ABSTRACT Obsessive-compulsive disorder (OCD) is a common heterogeneous psychiatric disorder manifesting with obsessions and compulsions. Obsessions are intrusive, recurrent, and persistent unwanted thoughts. Compulsions are repetitive behaviors or mental acts that an individual feels driven to perform in response to the obsessions. The heterogeneity of OCD includes themes of obsessions, types of rituals, presence or absence of tics, etiology, genetics, and response to pharmacotherapy. Complications of OCD include interpersonal difficulties, unemployment, substance abuse, criminal justice issues, and physical injuries. Areas of the brain involved in the pathophysiology include the orbitofrontal cortex, anterior cingulate gyrus, and basal ganglia. Overall, OCD may be due to a malfunction in the cortico-striato-thalamo-cortical circuit in the brain. Neurotransmitters implicated in OCD include serotonin, dopamine, and glutamate. Numerous drugs such as atypical antipsychotics and dopaminergic agents can cause or exacerbate OCD symptoms. The etiology includes genetics and neurological insults. Treatment of OCD includes psychotherapy, pharmacotherapy, electroconvulsive therapy, transcranial magnetic simulation, and in extreme cases surgery. Exposure and response prevention is the most effective form of psychotherapy. Selective serotonin reuptake inhibitors (SSRIs) are the preferred pharmacotherapy. Higher doses than listed in the package insert and a longer trial are often needed for SSRIs than compared to other psychiatric disorders. Alternatives to SSRIs include clomipramine and serotonin/norepinephrine reuptake inhibitors. Treatment of resistant cases includes augmentation with atypical antipsychotics, pindolol, buspirone, and glutamate-blocking agents.
SourceAvailable from: Daniel J. Mueller (Müller)[Show abstract] [Hide abstract]
ABSTRACT: Second generation antipsychotics (SGAs) have been implicated in the de novo emergence and exacerbation of obsessive-compulsive symptoms (OCS) in patients with schizophrenia. Among SGAs, clozapine, olanzapine, and risperidone are the most prominent agents associated with these sequelae, according to case reports. Comorbid OCS can impede recovery by compromising treatment benefits, medication compliance, and clinical prognoses. Previous reviews of SGA-induced OCS have predominantly focused on descriptive case reports, with limited attention paid toward experimental findings. To address this paucity of data, we sought to review the effects of SGAs on OCS in schizophrenia in the experimental literature, while addressing the role of different treatment (duration, dose, serum levels) and pharmacogenetic factors. Our findings suggest that clozapine confers the greatest risk of OCS in schizophrenia, with 20 to 28 % of clozapine-treated patients experiencing de novo OCS, in addition to 10 to 18 % incurring an exacerbation of pre-existing OCS. Clozapine can also yield full threshold obsessive-compulsive disorder (OCD), in some cases. Olanzapine is another high risk drug for secondary OCS which occurs in 11 to 20 % of schizophrenic patients receiving olanzapine therapy. At this time, there is insufficient experimental evidence to characterize the effects of other SGAs on OCS. Despite some experimental support for the involvement of longer treatment duration and genetic factors in mediating drug-induced OCS, more research is needed to clearly elucidate these associations. Based on these results, schizophrenic patients should be routinely monitored for OCS throughout the course of SGA treatment, particularly when clozapine or olanzapine is administered.Current Psychiatry Reports 11/2014; 16(11):510. DOI:10.1007/s11920-014-0510-8 · 3.05 Impact Factor
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ABSTRACT: Rationale Schedule-induced polydipsia (SIP) is an established model for studying compulsive behaviour in rats. Serotoninergic drugs effectively reduce compulsive drinking on SIP, and high compulsive drinker rats selected by SIP have shown differences in serotoninergic brain activity. However, the specific serotoninergic receptors that modulate compulsive SIP remain unclear. Objective We investigated the functional role of serotonin 5-hydroxytryptamine 2A or C (5-HT2A/C) receptors in compulsive SIP behaviour. Methods Rats were selected for low (LD) versus high drinking (HD) behaviour on SIP. The effects of the systemic administration of the selective serotonin reuptake inhibitor citalopram, selective norepinephrine reuptake inhibitor atomoxetine, serotonin 5-HT2A/C receptor agonist DOI hydrochloride ((±)-2,5-dimethoxy-4-iodoamphetamine), serotonin 5-HT2C receptor antagonist SB242084, serotonin 5-HT2A receptor antagonist ketanserin and M100907 were assessed on SIP. Subsequently, the effects of DOI were tested after the pre-administration of SB242084, ketanserin and M100907 on SIP. Results Citalopram and DOI reduced compulsive drinking in HD compared with LD rats on SIP. In contrast, SB242084 increased compulsive drinking in HD compared with LD rats on SIP. Atomoxetine, ketanserin and M100907 had no effect on SIP. The reduction in water intake produced by DOI was blocked by ketanserin and M100907, but not by SB242084 administration, in HD rats. Conclusions These findings highlight the contribution of serotoninergic 5-HT2A/C receptors compared with noradrenergic mechanisms on SIP and reveal the “therapeutic” activation of serotonin 5-HT2A in the inhibition of the compulsive drinking behaviour in HD rats. Thus, it may represent a potentially new marker of vulnerability and provides additional insight for potential treatments on compulsive behaviours in neuropsychiatric populations.Psychopharmacology 08/2014; 232(4). DOI:10.1007/s00213-014-3699-7 · 3.99 Impact Factor