What Role Does Serotonin Play in PTSD?

By Alexander Neumeister, MD | April 1, 2006

Although benzodiazepines administered as single agents have anxiolytic and anti-panic effects, their role in the treatment of PTSD is limited. Braun et al. (1990) demonstrated a modest, albeit significant, improvement in anxiety and depressive symptoms in 10 Israeli patients with PTSD using a short-acting benzodiazepine, alprazolam(Drug information on alprazolam) (Xanax), in a double-blind crossover study. However, there was no significant change in core PTSD symptoms. Administration of clonazepam(Drug information on clonazepam) (Klonopin) or alprazolam immediately following a traumatic event did not alter the onset of either anxiety or PTSD symptoms at one and six months (Gelpin et al., 1996). However PTSD patients randomized to benzodiazepines had a decrease in heart rate over time.

Van der Kolk et al. (1994) performed the first placebo controlled study of an SSRI (fluoxetine [Prozac]) in PTSD and demonstrated a significant improvement in all PTSD symptoms. In the largest placebo-controlled study of sertraline(Drug information on sertraline), the drug was shown to be effective in treating avoidance and hyperarousal symptoms but demonstrated no significant effect on reexperiencing/intrusion cluster of symptoms (Brady et al., 2000). Marshall and colleagues (2001) randomized patients to either 20 mg (n=183) or 40 mg (n=182) of paroxetine(Drug information on paroxetine), or placebo (n=186). Paroxetine-treated patients in both dosage groups demonstrated significantly greater improvement on all three clusters of PTSD (reexperiencing, avoidance/ numbing and hyperarousal) compared to placebo-treated patients at study end point.

However, one of the main limitations of SSRI treatment in PTSD is the time lag between initiating treatment and onset of clinical response, which can take up to six weeks. Furthermore, there could be an initial exacerbation of anxiety symptoms and insomnia that could lead to noncompliance or early discontinuation of treatment.

Conclusion

Researchers have successfully determined the neurocircuitry underlying mechanisms, such as fear and anxiety or extinction, which are believed to be abnormal in PTSD. Others have been successful in determining neurochemical correlates of PTSD symptoms. However, we have not yet sufficiently addressed the potential role of receptors and transporters that have been shown to regulate neurochemical mechanisms important for PTSD. More recent research has focused on the determination of genes and gene variants which determine transmitter synthesis and release in healthy people and individuals suffering from stress-related disorders. These studies will likely lead to an enhanced understanding of an individual’s vulnerability to environmental stressors.

In combination with modern imaging techniques, including fMRI and molecular imaging using PET, we will have novel insight into processes underlying stress-related disorders such as PTSD. Whereas fMRI will provide insight into neural connectivity of circuits involved in PTSD, the strength of PET imaging will be showing the neurochemical processes that underlie altered emotion processing or hyperarousal in patients with PTSD. The ultimate goal of these research efforts is to provide novel, improved treatments for people suffering from trauma-related symptoms.

Dr. Neumeister is associate professor and director of the Molecular Imaging Program in the department of psychiatry, Yale University School of Medicine. Dr. Neumeister indicated that he has nothing to disclose.

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What Role Does Serotonin Play in PTSD?

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