As we have noted in several posts, the depressive pole of bipolar disorder is often the more challenging to treat. In most cases, conventional antidepressants may require three to four weeks or even longer to become effective. In addition, most if not all of the most effective antidepressants may push a person with bipolar disorder from a depressive cycle into a mania.

For these reasons and others, researchers are constantly on the lookout for new treatments for depression that provide faster relief and have a more neutral side effect profile. Some medications that show promise are already in use in other medical applications. Back in August of this year, we wrote about one of these promising medications, Ketamine – originally used as an anesthetic.

Another medication that has shown some promise is scopolamine, which traditionally has been used to prevent nausea and vomiting caused by motion sickness.

In the spring of this year, researchers from the National Institutes of Health published a report in Biological Psychiatry entitled “Replication of scopolamine’s antidepressant efficacy in major depressive disorder: a randomized, placebo-controlled clinical trial.” These same researchers previously reported that “intravenous (IV) scopolamine administration produced rapid and robust antidepressant effects in a sample consisting of both unipolar and bipolar depressives.”

The new study focused exclusively on treating unipolar depression. Through this study, the researchers concluded: “These results replicate previous finding that scopolamine produces a rapid and robust antidepressant response.” Scopolamine temporarily blocks the muscarinic cholinergic receptor, a property it shares with the older tricyclic antidepressants.

From Elsevier’s press release entitled “A New Generation of Rapid-Acting Antidepressants?”

“Scopolamine was found to reduce symptoms of depression within three days of the first administration. In fact, participants reported that they experienced relief from their symptoms by the morning after the first administration of drug,” explained Dr. Furey. “Moreover, one-half of participants experienced full symptom remission by the end of the treatment period. Finally, participants remained well during a subsequent placebo period, indicating that the antidepressant effects persist for at least two weeks in the absence of further treatment.”

The efficacy of scopolamine is very interesting because the potent blockade of muscarinic receptors was a property of tricyclic antidepressant medications, the oldest type of antidepressants. With these medications, the muscarinic receptor blockade was mostly viewed as the cause of unwanted side effects, such as constipation, sedation, and memory impairments. Newer antidepressants, such as serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors, were explicitly designed to avoid blocking muscarinic receptors. Yet, the current data raise the possibility that this strategy may have increased safety and tolerability of these medications at the expense of providing effective and timely relief for depression symptoms.

Dr. John Krystal, Editor of Biological Psychiatry, commented that these findings “have the potential to raise expectations for new antidepressant treatments. Three-to-six weeks is a long time to wait for depression symptoms to be alleviated. Depressed people describe their emotional state using terms like ‘agony’ and others compare their condition to ‘living in hell’. Further, depression is a life-threatening condition for some, preventing them from performing basic self-care functions or causing them to exhibit self-destructive behavior.”

Although these findings open the door to a conceptually different approach to the treatment of depression, it remains to be seen whether rapid acting antidepressant effects will be viable clinically. One could imagine that they might mitigate hospitalization in some patients and enhance the overall effectiveness of the treatment of depression. However, this possibility remains to be demonstrated empirically in studies that show that a rapid-acting antidepressant treatment can be smoothly transitioned to definitive long-term treatment for depression.

Media Contact:

Christopher J. Pfister

Elsevier

c.pfister@elsevier.com

+1 215 239 3266

These studies are well designed and indicate the scopolamine reduces symptoms of depression in people with severe illness that had not responded to more traditional medications and treatments. This is potentially exciting news for those who suffer with depression – unipolar or bipolar type.

Like all of this research, much needs to be done before this type of treatment would be used in routine clinical settings, but the components of rapid response and effectiveness in those who had poor prognoses are areas that could significantly improve quality of life for many people suffering with depression. More research exploring these features is needed, but these studies and the studies on ketamine change the game and challenge our accepted ideas that it has to take a while for antidepressants to work.

Scopolamine’s mechanism of action seems to be through the muscarinic receptors, which is fascinating because that effect was present in old fashioned tri-cyclics and was thought to just be part of the side effects – not the treatment effect. This notion may provide new opportunities for developing or re-developing medications for depression that are truly unique – rather than just more “me-too” variations on serotonin and norepinephrine transmitters, which are most of the medicines we have now.

Photo by Rennett Stowe, available under a Creative Commons attribution, non-commercial license.

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    Last reviewed: 9 Dec 2010