Effect of alprazolam and diazepam on anxiety and panic attacks in panic disorder: a controlled study

Forty-eight patients currently experiencing panic attacks were randomly assigned to double-blind treatment with alprazolam, diazepam, or placebo. Efficacy was assessed using the Hamilton Rating Scale for Anxiety and a panic attack frequency rating scale. Results indicate that the two active treatments appeared equally effective in reducing both the frequency of panic attacks and the severity of generalized anxiety when compared with placebo. Overall, these data support the use of benzodiazepines in the treatment of panic disorder.     

Cerebral blood flow velocity in untreated panic disorder patients: a transcranial Doppler ultrasonography study.

BACKGROUND: The aim of this study was to compare resting cerebral blood flow velocity values of unmedicated patients in the acute phase of panic disorder with resting values of healthy control subjects. METHODS: Nineteen unmedicated panic disorder patients were assessed for degree of anxiety using the Hamilton Anxiety Scale. The patients and 20 healthy age-matched control subjects were then insonated at rest using transcranial Doppler ultrasonography (TCD). For TCD, the anterior, the middle, and the posterior cerebral arteries were insonated bilaterally in all patients. RESULTS: Compared with healthy age-matched control subjects, acute unmedicated panic disorder patients showed a significant increase in cerebral blood flow velocity, bilaterally in the middle and the anterior cerebral artery, and unilaterally in the left posterior cerebral artery. Cerebral blood flow velocity in the right middle cerebral artery correlated positively to the item "Fear" on the Hamilton Anxiety Scale, whereas pulsatility index in the posterior cerebral artery bilaterally and in the left middle cerebral artery correlated negatively to the item "Mood." CONCLUSIONS: Transcranial Doppler ultrasonography agrees well with validated psychometric methods. If follow-up studies confirm our findings, TCD could allow an objective assessment of the mental state of panic disorder patients and reliably discriminate panic disorder patients from normal control subjects.     

Tryptophan hydroxylase and serotonin transporter gene polymorphism does not affect the diagnosis, clinical features and treatment outcome of panic disorder in the Korean population

Panic disorder may be associated with defective serotonin (5-HT) neurotransmission. This study was to investigate the association between the tryptophan hydroxylase (TPH) gene and a serotonin transporter gene promoter polymorphism (5-HTTLPR), with panic disorder in a Korean population.

244 Korean patients with panic disorder and the 227 controls were genotyped by a polymerase chain reaction-based method. The severity of panic disorders was assessed by number of panic attacks during the previous 1 month, as well as scores for anticipatory anxiety, panic distress, and agoraphobic distress, as determined by a visual analogue scale (VAS). All the subjects completed the assessment measures including Spielberger State-Trait Anxiety Inventory-State (STAI-S), Spielberger State-Trait Anxiety Inventory-Trait (STAI-T), Beck Depression Inventory (BDI), Symptom Checklist-90-Revised (SCL-90-R), Revised Anxiety Sensitivity Index (ASI-R), Clinical Global Impression Scale – Severity of Illness (CGI-S), Panic Disorder Severity Scale (PDSS), and the Hamilton Depression Rating Scale (HAMD). Responder analyses were conducted based on changes in CGI-I scores after 10 weeks of treatment.

We found no significant differences in the genotype and allele frequencies in TPH A218C and 5-HTTLPR polymorphisms between the panic patients and the control group. Subgroup analyses in terms of comorbidities, response, and other primary clinical variables, indicated no differences in these polymorphisms. Our findings suggest that the TPH A218C polymorphism and 5-HTTLPR play no significant roles in the pathogenesis and clinical symptomatologies, at least in a Korean population.     

Otoneurological examination in panic disorder and agoraphobia with panic attacks: a pilot study

A battery of vestibular and audiological tests was administered to eight patients with panic disorder and 13 patients with agoraphobia and panic attacks, all of whom experienced dizziness during their panic attacks. Positional or spontaneous nystagmus was present in 67% of the subjects. Abnormal responses were found in caloric testing (56%), rotational testing (35%), and posturography (32%). Pure tone audiograms were abnormal in 26% of the subjects and acoustic reflexes were abnormal in 44% of the subjects. Six of eight patients tested had an abnormal brainstem auditory evoked potential. The possible importance of the findings and their implications for further research are discussed.     

