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PubMedDate not supplied

[Value of fluoxetine in obsessive-compulsive disorder in the adult: review of the literature].

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) with demonstrated efficacy in the treatment of major depressive episodes. Since 1985, it has been evaluated for the treatment of obsessive-compulsive disorder (OCD). The orbitofrontal cortex and caudate nucleus are cerebral structures believed to be involved in the pathogenesis of OCD, since hyperactivation of these territories in the basal state is corrected upon remission of symptoms induced by therapy with an SSRI or by behavioral psychotherapy. Furthermore, several studies have found abnormalities in serotoninergic transmission in the orbitofrontal cortex and SSRIs can increase serotonin release by desensitizing 5HTID autoreceptors. OCD is a severe, chronic psychiatric disorder frequently complicated by depressive episodes. Here we review the clinical trials of fluoxetine listed in the Medline and Embase computerized databases. Fluoxetine was found to be effective in OCD in all the published open-label studies as well as in placebo-controlled trials with an effective dose range of 40 to 60 mg daily. Clinical evaluation was carried out by using specific scales such as the Y-BOCS or NIMH-OC and improvement was observed after several weeks of therapy. These studies comprising an extended phase showed that efficacy was maintained--for three years in the longest study--resulting in a higher percentage of responders relative to the treatment initiation phase. A comparison of fluoxetine and clomipramine showed comparable efficacy and a superior safety profile, both in terms of anticholinergic side effects and cardiotoxicity or overdosage. The relapse rate was similar with both drugs. In the four meta-analyses appearing in the databases, two studies found similar efficacy for clomipramine and fluoxetine. There are few studies which directly compare the different SSRIs, apart from a comparison of fluoxetine and sertraline showing that both drugs have similar efficacy. With clomipramine, the SSRIs represent the first-line treatment recommended by the experts, in association with behavioral therapy to improve and maintain the clinical response over the long term. The guidelines recommend an optimal fluoxetine dose of 40 to 60 mg daily with a minimum treatment duration of 1 to 2 years. Efficacy should not be evaluated before 8 weeks to allow for onset of the therapeutic effects. Fluoxetine was found to have a good safety profile in these studies and the adverse effects described (insomnia, headache, diminished libido) rarely led to discontinuation of the treatment. Adverse effects such as nervousness or insomnia at the start of therapy were predictors of a good response to fluoxetine, as were the presence of remissions, the absence of prior pharmacologic therapy and a high impulsiveness score. A long history of the disorder, severity of the symptoms, collection obsessions, washing compulsions, obsessional slowness and comorbidity with a schizotypic personality or vocal or motor tics were associated with a poorer response. Fluoxetine also alleviates collateral depressive symptoms by significantly reducing suicidal ideation and impulsiveness in OCD patients. Our study indicates that fluoxetine is effective and well tolerated in OCD, placing it among the first-line treatments recommended by consensus conference guidelines.

Clinical Trials as Topic↗
PubMed1992

Hypochondriasis and obsessive compulsive disorder.

Hypochondriasis and OCD differ conceptually in the degree to which the patient's disease concerns are experienced as an intrusive mental event or a reasonable psychological response to a realistic health threat, in the degree to which the ideation is resisted, and in the presence of somatic sensations and medical help-seeking. There are, however, some similarities between the conditions, including the development of excessive, stereotyped, repetitive behaviors in an attempt to allay their anxiety. Empirical data on the degree of overlap between the conditions are too limited to permit definitive conclusions. The little that we do know, however, suggests that (1) the prevalence of OCD in hypochondriasis is probably elevated, but not extraordinarily so; (2) the prevalence of hypochondriasis in OCD is unknown; (3) fears about disease, illness, and injury are one of the more common forms of obsessions seen in OCD; and (4) there are several ill-defined and largely unexplored conditions, such as disease phobias, which appear to be very similar to both OCD and hypochondriasis. Clinical experience suggests that there may be a subgroup of hypochondriacal patients who are closer to the anxiety disorders in general and to OCD in particular. This subgroup might respond to the newer, antiobsessional, serotonin reuptake blocking agents.

Adult↗
PubMed1992

Assessment of severity and change in obsessive compulsive disorder.

