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Hallucinogens, serotonin and obsessive-compulsive disorder.

The serotonin (5-HT) neurotransmitter system has been implicated in the pathophysiology of several neuropsychiatric disorders, especially obsessive-compulsive disorder (OCD). Blockade of 5-HT reuptake appears to be an important initial neurobiological event in the therapeutic mechanism of action of antiobsessional drugs. However, for reasons that continue to be poorly understood, clinical improvement following initiation of treatment with 5-HT reuptake inhibitors can take up to eight to 12 weeks, and most patients do not fully improve. Recent data suggest that activation of 5-HT2A and/or 5-HT2C receptors may be important for the improvement of OCD symptoms. Most psychedelic drugs are potent agonists at 5-HT2A and 5-HT2C receptors and their binding potency to these receptors is strongly correlated with their human potency as hallucinogens. This article will briefly review the relevant clinical and preclinical studies relating to the effects of hallucinogens on OCD. These data suggest that activation of 5-HT2 receptors by hallucinogens may lead to acute reduction of, as well as possible longer-lasting beneficial effects on, the symptoms of OCD. Evidence for and against involvement of 5-HT2A and/or 5-HT2C receptors in the therapeutic effects of drug therapies for OCD are reviewed. Issues related to the pharmacological properties and safety of psychedelic drugs, when considered as potential treatments for patients with OCD, are summarized. The authors suggest that controlled trials of potent 5-HT2 agonists in people suffering from OCD are warranted.

Hallucinogens↗

Prevalence of obsessive-compulsive disorder in the British nationwide survey of child mental health.

Obsessive-compulsive disorder (OCD) is a disorder that appears to be under-diagnosed and under-treated, despite the evidence for effective treatments. There are variable estimates of OCD prevalence in the under-16s and published rates give little indication of age trends. The aim of this study was to establish the prevalence and associates of OCD in young people aged 5-15 years. The method was a nationwide (UK) epidemiological study of rates of psychiatric disorder in 5-15 year olds (1999 British Child Mental Health Survey): 10,438 children were assessed. Twenty-five children with OCD were identified (weighted overall prevalence 0.25%; 95% CI 0.14-0.35), with prevalence rising exponentially with increasing age. Compared with normal controls, children with OCD were more likely to be from lower socio-economic class and of lower intelligence. Only three of these children had been seen by specialist children's services. Although OCD is rare in young children, the rate increases towards the adult rates at puberty. Children with OCD have additional psychosocial disadvantage. The majority of the childhood cases identified in this survey appear to have been undetected and untreated.

Adolescent↗

Obsessive compulsive personality disorder and obsessive compulsive disorder: clinical characteristics, diagnostic difficulties, and treatment.

BACKGROUND: The overlap between obsessive compulsive personality disorder (OCPD) and obsessive compulsive disorder (OCD) has received increasing recognition and continues to be a source of much debate. With the advent of new research methodologies, researchers have attempted to distinguish whether OCPD and OCD are two distinct phenomena that can co-occur or whether they are similar, overlapping constructs. METHODS: MEDLINE was used to systematically review the OCPD and OCD literature published between 1991 and 2004. RESULTS: Using the more stringent DSM-IV criteria, results from OCD clinical samples suggest that the majority of individuals with OCD (75%) do not have OCPD. Similarly, results from personality disorder samples suggest that the majority of individuals with OCPD (80%) do not have OCD. CONCLUSIONS: While there is evidence that OCD and OCPD are linked, the literature does not support either one as a necessary or sufficient component of the other.

Humans↗

Visuospatial abilities, memory, and executive functioning in trichotillomania and obsessive-compulsive disorder.

Few studies have compared neuropsychological functioning in trichotillomania (TTM) and obsessive-compulsive disorder (OCD). In OCD, most studies suggest abnormal visuospatial abilities, memory, and executive functioning. We compared 23 TTM, 21 OCD and 26 healthy control individuals on neuropsychological tasks assessing these abilities. Neither the TTM nor the OCD groups suffered from generalized neuropsychological deficits compared to the healthy control group. TTM participants showed increased perseveration on the Object Alternation Task suggesting difficulties with response flexibility. OCD participants showed impaired ability to learn from feedback on the Wisconsin Card Sorting Test. Other executive functions, as well as memory and visuospatial abilities were unimpaired in TTM and OCD. Our data suggest that TTM and OCD are characterized by different patterns of neuropsychological dysfunction.