Increased antipanic efficacy in combined treatment with clomipramine and dixyrazine

A double-blind 12 week trial was undertaken to compare the effects of clomipramine + dixyrazine with clomipramine + placebo in the treatment of panic disorder with or without agoraphobia. Of 45 patients included (21 dixyrazine, 24 placebo), 16 dropped out (6 dixyrazine, 10 placebo). The number of panic attacks and the scores on the panic disorder subscale of the Hamilton Anxiety Rating Scale were significantly reduced in response to both treatment regimens, but the reduction was significantly greater in the dixyrazine group. The patients’ daily functioning was significantly more improved with the dixyrazine combination. The serum concentration of desmethylclomipramine monotherapy was significantly higher and the side effects significantly lower in the combined treatment with dixyrazine than with clomipramine monotherapy. Clomipramine combined with dixyrazine seems superior to clomipramine in the treatment of panic disorder.     

艾司西酞普兰与帕罗西汀治疗惊恐障碍的比较

目的探讨艾司西酞普兰对京恐障碍患者的疗效及不良反应。方法将66例惊恐障碍患者随机分为艾司西酞普兰组和帕罗西汀组,疗程8周,并用汉密顿焦虑量表（HAMA）、汉密顿抑郁量表（HAMD）、抗抑郁药不良反应评定量表（sERS）对患者治疗前后进行评估。结果在治疗的第1周、第2周末艾司西酞普兰组的HAMA分值均低于对照组,而在4、6、8周末,两组患者的HAMA分值差异无统计学意义。在治疗8周末时,艾司西酞普兰组治愈率为64．5％,有效率为90．3％,帕罗西汀组分别为63．3％、90．0％。两组差异无统计学意义。在不良反应方面,两组差异无统计学意义。结论艾司西酞普兰治疗惊恐障碍疗效与帕罗西汀相当,不良反应无明显差异。     

Clinical Characteristics of the Respiratory Subtype in Panic Disorder Patients

Objective

Panic disorder has been suggested to be divided into the respiratory and non-respiratory subtypes in terms of its clinical presentations. The present study aimed to investigate whether there are any differences in treatment response and clinical characteristics between the respiratory and non-respiratory subtypes of panic disorder patients.

Methods

Among the 48 patients those who completed the study, 25 panic disorder patients were classified as the respiratory subtype, whereas 23 panic disorder patients were classified as the non-respiratory subtype. All patients were treated with escitalopram or paroxetine for 12 weeks. We measured clinical and psychological characteristics before and after pharmacotherapy using the Panic Disorder Severity Scale (PDSS), Albany Panic and Phobic Questionnaire (APPQ), Anxiety Sensitivity Index-Revised (ASI-R), State-Trait Anxiety Inventory (STAI-T, STAI-S), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D).

Results

The prevalence of the agoraphobia was significantly higher in the respiratory group than the non-respiratory group although there were no differences in gender and medication between the two groups. The respiratory group showed higher scores on the fear of respiratory symptoms of the ASI-R. In addition, after pharmacotherapy, the respiratory group showed more improvement in panic symptoms than the non-respiratory group.

Conclusion

Panic disorder patients with the respiratory subtype showed more severe clinical presentations, but a greater treatment response to SSRIs than those with non-respiratory subtype. Thus, classification of panic disorder patients as respiratory and non-respiratory subtypes may be useful to predict clinical course and treatment response to SSRIs.     

Allergy in panic disorder patients: a preliminary report(1)

In this study of panic disorder patients, 71.8% were found to have allergies. Compared to the nonallergic subjects, the allergic subjects had more full-blown situational panic attacks and significantly higher scores on 7 of the 14 symptoms in the Hamilton Anxiety Scale. More subjects in the allergic group had comorbid anxiety disorders, but only the number with specific phobias was significantly higher than for the nonallergic. These results are discussed in terms of our present theories of panic disorder.     

