Trazodone in the treatment of panic disorder and agoraphobia with panic attacks

Eleven patients with panic disorder or agoraphobia with panic attacks completed an 8-week single-blind trial of trazodone (300 mg/day) without concurrent behavioral instructions. The measures of change included ratings of generalized and panic anxiety, phobias, and depression and a behavioral avoidance test, which were administered during a baseline period of placebo administration and at 4 and 8 weeks of the trial. There was significant improvement on all symptom dimensions, which suggests that trazodone may have specific antipanic and antiphobic actions and underscores the importance of serotonergic mechanisms in these anxiety disorders.     

Assessment of agoraphobia and panic disorder

1. 1. Phobia and panic are defined by the measures used.

2. 2. Rating scales, diaries, global measures, physiological measures, behavioural assessment.

3. 3. Three fear systems: physiological, cognitive and behavioral

4. 4. Concordance and discordance.

5. 5. Synchrony and desynchrony

6. 6. The Behavioural Approach Test at the Calgary General Hospital.

Hyperventilation-induced panic attacks in panic disorder with agoraphobia

Eight minutes of hyperventilation to an end-tidal PCO2 of less than 20 mmHg led to a panic attack in 7 of 12 patients with panic disorder with agoraphobia and only 1 of 12 normal controls. Patients experienced greater increases in panic symptoms than controls during hyperventilation. Patients who reported more distress from somatic symptoms of hyperventilation during the preceding week were more likely to panic during hyperventilation. Patients who panicked during hyperventilation exhibited a delayed recovery of normocapnia following hyperventilation. Hyperventilation by this protocol is an effective means of inducing panic attacks in the laboratory. A hyperventilation challenge may identify a subgroup of patients for whom hyperventilation symptoms are frequently associated with panic.     

Long-term treatment of panic disorder with agoraphobia in private practice

The author followed 67 patients with panic disorder with agoraphobia (PDA) for a minimum of 5 years in a private practice setting. They were treated with a combination of pharmacotherapy (antidepressants or benzodiazepines) and cognitive-behavioral psychotherapy. The author examines outcomes for three groups: A) 11 male patients, 10 of whom had comorbid conditions; B) 21 female patients with comorbid conditions; and C) 35 female patients without comorbid conditions. Symptom severity was assessed using the Panic Disorder Severity Scale (PDSS). Patients in all groups showed marked improvement in all the domains measured by the PDSS, with the greatest improvement in PDSS scores occurring during the first year in all three groups. Patients in groups A and B tended to plateau after 5 years of treatment and show no additional improvement thereafter, whereas patients in group C (women with "pure PDA") continued to improve, although at a gradually slower rate. However, after an average of 11 years of treatment, the majority of patients remained symptomatic. The presence of comorbid alcohol abuse or depression was associated with poorer outcomes. The results in this effectiveness study are generally not as good as the outcomes of published PDA follow-up efficacy studies, but appear to be superior to outcomes in cohorts of chronically anxious patients treated decades ago.     

Paroxetine in panic disorder with agoraphobia

A case of a panic disorder patient treated successfully in the long term with a selective serotonin re-uptake inhibitor, paroxetine, is reported. Based on this case, the relationship between pharmacotherapy and psychotherapy is discussed.     

Correlates of DSM-III personality disorder in panic disorder and agoraphobia

One hundred eighty-seven patients meeting DSM-III criteria for panic disorder (n = 26) or agoraphobia with panic (n = 161) were assessed with the Personality Diagnostic Questionnaire (PDQ), a self-rating scale designed to assess Axis II personality disorders and traits. Results replicated our earlier findings of a preponderance of dependent, avoidant, and histrionic features and the finding that patients exhibiting a greater number of personality traits were also significantly more symptomatic. Patients with the diagnosis of panic disorder did not differ on any personality disorder variables from patients with the diagnosis of agoraphobia with panic. Furthermore, none of the specific symptom dimensions, i.e., panic, anxiety, or agoraphobia, was selected as a unique predictor of any personality variables in the regression analyses. Rather, the most important correlates of personality disorder in these patients consisted of general factors such as dysphoric mood, social phobia, or interpersonal sensitivity, and Eysenck's neuroticism dimension. The results are discussed in light of recent findings suggesting a nonspecific link between panic disorder or agoraphobia and personality disorder.     

