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Background: Ketamine induces rapid and robust antidepressant effects, and many patients also describe dissociation, which is associated with antidepressant response. This follow-up study investigated whether antidepressant efficacy is uniquely related to dissociative symptom clusters., Methods: Treatment-resistant patients with major depressive disorder (MDD) or bipolar disorder (BD) (n = 126) drawn from three studies received a single subanesthetic (0.5 mg/kg) ketamine infusion. Dissociative effects were measured using the Clinician-Administered Dissociative States Scale (CADSS). Antidepressant response was measured using the 17-item Hamilton Depression Rating Scale (HAM-D). A confirmatory factor analysis established the validity of CADSS subscales (derealization, depersonalization, amnesia), and a general linear model with repeated measures was fitted to test whether subscale scores were associated with antidepressant response., Results: Factor validity was supported, with a root mean square error of approximation of .06, a comparative fit index of .97, and a Tucker-Lewis index of .96. Across all studies and timepoints, the depersonalization subscale was positively related to HAM-D percent change. A significant effect of derealization on HAM-D percent change was observed at one timepoint (Day 7) in one study. The amnesia subscale was unrelated to HAM-D percent change., Limitations: Possible inadequate blinding; combined MDD/BD datasets might have underrepresented ketamine's antidepressant efficacy; the possibility of Type I errors in secondary analyses., Conclusions: From a psychometric perspective, researchers may elect to administer only the CADSS depersonalization subscale, given that it was most closely related to antidepressant response. From a neurobiological perspective, mechanistic similarities may exist between ketamine-induced depersonalization and antidepressant response, although off-target effects cannot be excluded., (Published by Elsevier B.V.)

Depersonalization is a frequent symptom in depression and obsessive-compulsive disorder (OCD), but sometimes, it may be severe and concurrently diagnosed as a disorder. The treatment of depersonalization disorder both alone and comorbid with other psychiatric disorders is as yet unclear. This report presents the successful treatment with aripiprazole of concurrent depersonalization disorder in 3 patients with depression or OCD. The psychiatric disorders were diagnosed through structured clinical interviews. Assessments were by means of Yale-Brown Obsessive-Compulsive Scale, the Clinical Global Impression-Improvement Scale, and the 17-item Hamilton Rating Scale for Depression. Aripiprazole may be a beneficial psychotropic drug in the treatment of depersonalization disorder comorbid with OCD or depression, which is an important problem in clinical practice.

The individuals with depersonalizattion disorder suffer from a painful feeling that their body and mental experiences or the experiences of the environment seem become unreal, distant or mechanical. This phenomenon is often associated with other mental disorders, as in the case presented. Among the many psychoactive drugs studied, none of them has been shown to be the treatment of choice. Among those with which the best results are obtained are opioid receptor antagonists, the combination of selective serotonin reuptake inhibitors with lamotrigine and clorimipramine. We are presenting a resistant case that responded to lamotrigine.

Objective: Depersonalization disorders (DPDs) are highly prevalent in population. However, the effect of lamotrigine on outpatients with DPD without psychiatric comorbidity has not been studied in a double-blind placebo-controlled design., Method: Eighty patients (all men) were washed out from all medications. Each patient was randomized either to receive lamotrigine (40 patients) for 12 weeks or matched on placebo (40 patients) in a double-blind manner. Eligible participants, in addition to meeting the criteria for DPD from Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, were required to be between 18 and 65 years. Response was defined as a 50% reduction in the Cambridge Depersonalization Scale. Response effects with lamotrigine and placebo were compared by using analysis of variance and χ² tests. Six patients did not return for at least 1 subsequent assessment, and 74 patients dropped out (36 taking lamotrigine and 38 taking placebo) in the valuables study group., Results: Of the 36 lamotrigine-treated participants, 26 responded by 12 weeks versus 6 of the 38 placebo-treated participants (P < 0.001). The most common and problematic adverse effect in the lamotrigine group was rash., Conclusions: The authors believe this to be the first double-blind placebo-controlled randomization study to test the efficacy of lamotrigine in the management of outpatients with DPDs. These need to be replicated in a larger study group.

