Biomedical subjects

Michael Van Ameringen

Publications and source records attributed to Michael Van Ameringen.

15 recordsLinked to original sources

PubMed2006

Topiramate augmentation in treatment-resistant obsessive-compulsive disorder: a retrospective, open-label case series.

Serotonin reuptake inhibitors (SRIs) are considered first-line treatments for obsessive-compulsive disorder (OCD). Many patients achieve some response but remain symptomatic despite an adequate SRI trial. Recent neuroimaging data found abnormally high glutamatergic concentrations in children with OCD. Following selective serotonin reuptake inhibitor (SSRI) treatment, a decrease in OCD symptom severity was associated with a decrease in caudate glutamatergic concentrations. We initiated an investigation of adjunctive topiramate (an anticonvulsant agent with glutamatergic properties) in the treatment of patients with OCD who were partially or nonresponsive to SRI treatment. Sixteen consecutive outpatients with OCD (mean age = 41.1 years; range = 21-58 years), who were partial or nonresponders to SRI monotherapy or SRI combination therapy (antipsychotic, other antidepressant, or benzodiazepines), and had topiramate added over a minimum of 14 weeks, were reviewed. Baseline and endpoint Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I) were evaluated retrospectively. Eleven of 16 patients were responders (68.8%) with a CGI-I score of much improved or very much improved. The mean dose of topiramate was 253.1 +/- 93.9 mg/day. The mean time to response was 9.2 +/- 4.5 weeks. CGI-S scores decreased significantly from initiation of topiramate until 26 weeks, from 6.1 +/- 0.9 to 4.5 +/- 1.3 (P < .001). This case series suggests some preliminary evidence that the addition of topiramate may be useful in treatment-resistant OCD.

Adult↗

PubMed2005

Emerging treatments for child and adolescent social phobia: a review.

Social anxiety disorder, or social phobia (SP), is an anxiety disorder characterized by excessive fear of exposure to situations that involve potential scrutiny by others. SP is a common psychiatric problem in children and adolescents, often presenting with comorbid anxiety and mood disorders. Although the onset of SP is typically in late childhood or early adolescence, most afflicted individuals go undiagnosed for years, not seeking treatment until adulthood. First-line treatments for SP in adults support the use of pharmacotherapy and cognitive behavioral therapy. There is new and emerging data in youths with SP to support the use of similar treatments. This paper will review the clinical characteristics, epidemiology, and treatment of SP in youths. Current investigations using selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors, benzodiazepines, and monoamine oxidase inhibitors in youths will be reviewed. Several studies on the use of cognitive behavioral therapy in youths will also be examined. Practical guidelines for clinicians who treat children and adolescents are also presented.

Adolescent↗

PubMed2005

An evaluation of paroxetine in generalised social anxiety disorder.

It is estimated that social anxiety disorder affects approximately 13.3% individuals within the community at some point in their lifetime and is associated with significant functional impairment. A variety of drug groups have demonstrated efficacy in treating social anxiety disorder, including selective serotonin reuptake inhibitors (SSRIs). Paroxetine is an SSRI approved by the FDA and Health Canada for the treatment of a variety of psychiatric conditions. Paroxetine has been the most studied agent in social anxiety disorder and has been shown to be effective in short-term, fixed- and flexible-dose placebo-controlled trials, as well as in long-term treatment. The pharmacotherapy of social phobia will be reviewed, with a special focus on investigations with paroxetine.

