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Biomedical subjects

H G Westenberg

Publications and source records attributed to H G Westenberg.

At least 19 recordsLinked to original sources
PubMed2001

[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.

Adult↗
PubMed2001

Characteristics of patients with social phobia and their treatment in specialized clinics for anxiety disorders in the Netherlands.

BACKGROUND: Social phobia frequently occurs in the general population but is probably underreported due to comorbid disorders which mask the social phobia. Another reason might be that patients do not consult their general pratitioner due to embarrassment or an estimation of their condition. There are several treatments available for social phobia, but not enough is known about the efficacy of the different treatments strategies. METHODS: A retrospective, medical record-based study was carried out in four outpatient clinics specializing in treatment of anxiety disorders to investigate the characteristics of 64 patients with a DSM-IV axis diagnosis of social phobia who seeked help for their problems. Therapies for social phobia within these clinics and differences between these clinics were evaluated. RESULTS: Men with a high educational level tended to seek more help and comorbid disorders tended to cause more impairment in functioning. Further, there is a large delay between onset and therapy attendance (mean 14 years). Finally, there was consistency in the treatment of social phobia in these four clinics which consisted of cognitive behavioral therapy and/or medication. LIMITATIONS: The study is retrospective and based on medical records which means there was no objective measurement of the effectiveness of the therapies. CONCLUSIONS: Seventy-five percent of patients improved after treatment independent of the kind of therapy, the occurrence of comorbid disorders and the type of social phobia.

Adult↗
PubMed2001

The effect of olanzapine treatment on monoamine metabolite concentrations in the cerebrospinal fluid of schizophrenic patients.

The mechanism of action of both typical antipsychotics and the atypical antipsychotic, clozapine, may be related to the (changing) interaction of dopamine and serotonin in schizophrenia. This study examined the effect of olanzapine in schizophrenic patients on cerebrospinal fluid (CSF) metabolites of dopamine (homovanillic acid, HVA) and serotonin (5-hydroxyindoleacetic acid, 5-HIAA). Twenty-three male schizophrenic patients, who were drug-free for at least 2 weeks (mean drug-free period of 35 days +/- 43; median 16 days), underwent a lumbar puncture (LP). Patients were subsequently treated with olanzapine 10 mg/day for 6 weeks, after which the LP was repeated. CSF was assayed for HVA and 5-HIAA concentrations. Psychiatric symptoms were rated once a week. Olanzapine significantly increased HVA concentrations and the HVA/5-HIAA ratio while 5-HIAA concentrations were not altered. These changes did not significantly correlate with treatment response. A negative correlation was found between HVA concentrations and negative symptoms after olanzapine treatment. In conclusion, olanzapine treatment increases HVA concentrations and the HVA/5-HIAA ratio in CSF of schizophrenic patients, but these changes are unrelated to its clinical efficacy.

Adult↗
PubMed2000

Serotonergic blunting to meta-chlorophenylpiperazine (m-CPP) highly correlates with sustained childhood abuse in impulsive and autoaggressive female borderline patients.

BACKGROUND: Disturbances of affect, impulse regulation, and autoaggressive behavior, which are all said to be related to an altered function of the central serotonergic (5-HT) system, are prominent features of borderline personality disorder (BPD). A high coincidence of childhood physical and sexual abuse is reported in these patients. Animal studies indicate that early, sustained stress correlates with a dysfunctional central 5-HT system. Therefore, we hypothesize that sustained traumatic stress in childhood affects the responsivity of the postsynaptic serotonergic system of traumatized BPD patients. METHODS: Following Axis I, Axis II, and trauma assessment, a neuroendocrine challenge test was performed with the postsynaptic serotonergic agonist meta-chlorophenylpiperazine (m-CPP) in 12 impulsive and autoaggressive female patients with BPD and 9 matched healthy volunteers. RESULTS: The cortisol and prolactin responses to the m-CPP challenge in BPD patients were significantly lower compared to those in controls. Within the group of patients with BPD, the net prolactin response showed a high inverse correlation with the frequency of the physical (r = -.77) and sexual abuse (r = -.60). CONCLUSIONS: Our data suggest that severe and sustained traumatic stress in childhood affects the 5-HT system and especially 5-HT(1A) receptors. This finding confirms the data from animal research. The blunted prolactin response to m-CPP appears to be the result of severe traumatization and independent of the BPD diagnosis.

