Search

Background: To date, all clinical trials using a single therapeutic modality (psychotherapy or pharmacotherapy) have found that even the best validated treatments for adults with chronic Posttraumatic Stress Disorder (PTSD) leave a substantial proportion of patients with disabling residual symptoms., Method: We reviewed the treatment course of three research patients with PTSD who received trauma-focused psychotherapy after experiencing a partial response to medication. Structured diagnostic interviews, validated symptom measures, and standardized treatment approaches were used to assess treatment response., Results: All patients partially benefited from medication treatment, and the degree of benefit varied substantially. Also, all patients experienced an additional reduction in PTSD symptoms after a time-limited course of prolonged exposure therapy (PE). This finding differs from anecdotal observations among U.S. War veterans and has never been documented systematically among civilian adults with chronic PTSD., Conclusion: Maximizing treatment outcome in adults with chronic PTSD may require additional psychotherapy after a partial medication response, and further study is warranted.

Objective: Childhood trauma has been associated with increased risk for both panic disorder and dissociative symptoms in adulthood. The authors hypothesized that among individuals with a primary diagnosis of panic disorder, those experiencing depersonalization/derealization during panic attacks would be more likely to have a history of childhood trauma., Method: Rates of traumatic events were compared between panic disorder patients with (N=34) and without (N=40) prominent depersonalization/derealization during panic attacks. Symptom severity in the two groups was also examined., Results: Contrary to the authors' hypothesis, no evidence was found that depersonalization/derealization during panic attacks was associated with childhood trauma. Minimal differences in severity of illness were found between patients with dissociative symptoms and those without such symptoms., Conclusions: This finding is consistent with a multifactorial model of dissociation. Factors other than childhood trauma and general psychopathology may underlie vulnerability to dissociative symptoms in panic disorder.

Objective: This study compared dopamine D(2) receptor binding potential in patients with social phobia and healthy comparison subjects., Method: Dopamine D(2) receptor binding potential was assessed in 10 unmedicated subjects with generalized social phobia and no significant lifetime psychiatric comorbidity and 10 healthy comparison subjects matched for age and sex. Binding potential was measured in the striatum by using single photon emission computerized tomography and constant infusion of the D(2) receptor radiotracer [(123)I]iodobenzamide ([(123)I]IBZM)., Results: Mean D(2) receptor binding potential was significantly lower in the subjects with social phobia than in the comparison subjects. Within the social phobia group, there was a nonsignificant correlation of binding potential with the Liebowitz Social Anxiety Scale score., Conclusions: Generalized social phobia may be associated with low binding of [(123)I]IBZM to D(2) receptors in the striatum.

Objective: A new diagnosis can greatly influence scientific research, access to resources, and treatment selection in clinical practice. The authors review the historical evolution, rationale, empirical foundation, and clinical utility to date of the recently introduced diagnosis of acute stress disorder., Method: The conceptual basis and relevant methods for identifying a psychiatric syndrome are reviewed with respect to acute stress disorder, including selection of criteria for core symptoms; considerations of sensitivity and specificity of a syndrome definition; longitudinal course; and distinctions between normative and pathological phenomena. Particular attention is devoted to two major issues: the implications of the core feature requirement of three of five dissociative symptoms, and the question of whether there should be two separate diagnoses (acute stress disorder and post-traumatic stress disorder [PTSD]) describing posttraumatic syndromes. The widely divergent approaches in DSM-IV and ICD-10 are also reviewed., Results: The diagnosis of acute stress disorder does not appear to achieve the important objective of providing adequate clinical coverage for individuals with acute posttraumatic symptoms. The validity and utility of requiring peritraumatic dissociative symptoms as a core feature are questionable, as is the separation of essentially continuous clinical phenomena into two disorders with different criteria sets (acute stress disorder and PTSD) based on persistence of symptoms for 30 or more days., Conclusions: Longitudinal studies using acute stress disorder criteria, as well as broader considerations of the clinical and scientific functions that posttraumatic diagnoses should serve, suggest a need to reevaluate the current DSM-IV approach to posttraumatic syndromes.

Objective: The authors determined the effects of antipanic treatment with fluoxetine on human growth hormone (GH) response to the alpha 2 agonist clonidine., Method: Seventeen patients with panic disorder and 15 healthy volunteers were challenged with clonidine. Thirteen of the patients and 12 of the volunteers were given a second challenge with clonidine 12 weeks later. The patients received open fluoxetine and the healthy subjects received no treatment between challenges. Subjects with high baseline human GH levels (greater than 2 ng/ml) at the first and second challenges were excluded from further analysis., Results: The patients with panic disorder (N = 13 for the first challenge and N = 9 for the second) had significantly lower human GH responses to clonidine than the healthy subjects (N = 14 during the first challenge and N = 9 for the second) during both challenges, despite clinical improvement in eight of the nine patients at the time of the second challenge., Conclusions: Blunted secretion of human GH in response to clonidine in patients with panic disorder persists despite clinical recovery.