Anxiety Disorders↗

PubMed2005

The selective GABA reuptake inhibitor tiagabine for the treatment of generalized anxiety disorder: results of a placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and tolerability of tiagabine, a selective gamma-aminobutyric acid (GABA) reuptake inhibitor, in adults with generalized anxiety disorder (GAD). METHOD: This 8-week, randomized, double-blind, multicenter, placebo-controlled study enrolled patients with GAD (DSM-IV). Tiagabine was initiated at 4 mg/day and then flexibly dosed twice a day to a maximum dose of 16 mg/day. Study drug was tapered after week 8 in decrements of 2 mg every other day. Efficacy assessments included the Hamilton Rating Scale for Anxiety (HAM-A) and Sheehan Disability Scale. Adverse events, sexual functioning, and change in depressive symptoms were monitored. Data were collected from May 2003 to January 2004. RESULTS: A total of 266 patients (tiagabine, N = 134; placebo, N = 132) were included in safety analyses; 260 patients (tiagabine N = 130; placebo N = 130) were included in efficacy analyses. Tiagabine reduced symptoms of GAD according to the observed case and mixed models repeated-measures (MMRM) analyses but not the primary last-observation-carried-forward (LOCF) analysis. At final visit, the reduction from baseline in mean HAM-A total score was 11.8 for tiagabine, compared with 10.2 for placebo (LOCF analysis, p = .27). In a post hoc MMRM analysis, a significant difference in the mean reduction in HAM-A total score over the efficacy evaluation period was found, favoring tiagabine over placebo (p < .01). Tiagabine had an early onset of effect, as shown by significant reduction from baseline in mean HAM-A total score compared with placebo at week 1 (observed cases, p < .05). Tiagabine was generally well tolerated and not associated with changes in sexual functioning or depressive status. Symptoms of a discontinuation syndrome during taper were not observed. CONCLUSION: The primary LOCF analysis was negative; however, results from the observed case and MMRM analyses suggest that tiagabine may be a useful treatment option for adult patients diagnosed with GAD. These findings warrant further evaluation in randomized clinical studies.

Adult↗

PubMed2004

A PET provocation study of generalized social phobia.

In an investigation of the neural circuits that may mediate the subjective experience of social phobia (SP), six male patients with a primary DSM-IV diagnosis of generalized social phobia watched, in the presence of a group of "communication experts," a videotape of themselves giving an impromptu talk (Exposure condition). In the control Baseline condition, they viewed a videotape of a socially competent stranger giving a talk. Regional cerebral blood flow was measured thrice under each condition. The study revealed significant deactivations from Baseline during Exposure in the right lingual gyrus (BA 18) and in the right medial frontal gyrus (BA 11); significant activations during Exposure were not observed. Deactivation of these regions may reflect a strategy of visual avoidance employed by the patients to dampen their phobic experience.

Adolescent↗

PubMed2004

Optimizing treatment in social phobia: a review of treatment resistance.

Over the last 25 years, there has been a rapid expansion of our knowledge base of social phobia (SP). Although there are a number of well-validated treatment modalities, including pharmacotherapy and cognitive-behavioral therapy, significant gaps remain in our ability to achieve full remission in most patients. Despite advances in the neurobiology of SP, the etiology has yet to be determined. Investigations examining potential predictors of response have provided little guidance in selecting an appropriate treatment modality. These gaps in our knowledge have pushed us to examine issues related to treatment resistance. This paper presents a review of the current literature and issues related to treatment-resistant SP, including a discussion of the functional impairment associated with SP, definitions of treatment response and remission, as well as outcome measures that have been used in clinical investigations of SP. In addition, criteria for a standard treatment trial, predictors of treatment response, a review of treatment resistance studies, and potential directions for future research are examined. The most promising strategies to attain remission, will likely involve augmenting selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors with agents such as anticonvulsants, benzodiazepines, and antipsychotics as well as combining pharmacotherapy with cognitive-behavioral therapy. Our current treatment target of simply attaining a response needs to be refocused, so that an asymptomatic state and high end state functioning become the final goal of treatment.

Algorithms↗

PubMed2004

Predictors of response in generalized social phobia: effect of age of onset.