Adolescent↗
PubMed2000

The bovine protein alpha-lactalbumin increases the plasma ratio of tryptophan to the other large neutral amino acids, and in vulnerable subjects raises brain serotonin activity, reduces cortisol concentration, and improves mood under stress.

BACKGROUND: Increased brain serotonin may improve the ability to cope with stress, whereas a decline in serotonin activity is involved in depressive mood. The uptake of the serotonin precursor, tryptophan, into the brain is dependent on nutrients that influence the cerebral availability of tryptophan via a change in the ratio of plasma tryptophan to the sum of the other large neutral amino acids (Trp-LNAA ratio). Therefore, a diet-induced increase in tryptophan availability may increase brain serotonin synthesis and improve coping and mood, particularly in stress-vulnerable subjects. OBJECTIVE: We tested whether alpha-lactalbumin, a whey protein with a high tryptophan content, may increase the plasma Trp-LNAA ratio and reduce depressive mood and cortisol concentrations in stress-vulnerable subjects under acute stress. DESIGN: Twenty-nine highly stress-vulnerable subjects and 29 relatively stress-invulnerable subjects participated in a double-blind, placebo-controlled study. Subjects were exposed to experimental stress after the intake of a diet enriched with either alpha-lactalbumin or sodium-caseinate. Diet-induced changes in the plasma Trp-LNAA ratio and prolactin were measured. Changes in mood, pulse rate, skin conductance, and cortisol concentrations were assessed before and after the stressor. RESULTS: The plasma Trp-LNAA ratio was 48% higher after the alpha-lactalbumin diet than after the casein diet (P = 0.0001). In stress-vulnerable subjects this was accompanied by higher prolactin concentrations (P = 0.001), a decrease in cortisol (P = 0.036), and reduced depressive feelings (P = 0.007) under stress. CONCLUSIONS: Consumption of a dietary protein enriched in tryptophan increased the plasma Trp-LNAA ratio and, in stress-vulnerable subjects, improved coping ability, probably through alterations in brain serotonin.

Adolescent↗
PubMed2000

Anxiety disorders: a review of tricyclic antidepressants and selective serotonin reuptake inhibitors.

OBJECTIVE: Anxiety disorders are the most common mental health disorders. While the older tricylic antidepressants (TCAs) are efficacious in the treatment of many anxiety disorders, recent studies with fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) have emphasized the role of serotonin in the aetiology of these conditions. METHOD: We reviewed the efficacy, safety and tolerability of TCAs and SSRIs in the treatment of the most common anxiety disorders, specifically, panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, social phobia and generalized anxiety disorder. RESULTS: Both the TCA and SSRI antidepressants are effective in treating a wide variety of anxiety disorders. SSRIs, due to their greater safety and tolerability, should be the preferred choices in treating anxiety disorders in those instances where TCAs and SSRIs are considered equally effective. In the cases of OCD and social phobia, SSRIs are almost always preferable given that the TCAs do not appear effective in these disorders. CONCLUSION: Further research is needed on the naturalistic long-term use of the TCAs and SSRIs in the treatment of anxiety disorders.

Antidepressive Agents, Tricyclic↗
PubMed1999

Facing the challenge of social anxiety disorder.