Useful clinician-rated measures of OCD are now available. The Y-BOCS and NIMH Global OC both seem suitable for monitoring outcome in drug trials of OCD. These two scales seem relatively specific for symptoms of OCD and are sensitive to drug-induced changes in symptoms. Neither the Y-BOCS nor the NIMH Global OC confuse trait with state. There are ample data suggesting that the Y-BOCS is reliable and valid scale. Unlike some of the symptom inventories, such as the LOI and MOCI, final scores on the NIMH Global OC and Y-BOCS are not influenced directly by the type or number of obsessions and compulsions present. A computer-administered version of the Y-BOCS has been developed. Currently available patient-rated instruments suffer from serious shortcomings, including insensitivity to change and poor representation of patients with mono-symptomatic clinical pictures (e.g., hoarding alone). Some rating scales have been adapted for use in children with OCD. Several groups, including our own, have elected to use change scores on the 10-item Y-BOCS and a global measure of OCD, such as the NIMH Global OC or modified OGI, as the principal outcome variables in drug trials in patients with OCD. Several studies have selected a 35% decrease in Y-BOCS scores from baseline as indicative of clinically significant improvement. A limitation of all single-item global measures is that they cannot be resolved into smaller components. The more fine-grained analysis that is possible with the multi-item Y-BOCS makes it more desirable as a primary outcome measure, with a global scale as a secondary outcome measure.

Adult↗
PubMed1992

Clomipramine, clonazepam, and clonidine treatment of obsessive-compulsive disorder.

Serotonergic reuptake inhibitors have been the primary medications for treatment of obsessive-compulsive disorder (OCD); however, other serotonergic and alpha 2-adrenergic medications also have been reported to reduce obsessive-compulsive symptoms. In this study, we compare three medications with reported efficacy in OCD to a control medication, diphenhydramine, a medication without theoretical or demonstrated treatment benefit. The three active medications were clomipramine, a serotonergic reuptake inhibitor; clonazepam, a benezodiazepine with putative serotonergic properties; and clonidine, an alpha 2-adrenergic agonist. Twenty-eight subjects with DSM-III-R diagnosis of OCD rotated through 6-week trials of each of the four medications in a randomized, double-blind, multiple crossover protocol. Clomipramine and clonazepam were both effective relative to the control medication in reducing OCD symptoms. There was a significant cross-response between these two medications; however 40% of subjects failing clomipramine trials had a clinically significant response to clonazepam treatment. The control medication, diphenhydramine, itself produced a significant decrement in symptoms, whereas clonidine was ineffective in reducing OCD symptoms. Clonazepam improvement was unrelated to changes in anxiety and occurred early in treatment. Clonazepam was significantly more effective than the other medications during the first 3 weeks of treatment. The results confirm the efficacy of clomipramine in the treatment of OCD and suggest that clonazepam might be a useful alternative treatment for patients with this disorder.

Adult↗
PubMed2004

A qualitative analysis of nonresponse: management of treatment-refractory obsessive-compulsive disorder.

Serotonin reuptake inhibitors (SRIs), especially potent ones given at high doses over long periods of time, are often effective in the treatment of obsessive-compulsive disorder (OCD). However, a large percentage of patients do not respond to treatment with SRIs, and those who do respond often do not fully remit, which should be the standard goal of treatment in OCD. If a patient has been treated for several months and has not yet responded to treatment with several SRIs, the physician should perform a careful assessment of resistant and/or residual clinical symptoms and any comorbid conditions to determine which next-step treatment would be the most appropriate. One strategy for patients who have not responded to treatment with an SRI is to switch them to a serotonin-norepinephrine reuptake inhibitor, because some patients may respond better to agents that target multiple systems. Another promising approach is the augmentation of SRIs with neuroleptics. In addition, open trials have shown that intravenous (IV) clomipramine and IV citalopram may be effective in the treatment of resistant OCD. Novel pharmacotherapeutic treatments and electroconvulsive therapy have been attempted, with mixed success. Recently, researchers have been studying repetitive transcranial magnetic stimulation, vagal nerve stimulation, and neurosurgical approaches such as gamma knife capsulotomy and deep brain stimulation to learn if these procedures are effective in treating treatment-resistant OCD. Repetitive transcranial magnetic stimulation has possibilities not only as a therapy but also as an instrument that can help researchers describe the neurocircuitries involved in OCD. More results are needed before the effectiveness of the nonpharmacologic treatments for OCD can be determined.

Adrenergic Uptake Inhibitors↗
PubMed2005

Obsessive compulsive disorder--prevalence in Xhosa-speaking schizophrenia patients.

Obsessive compulsive disorder (OCD) has been reported in up to 31% of schizophrenia sufferers. This study evaluated the presence of OCD in a Xhosa-speaking schizophrenia group. Xhosa patients (N = 509, including 100 sibships) with schizophrenia were recruited from hospital and community settings. The patients underwent a structured clinical interview for the presence of lifetime co-morbid schizophrenia and OCD. Only 3 patients (0.5%) fulfilled criteria for OCD. No concordance for OCD was noted in the sibship group. Our findings differ from those in other parts of the world, and if replicated, might suggest unique protective environmental or genetic factors for OCD in certain ethnic groups.