Selective serotonin reuptake inhibitors (SSRIs) are the gold standard for the pharmacological treatment of generalized social phobia (GSP). However, little is known about the predictors of response to treatment. Two hundred and four outpatients with GSP were randomized to sertraline (Zoloft) or placebo, for a 20-week double-blind study, with a flexible dose range of sertraline 50 to 200 mg/d. Response was defined as the percentage of patients with a Clinical Global Impression-Improvement scale (CGI-I) of 1 (very much improved) or 2 (much improved). Outcome analyses were conducted using regression models including treatment group as a categorical predictor and study visit as a repeated measure. Dependent measures included Marks Fear Questionnaire (MFQ), Brief Social Phobia Scale (BSPS), CGI-I, and Sheehan Disability Scale (SDS). We investigated several possible predictors of response to treatment including DSM-IV comorbidity, age, sex, age of onset of GSP, and duration of illness. Patients with later-onset (especially adult-onset) GSP tend to have a better response to treatment than those with earlier-onset GSP. This result generally appears in our analyses as a 2-way interaction, where the association with response is greatest for patients with adult-onset GSP (in contrast to those with child or adolescent onset). This finding is most robust for symptom measures, but is still apparent for the Sheehan measure of disability at work. This advantage for later-onset GSP can be accounted for neither by severity of illness nor by duration of illness. Superior treatment outcome for later-onset GSP may be mediated by the degree of social and family disability.

Adolescent↗

PubMed2004

Antiepileptic drugs in the treatment of anxiety disorders: role in therapy.

Pharmacotherapy for anxiety disorders is an active area of research. A variety of drug groups have been shown to be effective in treating many of the anxiety disorders, with selective serotonin reuptake inhibitors (SSRIs) being considered first-line agents for virtually all anxiety disorders. There is a clinical need for alternative drug treatments, as many patients do not achieve a complete response and experience significant adverse effects. The successful use of antiepileptic drugs in mood disorders has led clinicians and researchers to investigate their potential efficacy in other psychiatric disorders, particularly in anxiety disorders. There have been a number of investigations conducted in the form of case reports, case series and open-label trials, suggesting the potential usefulness of antiepileptic drug treatment in a variety of anxiety disorders. More reliable evidence for the use of antiepileptic drugs in anxiety disorders can be gleaned from recent placebo-controlled trials. Thus far, the strongest placebo-controlled evidence has demonstrated the efficacy of pregabalin in treating social phobia and generalised anxiety disorder, while smaller or less robust controlled trials have suggested the potential efficacy of gabapentin in social phobia, lamotrigine in post-traumatic stress disorder, and valproic acid in panic disorder. Antiepileptic drugs may have a place in the treatment of anxiety disorders; however, further investigation is warranted to determine in what circumstances they should be used as monotherapy or as augmenting agents in individuals who are partially or non-responsive to conventional therapy.

Anticonvulsants↗

PubMed2004

An open trial of topiramate in the treatment of generalized social phobia.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are the current gold standard in the pharmacologic treatment of generalized social phobia. SSRIs are only effective in approximately 50% of individuals with generalized social phobia and can be associated with significant side effects. Based on the successful use of the anticonvulsants gabapentin and pregabalin in treating generalized social phobia, we conducted an open trial examining the efficacy of the glutamatergic and GABAergic anticonvulsant topiramate in the treatment of generalized social phobia. METHOD: Twenty-three adult outpatients with DSM-IV social phobia, generalized type, were entered into a 16-week open trial of topiramate, starting at 25 mg/day, and gradually titrated up to a maximum dose of 400 mg/day. RESULTS: Twelve of 23 patients completed the trial. In the intent-to-treat (ITT) analysis, 11 (47.8%) of 23 were responders by a Clinical Global Impressions Improvement (CGI-I) scale rating of "much" or "very much" improved. The mean drop in the Liebowitz Social Anxiety Scale (LSAS) score for the ITT group was 29.4%. The change in LSAS score from baseline to endpoint was significant for the ITT group (F = 3.44, df = 4,110; p = .01). In the completers group, 9 (75.0%) of 12 were responders by CGI-I at 16 weeks, with a mean drop in LSAS score of 45.1%. The rate of remission in the ITT sample, using a definition of an LSAS score of </= 30, gave a remission rate of 26.1% (6/23). CONCLUSION: This study suggests that topiramate may be effective in the treatment of generalized social phobia. These results also suggest the possibility that the neurotransmitters glutamate and GABA may be involved in the neurobiology of generalized social phobia.