Social anxiety disorder is at serious and prevalent disorder that leads to significant disability in the social and professional lives of patients. It is a chronic condition that frequently coexists with other psychiatric conditions such as depression or alcoholism. Pharmacotherapy with benzodiazepines, monoamine oxidase inhibitors and selective serotonin reuptake inhibitors (SSRIs) has been assessed. Alprazolam has modest efficacy, while a more robust response to clonazepam has been reported. Benzodiazepines, however, are not suitable for long-term treatment of a chronic condition such as social anxiety disorder and are ineffective against comorbid depression. Phenelzine has demonstrated efficacy but the need for dietary restrictions has limited its use. Conflicting results have been reported in placebo-controlled trials for moclobemide, with two studies showing moclobemide to be more effective than placebo while recent trials have reported less robust results. Based on clinical evidence, SSRIs are the first-line treatment in social anxiety disorder. The most extensive database for the treatment of social anxiety disorder exists for the SSRI, paroxetine. Three large multicentre, placebo-controlled, trials have been completed. In all three studies, a significantly greater proportion of patients responded to paroxetine treatment compared with placebo. Paroxetine is currently the only SSRI licensed for use in this condition.

Anti-Anxiety Agents↗
PubMed1999

Pharmacology of antidepressants: selectivity or multiplicity?

The understanding of mechanisms of antidepressant action has evolved over time. The strong antidepressant activity of the tricyclic antidepressants (TCAs) has supported the role of both norepinephrine and serotonin (5-HT) in depression and the mechanism involved in antidepressant action. The next generation of antidepressants included the selective serotonin reuptake inhibitors (SSRIs), further supporting the role of serotonin, while the selective norepinephrine reuptake inhibitors such as maprotiline and reboxetine underlined the relevance of norepinephrine. These developments suggest that either facilitation of serotonin or norepinephrine or both may lead to an antidepressant response. The next step was the development of mixed serotonin-norepinephrine reuptake inhibitors (SNRIs), exemplified by venlafaxine and milnacipran. As with the TCAs, the antidepressant activity of SNRIs is based on inhibition of norepinephrine and serotonin reuptake, but unlike TCAs they do not have anticholinergic, antihistaminergic, and cardiotoxic effects. Although norepinephrine is known to stimulate serotonin cell firing rate via the alpha1-adrenoceptors, norepinephrine and serotonin have independent antidepressant actions. The latest development has been the introduction of the noradrenergic and specific serotonergic antidepressant mirtazapine. Its antidepressant effect appears to be related to dual enhancement of central noradrenergic and serotonergic neurotransmission by blockade of alpha2-adrenoceptors. In addition, mirtazapine directly blocks 5-HT2 and 5-HT3 receptors, which may account for its anxiolytic and sleep-improving properties as well as its lack of adverse events that are typical of SSRIs.

Adrenergic alpha-Antagonists↗
PubMed1998

Effects of meta-chlorophenylpiperazine on cerebral blood flow in obsessive-compulsive disorder and controls.

BACKGROUND: A number of studies have shown that the serotonin receptor agonist meta-chlorophenylpiperazine (mCPP) can exacerbate symptoms in patients with obsessive-compulsive disorder (OCD). The aim of the present study was to study the effect of this compound on regional cerebral blood flow (rCBF) in patients and controls. METHODS: Seven OCD patients and 8 healthy controls were randomly allocated to a double-blind challenge study with mCPP (0.5 mg/kg orally). rCBF was measured by 99m-Tc-hexamethyl-propyleneamineoxime single photon emission computed tomography. RESULTS: mCPP did not induce OCD symptoms in patients, but caused a significant decrease in rCBF in OCD patients, but not in controls. The decrease was seen in the reference regions cerebellum and whole brain, and in the frontal cortex, caudate nucleus, putamen, and thalamus. CONCLUSIONS: The effect of mCPP on the reference regions in patients posed methodological problems in the normalization methods. A possible role of the cerebellum in OCD is discussed.

Adult↗
PubMed1998

Serotonin syndrome after challenge with the 5-HT agonist meta-chlorophenylpiperazine.

meta-Chlorophenylpiperazine (mCPP) is a non-selective 5-HT-receptor agonist/antagonist that is used extensively in psychiatry to assess central serotonergic function. We report on three patients who developed symptoms of the serotonin syndrome when they participated in an mCPP (0.5 mg/kg body weight p.o.) challenge test as part of a research protocol. They had relatively high plasma mCPP concentrations. The syndrome did not occur in normal volunteers who had comparable plasma concentrations of mCPP. Investigators should be aware of the possible occurrence of the serotonin syndrome after a single oral dose of mCPP.

