., Baldacchino, A., Schifano, F., & Deluca, P. (2005). Internet Pharmacies And Online Prescription Drug Sales: a cross-sectional study. Drugs: education prevention and policy, 12, 75-80. Retrieved July 10th 2008, from the Academic Search Premier database.

For more information about Cognitive Behavioral Therapy Dr. Allison Conner can be contacted through her website or at 212-258-2577.

Drugs for Depression

Although the Phase III pipeline of drugs for the treatment of depression is deep, including several compounds with new mechanisms of actions, none is expected to be approved in 2009. Pristiq (desvenlafaxine, the major metabolite of venlafaxine), Wyeth’s follow- up to Effexor (venlafaxine), was approved for depression in adults by the FDA in March and could gain ground in the clinic next year.

AstraZeneca submitted an sNDA in May for Seroquel XR for the treatment of generalized anxiety disorder, which was the first submission of an atypical antipsychotic medication for this indication. In February, the company submitted an sNDA for Seroquel XR for the treatment of depression.

In September, LaboPharm submitted an NDA for DDS-04A for the treatment of depression. This compound is the well-known antidepressant trazodone a 5-HT2 receptor antagonist, formulated for once-daily administration. The NDA was based on data from five pharmacokinetic studies and a North American study that included more than 400 patients.

New drugs on the horizon for late 2009/2010 U.S. approval include Valdoxan (agomelatine), which is in development by Novartis and Servier, and Saredutant (SR 48968), a Sanofi-Aventis compound. Valdoxan, which has a novel mechanism of action—melatonin (MT1 and MT2) receptor agonist and 5-HT2C receptor antagonist—and an attractive side-effects profile (i.e., no sexual dysfunction or weight gain), is anticipated.

Novartis is currently conducting four large-scale Phase III trials in the United States, all of which are scheduled to complete in 2009. A U.S. NDA might be submitted in 2009. Saredutant, a neurokinin-2 (NK2) receptor blocker, is well tolerated but has produced mixed results in long-term Phase III trials. Sanofi-Aventis will decide on regulatory submissions based on the results of two ongoing trials assessing saredutant in combination with escitalopram and paroxetine, which are scheduled for completion in the first half of 2009.

Drugs for Bipolar Disorder

Longer-acting injectable and oral formulations of approved atypical antipsychotic medications are the focus of late-stage drug development for bipolar disorder.

Janssen is currently marketing Risperdal Consta, a long-acting, injectable formulation of risperidone for the treatment of schizophrenia. The drug was developed by combining risperidone with the Alkermes’ Medisorb delivery system to maintain a therapeutic drug concentration when administered once every two weeks.

In 2008, Janssen submitted two supplemental New Drug Applications (sNDA) for bipolar indications. An sNDA submitted in April seeks approval for adjunctive maintenance treatment to delay the occurrence of mood episodes in patients with frequently relapsing bipolar disorder. A July sNDA submission looks to indicate Risperdal Consta as monotherapy for the maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes in adults.

Another long-acting atypical antipsychotic, AstraZeneca’s Seroquel XR (quetiapine extended-release tablets), was approved in October 2008 for acute treatment of depressive episodes associated with bipolar disorder and manic and mixed episodes associated with bipolar I disorder, as well as maintenance treatment of bipolar I disorder as adjunctive therapy to lithium or divalproex.

Drugs for Schizophrenia

Late-stage drug development for schizophrenia includes a new injectable formulation of an approved atypical antipsychotic and two new drug candidates with atypical antipsychotic mechanisms of action.

Janssen developed an injectable formulation of its antipsychotic, Invega (paliperidone extended-release) by combining it with Elan’s NanoCrystal technology to enable administration by intramuscular injection on a once-monthly schedule. In October 2007, the company submitted an NDA for the treatment of schizophrenia and prevention of symptom recurrence. In August 2008, the FDA requested additional data before approving the NDA, but did not require any additional studies. Janssen is currently evaluating the FDA response and will work with the agency to resolve outstanding questions. Potential advantages of Invega over Risperdal Consta include reduced dosing frequency (once monthly vs. once every two weeks) and no need for refrigeration.

In September, Lundbeck’s NDA submission seeking approval for Serdolect (sertindole) for the treatment of schizophrenia was accepted for review by the FDA. Serdolect is a new-generation atypical antipsychotic. It exhibits a higher level of limbic-selective increased dopaminergic activity than other atypical agents, which may contribute to an attractive extrapyramidal side-effect profile. Serdolect has been launched in Europe, South and Central America, Asia and the Middle East and has been administered to more than 70,000 patients.

Schering-Plough’s NDA submission for its new 5-HT2A- and D2 receptor antagonist Saphris (asenapine) was accepted by the FDA in November 2007 and is undergoing a standard review. Saphris is a fast-dissolving, sublingual tablet acquired by Schering-Plough when it combined with Organon BioSciences earlier in November 2007. The NDA seeks approval for schizophrenia and acute or mixed episodes associated with bipolar I disorder. In November 2008, top-line Phase III clinical trial results demonstrated the efficacy of Saphris in long-term schizophrenia relapse prevention. Approval and launch in 2009 are possible.

Drugs for Attention Deficit Disorder (ADHD)

A new drug with a nonstimulant mechanism of action may be approved in 2009 for the treatment of attention-deficit/hyperactivity disorder (ADHD). Intuniv (guanfacine extended-release tablets) is a selective alpha2A-agonist in development by Shire for the once-daily treatment of ADHD. The company submitted an NDA for monotherapy for the treatment of ADHD symptoms throughout the day in children aged 6 to 17 years and received an approvable letter from the FDA in June 2007. The FDA requested additional information, and the company has been conducting additional clinical work related to the drug’s label.

Immediate-release guanfacine, a medication used to treat high blood pressure, also is used off-label in ADHD.

Anticipated advantages of Intuniv over guanfacine include FDA approval specifically for ADHD and maintenance of blood concentration in the therapeutic range, which is problematic with immediate-release formulations. Another potential advantage: Intuniv is not a controlled substance, and is not associated with any known mechanisms for potential abuse or dependence.

An estimated 30% of children with ADHD cannot tolerate stimulant drugs or do not benefit from currently available ADHD medications. Intuniv also might have applications in combination with stimulant drugs to reduce aggression and insomnia associated with stimulants and adult patients. Shire hopes to gain FDA approval and launch Intuniv in the second half of 2009.