Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression.

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.

Aripiprazole in depersonalization disorder comorbid with major depression and obsessive-compulsive disorder: 3 cases.

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.

Eficacia de lamotrigina en un caso de trastorno de despersonalización resistente / The efficacy of lamotrigine in a resistant case of depersonalization disorder

Cuando sufre despersonalización, el individuo se queja espontáneamente de la vivencia de que su propia actividad mental, su cuerpo, su entorno o todos ellos, están cualitativamente transformados, de manera que se han vuelto irreales, lejanos o mecánicos. Este fenómeno está asociado frecuentemente con otros trastornos mentales, como en el caso que presentamos. Entre los muchos fármacos estudiados, ninguno ha mostrado ser el tratamiento de elección. Entre aquellos que han obtenido mejores resultados están los antagonistas de los receptores de los opioides, la combinación de inhibidores selectivos de la recaptación de la serotonina con lamotrigina, y la clorimipramina. Presentamos un caso resistente que respondió a lamotrigina (AU)

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(AU)

The efficacy of lamotrigine in a resistant case of depersonalization disorder.

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.

El metilfenidato en el trastorno por despersonalización: a propósito de un caso / Methylphenidate in depersonalization disorder: a case report

El síntoma de despersonalización aparece frecuentemente asociado a otros trastornos mentales, a efectos fisiológicos de substancias o a enfermedades médicas. Raramente, como es el caso presentado, las experiencias de despersonalización forman una entidad aislada, un trastorno de despersonalización primario. Entre los múltiples psicofármacos estudiados, ninguno de ellos ha demostrado ser el tratamiento de elección. Entre los que obtienen mejores resultados destacan: los antagonistas de los receptores de los opioides (naloxona y naltrexona), la combinación de inhibidores selectivos de la recaptación de la serotonina con lamotrigina y la clorimipramina. Y, aunque con prácticamente nula evidencia, se presenta un caso que respondió de forma espectacular al metilfenidato (AU)

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 (AU)

Methylphenidate in depersonalization disorder: a case report.

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.

Lamotrigine in the immediate treatment of outpatients with depersonalization disorder without psychiatric comorbidity: randomized, double-blind, placebo-controlled study.

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.

Cognitive-affective neuroscience of depersonalization.

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: pharmacological approaches.

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.

Lamotrigine as an add-on treatment for depersonalization disorder: a retrospective study of 32 cases.

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.