Adult↗
PubMed1998

Sumatriptan (5-HT1D receptor agonist) does not exacerbate symptoms in obsessive compulsive disorder.

The non-selective serotonin (5-HT) receptor agonist meta-chlorophenylpiperazine (mCPP) has been reported to elicit symptoms in patients with obsessive compulsive disorder (OCD). MK-212, another non-selective 5-HT receptor agonist, does not seem to induce obsessive compulsive symptoms in OCD patients. The major pharmacological difference between mCPP and MK-212 is their affinity for the 5-HT(ID) receptor. The aim of this study was to explore the role of the 5-HT(ID) receptor in the pathophysiology of OCD, by using a challenge paradigm with the selective 5-HT(ID) receptor agonist sumatriptan (Imigran). A randomized, double-blind, placebo-controlled crossover challenge with sumatriptan (100 mg PO) was performed in 15 OCD patients. Neither the obsessive compulsive symptoms nor mood or anxiety symptoms changed significantly following sumatriptan administration as compared to placebo. Sumatriptan did induce a significant increase in plasma growth hormone (GH) levels. In the present study, no indication were found for the role of the 5-HT(ID) receptor in the pathophysiology of OCD. It should be noted, however, that sumatriptan does not readily pass the blood-brain barrier. Selective 5-HT(ID) receptors with better brain penetrating properties may shed more light on the role of this 5-HT receptor subtype in OCD.

Adolescent↗
PubMed1998

The nature of social anxiety disorder.

The essential feature of social anxiety disorder (social phobia) is a fear of scrutiny by other people in social or performance situations. The level of anxiety experienced by the person with social anxiety disorder is excessive, and results in substantial impairment in the sufferer's social, family, and professional life. Three distinct subtypes of the disorder have been identified: generalized social anxiety disorder, in which the individual fears a multitude of social situations; nongeneralized social anxiety disorder, in which only 2 or 3 situations are feared; and public-speaking phobia. Results from a number of studies suggest that these subtypes of social anxiety disorder may represent distinct clinical syndromes, with the generalized subtype producing the most severe disability. Despite the prevalence of social anxiety disorder and the disability it causes, this condition remains underdiagnosed, and thus undertreated, by clinicians. This review discusses the barriers that prevent people who have this disorder from seeking help, and the steps that clinicians can take to aid their recognition and treatment of the disorder. It is only by effective diagnosis and treatment that the burden of social anxiety disorder will be lifted, allowing patients to resume a normal life.

Diagnosis, Differential↗
PubMed1998

Consensus statement on social anxiety disorder from the International Consensus Group on Depression and Anxiety.

OBJECTIVE: The goal of this consensus statement is to provide primary care clinicians with a better understanding of management issues in social anxiety disorder (social phobia) and guide clinical practice with recommendations for appropriate pharmacotherapy. PARTICIPANTS: The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Other faculty invited by the chair were Julio Bobes, Deborah C. Beidel, Yukata Ono, and Herman G. M. Westenberg. EVIDENCE: The consensus statement is based on the 7 review papers published in this supplement and on the scientific literature relevant to the issues reviewed in these papers. CONSENSUS PROCESS: The group met over a 2-day period. On day 1, the group discussed each review paper, and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all attendees. CONCLUSIONS: The consensus statement underlines the importance of recognizing social anxiety disorder and provides recommendations on how it may be distinguished from other anxiety disorders. It proposes definitions for response and remission and considers appropriate management strategies. Selective serotonin reuptake inhibitors are recommended as first-line therapy, and effective treatment should be continued for at least 12 months. Long-term treatment is indicated if symptoms are unresolved, the patient has a comorbid condition or a history of relapse, or there was an early onset of the disorder.

Anxiety Disorders↗
PubMed1997

Postsynaptic 5-HT1A receptors mediate 5-hydroxytryptamine release in the amygdala through a feedback to the caudal linear raphe.

