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New antidepressant development, until fairly recently, was at best a random, and at worst a problematic and frustrating, process. Often, medications that were developed for one thing were discovered quite accidentally to have much more important therapeutic effects for a completely different disorder. It has been well described that some of the original antipsychotics were originally developed to assist in anesthesia, and some of the original new antidepressants were originally intended to be medications for tuberculosis or psychosis. New antidepressant development was done on a "chemical" basis; that is, guesses were made as to compounds that would be safe and effective based on chemical structures of established medications. This was very much a trial-and-error process, since very little was known about how these drugs worked and very little could be measured beyond actually giving them to a patient.
New antidepressant development always has been and always will be a partnership between efficacy (ie, whether the drug is effective) and safety (ie, whether the drug can be tolerated by a patient). There were very few ways of knowing the answers to those two questions about any given compound unless you tried it, a process not without its obvious risks. It should be noted that vagus nerve stimulation for depression clearly meets the two main FDA requirements of safety and efficacy.
Medications to treat depression; mild, severe, bipolar, or treatment-resistant, make the news most frequently, and deservedly so. Their progress and approval can potentially benefit almost 8 million Americans who suffer from some form of depression. Because there seems to be more frequency now of depression that is treatment-resistant, meaning most methods of treatment (medications, psychotherapy, electroconvulsive therapy, or a combination of more than one treatment) have failed for a patient, the approval of new antidepressants from companies like Merck, Lilly, and Pfizer, are more important than ever. This is because a new class of medication for treating depression has not been developed in over a decade.
New antidepressant development is somewhat more sophisticated now in that some drugs can be developed biologically. This means that instead of guessing and experimenting with various chemical structures, hoping to find something that works, we can look at what we do know about receptors and transmitters and try to design drugs around that. For example, since researchers have discovered that antipsychotic drugs tend to be more effective when they block both D2 and 5HT2A receptors, scientists can go to the laboratory and design compounds that block both of those kinds of receptors. One can only assume that as our technology improves in this regard, researchers can be more specific and more directed in developing new antidepressants. Once an actual mechanism of drug action is found, multiple drugs can be developed to influence that mechanism. This can be seen with the drugs that focus their activity on the serotonin transporter, such as selective serotonin reuptake inhibitors and the newer generation of new antidepressant drugs in the pipeline now.
The Office of Research and Development of the Pharmaceutical Manufacturers Association reports that it takes an average of 12 years for an experimental drug to travel from laboratory to approval as a new antidepressant. According to a report by the Congressional Office of Technology Assessment, it takes over $800 million on average to get one new antidepressant from the laboratory to the patient.
In November of 2003, Merck abandoned a 10-year study of a new antidepressant that had originally worked as an anti-emetic (anti-vomiting) medication for patients undergoing chemotherapy. Scientists at the company believed the medication they were using, aprepitant, might help patients with depression because it blocked a protein called Substance P they said was also linked to depression. Unfortunately, clinical studies proved otherwise, and the project was abandoned. Because Merck had invested so much potential in this treatment for depression, the ditching of it has weakened their pipeline of future new antidepressants waiting for FDA approval Although this is may be a financial blow to Merck, it is a far more severe blow to the many patients with severe and treatment-resistant depression who could have benefited if this long-term project had it been successful.
Meanwhile, on December 29th, 2003, Lilly announced that a new antidepressant was approved by the FDA for the treatment of bipolar disorder (manic depression), which millions of Americans experience. Because this disorder is so difficult to treat, the development and approval of this new medication has been incredibly important. Patients with bipolar disorder are afflicted with debilitating mood swings that range from longer episodes of severe depression to smaller episodes of intense euphoria (mania). The new antidepressant, called Symbyax, combines the active ingredients of Prozac® (which treats depression) and Zyprexa® (which treats manic episodes of bipolar disorder [and unrelated, schizophrenia]). Because patients with bipolar disorder have longer depressive episodes than manic episodes, the indication for Symbyax is for the treatment of depressive episodes. Unfortunately, because the drug is a combination of two drugs already prescribed by themselves, some physicians are choosing not to prescribe it to their patients with bipolar disorder because of the risk of side effects a patient may experience from taking the combination drug.
However, the introduction of new drugs is not uncomplicated. Dr. David Printz, director of the Bipolar Disorder Research Clinic at New York State Psychiatric Institute( Columbia University Medical Center) said that he did not intend to prescribe Symbax. "Medications have been down this road before and there's relatively little flexibility in the combination produced."
Moreover, Printz said neither Prozac nor Zyprexa would be near the top of his list for treating bipolar depression. Prozac stays in the body longer than some other antidepressants in its class, raising the risk that the patient will swing from depression to mania, he said.
Approval of any new antidepressant means that we'll be seeing more advertisements imploring us to "ask your doctor" about them. This is good news. It means there are studies happening right now, as we're sitting at the computer or in front of the TV or at the office. People we don't even know, are concerned about those who suffer from the disease of depression. And because of their efforts and the willingness of depression sufferers to test these new drugs, we can be sure that every effort is being taken on a continual basis to develop new antidepressants, and that is a comfort in itself.
Click here for more information on the new antidepressant Symbac.
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