Adult↗
PubMed2005

[When thoughts become compulsions. Obsessive-compulsive disorder in children].

OCD (obsessive-compulsive disorder) is characterised by the presence of annoying, unwelcome and intrusive obsessions and compulsions. The obsessions appear over and over and the child recognize them as something strange and unwelcome, but at the same time they are clearly a product of his/her own mind and not a hallucination or a thought disorder as seen in psychotic disturbances. Compulsions are imposed actions that the child feels it has to perform, often in a certain pattern. Both children and adults can suffer from OCD. Almost 2/3 of adults with OCD report onset of their OCD symptoms in childhood or early adolescence. Previously, OCD among children and adolescents was considered to be rare, but newer epidemiologic surveys show that 1-1% of children and adolescents suffer from OCD in such a degree that they fulfil the diagnostic criteria. The prevalence varies surprisingly little in various countries regardless of cultural background.

Adolescent↗
PubMed1992

A double-blind, placebo controlled study of trazodone in patients with obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder (OCD) have been shown to be preferentially responsive to serotonin (5-HT) uptake-inhibiting antidepressants including clomipramine, fluoxetine, fluvoxamine, and sertraline. The nontricyclic antidepressant, trazodone, also possesses serotonin reuptake inhibiting properties and has been reported to be efficacious in OCD in several case reports and open trials. In order to investigate trazodone's potential antiobsessive efficacy in a controlled fashion, 21 patients with OCD were entered into a double-blind, parallel design comparison of trazodone and placebo. There were no significant differences in baseline rating scores of OCD or depressive symptoms between those who entered the trazodone phase (N = 13) versus those who entered the placebo phase (N = 8). As measured by standardized OCD and depression rating scales, there was no significant difference in OCD or depressive symptoms in the 17 patients who completed 10 weeks of trazodone (N = 11, mean daily dose, 235 +/- 10 mg) versus 10 weeks of placebo (N = 6) administration. In comparison to clomipramine and fluoxetine treatment which we have found to be associated with greater than 95% reduction in platelet 5-HT concentration, there was only a 26% mean reduction in platelet 5-HT concentration after 10 weeks of trazodone administration. These results indicate that trazodone lacks substantial antiobsessive effects and is associated with only modest reductions in platelet 5-HT concentrations.

Adolescent↗
PubMed2005

Computerized tomography compared with radiography in the diagnosis of lateral trochlear ridge talar osteochondritis dissecans in dogs.

In this retrospective study, we compared the value of radiographic and computerized tomographic (CT) imaging for the diagnosis of lateral trochlear ridge talar osteochondritis dissecans (LTRT-OCD) in 11 tarsocrural joints. The flexed dorsoplantar skyline and the planta-rolateral-dorsomedial projections were the most reliable for radiographic detection of OCD fragments (in 7 of the 11 joints). Overall, radiography detected OCD fragments in 8 of 11 joints. By contrast, the OCD fragments could be visualized and exactly localized by CT in all 11 joints. Computerized tomography allowed the talar ridges to be inspected without superimposition of any bony structures. This information may be very useful when minimal invasive techniques are used to treat LTRT-OCD lesions. The findings of this study suggest that CT is superior to radiography for making a diagnosis of LTRT-OCD in the dog.

Animals↗
PubMed2006

5-HT2c receptor activation induces grooming behaviour in rats: possible correlations with obsessive-compulsive disorder.

Excessive self-grooming in animal models of obsessive-compulsive disorder (OCD) is regarded as an equivalent of compulsive behaviour in OCD patients. Previous studies have suggested a key modulatory role of certain serotonin2 receptor subtypes both in grooming behaviour and OCD. Certain 5-HT2 receptor agonists were reported to exacerbate symptoms in OCD patients. Here we report that activation of the serotonin2c (5-HT2c) receptor induces self-grooming in rats, which result supports the hypothesis that selective stimulation of central 5-HT2c receptors exacerbates symptoms also in OCD. The present findings may help to understand serotonergic mechanisms underlying psychiatric disorders of the obsessive-compulsive spectrum and may progress the development of novel anxiolytic and anti-OCD medications.

Aminopyridines↗
PubMed1990

Obsessive-compulsive disorder: treatment with serotonin-selective uptake inhibitors, azapirones, and other agents.