Adult↗

Treatment benefit and the risk of suicidality in multicenter, randomized, controlled trials of sertraline in children and adolescents.

OBJECTIVE: The aim of this study was to examine the balance between the benefits of treatment and the risk of suicidality in children and adolescents in multicenter, randomized, controlled trials of sertraline versus placebo. METHOD: The published literature was searched for multicenter, randomized, placebo-controlled trials of sertraline for pediatric mental disorders. Four trials were identified: Two (pooled) in pediatric major depressive disorder (MDD; Wagner 2003) and two in obsessive-compulsive disorder (OCD; March et al. 1998; POTS Team 2004). Using intent-to-treat (ITT) analysis populations, the authors calculated the number needed to treat (NNT) for response and remission and the number needed to harm (NNH) for suicidality, and their ratio, for each clinical trial. RESULTS: NNTs ranged from 2 to 10, indicating clinically meaningful benefits. Benefit was greater for OCD than for MDD, and for adolescents as compared with children in MDD. No age effect was apparent for OCD. Suicidality was reported in 8 patients (5 assigned to sertraline and 3 assigned to placebo). All but 1 (a placebo-treated patient in the Pfizer OCD trial) were enrolled in the sertraline MDD trial. The NNH for suicidality in MDD was 64. Treatment emergent suicidality was more common in children (NNH 28.7) than in adolescents (NNH 706.3). Because no patient developed suicidality in sertraline-treated OCD patients, the NNH for sertraline in OCD approaches infinity. CONCLUSIONS: With the stipulation that doctor and patient preferences necessarily play a critical role in the choice of treatment, NNT to NNH ratios indicate a positive benefit-to-risk ratio for sertraline in adolescents with MDD and in patients of all ages with OCD.

Adolescent↗

Pharmacotherapy of obsessive-compulsive disorder in a health maintenance organization.

The adequacy of pharmacotherapy for patients with obsessive-compulsive disorder (OCD) in a large, prepaid HMO was studied. An analysis was made of the computerized records for December 1, 1994, through April 30, 1998, for members of a Kaiser Permanente plan in northern California who were six years of age or older and had had continuous membership during an index year (May 1, 1995, to April 30, 1996) (1,728 million members). A total of 880 adults and 168 children and adolescents with chart-review-confirmed OCD and a pharmacy benefit were identified. The percentage of patients with an adequate drug trial, defined as > or = 56 days of continuous treatment with a serotonin-reuptake inhibitor or phenelzine at dosages at or above established minimal effective dosages, was determined. Forty-three percent of the adults and 28% of the children and adolescents who were newly diagnosed with OCD in the index year had an adequate trial of medication in the year after their first visit for OCD. By the second six months after the index year, only 75.2% of newly treated adults and 60.9% of newly treated children and adolescents continuing in the health plan filled at least one anti-OCD prescription. During the second follow-up year, these figures fell to 60.4% and 38.9%, respectively. Continuing-care patients filling a prescription in the index year were more likely than newly diagnosed patients to fill prescriptions in the two-year follow-up period, but their treatment still decreased substantially. Despite the typically chronic course of OCD, many patients with OCD who were enrolled in a large HMO appeared not to receive an adequate trial of pharmacotherapy or ongoing pharmacotherapy.

Adolescent↗

Impact of craving on alcohol relapse during, and 12 months following, outpatient treatment.

