Panic attacks in generalized anxiety disorder.

Panic attacks have been reported by patients with generalized anxiety disorder (GAD) in response to catastrophic worry. This has not been characterized in the literature. We examined the prevalence of GAD panic attacks in an anxiety disorders clinic sample. Charts of 254 patients with DSM-IV GAD were retrospectively evaluated. The presence and type of panic attacks were examined as well as correlates including comorbidity, baseline symptom severity, demographic variables, and family history. Twenty-one percent had GAD panic attacks, 21.7% had situationally predisposed attacks, 15.6% had situationally bound attacks, and 39.4% had unexpected panic attacks. The individuals who had GAD panic attacks had higher scores on the Anxiety Sensitivity Index compared with those who also had other types of panic attacks. One in five patients with GAD reported GAD panic attacks; however, these individuals did not differ significantly on the correlates that were evaluated. These findings require replication and further evaluation.

The impact of changing diagnostic criteria in posttraumatic stress disorder in a Canadian epidemiologic sample.

BACKGROUND: Since its inclusion in DSM-III, posttraumatic stress disorder (PTSD) has undergone a number of changes in its diagnostic criteria, including the expansion of Criterion A (traumatic stressor), the addition of symptom duration (none specified in DSM-III), and the requirement for impairment or distress (Criterion F, DSM-IV only). METHOD: This study examined the impact of changes in PTSD diagnostic criteria using a Canadian PTSD epidemiologic sample. The rates of PTSD and its correlates were evaluated in a nationally representative random sample of 3,006 adults. DSM-III, DSM-III-R, DSM-IV, and ICD-10 criteria were employed. DSM-III, DSM-III-R, and ICD-10 rates were re-evaluated, substituting specific DSM-IV criteria (A-F). RESULTS: The prevalence rates of lifetime PTSD ranged from 13.4% (DSM-III) to 13.0% (ICD-10) to 12.2% (DSM-III-R) to 9.2% (DSM-IV); all rates differed significantly from each other (P < .001). Regardless of diagnostic criteria, most people reported more than 1-year duration of symptoms, although rates were significantly higher in those with DSM-IV PTSD (68.2%, P < .0001). Rates of comorbid major depressive disorder and alcohol and substance abuse and dependence were also significantly higher (P < .05) using the DSM-IV PTSD criteria, and those with DSM-IV PTSD reported significantly higher rates of help-seeking (P < .001). When Criterion F was added to earlier versions, lifetime PTSD rates became much closer to those obtained using DSM-IV criteria: 10.6% (DSM-III), 10.2% (DSM-III-R), and 9.9% (ICD-10); however, rates fluctuated when operational definitions of Criterion F were modified. DSM-III PTSD was also substantially affected by DSM-IV Criteria A and C. CONCLUSIONS: DSM-IV PTSD may identify a more severe disorder. The addition of the clinical significance criterion (F) appeared to affect the greatest change in prevalence rates. Defining Criterion F as having both clinically significant psychological distress and functional impairment lowered the diagnostic threshold to a greater degree than did either distress or impairment alone. This information may be useful for future revisions of PTSD diagnostic criteria.

Frontal brain oscillatory coupling in children of parents with social phobia: a pilot study.

Spectral coupling between delta and beta oscillations has been related to anxiety. The authors provide preliminary evidence that frontal brain oscillatory coupling discriminates children born to socially phobic versus healthy parents, despite there being no difference in parental perceptions of their children's shyness.

Adult attention deficit hyperactivity disorder in an anxiety disorders population.