Obsessive-compulsive disorder (OCD) has recently been recognized as a relatively common disorder, affecting one in 40 individuals in the United States. OCD has also been demonstrated to be at least partially drug-responsive, although fewer than 20 adequate, fully controlled treatment trials in OCD patients have been reported, all in the last decade. The partially selective serotonin (5-hydroxytryptamine, 5-HT) uptake inhibitor clomipramine has been the most studied drug and uniformly has been found to be of some benefit in patients with OCD. Several recent controlled trials with other, more highly selective 5-HT uptake inhibitors have also shown these drugs to be more effective than placebo. More recently, preliminary data from several studies have questioned whether buspirone, an azapirone with prominent 5-HT-related anxiolytic and possible antidepressant properties, may have direct therapeutic effects in OCD patients or may be a useful adjunct when used in combination with the selective 5-HT uptake inhibitor fluoxetine. These studies are reviewed briefly and evaluated in the context of investigations that used other drugs with serotonergic actions either alone or in combination with selective 5-HT uptake inhibitors in OCD patients.

Anti-Anxiety Agents↗
PubMed1991

A family study of Gilles de la Tourette syndrome.

Previous studies have demonstrated that Gilles de la Tourette syndrome (TS) is a familial disorder and that chronic tics (CT) and obsessive compulsive disorder (OCD) appear to be etiologically related to the syndrome. In the present study we report the results from a study of 338 biological relatives of 86 TS probands, 21 biologically unrelated relatives of adopted TS probands, and 22 relatives of normal subjects. The 43 first-degree relatives of the adopted TS and normal probands constituted a control sample. The rates of TS, CT, and OCD in the total sample of biological relatives of TS probands were significantly greater than in the relatives of controls. In addition, the morbid risks of TS, OCD, and CT were not significantly different in families of probands with OCD when compared to relatives of probands without OCD. These findings provide further evidence that OCD is etiologically related to TS.

Humans↗
PubMed1990

Neurobiology of obsessive compulsive disorder: a possible role for serotonin.

At the current time, it appears that the only medications with consistent antiobsessional effects are the potent serotonin uptake blockers (clomipramine, fluoxetine, and fluvoxamine). Not only is serotonin uptake blockade an apparent prerequisite for clinical improvement, but there is a correlation between the magnitude of clinical response and the reduction in various serotonin markers during treatment with these drugs. Further evidence for the importance of serotonin in pharmacologic mediation of antiobsessional effects comes from a recent study in which administration of a serotonin antagonist (metergoline) to obsessive compulsive disorder (OCD) patients partly reversed the clinical improvement observed with clomipramine treatment. Although these observations have implicated serotonin in the mechanism of antiobsessional drug action, there is still little evidence demonstrating a role for serotonin in the pathophysiology of OCD. This review summarizes various studies of serotonin function in untreated OCD patients and concludes that the most compelling evidence for an abnormality has come from single-dose challenge studies of serotonin receptor agonists in untreated OCD patients. These studies remain controversial, but a preliminary interpretation of the results suggests that OCD patients may be more sensitive than healthy controls to the behavioral effects of one such serotonin agonist, m-CPP. An abnormality in the sensitivity to endogenous serotonin may link OCD research to the broader scientific question of serotonin's role in the modulation of aggression.

Humans↗
PubMedDate not supplied

Gilles de La Tourette's syndrome and some forms of obsessive-compulsive disorder may share a common genetic diathesis.

Family aggregation and twin studies suggest that Gilles de La Tourette's syndrome (TS) and some forms of obsessive-compulsive disorder (OCD) are etiologically related. Neuroanatomically, the structures of the basal ganglia, thalamus and cortex have also been implicated in both TS and OCD suggesting a common neural substrate for these disorders. Neurochemical and neuropharmacological studies have provided less compelling data concerning this heuristically important association. Clinical studies have largely focused on the role of the nigrostriatal, mesolimbic and mesocortical dopaminergic systems in the pathophysiology of TS. In the case of OCD, serotoninergic systems originating in the raphe nuclei and projecting rostrally, have received considerable attention. Recent neuropathological studies of TS have implicated the endogenous opioid peptide, dynorphin, in the pathophysiology of TS. Animal studies have shown that dynorphin can modulate both dopaminergic and serotonergic systems. We have undertaken a cerebrospinal fluid (CSF) study to determine if abnormalities in dynorphin A concentration can be observed in drug-free TS and OCD patients. Preliminary results from this study suggest: 1) that TS patients have an elevated level of CSF dynorphin A (1-8) compared to normal controls; 2) that their level of CSF dynorphin is correlated with the severity of their OCD symptoms; 3) that some, but not all, OCD patients also have high levels of this neuropeptide in their CSF.