AIMS: This study investigated the relationship between craving in abstinent alcohol-dependent patients measured by the Obsessive Compulsive Craving Scale (OCDS) (Anton et al., 1995) and relapse during and after completion of an intensive outpatient treatment programme. METHODS: In a prospective study, participants were interviewed at entry to, and end of, an outpatient treatment programme, and 12 months after the end of the programme. To measuring craving the OCDS total score by Anton et al. (1995) and the three-factor model by Kranzler et al. (1999) were used. OCDS was administered at the beginning of treatment (when all patients were abstinent), and at the end of treatment in those who were abstinent and had completed the programme. RESULTS: Of 103 alcohol-dependent patients, 74 completed the treatment programme and at follow-up after 12 months 97% of these patients were personally re-interviewed. Thirty-two patients (31%) relapsed during the treatment phase. They had significantly higher craving measured by the total OCDS score and a significantly higher score on the subscales 'obsessions' and 'drinking control and consequences' compared to abstinent patients. Of the 74 patients who completed the programme 16% had a major relapse in the next 12 months. Major relapse was predicted by the total OCDS score and the subscale 'obsessions'. CONCLUSIONS: OCDS total score predicts relapse in outpatient treatment. Treatment and aftercare of patients with high craving should be intensified. In our study design, the subscales of the three-factor model by Kranzler et al. (1999) provided only little information gain compared to the OCDS total score.

Adult↗

A double-blind study of adjuvant buspirone hydrochloride in clomipramine-treated patients with obsessive-compulsive disorder.

In this study, 14 patients with obsessive-compulsive disorder (OCD) who had received at least 3 months of treatment with clomipramine were treated with the anxiolytic agent buspirone in a 10-week, double-blind study. Before the addition of buspirone, these patients as a group had shown a partial but incomplete reduction (averaging 28%) in OCD symptoms during clomipramine treatment alone. Because buspirone has been reported to be efficacious as a sole agent and as an adjunct agent in combination with fluoxetine in patients with OCD, we were interested in assessing whether buspirone added to clomipramine treatment would be associated with further significant reductions in OCD or depressive symptoms. Although adjuvant buspirone treatment was well tolerated in most subjects, mean OCD and depressive symptoms, as evaluated by standardized rating scales, did not significantly change from baseline scores achieved on clomipramine treatment alone, either after the addition of placebo for 2 weeks or buspirone (57 +/- 7 mg/day) for an additional 10 weeks. However on an individual basis, 4 (29%) of the 14 patients did have an additional 25% reduction in OCD symptoms after adjuvant buspirone treatment. This double-blind study suggests that adjunctive buspirone therapy is not generally associated with significant further clinical improvement in OCD or depressive symptoms compared with clomipramine monotherapy, but that there may be a subgroup of patients who do benefit from adjuvant buspirone therapy.

Adult↗

Neurobiology and clinical pharmacology of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a brain disorder with recognizable periods of onset, course, familial occurrence, epidemiology, phenomenology, and treatment response. Several manifestations of pathophysiology are beginning to be defined, although they may represent intermediate pathophysiology rather than primary etiology. Positron emission tomography studies have consistently identified hypermetabolism in the orbitofrontal cortex, caudate nucleus, and, sometimes, anterior cingulate cortex. Neuropsychologic testing frequently identifies abnormalities in visuospatial function. Abnormal levels of cerebrospinal fluid neurotransmitters and neuromodulators are identifiable in untreated patients with OCD and return toward normal levels after effective treatment. The most consistent pathophysiologic finding in OCD points toward an abnormality in serotonin neurotransmission. Therapeutic response to selective serotonin reuptake inhibitors and the absence of improvement with norepinephrine reuptake inhibitors and dopamine antagonists argue strongly for a role of serotonin in the pathophysiology and treatment of OCD. Despite this clear indication from treatment trials, probes and manipulations of the serotonin system and its specific receptors have not provided a useful understanding of specific abnormalities. Clomipramine or potent selective serotonin reuptake inhibitors are the pharmacotherapy of choice for OCD, with a more limited role reserved for monoamine oxidase inhibitors. If one selective serotonin reuptake inhibitor is ineffective, others may be beneficial, in addition to the different proserotonergic and nonserotonergic augmentation strategies that could be useful in treatment of resistant OCD patients. Nondrug therapies are also important in OCD: behavioral therapy is frequently helpful and neurosurgery is sometimes helpful when other treatments fail.

