As a third year medical student, I am required to prepare various evidence-based medicine projects related to patients that I see during a given rotation. Rotations are where I get the opportunity to see patients in the hospital in various specialty settings and apply the knowledge that I have acquired during the first two years of my medical education. My first rotation was psychiatry, where I met an adolescent girl with a very interesting diagnosis. The diagnosis was depersonalization disorder (DPD). This diagnosis and its potential treatment are the focus of my post this week. I investigated the current pathophysiologic theories along with current pharmacologic ideas for treatment.
DPD is characterized by an altered perception of self in which an individual experiences detachment from his or her body and personal memories, emotional and physical numbing, and a sense of living in a dream-like state. DPD patients often feel as though they are watching things happen to them. They do, however, remain aware of this unreality and feel like something is wrong with them (1). They can have a tendency to resort to extreme measures, such as cutting, in an attempt to “feel” and overcome the sensation of numbness.
There are currently no definitive treatments that have been developed regarding DPD. This is due largely to the fact that there is no well-defined pathology regarding its onset. Given its estimated prevalence of 0.8-2.0% in the general population, it is about as widespread as schizophrenia. Yet little research has been done to understand its root cause and treatment (1). Despite the epidemiologic studies that have shown this prevalence rate, it is still assumed to be rare and associated with other anxiety or psychotic disorders instead of being a primary condition on its own.
There are several hypotheses as to the causes of DPD. One notes an observed correlation with serotonin activity. Release of serotonin in the brain has been closely linked to behavior and mood. Drugs that change serotonin activity can induce symptoms of depersonalization, which suggests that serotonin disregulation is involved in DPD. However, follow up studies investigating the effects of selective serotonin reuptake inhibitors (SSRIs, which include many antidepressants) have shown minimal if any effect on DPD symptoms, only seeming to have effect in patients who also suffered from depression or anxiety (1).
Another hypothesis connects DPD to the glutamatergic system. Glutamate is one of the most abundant excitatory neurotransmitters in the brain and is involved in numerous cognitive functions such as learning and memory. Lamotrigine, a glutamate receptor antagonist, has been tried both as individual therapy and adjunct therapy on top of SSRIs. One double-blind placebo-controlled study looked at Lamotrigine as the sole treatment for individuals with DPD and no other co-occurring conditions. Patients given Lamotrigine over a 12 week period showed significant improvement compared to placebo (2). Thus, given the previous studies that looked at serotonergic system, it seems likely that both serotonergic and glutamatergic systems are at play in DPD.
A third line of study shows the opioid system as having promise in treating DPD. The opioid system is known to mediate stress-induced analgesia (or pain control) in such disorders as post-traumatic stress disorder. Activation of this system leads to decreased sensations of pain. Along with this, drugs targeting opioid receptors have been shown to induce a depersonalization-like state in healthy individuals (3). Therefore, treatments with opioid antagonists, like Naltrexone or Naloxone, have been investigated as ways to decrease DPD symptoms of emotional and physical numbness. In one small trial, Naltrexone was given to DPD patients for a period up to 10 weeks and showed an average 30% decrease in symptoms with several patients showing significant improvement based on multiple assessment methods (3).
These are just a few of the possible mechanisms and potential treatment routes for DPD. However, to go into all of them in one post would take too much time. Given the paucity of research that has been done on even understanding the mechanism underlying DPD, there is still much work to be done. Several studies have shown promise in regards to reduction of symptoms, but most of them so far have been small trials. There is a need to have several large double-blind control trials to further test these preliminary results before any definitive recommendations on treatment for DPD can be made.
Sierra, M. (2008). Depersonalization disorder: pharmacological approaches Expert Review of Neurotherapeutics, 8 (1), 19-26 DOI: 10.1586/14737184.108.40.206
Aliyev, N., & Aliyev, Z. (2011). Lamotrigine in the Immediate Treatment of Outpatients With Depersonalization Disorder Without Psychiatric Comorbidity Journal of Clinical Psychopharmacology, 31 (1), 61-5 DOI: 10.1097/JCP.0b013e31820428e1
Simeon, D., & Knutelska, M. (2005). An Open Trial of Naltrexone in the Treatment of Depersonalization Disorder Journal of Clinical Psychopharmacology, 25 (3), 267-270 DOI: 10.1097/01.jcp.0000162803.61700.4f