Cognitive style, alprazolam plasma levels, and treatment response in panic disorder

This study investigated an anxiety-prone cognitive style (measured by the Anxious Thoughts and Tendencies Questionnaire, AT&T) as a predictor of the acute response to increasing alprazolam plasma levels in panic disorder. Panic disorder patients (n=26) were treated with escalating doses of alprazolam for 4 weeks, then a fixed dose of 1 mg four times a day for 4 weeks. At 0, 1, 2, 3, 4, 6, and 8 weeks, trough alprazolam plasma levels; clinical, self-report, and performance measures; and vital signs were assessed. Panic attack data were from daily diaries. The repeated response measures were analyzed in relation to alprazolam plasma levels using SAS GENMOD, with patients classified as high or low on the baseline AT&T. Panic attacks, anticipatory anxiety, fear, avoidance, overall agoraphobia, the Hamilton Anxiety Rating Scale, and clinicians' global ratings improved with increasing alprazolam plasma levels. Hopkins Symptom Checklist-90 Anger-Hostility; Profile of Mood States Vigor, Confusion, and Friendliness; and speed and accuracy of performance worsened. Patients with high AT&T scores were worse throughout the study on situational panics, fear, avoidance, overall agoraphobia, the Hamilton Anxiety Rating Scale, the Hamilton Rating Scale for Depression, and Clinical Global Improvement; most Hopkins Symptom Checklist-90 clusters; Profile of Mood States Anxiety, Depression, and Confusion; and Continuous Performance Task omissions. We conclude that in panic disorder: (1) alprazolam has a broad spectrum of clinical activity related to plasma levels in individual patients; (2) sedation, disinhibition, and performance deficits may persist for at least a month after dose escalation ends; (3) marked anxiety-prone cognitions predict more symptoms throughout treatment, but do not modify the response to alprazolam and therefore should not influence the choice of alprazolam as treatment.     

Depersonalization in panic disorder: a clinical study

Panic disorder (PD) has been hypothesized to be a heterogeneous entity, with distinct clinical subgroups. The presence of depersonalization during panic attacks may distinguish a specific subgroup of PD. We sought to analyze the differential features of a subgroup of PD patients with depersonalization. A total of 274 patients with PD were assessed and divided into 2 groups according to the presence or absence of depersonalization. The Structured Clinical Interview for DSM-III-R (SCID-UP-R) was used to assess PD and comorbid disorders. The clinical scales administered included the Hamilton Anxiety and Depression Rating Scale (HARS and HDRS), the Marks and Mathews Fears and Phobia Scale, Panic-Associated Symptom Scale (PASS), and a panic attack symptoms inventory. A total of 66 patients (24.1%) exhibited depersonalization during the attacks. Patients with depersonalization appeared to be younger and had an earlier age at onset. PD was more severe in the depersonalization group (greater number of attacks, worse level of functioning, and higher scores on most self-rating scales). Also, depersonalization patients showed more comorbidity with specific phobia. Our results support the view that PD with depersonalization may be considered a distinct and more severe subcategory of PD.     

Panic disorder and hyperventilation

Respiratory abnormalities are associated with anxiety, particularly with panic attacks. Symptoms such as shortness of breath, "empty-head" feeling, dizziness, paresthesias and tachypnea have been described in the psychiatric and respiratory physiology related to panic disorder. Panic disorder patients exhibit both behaviorally and physiologically abnormal responses to respiratory challenges tests. OBJECTIVE: We aim to observe the induction of panic attacks by hyperventilation in a group of panic disorder patients (DSM-IV). METHOD: 13 panic disorder patients and 11 normal volunteers were randomly selected. They were drug free for a week. They were induced to hyperventilate (30 breaths/min) for 3 minutes. Anxiety scales were taken before and after the test. RESULTS: 9 (69.2%) panic disorder patients and one (9.1%) of control subjects had a panic attack after hyperventilating (p < 0.05). CONCLUSION: The panic disorder group was more sensitive to hyperventilation than normal volunteers. The induction of panic attacks by voluntary hyperventilation may be a useful and simple test for validating the diagnosis in some specific panic disorder patients.     

Panic attacks in patients with chronic schizophrenia: a complication of long-term neuroleptic treatment

Panic attacks meeting the diagnostic criteria for panic disorder (DSM-III-R) were found in nine (20%) of 45 patients suffering chronic schizophrenia for more than 5 years. The scores of the Hamilton Depression Rating Scale and the Simpson Angus Scale were significantly higher in the group of patients with panic attacks. They also tended to be taking neuroleptics in larger doses than in the other group. The present report suggests that long-term treatment with neuroleptics is closely related to the manifestation of panic attacks in chronic schizophrenia. It also suggests that when panic attacks are seen frequently in patients taking high doses of neuroleptics, dose reduction of neuroleptics should be considered.     