Animals↗

Tourette's syndrome: what are the influences of gender and comorbid obsessive-compulsive disorder?

OBJECTIVE: To explore the influence of gender and comorbid obsessive-compulsive disorder (OCD) on the phenomenology of Tourette's syndrome (TS). METHOD: TS proband groups defined by gender and comorbid OCD status were compared on a variety of sociodemographic variables, clinical characteristics, and perinatal complications. RESULTS: Compared to females, males more often onset with rage and had ever experienced any form of simple tics. Females onset with compulsive tics more often than males. Probands with comorbid OCD were more likely than those without OCD to onset with complex tics. Delivery complications, especially forceps deliveries, were associated with being male and with having OCD. Fetal exposure to relatively high levels of coffee, cigarettes, or alcohol predicted OCD in TS probands. Diagnosis of TS occurred at later ages among females than among males. Males and females displayed different age distributions. CONCLUSIONS: Males and females tend to experience different kinds of symptoms at onset. However, the overall experience of TS appears to be similar for both groups. Perinatal brain injury is implicated in the etiology of TS in some boys. Early brain injury may cause or exacerbate the development of OCD in some TS sufferers.

Adolescent↗

Decrease in caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder patients taking paroxetine.

OBJECTIVE: To measure in vivo neurochemical changes in the caudate nucleus in pediatric obsessive-compulsive disorder (OCD) before and after treatment. METHOD: Single-voxel proton magnetic resonance spectroscopic (1H-MRS) examinations of the left caudate were conducted in 11 psychotropic drug-naive children, aged 8 to 17 years, with OCD before and after 12 weeks of monotherapy with the selective serotonin reuptake inhibitor paroxetine (10-60 mg/day) and 11 healthy children aged 8 to 17 years. A different sample of 8 pediatric OCD patients and 8 healthy children had a 1H-MRS examination of occipital cortex. RESULTS: Caudate glutamatergic concentrations (Glx) were significantly greater in treatment-naive OCD patients than in controls but declined significantly after paroxetine treatment to levels comparable with those of controls. Decrease in caudate Glx was associated with decrease in OCD symptom severity. Occipital Glx did not differ between OCD patients and controls. CONCLUSIONS: These preliminary findings provide new evidence of Glx abnormalities in the caudate nucleus in pediatric OCD and suggest that paroxetine treatment may be mediated by a serotonergically modulated reduction in caudate Glx.

Adolescent↗

Regional cerebral blood flow abnormalities in early-onset obsessive-compulsive disorder: an exploratory SPECT study.

OBJECTIVE: Recent epidemiological and clinical data suggest that obsessive-compulsive disorder (OCD) may be subtyped according the age of onset of obsessive-compulsive symptoms. The regional cerebral blood flow (rCBF) single photon emission computed tomography (SPECT) technique was used to investigate whether the pathophysiology of OCD differs between early- and late-onset OCD subjects. METHOD: Resting rCBF was measured in 13 early-onset (<10 years) and 13 late-onset (>12 years) adult OCD subjects and in 22 healthy controls. Voxel-based rCBF comparisons were performed with statistical parametric mapping. RESULTS: Early-onset OCD cases showed decreased rCBF in the right thalamus, left anterior cingulate cortex, and bilateral inferior prefrontal cortex relative to late-onset subjects (p < .0005, uncorrected for multiple comparisons). Relative to controls, early-onset cases had decreased left anterior cingulate and right orbitofrontal rCBF, and increased rCBF in the right cerebellum, whereas late-onset subjects showed reduced right orbitofrontal rCBF and increased rCBF in the left precuneus. In early-onset subjects only, severity of obsessive-compulsive symptoms correlated positively with left orbitofrontal rCBF. CONCLUSIONS: rCBF differences in frontal-subcortical circuits between early-onset and late-onset OCD subjects were found, both in location and direction of changes. These results provide preliminary evidence that brain mechanisms in OCD may differ depending on the age at which symptoms are first expressed.

