Integration of Clozapine-associated Harm Obsessions into Cognitive Behavioral Conceptualization and Treatment Planning for Thought Broadcasting: A Case Study.

BACKGROUND AND OBJECTIVES: As many as 30% of individuals with a schizophrenia spectrum disorder experience obsessive-compulsive symptoms (OCS). Clozapine has demonstrated superior efficacy for the treatment of medication-resistant schizophrenia but it is also associated with an increased risk for OCS. Because pharmacologic management of clozapine-related OCS can be particularly challenging, cognitive behavioral therapy (CBT) should be considered. Nevertheless, there are few detailed accounts of CBT for OCS and schizophrenia. METHODS: The authors describe the interdisciplinary outpatient care of a client who had a 25-year history of schizoaffective disorder, bipolar type, and OCS. The case formulation was used to guide interventions to target core schemas of being dangerous and defective. The case study describes the cognitive behavioral formulation, treatment targets, treatment course, and functional and symptom response. RESULTS: The client received 21 sessions of a formulation-based CBT for psychosis protocol, which included a 6-session course of exposure with response prevention, consisting of imaginal and in vivo exposure to multiple salient harm stimuli. Reduced ratings of distress and a 50% reduction in OCS suggest that habituation and inhibitory learning occurred. The treatment of OCS resulted in the complete resolution of thought broadcasting. Subsequently, the client was more successful in his efforts to adhere to an action schedule. LIMITATIONS: The use of both the treatment approach described in this clinical case report and contemporaneous medication management preclude comment on the mechanism(s) of the therapeutic change observed in this case. CONCLUSIONS: This report presents a means of conceptualizing the interplay between thought broadcasting and harm obsessions and discusses considerations in identifying and treating individuals with similar comorbid conditions, particularly in the context of clozapine treatment for medication-resistant psychosis.

Impulse control disorders in patients with prolactinoma receiving dopamine agonist therapy: a prospective study with 1 year follow-up.

OBJECTIVE: To assess prospectively the prevalence of impulse control disorders (ICD), psychiatric symptoms, and their clinical correlates in patients with prolactinoma receiving dopamine agonists (DA) in comparison to those with non-functioning pituitary adenomas (NFA) and healthy controls (HC). METHODS: A total of 25 patients with prolactinoma, 31 with NFA, and 32 HCs were included in the study. All patients and controls were screened for the presence of ICDs and other psychiatric disorders using revised version of Minnesota Impulsive Disorders Interview (MIDI-R), Barratt Impulsiveness Scale (BIS-11), Symptom Check List (SCL-90-R) questionnaire and Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). RESULTS: We detected two new cases (8%) of ICD associated with DAs. Both cases presented with hypersexuality, which reversed totally or decreased upon discontinuation of the drug. The re-challenge of the DA in a smaller dose has led to either no symptoms or weaker symptoms than before. There was an increase in the number of patients who screened positive on obsession, interpersonal sensitivity, paranoid ideation, and additional items subscales of SCL-90-R in comparison to HCs at the end of the study period (p < 0.05 for all). Likewise, cumulative DA dose was positively correlated to obsession, interpersonal sensitivity, paranoid ideation, hostility, phobic anxiety subscales, and GSI scores of SCL-90-R (p < 0.05 for all). CONCLUSIONS: DAs are associated with a small but substantial short-term risk of ICD development and a broad range of psychiatric symptoms in patients with prolactinoma receiving DAs.

Methoxetamine affects brain processing involved in emotional response in rats.