Chromosome Mapping↗
PubMedDate not supplied

[Minor neurological signs in obsessive-compulsive disorders].

Present and classic observations allow us to relate the obsessive-compulsive disorder (OCD) with different structural and functional anomalies, disorders and neurological findings which let us elaborate etiopathogenic and therapeutic hypothesis. From this and from our experience in the study about soft neurologic signs (SNS) in psychiatry, we explored 20 patients with OCD (DSM-III), compared with 28 phobic disorders and 20 healthy controls, following a SNS protocol and picking up demographic and clinical variables. We besides administered intellectual efficiency exams (WAIS) and neuropsychological tests (Benton/Bender), blind to the SNS exploration. The OCD group showed a higher global incidence of SNS, and especially more alterations in movement's coordination in upper extremities and balance with a trend to show more anomalies in dominance-laterality. This higher incidence of SNS didn't correlate with age, familiar or personal psychiatric history, indicators of neuropsychological impairment and pharmacotherapy. Men with OCD showed more SNS than women did, and as men have higher schooling rates, we found a relationship between SNS and schooling. OCD group showed a trend to be more intelligent than healthy controls, reaching significant higher scores in verbal than in manipulative scales. This lower manipulative score could relate with SNS, suggesting a possible concordance or significant relation with neurobiologic hypothesis, but not supporting neuroevolutionary and organic impairment theories as OCD etiopathogenesis.

Educational Status↗
PubMed1988

The potential role of serotonin reuptake inhibitors in the treatment of obsessive compulsive disorder.

The authors examine the role of the serotonergic system in the modulation or genesis of obsessive compulsive disorder and the potential for the use of the new serotonin (5-HT) reuptake inhibitors in its treatment. The data available are still preliminary, but are accumulating rapidly, and appear to hold promise in helping to understand this disorder and treat it more effectively. An overview of the data available is presented to assist in the planning of future research in this subject area. At least six major questions need to be addressed by future work: (1) What are the major hypotheses regarding the involvement of the serotonin system in the modulation or genesis of OCD? (2) Is there a serotonin system defect associated with OCD? (3) Is a serotonin system defect the underlying cause of OCD? (4) Are serotonin reuptake inhibitors effective in the treatment of OCD? (5) Are the effects of the serotonin reuptake inhibitors that are effective in treating OCD mediated via the serotonin system or via another mechanism? and (6) Are these drugs worth pursuing as treatment of OCD?

Adolescent↗
PubMedDate not supplied

Computerized blood flow analysis for decision making in the treatment of osteochondritis dissecans.

Patients presenting the radiologic appearance of osteochondritis dissecans (OCD) require a decision as to further treatment. This often requires an invasive procedure. The noninvasive technique of computerized blood flow analysis (CBFA) has been used in 13 patients with OCD. In clinically early disease (four patients), there is always decreased flow in the area distal to the OCD lesion. Patients with intermediate OCD (four patients) showed characteristics of healing reflected in increased flow to the OCD lesion. These patients were left under observation and underwent spontaneous healing. Patients who showed no increase in flow or had decreased flow in the area of involvement (four patients) were clinically found to be nonviable OCD and required surgical intervention. The technique of CBFA therefore holds promise for decision making in the management of this disease.

Adolescent↗
PubMed1978

Possible immediate hypersensitivity reaction of the nasal mucosa to oral contraceptives.

Nasal provocation tests with suspension of oral contraceptive drugs (OCD) as well as of their components (Estrogen, Progestin, Non-hormonal components) were performed in two groups of women, mostly suffering from perennial rhinitis or pollinosis, and all taking oral contraceptive drugs. Thirteen of the 15 patients from the first experimental group, in whom the increase of the nasal complaints was anamnestically related to the oral contraception, and three of the 34 patients from the second experimental group (without anamnestical relation to the oral contraception) demonstrated a positive nasal mucosa response after topical challenge with OCD. All OCD positively reacting patients showed also a positive nasal mucosa response after challenge with the Estrogen and one patient also after Progestin challenge. Non-hormonal components did not cause any reaction. This nasal mucosa response was interpreted as a possible allergic reaction. Type I (immedicate hypersensitivity of the nasal mucosa due to Estrogen in blood contraceptives. This response begins within 10 minutes, reaches its maximum within 30 minutes, and does not disappear completely within 60 minutes in most patients. None of the patients from control groups (atopy--without OCD; OCD takers--without atopy; male volunteers without atopy) demonstrated any positive nasal mucosa response to OCD or their components.

Contraceptives, Oral↗