Adolescent↗

Refining treatment approaches in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) has emerged as a common but frequently hidden psychiatric disorder which inflicts an intolerable burden on sufferers and demands effective management. For many years, however, OCD was considered treatment resistant and it is only in the past 15 years that effective therapy has become available. The discovery that the symptoms of OCD could be controlled with clomipramine, but not with other tricyclic antidepressants, was a crucial step in the development of effective management of the condition. The ability of clomipramine to treat OCD derives from its potency as an inhibitor of serotonin reuptake. Serotonin reuptake inhibition has become the fundamental requirement for the pharmacological management of OCD. In the past decade selective serotonin reuptake inhibitors (SSRIs) have been shown to be effective in the management of OCD. Meta-analysis comparing the efficacy of clomipramine and SSRIs initially suggest that clomipramine is more effective than SSRIs, but changes in the clinical characteristics of trial populations over time indicate that the meta-analyses may be misleading. In the few direct comparisons of SSRIs and clomipramine, the two treatments have in fact proved equally effective. Attention is now shifting to the impact side effects on efficacy, a particularly important consideration for OCD patients who require long-term medication but are frequently reluctant to take drugs. The limited data available suggest that SSRIs are better tolerated than clomipramine and are therefore more likely to lead to a favourable treatment outcome.

Clomipramine↗

Predictors of response to pharmacotherapy with citalopram in obsessive-compulsive disorder.

Although serotonin reuptake inhibitors (SRIs) are the medications of choice in the treatment of obsessive-compulsive disorder (OCD), only 50-60% of patients respond to a single trial of any of these agents. Improved knowledge of the predictors of response to treatment may have important clinical implications. Data from a large randomized placebo-controlled trial of citalopram in OCD was analysed using logistic regression to determine predictors of response. Demographic (age, sex), clinical (OCD severity and duration, depression severity, prior treatment) and trial variables (citalopram dose, treatment duration) were included. Subjects with longer duration of OCD, more severe OCD symptoms or previous selective SRI use were less likely to be responders in the citalopram trial. In contrast, subjects who received adequate medication doses for sufficient periods of time in the citalopram trial were more likely to be responders. Despite greater awareness of OCD in recent years, there is evidence that the disorder continues to be underdiagnosed and undertreated. The data here emphasize the crucial importance of early diagnosis and treatment of OCD, and of pharmacotherapy with appropriate dose and duration.

Adolescent↗

Dissociative symptoms in patients with obsessive-compulsive disorder.

To clarify the relationship between dissociative symptoms and obsessive-compulsive disorder (OCD), 100 patients with OCD were assessed with standardized instruments measuring symptoms of OCD, dissociation, and depression. Diagnoses of personality disorders and dissociative disorders were made using structured interviews. Compared with a previous study, OCD patients had dissociation scores slightly higher than normal controls and comparable to patients with other anxiety disorders. Patients with elevated dissociation scores had more severe OCD symptoms, were more depressed, and were more likely to have a personality disorder than patients with low dissociation scores. Although dissociative symptoms were frequently reported by OCD patients, symptoms of OCD may also mimic dissociation in some patients.

Adult↗

Do parent and child behaviours differentiate families whose children have obsessive-compulsive disorder from other clinic and non-clinic families?

BACKGROUND: Limited research has been conducted investigating parent and child behaviour during family interactions in families who have a child with obsessive-compulsive disorder (OCD). While a number of authors in the field of childhood OCD have suggested possible parent and child behaviours that are characteristic of these families, few studies have attempted to explore these in a methodologically sound approach. METHOD: This study compared the observed behaviours of parents and children in families whose children were diagnosed with OCD, to families whose children were diagnosed with other anxiety disorders, externalising disorders and no clinical problems. During family discussions, parent and child behaviours and affect were coded using a Likert-scale system. Family members were rated on behavioural dimensions of control, warmth, doubt, avoidance, confidence, positive problem solving, and rewarding independence. RESULTS: Results indicated that parents and children in the OCD group could be clearly differentiated from families in the other groups based on parent and child behaviour. Mothers and fathers of OCD children were less confident in their child's ability, less rewarding of independence, and less likely to use positive problem solving. Children in the OCD group showed less positive problem solving, less confidence in their ability to solve the problem, and they displayed less warmth during their interactions with their parents. CONCLUSIONS: Parents and children in families where there is a child with OCD behave in a different manner during family interactions to other families. These findings offer interesting and important exploratory information relating to observed parent and child behaviour across different clinical and non-clinical groups. Limitations of this study are addressed and directions for further research are discussed.

