Table of Contents
There may be new hope on the horizon for patients suffering from posttraumatic stress disorder (PTSD). With only 60% of PTSD responding to current pharmacological approaches and a dismal 20% to 30% achieving full remission of PTSD symptomologies, it becomes clear that new pharmacological interventions must be investigated to relieve the suffering inherent in this type of trauma-based disorder. Aga-Mizrachi et al. (2014) offered one new pharmacological approach in their article, Methylphenidate and Desipramine Combined Treatment Improves PTSD Symptomology in a Rat Model.
Recognizing that attention-deficit/hyperactivity disorder (ADHD) symptomologies (e.g. poor concentration) often exist comorbidly within PTSD populations, the researchers (Aga-Mizrachi, et al., 2014) sought to test the effects of a combination of antidepressant drugs commonly used to treat PTSD (e.g. desipramine) and psychostimulant medications (e.g. methylphenidate) to reduce symptoms associated with ADHD. In addition, Aga-Mizrachi et al. (2014) also investigated the efficacy of specific drug combinations in improving metabolic abnormalities that have been found to contribute to such conditions as obesity and diabetes within PTSD populations (Jin, et al., 2009).
A study population of rats were randomly assigned to one of two groups (control versus stress exposure). The stress exposure rats were subjected to fear conditioning procedures (e.g. foot shocks) on a varying and unpredictable schedule over a four-week period. The rats subjected to fear conditioning procedures were then compared with the control group to identify the existence of three common PTSD behavioral symptomologies: re-experiencing, avoidance and hyperarousal. Those rats identified as exhibiting PTSD-like symptoms were then randomly assigned to different pharmacological treatment groups (e.g. desipramine alone or desipramine in combination with methylphenidate) and then studied for behavioral changes (e.g. improved social interaction after drug treatment) effected by the drug or a specific combination of drugs. After behavioral testing was completed, serum tests were performed to identify the presence (if any) of metabolic syndrome.
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The results of this study (Aga-Mizrachi, et al., 2014) indicated that rats treated with a combination of desipramine (DES) and methylphenidate (MPH) showed significant improvement in re-experiencing symptoms (e.g. lower immobility duration), avoidance symptoms (e.g. decreased social interactions) and hyperarousal (e.g. startle responses). In addition, the findings indicated that the combination of DES and MPH dramatically reduced proinflammatory cytokine responses. This reduction resulted in the effective return of serum levels (specifically those significant to metabolic syndrome) to normal conditions. Overall, the combination of DES and MPH proved beneficial in reducing PTSD symptoms in the areas of reexperiencing, avoidance and hyperarousal and in controlling the physiological impact of metabolic syndrome experienced within PTSD populations.
Critique
Aga-Mizrachi et al. (2014) provided a clear, concise and systematic presentation of the methodology design utilized in this study. The use of numerous graphs and illustrations were instrumental in understanding and determining the effects of the pharmacological treatments applied to the study animals. The researchers are to be commended for presenting a novel and alternative approach in the pharmacological treatment of individuals with PTSD. However, there are some areas in the design of this study that seem to reduce the predictive power of the findings when applied to human populations. For example, only short-term behavioral results were identified during the 13-week study. No long-term effects of the drugs or combination of drugs on the physiological or psychological changes observed could be ascertained after the 13 week program as the rats were euthanized and decapitated to obtain the serum samples necessary for analysis for metabolic syndrome. This precludes the analysis of such treatments in long range conditions and in identifying potential risks in using such combinations of drugs on humans.
In addition, the predictive power of using animal models to ascertain whether pharmacological treatments could bring about the same beneficial (or negative) impacts in human populations remains a controversial issue. The findings derived from such studies have often failed to translate to human populations. Rhrissorrakrai et al. (2015) contend that these failures rise from species-specific differences in response to specific stimuli. In other words, a specific species of rat (e.g. male Wistar rats) may or may not react to the administration of foot shocks in the same manner as a different species of laboratory rats (e.g. cloned rats). Therefore, the excitement generated by studies such as the one conducted by Aga-Mizrachi et al. (2014) must be tempered with caution until the time comes when the results can be replicated in other animal models and/or human studies.
Conclusion
Due to the minimal success rate of current pharmacological interventions for the treatment of posttraumatic stress syndrome (PTSD), it becomes evident that new and novel pharmacological approaches to treatment must be investigated. Aga-Mizrachi et al. (2014) presented one such investigation in the form of combining drugs used to treat PTSD with drugs used to treat ADHD and testing the behavioral changes effected by such drugs on animal models.
Although the use of animal models tempers external validity of such studies, using a carefully documented and systematic methodology design allowed the researchers to achieve a high degree of internal validity. The strong statistical differences in behaviors noted through the combined use of methylphenidate and desipramine show great promise and should help to promote future research in the use of pharmacological interventions for PTSD and provide hope for sufferers of a condition that has proved challenging to treat effectively.
References
- Aga-Mizrachi, S., Cumerblit-Sabba, A., Gurman, O., Balan, A., Shwam, G., Deshe, R., . . . Avital, A. (2014). Methylphenidate and desipramine combined treatment improves PTSD symptomatology in a rat model. Translational Psychiatry, 4:e447. doi:10.1038/tp.2014.82.
- Jin, H., Lanouette, N. M., Mudaliar, S., Henry, R., Folsom, D. P., Khandrika, S., . . . Jeste, a. D. (2009). Association with posttraumatic stress disorder with increased metabolic syndrome. Journal of Clinical Psychopharmacology, 29(3), 210-215. doi:10.1097/JCP.0b013e3181a45ed0
- Kelmendi, B., Adams, T. G., Yarnell, S., Southwick, S., Abdallah, C. G., & Krystal, J. H. (2016). PTSD: From neurobiology to pharmacological treatments. European Journal of Psychotraumatology, 7(1), 1-11. doi:10.1038/tp.2016.277.
- Rhrissorrakrai, K., Belcastro, V., Bilal, E., Norel, R., Poussin, C., Mathis, C., . . . Hoeng, J. (2015). Understanding the limits of animal models as predictors of human biology: Lessons learned from the sbv IMPROVER species translation challenge. Bioinformatics, 31(4), 471-483. doi:https://doi.org/10.1093/bioinformatics/btu611