Using brain microdialysis, it was demonstrated that the release of 5-hydroxytryptamine (5-HT) in the central nucleus of the amygdala is under inhibitory control of somatodendritic and postsynaptic 5-HT1A receptors. Systemic administration of flesinoxan, a selective 5-HT1A receptor agonist, significantly reduced the extracellular levels of 5-HT in the central nucleus of the amygdala. This effect could be completely antagonized by the 5-HT1A receptor antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)-N-(2-pyridyl)cyclohexane carboxamine trihydrochloride (WAY 100635). Local administration of these compounds by reversed microdialysis into the raphe nuclei revealed that extracellular 5-HT levels in the central nucleus of the amygdala can be regulated through 5-HT1A receptors in the caudal linear raphe nucleus, but not in the dorsal and median raphe nuclei. Interestingly, administration of flesinoxan into the central nucleus of the amygdala also decreased dialysate 5-HT levels both locally and in the caudal linear raphe nucleus. The former effect could be blocked by pretreatment with WAY 100635 when applied into the central nucleus of the amygdala, but not when applied into the caudal linear raphe nucleus. These data provide circumstantial evidence for the existence of a 5-HT1A receptor mediated feedback loop from the central nucleus of the amygdala to the caudal linear raphe nucleus.

Amygdala↗
PubMed1997

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 micrograms) 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.

Adolescent↗
PubMed1997

Effect of the selective serotonin reuptake inhibitor fluvoxamine on CCK-4 induced panic attacks.

Data from animal studies suggest a functional relationship between the cholecystokinin-ergic (CCK) and the serotonergic (5-HT) system. There is increasing evidence that the cholecystokinin-4 (CCK4) challenge test could be a valid experimental model for panic attacks in man. The aim of the present study is twofold; 1) to validate this model further and 2) to shed more light on the putative CCK/5-HT interaction. To this end, we studied the effect of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine on CCK4-induced panic attacks. Twenty-six panic disorder (PD) patients received, before and after a double blind 8-week treatment period with fluvoxamine (n = 17) or placebo (n = 9), a single blind bolus injection with 50 micrograms CCK4. Treatment with fluvoxamine (150 mg daily) significantly decreased the sensitivity of PD patients for CCK4 while placebo was without effect. Of the patients who responded to treatment, 83% no longer experienced a panic attack when rechallenged with CCK4, whereas in the non-responders group this was only 28%. In the fluvoxamine group the treatment response evaluated by the Hamilton Anxiety Scale (HAS) showed a statistically significant treatment effect. The results of this study strengthen the validity of the CCK4 test as an experimental human model for panic attacks and yield evidence supporting the hypothesis that both CCK and serotonin are implicated in the regulation of anxiety.

Adult↗
PubMed1997

Clinical effects of buspirone in social phobia: a double-blind placebo-controlled study.

BACKGROUND: The results of open pilot studies suggest that the serotonin-1A (5-HT1A) receptor agonist buspirone might be effective in social phobia. METHOD: In the present study, the efficacy of buspirone was investigated in patients with social phobia using a 12-week double-blind placebo-controlled design. Thirty social phobic patients (DSM-IV) were treated with either buspirone 30 mg daily or placebo. Efficacy of treatment was measured using the Social Phobia Scale (subscores anxiety and avoidance) and the Hamilton Rating Scale for Anxiety. RESULTS: Taking a reduction of 50% or more on the Social Phobia Scale as a criterion for clinically relevant improvement, only 1 patient on buspirone and 1 on placebo were classified as responder to treatment. A subjective and clinically relevant improvement was reported by 4 patients (27%) on buspirone and 2 patients (13%) on placebo. There were no statistically significant differences between buspirone and placebo on any of the outcome measures. Generally speaking, buspirone was well tolerated. CONCLUSION: The results of the study do not support the results of open studies, in which a reduction of social anxiety and social avoidance was reported in patients with social phobia treated with buspirone.

Buspirone↗