Adolescent↗

Episodic memory impairment in bipolar disorder and obsessive-compulsive disorder: the role of memory strategies.

BACKGROUND: There is evidence that individuals with bipolar disorder exhibit neuropsychological impairments not only during mood episodes but also when they are euthymic. One of the most consistently reported cognitive problems in euthymic individuals with bipolar disorder is an impairment in verbal episodic memory. Verbal learning and memory depend on individuals' ability to organize verbal information appropriately during learning. The purpose of the present study was (i) to determine whether episodic memory impairment in euthymic individuals with bipolar disorder is mediated by impairments in organization of verbal information during learning and (ii) to compare the characteristics of memory impairment in bipolar disorder with that previously found in obsessive-compulsive disorder (OCD). METHODS: Study participants were 30 individuals with DSM-IV bipolar I disorder (BP-I), 30 individuals with DSM-IV OCD and 30 normal control participants matched for age, gender and education. Participants completed the California Verbal Learning Test (CVLT), a well-established measure of verbal learning and memory that enables assessment of verbal organization strategies during learning. RESULTS: Compared with control subjects, both BP-I and OCD participants showed impaired performance in long-delayed free recall and verbal organization strategies during learning. BP-I participants showed greater long-delay free recall difficulties but not greater verbal organization difficulties during learning than OCD participants. For OCD participants, the long-delay recall impairment was mediated by difficulties using verbal organizational strategies during learning. In contrast, the group difference in long-delayed free recall between BP-I and control participants remained significant even when semantic clustering was introduced as a mediator. This indicated that BP-I participants' long-delayed free recall difficulties were mediated to a lesser extent by difficulties using verbal organizational strategies than for OCD participants. CONCLUSIONS: Verbal episodic memory problems in individuals with bipolar I disorder and OCD are mediated to different degrees by difficulties using semantic clustering encoding strategies compared with control participants.

Adult↗

Impulse control disorders in patients with obsessive-compulsive disorder.

The purpose of the present paper was to identify the rate of prevalence of impulse control disorders (ICD) in patients with obsessive-compulsive disorder (OCD) and to compare patients with OCD with and without ICD with regard to sociodemographic, clinical and prognostic characteristics. Forty-five patients with OCD were assessed by means of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (4th edn, DSM-IV) plus additional modules for the assessment of ICD and examined using the Yale-Brown Obsessive-Compulsive Scale, the Clinical Global Impression, the Beck Depression Inventory, the Hamilton Depression Rating Scale, and the Global Assessment of Functioning. These patients were treated with serotonin re-uptake inhibitors (SRI) and followed for a variable period of time. Individuals with ICD (here defined as including not only the impulse control disorders not elsewhere classified of the DSM-IV, but also other disorders in which impulse control is a prominent feature such as alcohol and drug dependence, paraphilias and bulimia nervosa/binge eating disorder) were compared to those without ICD using the Mann-Whitney U-test and the Pearson's goodness of fit chi2 test. Sixteen patients with OCD (35.5%) displayed comorbid ICD. Patients with ICD were characterized by a significantly earlier age at OCD onset (P=0.04), a more insidious appearance of OCD symptoms (P=0.04), a higher rate of comorbid anxiety disorders (P=0.03), a greater number (P=0.02) and severity of compulsive symptoms (P=0.04), an increased rate of counting compulsions (P=0.02), and a higher number of required SRI trials (P=0.01). When OCD is found in association with ICD, the clinical picture is characterized by a greater severity of the obsessive-compulsive symptoms at presentation and by the requirement of a greater number of therapeutic attempts during follow up.

Adult↗