Objective: The authors used the family study method to test the hypothesis that sodium lactate response defines two subtypes of panic disorder., Method: Rates of panic disorder in 142 first-degree relatives of patients who responded to sodium lactate, 88 first-degree relatives of patients who did not respond to sodium lactate, and 231 first-degree relatives of never mentally ill subjects were compared., Results: No difference in familial transmission of panic disorder was found between the two patient groups., Conclusions: The findings do not support the notion that panic disorder subtypes are associated with lactate sensitivity.

Objective: The authors review the empirical data on generalized anxiety disorder, a diagnostic category that has been among the more conceptually challenging in psychiatric nosology., Method: Published studies and recent findings that were considered by the Generalized Anxiety Disorder Subcommittee of the DSM-IV Anxiety Disorders Work Group are reviewed. Among the issues examined are diagnostic reliability, comorbidity, boundaries with other disorders, and clinical features., Results: A variety of data on the reliability and validity of generalized anxiety disorder have been produced. Some authors have suggested that generalized anxiety disorder is better conceptualized as a vulnerability that should be located on axis II, and others have recommended that the category be eliminated. Although the diagnostic reliability of generalized anxiety disorder is lower than that of other anxiety disorders, the features constituting the diagnostic criteria for generalized anxiety disorder have been found to be reliable. An important development has been the determination of a set of somatic symptoms associated with generalized anxiety disorder that differs substantially from those for other anxiety disorders. These findings led to reduction in the number of items in the symptom criterion, from 18 in DSM-III-R to six in DSM-IV. Another substantial revision is greater emphasis on the uncontrollability of worry., Conclusions: Whereas the data on construct and discriminant validity, age at onset, course, familial transmission, and response to treatment generally support the DSM-IV definition of generalized anxiety disorder, the construct continues to have weaknesses and further research is needed.

Objective: This field trial was designed to answer four questions. First, are patients presenting with anxious or depressed symptoms that are associated with significant impairment but do not meet DSM-III-R definitional thresholds for axis I anxiety or mood disorders? Second, is the impairment experienced by these patients simply the consequence of the severity of their medical conditions? Third, what percent of these patients present with depressive symptoms only, anxious symptoms only, and a mixture of both? Fourth, how should the operational criteria for the syndrome(s) presented by these patients be defined?, Method: A total of 666 patients from five primary care medical sites and two outpatient mental health sites were administered a semistructured psychiatric interview., Results: Patients presenting with affective symptoms that did not meet definitional thresholds for DSM-III-R axis I disorders were at least as common as patients with several of the already established anxiety and mood disorders in each of the seven sites, and their disorders were associated with significant distress or impairment. A nonspecific pattern of anxious and depressed symptoms was the modal presentation among these patients with currently subdefinitional threshold disorders, and they could be significantly differentiated in terms of current symptoms from patients presenting with a principal diagnosis of generalized anxiety disorder, major depressive episode, or panic disorder with agoraphobia., Conclusions: The authors recommend that a mixed anxiety-depression category be included in the DSM-IV appendix for proposed diagnostic categories that need further study. A criteria set is proposed.

Objective: Ataque de nervios ("attack of nerves") is an illness category used frequently by Hispanic individuals to describe one or more particular symptom complexes. A review of the literature on ataque suggested some overlap with panic disorder. This study investigated the overlap with panic disorder as well as other DSM-III-R axis I disorders., Method: Hispanic subjects seeking treatment at an anxiety disorders clinic (N = 156) were assessed with a specially designed questionnaire for self-report of ataque de nervios and panic symptoms and with structured or semistructured psychiatric interviews for axis I disorders., Results: Seventy percent of the subjects reported at least one ataque de nervios; 80% of these were female, whereas 57% of the group without these attacks were female. There were no differences in DSM-III-R diagnoses between the groups with and without ataque de nervios. Ataque was frequently associated with one or more anxiety and affective disorders, including panic disorder, generalized anxiety disorder, recurrent major depression, and anxiety not otherwise specified. Of the 45 subjects with both ataque de nervios and primary panic disorder, 80% appeared to have labeled panic disorder as ataque. Ataque de nervios was associated with panic symptoms even in subjects without panic disorder, but the self-reporting of ataque conveyed additional clinical information about the subjects with panic disorder. Ataque de nervios was similar in frequency and symptoms among subjects of Dominican and Puerto Rican origin., Conclusions: Ataque de nervios overlaps with panic disorder but is a more inclusive construct. Further study of its interrelation with axis I disorders is needed.

