Autonomic innervation of the nasal mucosa

The nasal passages play a crucial role in the protection and functioning of the lower airways. Consequently the nerve supply of the nasal mucosa is extensive, which is related to an immediate and adequate reaction upon a variety of external and internal stimuli. A brief review of the present knowledge on nasal autonomic innervation and pharmacology will be given. There is special attention to more advanced methods, such as radioligand receptor binding techniques, which might augment our insight in the significance of the nervous system in nasal (patho)physiology. Furthermore data on the secretory activity of the nasal glands in the rat and its neural regulation will be accentuated.     

Decreased thalamic blood flow in obsessive-compulsive disorder patients responding to fluvoxamine

Functional imaging studies have pointed to a role of the orbitofrontal cortex (OFC), striatum and thalamus in the pathophysiology of obsessive-compulsive disorder (OCD). Effective treatment has been found to change brain activity within this circuitry. The aim of the present study was to explore possible differential effects of OCD responders and non-responders to drug treatment on the regional cerebral blood flow (rCBF). Measurements of rCBF were carried out in 15 out of 22 patients with OCD who completed an open-label trial with fluvoxamine. Patients were studied with 99mTc-HMPAO single photon emission computed tomography (SPECT) before and after 12 weeks of treatment. In addition, structural magnetic resonance imaging was obtained on all patients. Regions of interest comprised the OFC, caudate nucleus, putamen and thalamus. Seven patients responded to treatment. Levels of rCBF decreased significantly in the left caudate nucleus and the left and right putamen in both responders and non-responders to treatment. In responders, but not in non-responders, a significant decrease in rCBF was found in the right thalamus. Pre-treatment cerebellar and whole brain HMPAO uptake was significantly higher in responders to treatment compared with non-responders. We suggest that the thalamus plays a central role in the response to drug treatment.     

A double-blind switch study of paroxetine and venlafaxine in obsessive-compulsive disorder

BACKGROUND: The treatment guidelines for obsessive-compulsive disorder (OCD) propose to switch serotonin reuptake inhibitors (SRIs) in case of refractoriness. However, no controlled research has been published yet that prospectively examined the effects of changing SRIs. This article describes the first double-blind switch study of 2 SRIs in patients with OCD. METHOD: 150 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/day of venlafaxine (N = 75) or 60 mg/day of paroxetine (N = 75). Primary efficacy was assessed by the change from baseline on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and nonresponse was defined as less than 25% reduction on the Y-BOCS. After a 4-week tapering phase, 43 nonresponders were switched to 12 additional weeks of the alternate antidepressant, of which 16 patients received venlafaxine and 27 received paroxetine. RESULTS: Eighteen of 43 patients benefited from a switch to the alternate SRI with a mean +/- SD decrease of at least 25% on the Y-BOCS. At the end of 12 weeks, responder rates were 56% for paroxetine (15/27) and 19% for venlafaxine (3/16). An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 1.8 +/- 3.5 in the venlafaxine group and 6.5 +/- 7.1 in the paroxetine group. After 2 consecutive SRI trials, 109 of 150 patients (73%) achieved a Y-BOCS decrease of at least 25%. CONCLUSION: The results of the current study show that 42% of the nonresponders benefited from a crossover to the other SRI, and that paroxetine was more efficacious than venlafaxine in the treatment of nonresponders to a previous SRI trial. Switching SRIs in case of refractoriness may be considered a useful strategy for patients with OCD.     

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

SUMMARY: 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.     

Inadequate pharmacotherapy in patients with obsessive-compulsive disorder

OBJECTIVE: To determine the adequacy of drug treatment for patients with obsessive compulsive disorder (OCD). DESIGN: Retrospective. METHOD: One hundred and fifty outpatients with OCD, admitted at the University Medical Centre in Utrecht, the Netherlands, were evaluated for severity as measured with the 'Yale-Brown obsessive compulsive scale' (Y-BOCS). RESULTS: At the intake, 35% of the patients used no medication, 58% used an antidepressant, less than 1% an antipsychotic and 6% a benzodiazepine. The average active dose was taken by 12% of the patients, 5% took the maximum dosage and 41% too low a dosage. Consequently, 6 out of the 10 patients used the correct medication (antidepressant) and less than 20% used a sufficiently high dosage. Of the patients, 38% had never previously taken antidepressants, 31% had previously used one antidepressant, 17% two different antidepressants and 12% at least three different antidepressants; 13% had taken the antidepressant at the highest dosage, 18% at the average active dosage and 31% at too low (thus ineffective) a dosage. This means that from a pharmacotherapeutic viewpoint not more than 1 in 8 patients had had an adequate treatment history. CONCLUSION: The results of this study show that only 1 in 8 OCD patients were treated appropriately.     

Hemispheric and gender related differences in the midcingulum bundle: a DTI study

The midcingulate cortex and therefore the underlying midcingulum bundle (MCB) as well play a major role in attention. Although a specific structure's function does strongly depend on its neuroanatomical characteristics, research assessing the morphological variability of the midcingulate region is rather sparse. The present study examined the micro- and macrostructure of the MCB in both hemispheres by means of diffusion-tensor imaging. Besides, effects of gender (Female = 40, Male = 39) and handedness (Lefthanders = 45, Righthanders = 34) were assessed as well. Measures of fractional anisotropy, mean diffusion, as well as the white matter volumes of the MCBs were assessed. By integration of multi-modal images, the MCB was isolated and confounding with callosal fibers was avoided. Evidence was found indicating differences between hemispheres and gender regarding both volume and microstructural characteristics of the MCB. Interestingly, gender-related effects seem to be substantially associated with variations in individual brain volumes. Handedness did not emerge as relevant factor in the analyses. These findings might indicate a higher functional connectivity of the left MCB and in males as compared to females.     

On the significance of cholecystokinin receptors in panic disorder

1. 1.Interest in the biological aspects of panic disorder has been focussed mainly on the noradrenergic and serotonergic systems in the brain.

2. 2. Recently evidence has been found that Cholecystokinin (CCK) receptors in the Central Nervous System (CNS) may be involved in panic disorders. This hypothesis is based on the results of animal electrophysiological studies, animal models of anxiety and on challenge test using CCK fragments in humans.

3. 3. In this review, the studies evaluating the putative involvement of CCK, and especially CCK-B receptors, in panic disorder will be discussed.

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. Received: 13 May 1996/Final version: 27 September 1996