A comparison of paroxetine,clomipramine and placebo in the treatment of panic disorder

The aim of this 12-week, double-blind, parallel group, placebo-controlled study was to compare paroxetine with clomipramine in 367 patients with DSM-III-R defined panic disorder. Efficacy assessments included the daily panic attack diary, the Clinical Global Impression Scale, the Hamilton Anxiety Rating Scale, the Marks Sheehan Phobia Scale and the Sheehan Disability Scale. Paroxetine produced significant improvements compared with placebo in various measurements of panic attack frequency, and was as effective as clomipramine. However, paroxetine appeared to have a more rapid onset of action than clomipramine in reducing the number of panic attacks to zero. There was an equivalent improvement with both paroxetine and clomipramine in the supportive efficacy variables which assessed associated aspects of therapeutic improvement. Significantly more adverse effects were reported in the clomipramine group compared with the paroxetine group, while there was no difference between the paroxetine and placebo groups.     

Selective cognitive deficits in obsessive-compulsive disorder compared to panic disorder with agoraphobia

OBJECTIVE: Visual-spatial and executive functions deficits have been reported in obsessive-compulsive disorder (OCD). We investigated their specificity comparing cognitive function in OCD, panic disorder with agoraphobia (PD/A) and controls by a comprehensive neuropsychological battery. METHOD: Fifty-five subjects (25 OCD, 15 PD/A, 15 controls) without current depressive episode underwent structured clinical interview for DSM-IV, Yale-Brown Obsessive Compulsive Scale, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale. Neuropsychological battery assessed: executive functions, visual discrimination, spatial memory and learning, verbal memory, general intellectual functioning. RESULTS: OCD showed controlled fluency, visual-spatial construction, learning and memory deficits; PD/A spatial learning impairment. OCD was discriminated from PD/A and controls by three tests scores, predicting group membership for 76.4% of the cases. CONCLUSION: Visual-constructive and controlled fluency deficits seem specific in OCD, while the spatial learning deficit, shared with PD patients, may not be disorder-specific, but anxiety-related. Results support the proposed ventral frontal-striatal circuit involvement in OCD.     

The latent structure of anxiety symptoms in anxiety disorders.

OBJECTIVE: Research in the psychopathology of panic and anxiety disorders, particularly agoraphobia, suggests that fear of fear may be the basis of these conditions. However, there is little empirical research on the definition and validity of the concept of fear of fear in a clinical study group. The authors' aims are 1) to determine empirically if particular associations between symptoms and beliefs exist in a group of patients with anxiety disorders and what underlying dimensions of perceived threat they represent and 2) to assess the relative importance of these associations in agoraphobia with panic attacks, panic disorder, social phobia, and generalized anxiety disorder. METHOD: In an anxiety disorders treatment unit, 390 outpatients with anxiety disorders diagnosed according to DSM-III criteria completed the Anxiety Symptoms and Beliefs Scale. RESULTS: A principal components analysis of the patients' ratings on the Anxiety Symptoms and Beliefs Scale produced a four-factor solution in which specific sets of anxiety symptoms loaded with specific beliefs. These four factors were interpreted as respiratory symptoms, vestibular symptoms, autonomic arousal, and psychological threat. Respiratory and vestibular symptoms were more associated with panic disorder diagnoses than with social phobia and generalized anxiety disorder diagnoses. CONCLUSIONS: These findings support a conception of fear of fear in anxiety disorders as fearful beliefs concerning the experience of anxiety symptoms. Associations between symptoms and fear of fear are present across anxiety disorders but are most pronounced in agoraphobia with panic attacks.     

Association of levels of N-acetyl-beta-glucosaminidase with severity of psychiatric symptoms in panic disorder

Urinary levels of N-acetyl-β-glucosaminidase (NAG) were measured in 58 patients with panic disorder. NAG levels were found to be significantly related to the severity of 23 of 72 mood states, measured by the Profile of Mood States, which were grouped in three categories: hostility or irritability, sadness, and panic. A similar result was found in a previous study of bipolar patients. NAG levels were also related to scores on the Hamilton Rating Scale for Anxiety and the Sheehan Patient-Rated Anxiety Scale. It is speculated that NAG could be a marker for serotonin.     