The authors examined the relation between retrospectively reported childhood separation anxiety disorder and adult DSM-III-R anxiety disorders in 252 outpatients at an anxiety disorders research clinic. The prevalence of childhood separation anxiety disorder was significantly greater among patients with two or more lifetime adult anxiety disorder diagnoses than it was among patients with only one anxiety disorder, suggesting that childhood separation anxiety disorder may be a risk factor for multiple anxiety syndromes in adulthood.

Objective: Patients with panic disorder are behaviorally hypersensitive to CO2 inhalation and may also be biologically hypersensitive. A report by Mathew et al. showed, however, that administration of the carbonic anhydrase inhibitor acetazolamide, which is believed to increase brain CO2 level, did not cause panic in panic disorder patients. The authors of the present study noted that respiratory frequency did not increase in the earlier experiment and wondered whether respiratory stimulation occurred during acetazolamide administration, as would be expected if CO2 level increases significantly., Method: Ten patients with panic disorder and six normal control subjects received injections of acetazolamide, 1 g i.v., as per the Mathew et al. protocol, during breath by breath measurement of both tidal volume and frequency of respiration., Results: Three patients had panic attacks, one before receiving acetazolamide, one during the injection, and one 2 minutes after injection. Only the last of these attacks appeared possibly attributable to acetazolamide. None of the control subjects panicked. Neither patients nor control subjects exhibited meaningful change in tidal volume, respiratory frequency, or minute ventilation, and both groups experienced a trend toward significant decrease in overall levels of anxiety and dyspnea after acetazolamide injection., Conclusions: The authors replicated the earlier finding that acetazolamide is not panicogenic in patients with panic disorder but also showed that at the dose given, there is no meaningful effect on ventilation. If acetazolamide does affect CO2 levels it does so in a way that does not stimulate ventilation. Therefore, the acetazolamide injection results of Mathew et al. and of the present study do not challenge hypotheses linking panic attacks to hypersensitive respiratory control mechanisms.

Objective: The authors assessed the substance and diagnostic specificity of carbon-dioxide-induced panic since, in addition to the specific biochemical effects of inhaled carbon dioxide (CO2), simple physiologic distress is also frequently implicated as a panicogenic factor during respiratory challenge studies with CO2 in patients with anxiety disorders., Method: Eighteen patients with panic disorder, 20 with social phobia, and 23 psychiatrically normal subjects inhaled a mixture of 35% CO2 and 65% O2 for 30 seconds through a face mask. They also breathed for 30 seconds through a valve reducing the diameter of the airway. A double-blind, counterbalanced, randomized design was used., Results: In spite of important similarities between the two interventions, including the induction of equal amounts of subjective respiratory distress, carbon dioxide inhalation was significantly more potent than increased airway resistance in provoking panic in the anxiety disorder patients. The patients with panic disorder were significantly more sensitive to CO2 than were the patients with social phobia or the normal subjects., Conclusions: Carbon dioxide inhalation appears to have a specific panicogenic effect in panic patients that goes beyond simple breathlessness.

Six patients with panic disorder who had panicked during sodium lactate infusion were given cognitive-behavioral treatment for 12-24 weeks. After treatment they underwent another lactate infusion, and four patients were rates as having no panic, suggesting that reduced vulnerability to lactate accompanies remission of panic. Controlled trials of cognitive-behavioral therapy and use of lactate infusion as a measure of remission are recommended.

Four men with paruresis received trials of atenolol or phenelzine or both. Atenolol was effective in one patient. Three patients had a poor response to phenelzine, and they all experienced troublesome side effects.

Alprazolam treatment was tapered in 17 panic patients at a rate of 10% of the starting dose every 3 days. Only four subjects completed withdrawal on schedule (4-5 weeks); four additional subjects discontinued treatment in 7-13 weeks. During withdrawal 15 patients had recurrent or increased panic attacks and nine had significant new withdrawal symptoms. Most common among the latter were malaise, weakness, insomnia, tachycardia, lightheadedness, and dizziness. None had seizures, psychosis, or significant neurological or EEG abnormalities. Results indicate that relapse and withdrawal are important considerations in the choice of alprazolam treatment for panic attacks.

The authors describe five patients with body-dysmorphic disorder who responded preferentially to serotonin reuptake blockers. They review the literature, describe how patients with excessive concern about body abnormalities lie along a spectrum of doubt and certainty, and discuss similarities and differences between this disorder and obsessive-compulsive disorder.

Panic attacks followed sodium lactate infusions in one of seven patients with obsessive-compulsive disorder and 26 of 48 patients with panic disorder or agoraphobia with panic attacks. This suggests that lactate-induced panic is specific to the latter groups.

Seven male panic patients did not panic but were significantly more sensitive to steady-state carbon dioxide inhalation than five male normal control subjects. The male patients' hypersensitivity to carbon dioxide was unrelated to current state of anxiety or acute panic.