The relationship of panic disorder to agoraphobia

Twenty patients with agoraphobia or panic disorder were compared to each other using multiple variables of clinical illness. No differences were found. Only one of thirteen agoraphobic patients did not experience panic attacks. The agoraphobia symptoms never preceded the panic attacks in those twelve patients experiencing both agoraphobia and panic attacks. This study data and that of others is most consistent with the hypothesis that agoraphobia is a secondary manifestation of panic disorder.     

Marijuana precipitation of panic disorder with agoraphobia

We report the case of a 16-year-old adolescent with the onset of a panic disorder with agoraphobia after a first panic attack during marijuana intoxication. There was a good response to standard cognitive behavioural therapy for panic disorder.     

Treatment of panic disorder and agoraphobia with clonazepam

Clonazepam, a high-potency benzodiazepine marketed for the treatment of minor motor epilepsy, was used to treat 50 patients with panic disorder (N = 22) or agoraphobia with panic attacks (N = 28). Of the 50 patients, 41 had previously been poorly responsive to standard pharmacologic therapies. At a mean dose of only 1.9 (+/- 1.0) mg/day, 39 patients (78%) responded. No serious adverse effects were encountered. This study, although retrospective and uncontrolled, suggests that clonazepam, like alprazolam, may be effective in blocking panic attacks. A possible common mechanism for the two drugs as high-potency benzodiazepines is discussed.     

Differential familial liability of panic disorder and agoraphobia

To examine the familial liability of panic disorder (PD) and agoraphobia (AG) in a community sample, namely the effect of parental PD and AG on the offspring's risk to develop either or both conditions in adolescence or adulthood. A representative community sample of N=3,021 adolescents and young adults aged 14-24 years at baseline was followed up over a period of 10 years in up to four waves. Family information was assessed by either direct interviews with at least one parent or by using subjects' family history information at either wave (N=3,014). Diagnoses and selected symptoms were assessed in both, parents and subjects, by using a standardized diagnostic interview (DSM-IV M-CIDI) with its respective family history module. (1) Parental panic attacks (PA), PD, and AG were all shown to be associated with an increased risk of offspring to also develop PA, PD, and AG. (2) Associations of parental PD were present irrespective of parental AG, whereas parental AG without PD was not associated with an increased offspring risk. (3) Outcome risk was particularly elevated in offspring of parents with PD+AG. (4) Parental PD or AG was not associated with an earlier age of onset of any syndrome in the offspring. We confirmed and expanded previous results from clinical samples that comorbid PD and AG aggregate in families. AG without PD is not familial, but it might enhance the familial transmission of PD.     

Diazepam and propranolol in panic disorder and agoraphobia

The response to diazepam and propranolol hydrochloride was compared in 21 patients who (with one exception) met DSM-III criteria for panic disorder and agoraphobia. Each drug was administered for two weeks in double-blind fashion according to a crossover design. The response to diazepam was significantly superior on all measures. By observer rating, 18 patients showed at least moderate improvement with diazepam compared with seven receiving propranolol. Panic attacks and phobic symptoms responded to diazepam, but not to propranolol. The results suggest that benzodiazepines constitute effective short-term treatment for these newly defined disorders.     