The symptom of depersonalization is frequently associated with other mental disorders, physiological effects of substances or medical diseases. However, it is rare that, as in the case presented, the experiences of depersonalization form an isolated entity, a primary depersonalization disorder. Among the many psychoactive drugs studied, none of them has been shown to be the treatment of choice. Among those with which the best results are obtained are opioid receptor antagonists (naloxone and naltrexone), the combination of selective serotonin reuptake inhibitors with lamotrigine and clorimipramine. Although with virtually no evidence, we are presenting a case that responded spectacularly to methylphenidate.

Depersonalization disorder (DPD) is characterized by a subjective sense of detachment from one's own being and a sense of unreality. An examination of the psychobiology of depersonalization symptoms may be useful in understanding the cognitive-affective neuroscience of embodiment. DPD may be mediated by neurocircuitry and neurotransmitters involved in the integration of sensory processing and of the body schema, and in the mediation of emotional experience and the identification of feelings. For example, DPD has been found to involve autonomic blunting, deactivation of sub-cortical structures, and disturbances in molecular systems in such circuitry. An evolutionary perspective suggests that attenuation of emotional responses, mediated by deactivation of limbic structures, may sometimes be advantageous in response to inescapable stress.

Depersonalization disorder (DPD) is a chronic and distressing condition with a prevalence in the general population between 0.8 and 2%. Several neurobiological studies in the last decade have shown that patients have suppressed limbic activation to emotional stimuli. Such findings are in line with a model which suggests that the condition is generated by an anxiety-triggered, 'hard-wired' inhibitory response to threat. Such a mechanism would ensure the preservation of adaptive behavior, during situations normally associated with overwhelming and potentially disorganizing anxiety. In DPD, such a response would become chronic and dysfunctional. Depersonalization remains a condition for which no definitive treatment exists, and for which conventional medications, such as antidepressants or antipsychotics, have been found to be of little value. Fortunately, a few promising lines of pharmacological treatment have emerged in recent years, although more rigorous studies are needed. For example, a number of studies suggest that opioid receptor antagonists such as naltrexone and naloxone are useful in at least a subgroup of patients. In spite of initial expectations, the use of lamotrigine as a sole medication has not been found useful. However, open-label trials suggest that its use as an add-on treatment with selective serotonin reuptake inhibitors (SSRIs) is beneficial in a substantial number of patients. Similarly, the use of clonazepam, particularly in conjunction with SSRI antidepressants, appears to be beneficial in patients with high levels of background anxiety. In line with the stress-related model of depersonalization, those neurotransmitter systems of relevance to depersonalization are known to play important inhibitory roles in the regulation of the stress response.

Objectives: Depersonalization disorder (DPD) is a chronic condition characterized by the persistent subjective experience of unreality and detachment from the self. To date, there is no known treatment. Lamotrigine as sole agent was not found to be effective in a previous small double-blind, randomized crossover trial. However, evidence from open trials suggests that it may be beneficial as an add-on medication with antidepressants., Methods: We report here an extended series of 32 patients with DPD in whom lamotrigine was prescribed as an augmenting medication. Most of the patients were receiving selective serotonin reuptake inhibitors., Results: Fifty-six percent (n = 18) of patients had a more than or equal to 30% reduction on the Cambridge Depersonalization Scale score at follow-up. Both maximum dose of lamotrigine used and before treatment Cambridge Depersonalization Scale scores showed positive correlations with the percentage of response., Conclusions: The results of this trial suggest that a significant number of patients with DPD may respond to lamotrigine when combined with antidepressant medication. The results are sufficiently positive to prompt a larger controlled evaluation of lamotrigine as "add-on" treatment in DPD.