Adult↗

PubMed2003

A confirmatory factor analysis of a self-report version of the Liebowitz Social Anxiety Scale.

One of the most popular measures of social phobia is the Liebowitz Social Anxiety Scale (LSAS; Liebowitz, 1987). The LSAS is a 24-item semi-structured interview measure of fear and avoidance experienced in a range of social and performance situations. Recently, the LSAS has been modified to a self-report version (LSAS-SR) by several independent groups (Cox, Ross, Swinson, & Direnfeld, 1998; Fresco et al., 2001; Mancini, Van Ameringen, & Oakman, 1999). A self-report version offers ease of administration, but it may differ from the structured interview version in its psychometric properties. We conducted confirmatory factor analyses of the self-report version of the LSAS using data from a sample of 188 outpatients with anxiety disorders. The structure and psychometric properties of the LSAS-SR are highly similar to that of the LSAS and robust across groups of patients with a variety of primary anxiety disorders. We argue in favor of adopting the 4-factor model for the LSAS proposed by Safren et al. (1999) instead of the models implied by the scoring instructions for the LSAS.

Adult↗

PubMed2003

Quality of life and the anxiety disorders.

Quality of life (QoL) is a concept that has become increasingly used in mental health care. Recent studies have compared the impact of different anxiety disorders on different domains of QoL; however, instruments generally used to assess QoL in this population have varying specificity, considerable redundancy, and occasionally inappropriate content. Three hundred and sixty consecutive admissions to an anxiety disorders clinic were assessed. Participants and clinicians completed a number of QoL measures. Results indicated that impairment measures designed for use with anxiety-disordered samples in fact assess only occupational functioning and relationships and activities outside of occupation, and that individuals with Social Phobia (SP) were more impaired on the latter than those with Panic Disorder (PD). Furthermore, only Social Phobia accounted for unique variance in the three Medical Outcome Study Health Survey (MOS) subscales relevant to quality of life. Of the MOS subscales relevant to symptoms, mood regulation, physical functioning, and pain were associated with compromised overall QoL.

Activities of Daily Living↗

PubMed2003

The impact of anxiety disorders on educational achievement.

Anxiety disorders typically have an age of onset in childhood and adolescence, resulting in significant disability in social and occupational functioning. Epidemiological evidence suggests that persons with psychiatric disorders and perhaps especially social phobia are at increased risk for premature withdrawal from school [Am. J. Psychiatry 157 (2000) 1606]. In order to further determine the impact of anxiety disorders on school functioning and/or premature withdrawal from school, 201 patients meeting DSM-IV criteria for a primary anxiety disorder completed a school leaving questionnaire as well as self-report measures of anxiety, depression, and social adjustment. About 49% (n = 98) reported leaving school prematurely and 24% of those indicated that anxiety was the primary reason for this decision. Patients who had left school prematurely were significantly more likely to have a lifetime diagnosis of generalized social phobia, a past history of alcohol abuse/dependence and a greater number of lifetime diagnoses than those who completed their desired level of education. This study suggests that anxiety disorders, and perhaps especially generalized social phobia, are associated with premature withdrawal from school. Further studies are required to determine methods for early identification and treatment of anxiety disorders in school aged children to enable these students to reach their full potential.

Adolescent↗

PubMed2003

WCA recommendations for the long-term treatment of social phobia.