BACKGROUND AND PURPOSE: Methoxetamine (MXE) is a novel psychoactive substance that is emerging on the Internet and induces dissociative effects and acute toxicity. Its pharmacological effects have not yet been adequately investigated. EXPERIMENTAL APPROACH: We examined a range of behavioural effects induced by acute administration of MXE (0.5-5 mg·kg-1 ; i.p.) in rats and whether it causes rapid neuroadaptive molecular changes. KEY RESULTS: MXE (0.5-5 mg·kg-1 ) affected motor activity in a dose- and time-dependent manner, inducing hypermotility and hypomotility at low and high doses respectively. At low and intermediate doses (0.5 and 1 mg·kg-1 ), MXE induced anxious and/or obsessive-compulsive traits (marble burying test), did not significantly increase sociability (social interaction test) or induce spatial anxiety (elevated plus maze test). At a high dose (5 mg·kg-1 ), MXE induced transient analgesia (tail-flick and hot-plate test), decreased social interaction time (social interaction test) and reduced immobility time while increasing swimming activity (forced swim test), suggesting an antidepressant effect. Acute MXE administration did not affect self-grooming behaviour at any dose tested. Immunohistochemical analysis showed that behaviourally active doses of MXE (1 and 5 mg·kg-1 ) increased phosphorylation of ribosomal protein S6 in the medial prefrontal cortex and hippocampus. CONCLUSIONS AND IMPLICATIONS: MXE differentially affected motor activity, behaviour and emotional states in rats, depending on the dose tested. As reported for ketamine, phosphorylation of the ribosomal protein S6 was increased in MXE-treated animals, thus providing a 'molecular snapshot' of rapid neuroadaptive molecular changes induced by behaviourally active doses of MXE.

Behavioral effects and somnolence due to levetiracetam versus oxcarbazepine - a retrospective comparison study of North Indian patients with refractory epilepsy.

PURPOSE: Levetiracetam (LEV) is often chosen early in the treatment of refractory epilepsy; however, its adverse effects have largely been studied as part of clinical trials. Oxcarbazepine and valproate (VPA) are the other commonly used AEDs and, hence, serve as good comparators. This study was conducted to evaluate behavioral abnormalities and somnolence among patients with epilepsy being treated with LEV and/or OXC compared with those receiving VPA. METHOD: Data of consecutive patients attending our intractable epilepsy clinic over a 2 1/2-year period were reviewed, and patients with at least one seizure a month, who had been initiated on either or a combination of LEV, VPA, or OXC, were included for analysis. Data regarding behavioral adverse effects, daytime somnolence (EDS), and weight changes were collected apart from those regarding any major effect necessitating dose reduction or discontinuation of the AED. RESULTS: Among a total of 445 patients screened, 292 (93 F, median age: 21years [range: 8-54]; 237 focal and 55 generalized epilepsy) fulfilled inclusion criteria. Median epilepsy duration was 11years. Levetiracetam had been introduced in 114 patients, VPA in 134, and OXC in 151 during the study period. Twenty-three were on LEV+OXC, 27 on LEV+VPA, and 33 on VPA+OXC. Behavioral disturbances (irritability, obsessive manifestations, aggressiveness, and frank psychosis) were observed in 43 patients; 23 on introduction of LEV (20.2%); LEV was discontinued in 10 (9%). Daytime somnolence was reported by 28 patients, 15 on OXC (10%); 8 received oral modafinil for the same, while none discontinued this AED. Only one patient on LEV and 3 on VPA reported EDS. Menstrual disturbances were reported by 9, weight gain by 3, and severe hair loss by 2 females on VPA. CONCLUSION: Behavioral disturbances with levetiracetam are common among patients with refractory epilepsy while somnolence is common with oxcarbazepine. Antiepileptic drugs should be selected with this in perspective.

Differential effects of antipsychotic agents on obsessive-compulsive symptoms in schizophrenia: a longitudinal study.

Indirect evidence supports the assumption that antiserotonergic second-generation antipsychotics (SGA) induce and aggravate obsessive-compulsive symptoms (OCS) in schizophrenia. However, multimodal studies assessing the long-term interaction of pharmacotherapy and psychopathology are missing. Over 12 months, we followed-up 75 schizophrenia patients who were classified into two groups according to antipsychotic treatment: clozapine or olanzapine (group I) versus aripiprazole or amisulpride (group II). We applied the Yale Brown Obsessive Compulsive Scale (YBOCS) and investigated between-group changes over time as the primary endpoint. Group I showed markedly higher YBOCS scores at both time points. Repeated measure analyses of variance (ANOVAs) revealed significant interaction effects of group and time (per protocol sample (PP): p=0.006). This was due to persistently high OCS severity within group I, and decreasing YBOCS scores within group II. OCS severity correlated significantly with the negative and general psychopathology subscales of the Positive and Negative Syndrome Scale (PANSS), as well as with depressive symptoms. The progressive differences in OCS severity between our groups support the assumption of differential pharmacodynamic effects on comorbid OCS in schizophrenia. Further studies should address the pathogenetic mechanism, define patients at risk and facilitate early detection as well as therapeutic interventions.