Twelve patients with DSM-III diagnoses of panic disorder and four normal volunteers were studied during hyperventilation of room air and increased ventilation stimulated by 5% CO2. Patients also underwent sodium lactate infusion. Eight of the patients had a panic attack during sodium lactate infusion, seven during CO2 inhalation, and three during room-air hyperventilation. Since CO2 increases the firing of the locus ceruleus, and since sodium lactate infusion is known to increase cerebral CO2, these findings are consistent with other evidence implicating the locus ceruleus in panic anxiety.

Six of eight patients with obsessive-compulsive disorder had an exacerbation of symptoms when given m-chlorophenylpiperazine. Fenfluramine and placebo produced mild improvement. Six patients given intravenous clonidine experienced marked reduction in obsessions. Implications for serotonergic and noradrenergic hypotheses of obsessive-compulsive disorder are discussed.

In an open trial, five of eight panic disorder patients and none of five control subjects panicked after inhalation of two breaths of 35% CO2 and 65% O2; none panicked after placebo. Using 35% CO2 to induce panic is safe, simple, and well tolerated and may provide a valuable laboratory model of panic.

To determine whether endogenous opiates are involved in panic anxiety, the authors challenged 12 patients with panic attacks with intravenous naloxone hydrochloride alone or combined with sodium lactate. Naloxone did not produce panic attacks or alter responses to lactate.

Sixty patients with probable atypical depression--defined as meeting Research Diagnostic Criteria for depressive illness, having reactive mood, and having one of four associated symptoms (hyperphagia, hypersomnolence, leaden feeling, and sensitivity to rejection)--took part in a study contrasting phenelzine, imipramine, and placebo. Phenelzine was found to be superior to imipramine and placebo. These results were compared to results from a sample of 120 patients with identical characteristics, except that they had more than one associated atypical symptom (full atypical syndrome). The size of the drug effect was comparable in patients with full atypical and partial atypical syndromes.

To determine whether the lactate-induced panic of patients with panic attacks results from hyperinsulinism balanced by epinephrine-enhanced gluconeogenesis, the authors measured 10 subjects' insulin levels exactly when the lactate-induced attacks began. The insulin levels were normal.

Forty-three patients with panic disorder or agoraphobia with panic attacks and 20 control subjects received 0.5 M racemic sodium lactate intravenous infusions, single-blind as to duration and sequence. During the procedure, pulse; blood pressure; blood L-lactate and pyruvate; plasma ionized calcium, phosphate, prolactin, epinephrine, norepinephrine, and cortisol levels; and venous PCO2, pH, and bicarbonate were measured in an attempt to clarify the mechanism of lactate-induced panic attacks. During the infusion, 72% of the patients but none of the control subjects had panic attacks. The laboratory findings suggest that peripheral catecholamine surge is not the mechanism by which lactate causes panic, although elevated epinephrine may be a predisposing factor. Heightened central noradrenergic activity was present in many but not all of the attacks. Contrary to previous hypotheses, neither depression of ionized calcium nor induction of metabolic alkalosis appears sufficient to cause panic during lactate infusion.

Lactate infusions produced panic attacks in one of 15 patients with social phobia, four of nine with agoraphobia, and 10 of 20 with panic disorder in a blind study. The proportion of patients with social phobia who panicked in response to lactate was significantly lower than that of patients with agoraphobia or panic disorder. These findings lend validity to the DSM-III classification of anxiety states. They also suggest that the pathophysiology of social phobia differs from that of disorders characterized by spontaneous panic attacks.

Many patients with panic disorder believe hypoglycemia causes their symptoms. Of 10 patients with panic disorder given sodium lactate to induce panic, none had evidence of low blood sugar levels when they began to experience anxiety symptoms.

To assess the role of peripheral epinephrine in social anxiety, the authors infused 11 patients meeting DSM-III criteria for social phobia with intravenous epinephrine over 60 minutes. Although the mean plasma epinephrine level increased from 113 to 928 pg/ml, only one of the 11 patients experienced observable anxiety; this finding suggests that an increase in plasma epinephrine level alone is inadequate to cause social anxiety. Of the variables measured, only the average minute volume correlated with self-rated anxiety. Ventilatory indexes might be better correlates of subjective anxiety than other physiological variables.

Anxiety disorders, the most common psychiatric conditions in the United States, have generated a great deal of research and scientific debate. Panic disorder, the best-studied anxiety disorder, is often believed to be either a biological disease or a psychological disease. The authors present a neuroanatomical model of panic disorder that attempts to reconcile these views. The model locates the three components of the disease--the acute panic attack, anticipatory anxiety, and phobic avoidance--in three specific sites of the CNS: the brainstem, limbic system, and prefrontal cortex, respectively. The authors suggest experiments to test their model.