Adult Attention Deficit Hyperactivity Disorder (ADHD) is a life-long, chronic disorder, which has its onset in childhood and is associated with significant functional impairment. ADHD appears to be highly comorbid with other psychiatric disorders, however, literature is lacking concerning ADHD/anxiety comorbidity. To that end, we examined the prevalence of ADHD in an anxiety disorder sample. Consecutive patients referred to an anxiety disorders clinic completed a variety of anxiety disorder self-report measures as well as the Adult ADHD self-report scale and were clinically assessed using the Structured Clinical Interview for DSM-IV, and the ADHD module of the Mini International Neuropsychiatric Interview. Of the 129 patients assessed, the rate of adult ADHD was 27.9%. The mean age of the sample was 33.1 ± 12.5 years, and the mean baseline CGI-S was 4.6 ± 1.1 (moderate to marked severity). The majority of the sample was female (63.6%) and single (49.5%). The most common comorbid disorders associated with ADHD were major depressive disorder (53.8%), social phobia (38.5%), generalized anxiety disorder (23.1%), and impulse control disorders (30.8%). Individuals with ADHD had higher symptom severity scores for obsessive-compulsive disorder, (P≤ 0.05) and for GAD (P≤ 0.05) and reported a significantly earlier age of onset for depression as compared to those without (P≤ 0.05). The prevalence of adult ADHD was higher in our anxiety disorders clinic sample than found in the general population. Clinical implications of these findings are discussed.

The burden of anxiety disorders on the family.

It is well established that individuals with anxiety disorders experience significant impairments in social and occupational functioning. However, the impact of anxiety disorders on family members has not been adequately studied. The objective of the present study was to examine the burden experienced by relatives of anxiety disorder patients. In all, 74 outpatients and 74 family members participated in the study. Family members completed measures that assessed the impact of having an anxiety disordered relative. Results indicate that family members experience significant burden. The burden encompasses several domains including negative effects on physical health, psychological well-being, and family functioning. Burden was positively correlated with the severity of the patient's condition. The presence of a comorbid mood disorder in patients was associated with increased burden. Health-care professionals should assess the impact of anxiety disorders on the patient's family and provide interventions to reduce burden and improve the quality of life of family members.

Potential use of Internet-based screening for anxiety disorders: a pilot study.

BACKGROUND: The Internet is a widely used resource for obtaining health information. Internet users are able to obtain anonymous information on diagnoses and treatment, seek confirmatory information, and are able to self-diagnose. We posted a self-report diagnostic screening questionnaire for DSM-IV anxiety and mood disorders (MACSCREEN) on our clinic website. METHOD: Three hundred and two individuals completed the MACSREEN. For those who qualified for a DSM-IV disorder, self-report symptom severity measures were completed for the specified disorder: Quick Inventory of Depressive Symptomatology, self-report, Social Phobia Inventory, GAD-7, Davidson Trauma Scale, Panic and Agoraphobia Scale, and Yale/Brown Obsessive Compulsive Scale, self-report. Cutoff scores for each self-report measure were used to evaluate clinically significant symptom severity. Respondents were also asked to complete a series of questions regarding their use of the Internet for health information. RESULTS: The mean age of the MACSCREEN sample was 35.2 years (±13.9), where the majority (67.2%) were female. The most frequently diagnosed conditions were social phobia (51.0%), major depressive disorder (32.4%), and generalized anxiety disorder (25.5%). Sixty-five percent of the sample met criteria for at least one disorder. Most respondents reported completing the MACSCREEN, as they were concerned they had an anxiety problem (62.3%). The majority of respondents reported seeking health information concerning specific symptoms they were experiencing (54.6%) and were planning to use the information to seek further assessment (60.3%). CONCLUSION: Individuals with clinically significant disorder appear to be using the Internet to self-diagnose and seek additional information.

A randomized, double-blind, placebo-controlled trial of olanzapine in the treatment of trichotillomania.

