A cost-effective approach to the use of selective serotonin reuptake inhibitors in a Veterans Affairs Medical Center.
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In light of the tremendous expansion in the number of selective serotonin reuptake inhibitors available to the clinician, the Pharmacy and Therapeutics Committee of the Denver Veterans Affairs Medical Center considered the advantages and disadvantages of fluoxethine, paroxetine, and sertraline, to determine which agent or agents would be carried on the formulary. The committed recommended sertraline as the preferred agent for the treatment of depression, panic disorders, and obsessive-compulsive disorders. The purpose of this retrospective study was to assess the economic outcome of that decision. The study population consisted of patients at the medical center who were receiving selective serotonin reuptake inhibitors during January through March of 1994 and those were receiving these agents between September 1995 and January 1996. The expanded collection period in 1995-96 was due to a relatively new medical center policy to offer 90-day fills on medication to reduce costs. The extended collection period assured a 100% sample of patients receiving these agents. The 1994 fluoxetine to sertraline dosage equivalency ratio was 20 mg:55.6 mg, based on average daily doses of fluoxetine and sertraline of 32.7 and 90.9 mg, respectively. The cost to the medical center for an average daily dose of fluoxetine was $1.86; sertraline cost $1.22 per day. The 1996 fluoxetine to sertraline dosage equivalency ratio (20 mg:51.3 mg) had not changed significantly since 1994, indicating that the dose of 20 mg of fluoxetine remained very close to a 50-mg dose of sertraline. The average daily doses of fluoxetine and sertraline (34.9 mg and 89.7 mg, respectively) were not significantly different than the 1994 doses. Only 33 patients had been prescribed paroxetine (average daily dose, 32.4 mg). On the basis of these values, the average daily cost of fluoxetine to the medical center was $2.01, compared with $1.18 for sertraline and $1.24 for paroxetine. This $0.83 per patient per day drug acquisition cost difference between fluoxetine and sertraline results in a drug cost reduction of $302,674 per year. (+info)
Clarifying an ambiguous functional analysis with matched and mismatched extinction procedures.
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Results of functional analysis were ambiguous in suggesting that self-injurious behavior (SIB) was maintained by escape, sensory reinforcement, or both. To help clarify these results, we compared escape extinction, sensory extinction, and the combined treatments. Sensory extinction proved to be a necessary and sufficient treatment, whereas escape extinction failed to decrease SIB. These analyses helped to clarify the function of SIB and to identify an effective and efficient treatment. (+info)
OCD-Like behaviors caused by a neuropotentiating transgene targeted to cortical and limbic D1+ neurons.
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To study the behavioral role of neurons containing the D1 dopamine receptor (D1+), we have used a genetic neurostimulatory approach. We generated transgenic mice that express an intracellular form of cholera toxin (CT), a neuropotentiating enzyme that chronically activates stimulatory G-protein (Gs) signal transduction and cAMP synthesis, under the control of the D1 promoter. Because the D1 promoter, like other CNS-expressed promoters, confers transgene expression that is regionally restricted to different D1+ CNS subsets in different transgenic lines, we observed distinct but related psychomotor disorders in different D1CT-expressing founders. In a D1CT line in which transgene expression was restricted to the following D1+ CNS regions-the piriform cortex layer II, layers II-III of somatosensory cortical areas, and the intercalated nucleus of the amygdala-D1CT mice showed normal CNS and D1+ neural architecture but increased cAMP content in whole extracts of the piriform and somatosensory cortex. These mice also exhibited a constellation of compulsive behavioral abnormalities that strongly resembled human cortical-limbic-induced compulsive disorders such as obsessive-compulsive disorder (OCD). These compulsive behaviors included episodes of perseverance or repetition of any and all normal behaviors, repetitive nonaggressive biting of siblings during grooming, and repetitive leaping. These results suggest that chronic potentiation of cortical and limbic D1+ neurons thought to induce glutamatergic output to the striatum causes behaviors reminiscent of those in human cortical-limbic-induced compulsive disorders. (+info)
Serotonin and drug-induced therapeutic responses in major depression, obsessive-compulsive and panic disorders.
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The therapeutic effectiveness of antidepressant drugs in major depression was discovered by pure serendipity. It took over 20 years before the neurobiological modifications that could mediate the antidepressive response were put into evidence. Indeed, whereas the immediate biochemical effects of these drugs had been well documented, their antidepressant action generally does not become apparent before 2 to 3 weeks of treatment. The different classes of antidepressant treatments were subsequently shown to enhance serotonin neurotransmission albeit via different pre- and postsynaptic mechanisms. Clinical trials based on this hypothesis led to the development of treatment strategies producing greater efficacy and more rapid onset of antidepressant action; that, is lithium addition and pindolol combination, respectively. It is expected that the better understanding recently obtained of the mechanism of action of certain antidepressant drugs in obsessive-compulsive and panic disorders will also lead to more effective treatment strategies for those disorders. (+info)
A complete genome screen in sib pairs affected by Gilles de la Tourette syndrome. The Tourette Syndrome Association International Consortium for Genetics.