Suicidal obsessions as dose dependent side-effect of clozapine.

OBJECTIVE: Although numerous reports suggest that different atypical antipsychotics can exacerbate or induce (de novo) obsessive-compulsive symptoms, there is no report of the development of ego-dystonic, suicidal obsessions during treatment with these medications. Here, the authors report the first case of clozapine-induced suicidal obsessions. METHOD: The authors report a case of a patient diagnosed with bipolar disorder and who developed suicidal obsessions in the weeks after the dose of clozapine was increased from 150 mg/day to 300 mg/day. RESULTS: Symptoms quickly resolved after the treatment with clozapine was changed to the treatment with quetiapine and sodium valproate. Suicidal obsessions decreased promptly, within a few days, and disappeared completely when the dose of clozapine was 100 mg/day, quetiapine 600 mg/day, and sodium valproate 900 mg/day, 16 days after the initiation of changes in the medications. CONCLUSION: The case report emphasizes the crucial need of differentiation between genuine suicidal desires and ego-dystonic suicidal obsessions. The authors suggest that in similar cases a change in antipsychotic medications to those with stronger antidopaminergic properties and lower 5HT2 receptor affinity should be considered, but also assume that the use of sodium valproate in treatment of obsessive-compulsive symptoms deserves further study.

Changes in artistic style and behaviour in Parkinson's disease: dopamine and creativity.

We present a PD patient in whom dopamine agonists awoke a hidden creativity that led to a gradual increase in painting productivity evolving to a disruptive impulsive behaviour that shared many features with punding. A dramatic change in painting style related to a more emotional experience during the process of creation developed after treatment onset. This case suggests that changes in creativity in PD seem to be related to dopaminergic imbalance in the limbic system.

Lamotrigine-induced obsessional symptoms in a patient with bipolar II disorder: a case report.

Lamotrigine is an anticonvulsant that appears to have a mainly antidepressant effect and is indicated for the maintenance treatment of bipolar depression. Literature associated with obsessional symptoms related to lamotrigine treatment is limited. We report the emergence of obsessive symptoms during treatment with lamotrigine in a patient who subsequently experienced significant improvement after dose reduction and stopping of this medication. The obsessive symptoms associated with lamotrigine treatment were observed after the lamotrigine dose was increased to 100 mg/day. The possible mechanisms, including inhibition on the presynaptic release of glutamate and alteration of striatal dopamine uptake, are discussed. It is unclear why lamotrigine induces obsessions in some patients. Controlled studies are necessary to identify the population at risk for obsessionality in bipolar illness following treatment with lamotrigine and to investigate a possible dose-response relationship between obsessive symptoms and lamotrigine.

Modulation of quinpirole-induced compulsive-like behavior in rats by environmental changes: implications for OCD rituals and for exploration and navigation.

BACKGROUND: Rats treated chronically with the D2-3 dopamine agonist quinpirole were previously proposed as an animal model of obsessive-compulsive disorder (OCD) since their behavior is based on repeated, compulsive-like persistent traveling between a few places in the open field. The aim of the present study was to determine properties of the physical environment that shape such behavior. For this, quinpirole-treated rats were first exposed to an arena with an array of objects (landmarks) and after the development of compulsive-like behavior, the arena was manipulated by multiplying the number of objects, changing their spacing, relocating object array, or removing the objects. RESULTS: When the number of objects was retained but they were spaced further apart, rat routes converged at 1-2 of the objects and at the corner at which the rats had been introduced into the arena (start corner). When object spacing was retained but their number was increased, the rats traveled between the objects with the routes converging only at the start corner. Finally, when object array was relocated to different places within the arena, the rats extended their routes from the start corner to the object array, regardless of array location. CONCLUSION: Quinpirole-treated rats organized and updated their progression primarily according to the proximal layout of landmarks, but did so with excessive repetitions compared with saline-treated rats. The behavior of quinpirole-treated rats paralleled human OCD rituals that are linked to the immediate physical environment, featuring an excessive rate of performance. Finally, when only a few objects were present, they were perceived by the rats as positional cues (beacons) that routes converged at them. In contrast, in the presence of many objects, the routes passed between the objects as if using them as directional cues.