BACKGROUND: Trichotillomania has been considered as part of the obsessive-compulsive disorder spectrum; however, trichotillomania treatment with obsessive-compulsive disorder medications has largely been unsuccessful. OBJECTIVE: To determine whether a dopaminergic treatment as used in tics and Tourette's syndrome would be effective in trichotillomania. METHOD: Twenty-five participants with DSM-IV trichotillomania participated in a 12-week, randomized, double-blind, placebo-controlled trial of flexible-dose olanzapine for trichotillomania. Recruitment occurred between August 2001 and December 2005, and follow-up was completed in February 2006. The primary outcome measure was the Clinical Global Impressions-Improvement (CGI-I) scale, and secondary measures of efficacy included the Yale-Brown Obsessive Compulsive Scale for Trichotillomania (TTM-YBOCS) and the Clinical Global Impressions-Severity of Illness (CGI-S) scale. RESULTS: Eleven of 13 participants (85%) in the olanzapine group and 2 of 12 (17%) in the placebo group were considered responders according to the CGI-I (P = .001). There was a significant change from baseline to end point in the TTM-YBOCS (P < .01) and the CGI-S (P < .001). The mean ± SD dose of olanzapine at end point was 10.8 ± 5.7 mg/d. Twenty-one of 25 patients (84%) reported at least 1 adverse event, but no adverse events resulted in early withdrawal from the study. CONCLUSION: Olanzapine seems to be a safe and effective treatment for primary DSM-IV trichotillomania. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00182507.

The prevalence of migraine headaches in an anxiety disorders clinic sample.

The association between migraine and psychiatric disorders has been reported in both clinical and epidemiological studies. The prevalence of psychiatric disorders has been found to be increased among individuals with migraine. Studies assessing migraine in psychiatric patients are limited and the majority of these studies have focused solely on examining patients with major depression. In the present study, we examined the prevalence and characteristics of migraine headache in an anxiety disorders clinic sample in order to better understand the relationship between these commonly associated conditions. We evaluated 206 consecutive outpatients to an Anxiety Disorders Clinic for the prevalence of migraine. The presence of migraine was established using International Headache Society Criteria. Subjects completed a modified self-report version of the Headache Diagnostic Questionnaire. In order to assess the relationship between migraine and anxiety disorder symptom severity, subjects completed standardized measures of symptom severity. The prevalence of migraine in our anxiety disorder clinic sample was 67%. Anxiety disorder patients with migraine presented with a significantly greater number of comorbid psychiatric disorders than patients without migraine (P= 0.012). The prevalence of migraine was significantly higher in patients with a diagnosis of either panic disorder with agoraphobia (P= 0.048) or major depressive disorder/dysthymia (P= 0.008) compared to other psychiatric disorders. The severity of anxiety disorder symptoms was significantly higher in patients with migraine compared to patients without migraine. This study suggests that there is an increased prevalence of migraine headaches among anxiety disorder patients as compared to the general population. Migraine comorbidity may have important clinical implications, such that the treatment of one condition could potentially ameliorate the development or progression of the other. Further research is required to better understand the nature and implications of the association between migraine and psychiatric disorders.

Pharmacotherapy for social anxiety disorder: an update.

Since the emergence of social phobia into the diagnostic nomenclature, we have seen an exponential expansion in our knowledge regarding effective treatment of this disorder. The literature clearly supports the use of SSRIs and the SNRI venlafaxine ER as first line pharmacological agents in the treatment of GSAD. In this article, treatment studies of pharmacotherapy of social phobia are summarized. Additional issues such as comparative efficacy, treatment resistance and relapse-prevention are reviewed.

Childhood maltreatment linked to greater symptom severity and poorer quality of life and function in social anxiety disorder.

BACKGROUND: There is a paucity of data examining the prevalence and impact of childhood maltreatment in patients presenting with a primary diagnosis of social anxiety disorder (SAD). We thus examined the presence of a broad spectrum of childhood maltreatment, including physical, sexual, and emotional abuse and neglect, in treatment-seeking individuals with the generalized subtype of SAD (GSAD). We hypothesized that a history of childhood maltreatment would be associated with greater SAD symptom severity and poorer associated function. METHODS: One hundred and three participants with a primary diagnosis of GSAD (mean age 37+/-14; 70% male) completed the well-validated, self-rated Childhood Trauma Questionnaire (CTQ), as well as measures of SAD symptom severity and quality of life. RESULTS: Fully 70% (n=72) of the GSAD sample met severity criteria for at least one type of childhood abuse or neglect as measured by the CTQ subscales using previously established thresholds. CTQ total score adjusted for age and gender was associated with greater SAD severity, and poorer quality of life, function, and resilience. Further, the number of types of maltreatment present had an additive effect, with specific associations for emotional abuse and neglect with SAD severity. CONCLUSIONS: Despite the use of validated assessments, our findings are limited by the retrospective and subjective nature of self-report measures used to assess childhood maltreatment. Nonetheless, these data suggest a high rate of childhood maltreatment in individuals seeking treatment for GSAD, and the association of maltreatment with greater disorder severity suggests that screening is clinically prudent.