Thyroid hormones in panic disorder, panic disorder with agoraphobia, and generalized anxiety disorder

Fifty-two patients with generalized anxiety disorder who had symptoms persisting for at least 6 months, 41 patients suffering from either panic disorder (32 patients) or panic disorder with agoraphobia (9 patients), and 14 control subjects were screened for thyroid disease. Total serum thyroxine (TT4), serum-free thyroxine index (FT4I), and triiodothyronine resin uptake (T3RU), were examined for the entire sample, using a one-way analysis of variance (ANOVA). No significant differences were found in TT4 (p = .24), FT4I (p = .24), and T3RU (p = .19). Thyroid-stimulating hormone (TSH) was examined in a subsample of 10 patients with generalized anxiety disorder, 11 with panic disorder or panic disorder with agoraphobia, and 10 controls. One-way ANOVA again showed no significant differences, although there was a trend (p = .07). This is the first report that compares generalized anxiety disorder patients, panic disorder patients, and patients with panic disorder and agoraphobia with controls on measures of thyroid function. It is also the first to report normal values in the thyroid indices of generalized anxiety disorder patients.     

Characteristics of agoraphobia in women and men with panic disorder with agoraphobia

We compared female and male patients with panic disorder with agoraphobia (PDA) in terms of characteristics of agoraphobia (AG). Ninety-five patients (73 women and 22 men) with the SCID-based diagnosis of PDA were administered the National Institute of Mental Health Panic Questionnaire (NIMH PQ), and women and men were compared on the items of the NIMH PQ that pertain to AG and symptoms of panic attacks. Male and female patients did not differ significantly with respect to demographic characteristics, age of onset of panic disorder and AG, duration of PDA, and severity and frequency of symptoms experienced during panic attacks. Women avoided more situations than did men, but this difference was not statistically significant. Women avoided buses and being in unfamiliar places alone significantly more often. The only situation that was avoided more often by men, although not significantly, was staying at home alone. Women were significantly more likely to stay at home to avoid agoraphobic situations and significantly less likely to go outside of home alone. When going outside, women required a companion significantly more often. There were significantly more married women than married men who required a spouse as a companion, and significantly more women with children than men with children who required a child as a companion. Women thought that AG had affected the overall quality of their lives significantly more adversely. Whereas the overall “profile” of agoraphobic situations does not seem to distinguish between female and male patients with AG, females may be more impaired and appear more dependent than men in terms of requiring companions to move outside of the home. Cultural and psychological factors may be most likely to account for these findings. Depression and Anxiety 8:8–13, 1998. © 1998 Wiley-Liss, Inc.     

Alprazolam plasma concentrations and treatment response in panic disorder and agoraphobia.

OBJECTIVE: The authors' goal was to evaluate the relationship between plasma concentrations of alprazolam and both treatment response and side effects in patients with panic disorder and agoraphobia. METHOD: Ninety-six patients with panic disorder and agoraphobia were treated at three sites in a 6-week, fixed-dose, double-blind, placebo-controlled, dose-response study of 2 mg/day or 6 mg/day of alprazolam. Assessments were made of panic attacks, avoidance behavior, generalized anxiety, and global response. Blood samples were collected throughout the study and analyzed for alprazolam and other benzodiazepines. RESULTS: Patient compliance with the protocol was judged to be good on the basis of plasma concentrations. According to logistic regression analysis, the relationships between plasma alprazolam concentration and response, as reflected by number of panic attacks reported, phobia ratings, physicians' and patients' ratings of global improvement, and the emergence of side effects, were significant. However, there was no significant relationship between plasma alprazolam concentration and the degree of generalized anxiety symptoms. CONCLUSIONS: The authors conclude that plasma concentration of alprazolam is related to treatment response, particularly in panic attacks. The alprazolam concentration associated with treatment response or with emergence of a given side effect varied widely among individuals, highlighting the necessity for individualized dose adjustment to obtain optimal treatment response while minimizing side effects.     

Prodromal symptoms in panic disorder with agoraphobia

Of 20 patients suffering from panic disorder with agoraphobia, 18 reported experiencing agoraphobic avoidance, generalized anxiety, and/or hypochondriacal fears and beliefs before the first panic attack. The prevalence of these symptoms in the patients was significantly higher than the prevalence in 20 healthy control subjects. The results indicate that phobic avoidance in panic disorder with agoraphobia may not be secondary to the panic attacks, a finding that runs counter to the current DSM-III-R classification of anxiety disorders.