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Rapidly-Acting Antidepressant Shows Promise

In a recent issue of Biological Psychiatry, researchers from the NIH have reported that a medication called scopolamine appears to produce replicable rapid improvement in mood in patients with unipolar depression. Scopolamine temporarily blocks the muscarinic cholinergic receptor, thought to be overactive in people suffering from depression. Previously, the NIH team had demonstrated scopolamine’s anti-depressive effect in both unipolar and bipolar depression. The current study replicates these findings in an independent sample of unipolar depression patients. Conventional antidepressant treatments generally require three to four weeks to become effective, thus the discovery of treatments with a more rapid onset is a major goal of biological psychiatry. The authors noted that the first drug found to produce rapid improvement in mood was the synthetic NMDA glutamate receptor antagonist known as ketamine. Scopolamine is an alkaloid compound obtained from plants of the nightshade family (Solanaceae), such as henbane, jimson weed, Angel's Trumpets, corkwood, and belladonna (“deadly nightshade”). "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. Maura Furey, co-author of the new report. "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, the authors suggested, 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, from the Yale University School of Medicine and the editor of Biological Psychiatry, was not involved in the study and he commented that the 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."

The authors noted that, although their findings open the door to a conceptually different approach to the treatment of depression, it remains to be seen whether rapidly-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.

The results of the new scopolamine study were published in the February 1, 2010 issue of Biological Psychiatry. [Press release] [Biological Psychiatry abstract]