Panic symptoms in schizophrenia: comorbidity and clinical correlates

The aim of the present study was to investigate the prevalence of panic attack (PA) and panic disorder (PD) in patients with schizophrenia and detect the clinical features. Forty-nine patients with schizophrenia were included in the study. Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HDRS), Clinical Global Impression (CGI), Extrapyramidal Symptom Rating Scale (ESRS) and Bandelow Panic and Agoraphobia Rating Scale were administered. Fifteen patients were found to have PA and seven patients had PD. Patients with panic symptoms had higher scores of PANSS, HDRS, CGI and ESRS. Comorbid panic symptoms in schizophrenia may be related to positive symptoms, extrapyramidal side-effects and depression.     

西酞普兰治疗惊恐障碍对照研究

目的探讨西酞普兰对惊恐障碍患者的疗效及副作用。方法对46例惊恐障碍患者随机分成西酞普兰治疗组、帕罗西汀对照组,并用HAMA、GAS、SERS对患者治疗前后进行评估。结果除了在治疗第1周末,西酞普兰治疗组的HAMA分值高于对照组外,在第2、4、6周末,两组患者的HAMA、GAS分值差异均无显著性意义。西酞普兰组患者在治疗6周末,治愈率及有效率分别为63.2%、84.2%,而帕罗西汀组分别为68.2%、90.9%,与帕罗西汀组相比差异无显著性意义。西酞普兰组平均剂量(41.87±15.36)mg/d;帕罗西汀组平均剂量(40.91±14.44)mg/d。在副作用方面,两组患者差异也无统计学意义。结论西酞普兰治疗惊恐障碍患者疗效及副作用与帕罗西汀相当。     

Clinical features and co-morbidity of social phobics in Turkey.

The aim of this study is to investigate the clinical features and frequency and importance of related co-morbid disorders of social phobia in a clinical sample. Eighty-seven patients meeting DSM-III-R diagnostic criteria for social phobia were studied. All patients were assessed by using a semi-structured socio-demographic form, the Structured Clinical Interview for DSM-III-R, Manual for the Structured Clinical Interview for DSM-III-R Personality Disorders, Liebowitz Social Anxiety Scale, Hamilton Rating Scale for Depression and Hamilton Rating Scale for Anxiety. Sixty-eight (78.2%) of the group were male, 19 (21.8%) were female. The ages varied between 16-58 years, with a mean of 26.2 years (SD = 8.5). Fifty-one point seven percent of the subjects were assessed as having a co-morbid axis I disorder, of which 12.6% consisted of panic disorder and 10.3% agoraphobia. An additional axis II disorder had been found in 67.8% of the subjects, and 54.0% of them had been diagnosed as having avoidant personality disorder. The frequency of co-morbid disorders in our social phobic sample is lower than most of the studies in the literature. The interface between social phobia and avoidant personality disorder needs to be studied and discussed further.     

Residual symptoms and comorbidity in panic disorder.

Background: The aim of this study was to assess the outcome of the comorbid conditions of panic disorder after 1 year of treatment, emphasizing the detection of residual symptoms and their relationship to other clinical variables. Methods: Subjects (N = 64) were assessed by the Structured Clinical Interview for DSM-III-R and the Eysenck Personality Questionnaire. Comorbidity with other disorders, scores on Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale were assessed at baseline and after 12 months. Criteria for residual anxiety/somatic symptoms were defined. Results: Reduction in generalized anxiety disorder rates accounted for a significant decrease in comorbidity at 1-year follow-up, with regard to baseline assessment. When the more severe symptoms of the disorder had remitted, a third of the patients referred physical symptoms with some concern over a fluctuating state of anxiety. The said symptoms were neither a recurrence of panic disorder nor did they account for other anxiety or somatoform disorders. Lower scores on extraversion predict higher risk of residual symptoms. Discussion: The persistence of residual anxiety/somatic symptoms in a third of the patients who apparently achieved a good response to treatment of panic disorder might characterize a minor form of chronic persistence of this condition. Conclusions: The subgroup of patients with residual symptoms would not be detectable by follow-up studies, which focus on the assessment of relapse of panic disorder by means of strictly defined diagnostic criteria.