Treatment Of Depersonalization Disorder Research Articles

Ventrolateral prefrontal cortex repetitive transcranial magnetic stimulation in the treatment of depersonalization disorder: A consecutive case series

Case reports and an open trial have reported promising responses to repetitive transcranial magnetic stimulation (rTMS) to prefrontal and temporo-parietal sites in patients with depersonalization disorder (DPD). We recently showed that a single session of rTMS to the ventrolateral prefrontal cortex (VLPFC) was associated with a reduction in symptoms and increase in physiological arousal. Seven patients with medication-resistant DSM-IV DPD received up to 20 sessions of right-sided rTMS to the VLPFC for 10 weeks. Stimulation was guided using neuronavigation software based on participants’ individual structural MRIs, and delivered at 110% of resting motor threshold. A session consisted of 1Hz repetitive TMS for 15min. The primary outcome measure was reduction in depersonalization symptoms on the Cambridge Depersonalization Scale (CDS). Secondary outcomes included scores on the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). 20 sessions of rTMS treatment to right VLPFC significantly reduced scores on the CDS by on average 44% (range 2–83.5%). Two patients could be classified as “full responders”, four as “partial” and one a non-responder. Response usually occurred within the first 6 sessions. There were no significant adverse events. A randomized controlled clinical trial of VLPFC rTMS for DPD is warranted.

ID 190 – Treatment of depersonalization disorder with high frequency left-sided repetitive transcranial magnetic stimulation

Objectives The patient is a 30 year old single Asian male physician in the US Navy with depression. He is physically healthy with a longstanding history of depersonalization symptoms including feelings of unreality, detachment, numbing, and feeling that his mind is empty of thoughts and memories. He started Bupropion XL 300 mg daily which improved his depressive symptoms though he continued to have depersonalization symptoms and was referred for treatment with rTMS. Methods Pretreatment Montgomery–Asberg Depression Rating Scale (MADRS) was 12, Cambridge Depersonalization Scale (CDS) was 149 (endorsed 20 of 29). He began right DLPFC 1 Hz rTMS. Depressive symptoms improved but depersonalization symptoms continued, with scores of MADRS 2 and CDS 100 (endorsed 17 of 29). He was thus switched to left DLPFC 10 Hz rTMS. Results He continued treatment through session 22 with scores of MADRS 2, and CDS 43 (endorsed 13 of 29). Conclusions There have been two case reports in which rTMS was effective in reducing symptoms of DPD, both using high frequency (20 Hz) rTMS to the left DLPFC. Key Message Given its effectiveness in our patient, the use of high frequency rTMS to the left DLPFC for treatment of DPD should be further explored.

Depersonalization disorder may be related to glutamate receptor activation imbalance

Low-dose ketamine administration mimics, both clinically and on gross neuroimaging, depersonalization disorder. The perceptual effects of ketamine may be due to secondary stimulation of glutamate release and lamotrigine, possibly by inhibited glutamate release, may reduce some of ketamine’s so-called dissociative effects. However, lamotrigine does not seem to be useful in the treatment of depersonalization disorder. Glutamate release in prefrontal cortex is increased by subanaesthetic doses of ketamine, resulting in increased inhibition, possibly via intercalated GABAerg cells, of projections from amygdala, affecting structures critically involved in depersonalization. I speculate that, in depersonalization disorder, the increased glutamate activity in prefrontal cortex is due to intrinsic imbalance, resulting in long-term potentiation, at the postsynaptic glutamate receptors on the GABAerg interneurons while the same receptor abnormality at the synapses on the intercalated GABAerg cells of the amygdala result in long-term depression in the case of either normal or high glutamate release.

Temporo-parietal junction stimulation in the treatment of depersonalization disorder

This is the first clinical trial of repetitive Transcranial Magnetic Stimulation (rTMS) in depersonalization disorder (DPD). After 3 weeks of right temporo-parietal junction (TPJ) rTMS, 6/12 patients responded. Five responders received 3 more weeks of right TPJ rTMS showing 68% DPD symptoms improvement. Right TPJ rTMS was safe and effective.

Treatment of depersonalization disorder with fluoxetine: a case report

Materials and methods A 23-year old single man had a 1-year history of primary depersonalization disorder. He described feeling “detached from my body, as if I was observing myself from the outside, cut off from emotions and feelings, feeling as if I had completely lost my self and feeling like I was in a dream”. He felt far removed from everything. The patient was treated with fluoxetine 10 mg/day, which was slowly raised to 40 mg/day.

An Open Trial of Naltrexone in the Treatment of Depersonalization Disorder

Depersonalization disorder (DPD) remains one of the few disorders in modern psychiatry for which no treatments are established that are even partially effective, whether pharmacological or psychotherapeutic. Depersonalization disorder is a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition dissociative disorder characterized by a pervasive subjective sense of unreality and detachment with intact reality testing. Two recent controlled medication trials, one with lamotrigine and one with fluoxetine, failed to show efficacy. There is some evidence for dysregulation of endogenous opioid systems in depersonalization, and a few studies have suggested that opioid antagonists may have efficacy in the treatment of dissociation and depersonalization symptoms. In this prospective open treatment trial, 14 subjects were recruited and treated with naltrexone for 6 weeks to a maximum dose of 100 mg/d (first 7 subjects) or 10 weeks to a maximum dose of 250 mg/d (next 7 subjects). Mean naltrexone dose was 120 mg/d. There was an average 30% reduction of symptoms with treatment, as measured by 3 validated dissociation scales. Three patients were very much improved, and 1 patient was much improved with naltrexone treatment. These findings are potentially promising in a highly treatment-refractory disorder for which no treatment guidelines exist and warrant a randomized controlled trial.

A placebo-controlled, cross-over trial of lamotrigine in depersonalization disorder

There is evidence to support the view that glutamate hyperactivity might be relevant to the neurobiology of depersonalization. We tested the efficacy of lamotrigine, which reduces glutamate release, as a treatment for patients with depersonalization disorder. A double-blind, placebo-controlled, cross-over design was used to evaluate 12 weeks of treatment of lamotrigine. Subjects comprised nine patients with DSM-IV depersonalization disorder. Changes on the Cambridge Depersonalization Scale and the Present State Examination depersonalization/derealization items were compared across the two cross-over periods. Lamotrigine was not significantly superior to placebo. None of the nine patients was deemed a responder to the lamotrigine arm of the cross-over. Lamotrigine does not seem to be useful as a sole medication in the treatment of depersonalization disorder.