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Gilles de la Tourette syndrome is a neuropsychiatric disorder characterized by waxing and waning multiple motor and phonic tics with a complex mode of inheritance. Previous attempts, which used large multigenerational families to localize susceptibility loci, have been unsuccessful. In this report, the results of the first systematic genome scan, using 76 affected-sib-pair families with a total of 110 sib pairs, are summarized. While no results reached acceptable statistical significance, the multipoint maximum-likelihood scores (MLS) for two regions (4q and 8p) were suggestive (MLS > 2.0). Four additional genomic regions also gave multipoint MLS scores between 1.0 and 2.0. (+info)
Localized orbitofrontal and subcortical metabolic changes and predictors of response to paroxetine treatment in obsessive-compulsive disorder.
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Previous positron emission tomography (PET) studies of patients with obsessive-compulsive disorder (OCD) have found elevated glucose metabolic rates in the orbitofrontal cortex (OFC) and caudate nuclei that normalize with response to treatment. Furthermore, OCD symptom provocation differentially activates specific subregions of the OFC, which have distinct patterns of connectivity and serve different functions. Therefore, we sought to determine the role of specific subregions of the OFC and associated subcortical structures in mediating OCD symptoms, by determining how glucose metabolism in these structures changed with paroxetine treatment of OCD patients. We also sought to determine whether pretreatment OFC metabolism would predict response to paroxetine, as it has for other OCD treatments. Twenty subjects with OCD received [18F]-fluorodeoxyglucose (FDG)-PET scans before and after 8 to 12 weeks of treatment with paroxetine, 40 mg/day. In patients who responded to paroxetine, glucose metabolism decreased significantly in right anterolateral OFC and right caudate nucleus. Lower pretreatment metabolism in both left and right OFC predicted greater improvement in OCD severity with treatment. These results add to evidence indicating that orbitofrontal-subcortical circuit function mediates the symptomatic expression of OCD. Specific subregions of the OFC may be differentially involved in the pathophysiology of OCD and/or its response to pharmacotherapy. (+info)
Psychotic episodes during zonisamide treatment.
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Several articles have appeared over the last years devoted to mental side effects during zonisamide (ZNS) treatment. In this study, we were particularly interested in psychotic episodes. Seventy-four epileptic patients with a history of ZNS treatment were surveyed retrospectively over the period spanning 1 March 1984 to 30 June 1994. They were divided into two groups according to the presence or absence of psychotic episodes during ZNS treatment. We analysed various factors pertaining to psychotic episodes during ZNS treatment. Of the 74 patients 14 had psychotic episodes. We found that the incidence of psychotic episodes during ZNS treatment was several times higher than the previously reported prevalence of epileptic psychosis, and that the risk of psychotic episodes was higher in young patients. In 13 patients, psychotic episodes occurred within a few years of commencement of ZNS. In children, obsessive-compulsive symptoms appeared to be related to psychotic episodes. It is important to terminate ZNS as soon as possible if psychotic episodes develop and never restart, even if seizures become worse. It cannot definitely be proved that ZNS causes psychotic episodes, as information on mental side effects during ZNS monotherapy is scant, but it does appear likely that ZNS contributes to psychotic episodes during polytherapy. (+info)
Obsessive-compulsive disorder and delusions revisited.
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BACKGROUND: The concept of fixed, unshakeable (delusional) beliefs within the context of obsessive-compulsive disorder (OCD) is one that has received varying amounts of attention in the literature, and has not yet received universal acknowledgement. There are good grounds for including these cases within the diagnostic concepts of OCD, with significant implications for clinical management. AIMS: To present cases with unusual OCD, in order to re-evaluate the issue of delusions and OCD. METHOD: The cases of five subjects with delusions in the course of obsessive-compulsive disorder are presented to illustrate 'delusional' OCD. The management and outcome of these cases are discussed. RESULTS: Fixity and bizarreness of beliefs in OCD occur on a continuum from 'none' to 'delusional intensity' and may fluctuate within subjects. CONCLUSIONS: The idea that these cases may represent a form of OCD has implications for management, as, if this is correct, they should be able to respond to appropriate behavioural and/or pharmacological strategies used in OCD. (+info)