5-HTP and Anxiety

The first study investigating the possible anti-anxiety effects of 5-HTP was published in 1985. This was a small, uncontrolled pilot study conducted in the Netherlands. The subjects were 10 individuals diagnosed with anxiety disorders according to standard criteria (seven of the patients had "panic disorder;" three had "generalized anxiety disorder"). 5-HTP treatment (300 mg/day) lasted 12 weeks, during which their level of anxiety was assessed weekly using the Spielberger State-Trait Anxiety Inventory (STAI) and the Hamilton Anxiety Scale (HAS).

By week 12, panic attacks had almost completely disappeared in the seven patients suffering from that disorder; overall 9/10 patients showed improvement as measured by the STAI and HAS scales. Improvement was apparent by week 4 and continued until week 8, after which it leveled off. Significant improvement was seen for depression, anxiety and phobic anxiety.

Although this study was limited by the small number of subjects and a lack of proper controls, the same investigators conducted a larger double-blind, comparative, placebo-controlled study a few years later. The results showed that 5-HTP had significant activity that was on a par with the anti-anxiety drug clomipramine (Anafranil7) on some measures, but not on others. In this study, 45 patients diagnosed with anxiety disorders (generalized anxiety disorder, panic disorder, agoraphobia, or OCD) were randomly assigned to receive either 5-HTP, clomipramine, or placebo. The trial lasted 8 weeks. The results showed that both 5-HTP and clomipramine were about equal and both were significantly superior to placebo in reducing anxiety beginning at week 2 on this measure of anxiety (State-Anxiety Inventory, A-STATE). On other measures, 5-HTP was generally superior to placebo but less effective than clomipramine. Since these investigators used a lower maximum dose of 5-HTP (150 mg/day) in this study than they used in their earlier study (300 mg/day), it is possible that a higher dose would have produced a more dramatic result.

As we noted above, the relationship between serotonin and anxiety appears to be quite complex. For example, anxiety can be relieved both by agents that interfere with serotonergic function (eg, benzodiazepines) as well by agents that enhance serotonergic function (eg, 5-HTP and SSRIs). In addition, treatment with 5-HTP and SSRIs has sometimes been reported to result in an aggravation of anxiety (or depression) during the first week or two of therapy before clinical improvement occurs.

Scientists have not yet pinned down the reason for these paradoxical responses. The hypothesis that has the most support at the present time suggests that reducing serotonergic activity generally lowers anxiety. In people with anxiety disorders, serotonin receptors become hypersensitive. In other words, they overreact to a burst of serotonin molecules that would normally not increase anxiety. Thus, when a person with an anxiety disorder takes 5-HTP or an SSRI, the extra serotonin produced initially overstimulates these hypersensitive receptors and may lead to an aggravation of the anxiety. With continued stimulation, though, these receptors eventually become less sensitive -- a process known as downregulation -- and anxiety levels eventually decline.