Harold J.G.M. van Megen

Pentagastrin induced panic attacks: enhanced sensitivity in panic disorder patients.

The effects of pentagastrin, a synthetic analogue of the cholecystokinin tetrapeptide (CCK4), were studied in 15 patients with panic disorder and 15 healthy controls. Three different intravenous dosages of pentagastrin (0.1, 0.3 and 0.6 µg/kg) and saline were investigated. Subjects were randomly allocated to two of the four treatment groups and tested on two separate occasions, 1 week apart, using an unbalanced double-blind incomplete block design. The mean panic rate with pentagastrin was 55% (12/22) for patients and 5% (1/22) for controls. None of the subjects panicked with saline. The frequency of panic attacks between the three pentagastrin doses in patients was not different. One control subject had a panic-like attack at the highest dose of pentagastrin. These findings concur with previous studies on the panicogenic effect of CCK4 and pentagastrin and suggest a greater sensitivity for CCK receptor agonists in patients suffering from panic disorder than in healthy controls.

Cholecystokinin in anxiety

Cholecystokinin (CCK) plays an important role in both the alimentary tract and the central nervous system (CNS). At present it seems to be the most abundant neuropeptide in the CNS. This paper reviews the CCK neuronal system and its interactions with gamma-aminobutyric acid (GABA) and serotonin (5-hydroxytryptamine; 5-HT). In addition, its putative role in anxiety will be discussed on the basis of animal data and studies in healthy volunteers and panic disorder patients. According to these investigations, the CCK4 challenge test fulfills most criteria for an ideal panicogenic agent and evidence has been found that CCKB receptor antagonists might possess anxiolytic properties in man.

Spatial working memory deficits in obsessive compulsive disorder are associated with excessive engagement of the medial frontal cortex.

Recent studies have shown that obsessive compulsive disorder (OCD) is associated with a specific deficit in spatial working memory, especially when task difficulty (i.e., working memory load) is high. It is not clear whether this deficit is associated with dysfunction of the brain system that subserves spatial working memory, or whether it is associated with a more generalized effect on executive functions. In contrast to studies in healthy volunteers and schizophrenia, spatial working memory in OCD has not been investigated before using functional neuroimaging techniques. We conducted a functional MRI study in 11 treatment-free female patients with OCD and 11 for sex-, age-, education-, and handedness pairwise-matched healthy controls in order to assess performance on a parametric spatial n-back task as well as the underlying neuronal substrate and its dynamics. Patients with OCD performed poorly at the highest level of task difficulty and engaged the same set of brain regions as the matched healthy controls. In this set, the effect of difficulty on magnitude of brain activity was the same in patients and in controls except for a region covering the anterior cingulate cortex. In this region activity was significantly elevated in patients with OCD at all levels of the parametric task. These findings do not provide evidence for a deficit of the spatial working memory system proper, but suggest that the abnormal performance pattern may be secondary to another aspect of executive dysfunctioning in OCD.

A double blind comparison of venlafaxine and paroxetine in obsessive-compulsive disorder.

While the usefulness of clomipramine and selective serotonin reuptake inhibitors (SSRIs) in obsessive-compulsive disorder (OCD) has been established, the efficacy of serotonin-norepinephrine reuptake inhibitors remains to be determined. This report describes the first randomized double-blind comparison study of an SNRI in patients with obsessive-compulsive disorder. The current study compares the efficacy and tolerability of venlafaxine with paroxetine. One hundred and fifty patients with primary OCD according to DSM-IV criteria were randomly assigned in a 12-week double-blind trial to receive dosages titrated upward to 300 mg/d of venlafaxine (n = 75) or 60 mg/d of paroxetine (n = 75). Primary efficacy was assessed by the change from baseline on the Yale-Brown obsessive-compulsive scale (Y-BOCS). Other assessments throughout the trial included the Hamilton depression rating scale, and the Hamilton anxiety rating scale. An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 7.2 ± 7.5 in the venlafaxine group and of 7.8 ± 5.4 in the paroxetine group. In both treatment groups, a responder rate (decrease > 35% on the Y-BOCS) of approximately 40% was found. There were no significant differences between venlafaxine and paroxetine with regard to response or responder rates. The incidence of adverse events for venlafaxine and paroxetine was comparable. The most common side effects for venlafaxine were somnolence, insomnia, a dry mouth, and sweating; and for paroxetine somnolence, sweating, nausea, and headache. These results show that venlafaxine was equally effective to paroxetine in treating patients with OCD. Venlafaxine may be a useful therapy for obsessive-compulsive patients, but is not superior to SSRIs.