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 19-year-old patient had developed a depersonalisation disorder following the use of considerable amounts of cannabis for several weeks two years before. The symptoms decreased sharply after treatment with a serotonergic antidepressant. In cases of persistent or recurrent symptoms of depersonalisation, both psychiatric and somatic causes should be looked for. In cases of primary depersonalisation, the use of (soft) drugs should be considered in the differential diagnosis. Various forms of pharmaco- and psychotherapy seem to be able to reduce the symptoms. However, the effectiveness of no treatment has yet been proven.

Background: Despite anecdotal reports that serotonin reuptake inhibitors may improve depersonalisation, there is no proven efficacious treatment for depersonalisation disorder., Aims: To investigate the efficacy of fluoxetine in the treatment of depersonalisation disorder., Method: Fifty-four people who met DSM-IV criteria for depersonalisation disorder were recruited through newspaper advertisements, and 50 were randomised to a 10-week, double-blind trial of fluoxetine 10-60 mg/day or placebo. Primary outcome measures were the Dissociative Experiences Scale-Depersonalisation Factor, the Depersonalization Severity Scale and the Clinical Global Impression-Improvement (CGI-I) scale., Results: Intention-to-treat analysis revealed that fluoxetine (mean dosage 48 mg/day) was not superior to placebo except for a clinically minimal but statistically significantly greater improvement in CGI-I score in the fluoxetine group prior to covarying for anxiety and depression (2.9 v. 3.6). Depersonalisation was significantly more likely to improve if comorbid anxiety disorder improved., Conclusions: Fluoxetine was not efficacious in treating depersonalisation disorder, despite the commonly reported clinical use of serotonin reuptake inhibitors for this condition.

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.

Carbamazepine-induced pitch perception shifts have rarely been described. Two cases of shifted pitch perception developing during medication with carbamazepine are described. Case 1 possessed absolute pitch. Her pitch perception shift disappeared with the discontinuance of carbamazepine. Case 2 did not have absolute pitch. Even though he experienced a pitch perception shift, he developed a tolerance to the shift. We concluded that carbamazepine was the cause of the pitch perception shift in the first case, while the second case probably became attuned to the change in pitch perception because he did not possess absolute pitch.

To test the hypothesis of the role for the opioid system in the pathogenesis of depersonalization, the effect of naloxone (an opioid receptor blocker) on the symptoms and corticosteroids secretion was studied in patients with depersonalization syndrome. Fourteen depersonalization patients were treated with naloxone: 11 patients received single doses (1.6 or 4 mg i.v.) and three others received multiple infusions, with the maximal dosage being 10 mg, and the effect of naloxone on symptom severity was determined. In eight patients, the cortisol, cortisone and corticosterone content in the blood plasma was determined prior to and after the 4 mg naloxone infusion. A reversed-phase microcolumn high-performance liquid chromatography with ultraviolet detection was applied for assessment of glucocorticoids. In three of 14 patients, depersonalization symptoms disappeared entirely and seven patients showed a marked improvement. The therapeutic effect of naloxone provides evidence for the role of the endogenous opioid system in the pathogenesis of depersonalization.

Our aim was to develop a clinician-rated scale assessing depersonalization severity for use in clinical trials of Depersonalization Disorder and trauma-related disorders in general. The 6-item Depersonalization Severity Scale (DSS) was administered to 63 participants with DSM-IV Depersonalization Disorder as diagnosed by the SCID-D, and its psychometric properties were examined. The sensitivity of the DSS and of the Dissociative Experiences Scale (DES) to treatment change was assessed in blinded, controlled settings. Individual items were widely distributed across the severity range. Interrater reliability was excellent and internal consistency was moderate. The DSS had high convergent and discriminant validity and was sensitive to treatment change. The DES was also sensitive to treatment change. We recommend piloting the DSS in future treatment trials of trauma-spectrum disorders.