Trichotillomania in youth: a retrospective case series.

BACKGROUND: The purpose of this study was to investigate the outcome of the naturalistic treatment of youth with Trichotillomania (TTM) in an anxiety disorders clinic sample. METHODS: A retrospective chart review was conducted on 11 treated patients between the ages of 6 and 17, with DSM-IV TTM. RESULTS: Ten patients were initially treated with a serotonin reuptake inhibitor (SRI), whereas one patient was initially treated with an antipsychotic. Three of the 10 patients who started with an SRI had a response (Clinical Global Impression-Improvement Scale (CGI-I)>or=2) in TTM symptoms. Nine patients of the 11 patients were treated with an antipsychotic medication (in 8 patients the antipsychotic was added after an initial trial with an SRI, in 1 patient the antipsychotic was the first line agent), 2 patients remained on an SRI; 8/9 were responders to antipsychotic treatment and 2 patients remitted (complete cessation of hair pulling). Adverse events to the SRI or antipsychotic were experienced by 7/11 patients but did not lead to treatment discontinuation. CONCLUSIONS: This retrospective case series suggests that youth with TTM maybe responsive to pharmacological interventions with SRIs and/or antipsychotic agents, although the response seemed to be more robust with antipsychotics. These preliminary findings will need to be replicated in a larger scale controlled design.

Post-traumatic stress disorder in Canada.

Post-traumatic stress disorder (PTSD) has become a global health issue, with prevalence rates ranging from 1.3% to 37.4%. As there is little current data on PTSD in Canada, an epidemiological study was conducted examining PTSD and related comorbid conditions. Modified versions of the Composite International Diagnostic Interview (CIDI) PTSD module, the depression, alcohol and substance abuse sections of the Mini International Neuropsychiatric Interview (MINI), as well as portions of the Childhood Trauma Questionnaire (CTQ) were combined, and administered via telephone interview in English or French. Random digit dialing was used to obtain a nationally representative sample of 2991, aged 18 years and above from across Canada. The prevalence rate of lifetime PTSD in Canada was estimated to be 9.2%, with a rate of current (1-month) PTSD of 2.4%. Traumatic exposure to at least one event sufficient to cause PTSD was reported by 76.1% of respondents. The most common forms of trauma resulting in PTSD included unexpected death of a loved one, sexual assault, and seeing someone badly injured or killed. In respondents meeting criteria for PTSD, the symptoms were chronic in nature, and associated with significant impairment and high rates of comorbidity. PTSD is a common psychiatric disorder in Canada. The results are surprising, given the comparably low rates of violent crime, a small military and few natural disasters. Potential implications of these findings are discussed.

Symptom relapse following switch from Celexa to generic citalopram: an anxiety disorders case series.

Generic agents do not require large clinical trials of safety and efficacy to enter the market, although they must demonstrate both pharmacological and bioequivalence to the brand name drug. Bioequivalence is attained when the extent of absorption of the generic falls within an FDA predefined range relative to the brand name drug. This potential variation in bioequivalence is not thought to be clinically meaningful, however, there are reports of a lack of therapeutic equivalence between some generic medications and the brand name. This study examines the potential risks posed by a switch from Celexa to generic citalopram. Twenty patients at an Anxiety Disorders Clinic who were unknowingly switched to generic citalopram, from Celexa (Lundbeck, Montreal, Quebec, Canada) and experienced a re-emergence of their anxiety symptoms or development of new adverse events are described in this case series report. The mean time for re-emergence of symptoms or development of adverse events was 3.4 +/- 1.6 weeks (range 0.5-8 weeks). All patients reestablished previous treatment response with a change back to Celexa in a mean time of 3.8 +/- 2.6 weeks (range 0.7-12 weeks). Given these results, it is important for clinicians to be aware of the potential for loss of treatment effect or symptom re-emergence posed by a switch to a generic agent. Randomized, double blind, controlled investigations would likely provide useful information as current bioequivalence and pharmacological equivalence do not necessarily translate into clinical equivalence.

Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma.

Activation of NF-kappaB has been noted in many tumor types, however only rarely has this been linked to an underlying genetic mutation. An integrated analysis of high-density oligonucleotide array CGH and gene expression profiling data from 155 multiple myeloma samples identified a promiscuous array of abnormalities contributing to the dysregulation of NF-kappaB in approximately 20% of patients. We report mutations in ten genes causing the inactivation of TRAF2, TRAF3, CYLD, cIAP1/cIAP2 and activation of NFKB1, NFKB2, CD40, LTBR, TACI, and NIK that result primarily in constitutive activation of the noncanonical NF-kappaB pathway, with the single most common abnormality being inactivation of TRAF3. These results highlight the critical importance of the NF-kappaB pathway in the pathogenesis of multiple myeloma.

Behavioral and psychophysiological characteristics of children of parents with social phobia: a pilot study.

Recent studies have noted a relation between the pattern of resting frontal EEG activity and individual differences in affective style in typically developing infants, children, and adults. The authors conducted a pilot study to investigate the pattern of frontal EEG activity during a resting condition (eyes-open, eyes-closed) in a group of children who had one parent clinically diagnosed with social phobia (SP; n = 6) and in a group of typically developing children of similar age with healthy parents (n = 7). Patients with a primary DSM-IV diagnosis of SP with at least one biological child were recruited from the Anxiety Disorders Clinic at McMaster University Medical Centre. We found that children of parents clinically diagnosed with SP tended to exhibit higher overall resting frontal EEG activity compared with the children of healthy parents. This pattern of overall high EEG activity that is specific to the frontal region is similar to that observed in socially anxious profiles. Preliminary findings are discussed in terms of how overall resting frontal brain activation may be an early psychophysiological marker for placing children of parents with social phobia at risk for socioemotional problems before such problems emerge.

Nefazodone in the treatment of generalized social phobia: a randomized, placebo-controlled trial.

OBJECTIVE: Numerous studies have demonstrated the efficacy of serotonergic antidepres-sants, particularly the selective serotonin reuptake inhibitors (SSRIs), in the treatment of social phobia. We evaluated the efficacy, safety, and tolerability of nefazodone, a 5-HT(2) antagonist, in patients with generalized social phobia (GSP). METHOD: One hundred five patients with GSP (confirmed using the Structured Clinical Interview for DSM-IV) from 4 Canadian outpatient anxiety clinics were assigned randomly to nefazodone (300-600 mg/day, flexible dose) or placebo for 14 weeks of double-blind treatment. Data were collected from October 12, 1999, through December 8, 2001. Primary efficacy outcomes were the Clinical Global Impressions-Improvement scale (CGI-I) score and the Liebowitz Social Anxiety Scale score. RESULTS: In the intent-to-treat sample, 16 (31.4%) of 51 subjects taking nefazodone and 12 (23.5%) of 51 subjects taking placebo were rated as much or very much improved on the CGI-I at endpoint (chi(2) = 0.79, p = .38). With the exception of the Social Phobia Scale, no significant differences were found in measures of social phobia when comparing the nefazodone and placebo groups. CONCLUSION: These findings suggest that nefazodone is not an effective agent in the treatment of GSP. These data parallel some recent findings with the use of the SSRI fluoxetine in GSP. The lack of efficacy of 2 serotonergic antidepressants in GSP suggests that serotonin reuptake inhibition may not be the only mechanism of action required for efficacy to occur in the treatment of GSP.

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.

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.

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.

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.