What is the best approach for treating patients with social phobia (social anxiety disorder) over the long term? Social phobia is the most common anxiety disorder, with reported prevalence rates of up to 18.7%. Social phobia is characterized by a marked and persistent fear of being observed or evaluated by others in social performance or interaction situations and is associated with physical, cognitive, and behavioral (ie, avoidance) symptoms. The onset of social phobia typically occurs in childhood or adolescence and the clinical course, if left untreated, is usually chronic, unremitting, and associated with significant functional impairment. Social phobia exhibits a high degree of comorbidity with other psychiatric disorders, including mood disorders, anxiety disorders, and substance abuse/dependence. Few people with social phobia seek professional help despite the existence of beneficial treatment approaches. The efficacy, tolerability, and safety of the selective serotonin reuptake inhibitors (SSRIs), evidenced in randomized clinical trials, support these agents as first-line treatment. The benzodiazepine clonazepam and certain monoamine oxidase inhibitors (representing both reversible and nonreversible inhibitors) may also be of benefit. Treatment of social phobia may need to be continued for several months to consolidate response and achieve full remission. The SSRIs have shown benefit in long-term treatment trials, while long-term treatment data from clinical studies of clonazepam are limited but support the drug's efficacy. There is also evidence for the effectiveness of exposure-based strategies of cognitive-behavioral therapy, and controlled studies suggest that the effects of treatment are generally maintained at long-term follow-up. In light of the chronicity and disability associated with social phobia, as well as the high relapse rate after short-term therapy, it is recommended that effective treatment be continued for at least 12 months.

Adult↗

PubMed2002

Does SSRI augmentation with antidepressants that influence noradrenergic function resolve depression in obsessive-compulsive disorder?

BACKGROUND: Obsessive compulsive disorder (OCD) often coexists with major depressive disorder (MDD). Serotonergic antidepressant medications have emerged as the treatment of choice for both OCD and MDD. In the usual course of events, both the patient's OCD and depressive symptoms improve in parallel following initiation of serotonin reuptake inhibitor (SRI) treatment for OCD. However, such is not always the case. We report here on a series of ten patients whose OCD but not depression improved following a trial of SRI therapy. METHOD: Ten patients with OCD and comorbid MDD who experienced a worsening or exacerbation of depressive symptoms while being maintained on an adequate dose of SRI therapy were treated using a combination of SRIs and agents with effects on noradrenergic reuptake. Response to treatment was based on clinician-ratings of severity and improvement of OCD and MDD (CGI-S and CGI-I). RESULTS: Following augmentation, nine of the ten patients had a significant improvement/resolution of their MDD, with little further change in the severity of their OCD. LIMITATIONS: Inferences from the results of this study are limited by the lack of a control group, the small sample size, and the use of nonstandardized ratings as measures of symptom severity. CONCLUSIONS: These results are of practical significance to clinicians insofar as they suggest a possible guideline to clinicians treating depression in OCD with SSRIs without success.

Adult↗

PubMed2002

Topiramate treatment for SSRI-induced weight gain in anxiety disorders.

BACKGROUND: Antidepressants, including selective serotonin reuptake inhibitors (SSRIs), have been associated with significant weight gain, a problem that frequently leads to noncompliance and premature discontinuation of treatment. Topiramate is a novel anticonvulsant that has also been used as a mood stabilizer and augmentation agent in mood disorders. Topiramate has been observed to have an interesting side effect of weight loss in some individuals. In this study, topiramate was added to the treatment regimen of patients with a primary DSM-IV anxiety disorder who had experienced substantial SSRI-induced weight gain, in an attempt to induce weight loss. METHOD: Topiramate was added to SSRI treatment in 15 anxiety disorder patients, starting at a dose of 50 mg/day and titrating up to a target daily dose of 100 mg/day, with a maximum dose of 250 mg/day. Subjects' weight was measured at baseline and after 5 and 10 weeks of treatment. RESULTS: Before topiramate treatment, SSRI-treated subjects in this sample had gained a mean of 13.0 +/- 8.4 kg (28.6 +/- 18.5 lb). After the addition of a mean dose of 135.0 +/- 44.1 mg/day of topiramate for approximately 10 weeks, subjects lost a mean of 4.2 +/- 6.0 kg (9.3 +/- 13.3 lb). CONCLUSION: Topiramate may have a role in managing SSRI-induced weight gain in anxiety disorder patients.

Adult↗