Axis I and II comorbidity in a large sample of patients with obsessive–compulsive disorder

BACKGROUND No study has reported yet on the prevalence of both comorbid DSM-IV axis I and personality disorders in a large cohort of OCD patients, and little is known about differences in clinical characteristics between OCD patients with and without comorbid symptoms. OBJECTIVE To examine the cross-sectional prevalence of comorbid DSM-IV axis I, and personality disorders in a population of patients with primary obsessive-compulsive disorder (OCD). METHOD 420 outpatients with OCD were evaluated for comorbid pathology, demographic, and clinical characteristics. RESULTS Forty-six percent of the patients were diagnosed with a comorbid disorder. Twenty-seven percent met the criteria for at least one comorbid axis I disorder, 15.6 percent for a comorbid personality disorder, and 20.4 percent for both a comorbid axis I disorder and a personality disorder. LIMITATIONS A limitation of the current study is that the sample was drawn from a psychiatric department specialised in anxiety disorders, which might have underestimated the rate of comorbid diagnoses. CONCLUSION Comorbid diagnoses occur less frequently than would be expected on the basis of comparable comorbidity studies in OCD. Associated axis I comorbidity did not affect clinical severity of OCD, but was related to higher levels of depression and anxiety, whereas axis II comorbidity impaired to a higher extent the overall functioning.

Use of factor analysis to detect potential phenotypes in obsessive-compulsive disorder.

This study aimed to identify symptom dimensions in obsessive-compulsive disorder (OCD) in order to reveal distinct clinical phenotypes. Factor analysis of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) checklist on item level was performed on data from 335 outpatients with primary OCD. The relationship of demographic and clinical characteristics to the resulting factor scores was examined. A principal component analysis identified the following five consistent symptom dimensions: (1) contamination and cleaning, (2) aggressive, sexual and religious obsessions, (3) somatic obsessions and checking, (4) symmetry and counting/arranging compulsions and (5) high-risk assessment and checking. We observed significant differences in sex distribution, age of onset, Y-BOCS scores and familial prevalence of OCD in relation to the symptom dimensions. These findings provide further evidence for distinct clinical phenotypes in OCD.

The cholecystokinin-B receptor antagonist CI-988 failed to affect CCK-4 induced symptoms in panic disorder patients

The effects of the cholecystokinin-B (CCK-B) receptor antagonist CI-988 on symptoms elicited by the cholecystokinin tetrapeptide (CCK4) were studied in DSM-IIIR patients with panic disorder. The study employed a double-blind, two-period incomplete block design. Patients (n=14) received two different dosages of CI-988 (50 mg or 100 mg) or placebo 2 h prior to an IV bolus injection of CCK4 (20 µg) on two separate occasions. The primary efficacy parameter was the total intensity score on the Panic Symptoms Scale (PSS). Secondary parameters were the number of panic symptoms, time to and occurrence of the first panic symptoms, duration of symptoms, intensity of apprehension and the percentage of patients who did not have a panic attack. The PSS failed to show a statistically significant treatment effect on any of these outcome measures. The average panic rate was 50%, 14.3% and 37.5% after placebo, 50 and 100 mg CI-988, respectively. The differences in panic rate were not statistically significant. The results of this study suggest that CI-988 in doses up to 100 mg is not effective in reducing symptoms of panic anxiety induced by CCK4.

