In Brief

Researchers say they're pursuing promising new medications for depression, schizophrenia, bipolar disorder and drug and alcohol abuse. Yet while acknowledging that progress, some psychologists and other researchers say that much of what's being offered as new medications are variations of existing treatments-and that big breakthroughs don't appear imminent.

"We haven't had a huge breakthrough in a long time," says Dan Egli, PhD, a psychologist with a private practice in Williamsport, Pa., who chaired an APA task force that developed prescriptive authority education guidelines. "We don't have the brain figured out, and we're in the infancy of discovery."

In particular, says Egli, patients need new medications that start to work more quickly, have fewer side effects and interactions with other drugs, and relieve more symptoms.

"We have a pipeline problem," adds Douglas Hoffman, PhD, a neuropsychopharmacology researcher who teaches in several clinical programs around the country. Instead of concentrating on developing new medications, says Hoffman, pharmaceutical companies are looking for ways to sell "old drugs in new bottles," mainly because of the enormous costs of drug development.

In Hoffman's view, pharmaceutical companies have more profit incentive to take medications that have already gone through all the development costs and clinical trials, slightly change the formula, and apply for the 17-year patent protection of a new drug.

Still, there is some promise. In the major categories of mental illness and substance abuse, researchers point to potential in the following areas:

  • Depression. Scientists with the National Institute of Mental Health recently found that small amounts of the anesthetic ketamine block a receptor on brain cells called NMDA, thereby boosting the activity of another receptor, AMPA, says Husseini Manji, MD, director of the institute's Mood and Anxiety Disorders Program. Both NMDA and AMPA are receptors for the neurotransmitter glutamate.

As a neurotransmitter, glutamate is believed to play a role in mood regulation, cognition and the ability to experience pleasure, Manji says.

In the research, some study participants who hadn't responded to pharmacological antidepressant treatments in the past reported relief of symptoms within hours, raising the possibility of developing medications that could quickly relieve symptoms of depression.

In addition, studies looking at inhibitors of an enzyme called protein kinase C in the brain suggest possibilities for rapid treatment of manic episodes for people with bipolar disorder, Manji says.

Meanwhile, based on MRI scans that found shrinkage in nerve pathways in patients with major depression or bipolar disorder, another new treatment possibility lies in developing medications that help nerve cells grow, Manji says.

  • Schizophrenia. Existing antipsychotic medications can relieve symptoms, such as delusions and hallucinations, but new medications are needed to improve patients' cognitive symptoms and other problems that impair their social functioning, says Nina Schooler, PhD, a professor of psychiatry and behavioral sciences at the State University of New York Downstate Center, who conducts clinical trials of medications and psychosocial treatments for schizophrenia. Recent research is geared toward finding agents that activate nicotinic receptors in the brain, with the hope of targeting the symptoms that current antipsychotic medications don't treat, such as flat affect and poverty of speech.

  • Alcohol dependence. One possible avenue for treatment for alcohol dependency is a time-release form of naltrexone, which might be able to reduce alcohol cravings, says Mark Willenbring, MD, of the National Institute on Alcohol Abuse and Alcoholism. Researchers who studied the anti-convulsant drug topiramate found that it reduced the amount of heavy drinking, possibly by dampening the stress-response reaction that triggers some to drink.

Because most people who develop alcohol dependence never seek treatment for a variety of reasons, including stigma, inconvenience and cost, Willenbring hopes that in the long-term, physicians will be able to prescribe medications for alcohol dependence, much like people experiencing depression can be prescribed antidepressants by their primary-care providers.

  • Opioid dependence. Approval from the Food and Drug Administration of buprenorphine for opiate dependence treatment, along with a waiver allowing physicians to prescribe it, has given many more patients access to effective, long-term medication assisted treatment, says Gregory Brigham, PhD, director of research at a substance abuse and mental health treatment center in Columbus, Ohio. One study has found that patients who were given a short-term buprenorphine taper were twice as likely to continue in treatment beyond detoxification, Brigham says. An opioid, buprenorphine is a "partial agonist" and does not produce the euphoria of heroin. The dose of buprenorphine given is gradually reduced, preventing the severe nausea and cramping of heroin withdrawal. Another promising innovation under study is an injectable form of naltrexone that blocks the effects of opioids.