Background: Although there is a dire paucity of data on the pharmacologic treatment of depersonalization disorder, there have been a few reports in the literature suggesting that selective serotonin reuptake inhibitors may be of therapeutic benefit. In this study, we undertook to evaluate the efficacy of the potent serotonin reuptake inhibitor clomipramine in treating depersonalization., Methods: Eight subjects with DSM-III-R depersonalization disorder were entered into a double-blind crossover trial consisting of 8 weeks desipramine and 8 weeks clomipramine. Due to the very small size of the trial findings are presented descriptively., Results: Of 7 subjects who entered the clomipramine trial, two showed significant improvement in depersonalization. Three subjects dropped out early, unable to tolerate adverse effects. Of 6 subjects who entered the desipramine trial, I showed significant improvement in depersonalization. One clomipramine responder was subsequently followed in open maintenance treatment with clomipramine for 4 years, and her depersonalization symptoms remained in almost complete remission, with relapses upon each attempt to taper off or switch medication., Conclusions: Clomipramine may be a promising pharmacologic treatment for primary depersonalization disorder and warrants further investigation.

The 'designer drug' 3,4-methylenedioxy-metamphetamine (MDMA; 'Ecstasy'), which has become increasingly popular in the past few years, is supposed to induce a feeling of euphoria with amphetamine-like stimulant effects. It was for some time considered harmless, but neurotoxic effects on serotonergic neurons are now well documented. To supplement case reports on different drug-induced psychopathological and somatic complications published in recent literature, the case of a 21-year-old female patient is reported, who exhibited a protracted psychotic depersonalization disorder with suicidal tendency after the first intake of two tablets of "ecstasy". In the course of six months the symptoms remitted only gradually despite administration of a serotonin re-uptake inhibitor, 'flash-backs' occurring repeatedly.

Eight patients with depersonalization disorder or with depersonalization symptoms in association with obsessive-compulsive and panic disorders were treated with serotonin reuptake blockers. There was clinical overlap of depersonalization disorder with obsessive-compulsive disorder, and the co-occurrence of obsessive-compulsive and panic features with depersonalization in these patients was associated with a favorable treatment outcome. The chronicity of illness and lack of prior response to a variety of treatments in these patients highlights the positive outcome with this treatment. In addition, issues are raised regarding the current hierarchical exclusion of depersonalization disorder in the presence of obsessive-compulsive and panic disorders.

Primary depersonalization disorder is believed to be resistant to treatment. However, we report the successful treatment of a case with desipramine and suggest that, because there is a link between depersonalization and anxiety disorders, tricyclic antidepressants may prove effective for depersonalization.

Severe depersonalization at times constitutes a chronic and disabling syndrome for which there is no generally established etiology or treatment. Two cases in which young female patients with severe depersonalization became floridly manic in response to stimulant and antidepressant drug treatment are reported, and the clinical and theoretical implications of these phenomena are discussed.

The author reports two cases in which depersonalization occurred during the waking consciousness of individuals who had engaged in meditative techniques designed to alter consciousness. Psychiatrists should be aware of this phenomenon, as the number organizations in the "consciousness movement" is increasing, and should ask people manifesting depersonalization about any involvement in activities leading to altered states of consciousness. In some cases it might be appropriate to refer such patients to responsible groups that teach altered consciousness by meditation as an egosyntonic desirable state. The author cautions against the use of phenothiazines in cases where depersonalization is a prominent feature.

The manifestation of depersonalisation, its relationship with anxiety and depression, as well as its influence on the course of endogenous psychoses were investigated. Forty patients with severe depersonalisation were treated with the benzodiazepine, phenazepam, and 14 with clozapine. The data indicate that depersonalisation results from anxiety; it follows an anxiety attack and is successfully treated with anxiolytic drugs. In the case of endogenous depression, depersonalisation leads to lingering depressive phase, increasing the patients' resistance to antidepressive therapy. The protective and the harmful role of depersonalisation is discussed.