Effect of a pharmacological intervention on quality of life in patients with obsessive-compulsive disorder.

Patients with obsessive–compulsive disorder (OCD) not only suffer from obsessive–compulsive symptoms, but also the disorder is associated with aberrant social functioning and a diminished quality of life (QoL). Although studies concerning the effect of treatment interventions on symptoms are common, studies with regard to the effect of treatment interventions on QoL are scarce. We examined the effect of a pharmacological intervention on QoL in 150 patients with OCD. Furthermore, we studied whether two different drugs, venlafaxine and paroxetine, differed in their effect on QoL. Finally, we examined whether any found improvement in QoL was related to improvement in symptoms and/or the baseline self-directedness score, which is one of the character dimensions of the psychobiological model of Cloninger. We demonstrated that QoL, as assessed with the Lancashire Quality of Life Profile, improved following pharmacological intervention, for which paroxetine and venlafaxine appeared to be equally effective. Furthermore, neither improvement in symptoms, nor baseline self-directedness, was associated with the improvement in QoL.

Symptom dimensions in obsessive-compulsive disorder: Factor analysis on a clinician-rated scale and a self-report measure

Although obsessive-compulsive disorder (OCD) is regarded as a unitary nosological entity, it encompasses a rich variety of heterogeneous mental and behavioural phenomena. The identification of clinical subtypes within this broad concept has been a focus of attention in recent years. In the present study, we administered a clinician-rated scale, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) with the Y-BOCS Symptom Checklist (Y-BOCS CL), as well as a self-report questionnaire, the Padua Inventory revised (PI-R), to 150 outpatients with OCD. A principal component analysis on the Y-BOCS CL, along with the PI-R, identified 6 consistent symptom clusters: (1) contamination obsessions and cleaning compulsions, (2) sexual/religious/somatic obsessions and checking, (3) high risk assessment and checking, (4) impulses and fear of loss of control, (5) need for symmetry and exactness, and ordering and counting compulsions, and finally (6) rumination. The Y-BOCS CL and PI-R showed great overlap and consistency regarding content and severity of the OCD symptoms. On inspection of items with identical content, only half of the items showed significant agreement. Both inventories have unique factors: rumination is represented solely in the PI-R, somatic obsessions and checking solely in the Y-BOCS CL. This means that the use of both clinician-administered and self-report measures is recommended, so that the entire spectrum of symptoms is represented.

A score for predicting response to pharmacotherapy in obsessive-compulsive disorder.

Although there have been many attempts to find predictors of therapeutic response to antidepressant treatment of obsessive–compulsive disorder (OCD), few reports have evaluated the joint predictive value of a number of clinical characteristics. This study aimed to identify clinical predictors of outcome in OCD, and to develop an easily applicable method to predict response to drug treatment. One hundred and fifty patients with primary OCD according to DSM-IV criteria were randomly assigned in a 12-week, double-blind, comparison trial with a selective serotonin reuptake inhibitor (paroxetine), and a serotonin-noradrenaline reuptake inhibitor (venlafaxine). The primary efficacy parameter was the Yale–Brown obsessive–compulsive scale (Y-BOCS) score, and response to treatment was prospectively defined as a ≥ 35% decrease from the beginning. A stepwise multivariate analysis was used to identify predictors. The absence of previous therapies, moderate baseline severity of obsessive–compulsive symptoms (Y-BOCS score < 23), and low Hamilton Depressive Rating Scale scores (6–15) were found to be prognostic determinants of good response to pharmacotherapy. The prognostic ability of the prediction model to discriminate between responders and non-responders was quantified as the area under the receiver operating/operator characteristic curve (ROC area), which was 0.71 (95% confidence interval 0.63–0.8), demonstrating a reasonable discriminatory power. This study is the first to present a model that can estimate by the use of prediction rules the probability of treatment response to antidepressants in patients with OCD.