An association of intrusive, repetitive phrases with lamotrigine treatment in bipolar II disorder.

INTRODUCTION: Bipolar disorder is frequently associated with obsessional symptoms. However, no reports have identified a pattern of obsessionality that is associated with a specific mood stabilizer treatment. METHODS: A chart review was conducted on five patients with bipolar II disorder who spontaneously reported a form of obsessionality characterized by intrusive, recurrent phrases after taking lamotrigine. RESULTS: Development of the phrases occurred from 7-42 years after mood disorder onset and occurred only after initiation of lamotrigine treatment. The phrases improved with lamotrigine discontinuation or dose reduction and recurred with lamotrigine re-challenge or upon dose escalation. CONCLUSION: A possible mechanism for the development of the intrusive phrases involves the influence of lamotrigine on glutamatergic regulation in a bipolar II disorder population vulnerable to the expression of obsessionality. Limitations of this report include its observational nature, small number of cases reported, and confound of concomitant medication use.

Effect of acute intravenous clomipramine and antiobsessional response to proserotonergic drugs: is gender a predictive variable?

BACKGROUND: Previous studies on serotonergic responsivity in obsessive-compulsive disorder (OCD) showed about 50% of patients experiencing an acute worsening of OC symptoms when administered meta-chlorophenylpiperazine or i.v. clomipramine. The aim of this study was to determine what variables influence the response to acute i.v. clomipramine. Could this response be predictive of the response to chronic treatment with two serotonergic drugs with differing selectivity profiles: clomipramine and fluvoxamine? METHODS: Fifty OC patients were consecutively recruited. All underwent a challenge with 25 mg i.v. clomipramine and placebo and were administered 10-week oral clomipramine or fluvoxamine according to a double-blind design. The efficacy of the antiobsessional treatment was evaluated by Yale-Brown Obsessive-Compulsive Scale and Clinical Global Impression scale scores. RESULTS: Obsessions worsened in 42% patients as rated by change values in 100-mm visual analogue scale scores for the clomipramine vs. placebo infusion. There was a significant difference in gender distribution between "worsened" and "unchanged" patients, since female subjects were more frequently "unchanged." Thirty-one patients completed the 10-week treatment. According to both qualitative and quantitative evaluations, female subjects showed a better antiobsessional response, and this difference was enhanced in the clomipramine-treated group. CONCLUSIONS: Results suggest a role for reproductive hormones in the pathophysiology or treatment of OC patients.

Obsessional symptoms associated with risperidone treatment.

OBJECTIVE: The aim of this paper is to report the occurrence of obsessional symptoms with risperidone treatment in a patient with no past history of obsessive-compulsive symptoms. CLINICAL PICTURE: A 26-year-old, single, Chinese lady with a chronic untreated schizophrenic illness was prescribed risperidone after she experienced side effects with other antipsychotic medication. After the second week on risperidone, she developed obsessional symptoms. TREATMENT AND OUTCOME: The obsessional symptoms responded to treatment with low dose clomipramine. CONCLUSION: The potential for the newer antipsychotic medication to precipitate or exacerbate obsessive-compulsive symptoms during treatment for schizophrenia must be borne in mind.

Long-term adverse effects of brief marijuana usage.

Marijuana is known to produce a number of short-lived side effects as well as longer lasting adverse effects resulting from chronic usage. The author wishes to draw attention to the occurrence of long lasting adverse effects which appear to be brought on by one-time usage of marijuana. The author has seen several such cases, 2 of which are presented here. These individuals were functioning well in the presence of mild to moderate psychopathology prior to using marijuana. Subsequently they functioned on a lower level for at least several months and the degree of psychopathology noted was greater.