Treatment of endogenous anxiety with phobic, hysterical, and hypochondriacal symptoms.

Endogenous anxiety (anxiety hysteria, agoraphobia with panic attacks) is characterized by sudden, spontaneous panic attacks accompanied by multiple autonomic symptoms, overwhelming fear, a flight response, and polyphobic behavior. Psychotherapy, behavior therapy, and tranquillizers have been of limited success in treating this syndrome. Fifty-seven patients severely disabled by the syndrome for a mean period of 13 years completed the three-month study. Randomly assigned in a double-blind, placebo-controlled design to imipramine hydrochloride, pheneizine sulfate, or placebo, they were seen in supportive group therapy every two weeks. Patients in the pheneizine and imipramine cells showed significant improvement ovehe persistent trend for pheneizine to be superior to imipramine achieved significance only on the Work and Social Disability Scale and the Sympton Severity and Phobic Avoidance Scale. The implications for classification and theory are discussed.

Immunological response to stress in agoraphobia and panic attacks.

The authors studied in vitro immune function as measured by lymphocytic proliferative response to mitogen stimulation in 36 patients with agoraphobia and panic attacks who were participating in a double-blind placebo-controlled psychopharmacological study of anxiety disorder. No significant difference in immune status was observed between panic patients and healthy controls.

Efficacy of extended-release venlafaxine in nondepressed outpatients with generalized anxiety disorder.

OBJECTIVE: This study evaluated the efficacy and safety of fixed doses of once-daily extended-release (XR) venlafaxine in outpatients with generalized anxiety disorder without concomitant major depressive disorder. METHOD: Adult outpatients with generalized anxiety disorder but not major depressive disorder with total scores of 18 or higher on the Hamilton Rating Scale for Anxiety and scores of 2 or higher on its anxious mood and tension factors were eligible. Patients were randomly assigned to receive placebo or venlafaxine XR (75, 150, or 225 mg/day) for 8 weeks. Primary efficacy variables were final total and psychic anxiety factor scores on the Hamilton anxiety scale and final severity and global improvement item scores on the Clinical Global Impression (CGI) scale. RESULTS: Of the 377 patients entering the study, 370 were included in a safety analysis and 349 in an efficacy analysis. Adjusted mean scores at 8 weeks (last-observation-carried-forward analysis) were significantly lower for one or more of the venlafaxine XR groups in four of four primary and three of four secondary outcome measures than for the placebo group. These included a change of 1.7 (versus 1.3) from baseline on CGI severity item scores and a final score of 2.2 (versus 2.6) on the CGI global improvement item. All doses of venlafaxine XR were well tolerated. CONCLUSIONS: Venlafaxine XR is an effective and well-tolerated option for the short-term treatment of generalized anxiety disorder in outpatients without major depressive disorder.

The prevalence of mitral valve prolapse in patients with panic disorders.

Of 131 patients with panic disorder or agoraphobia, 44 (34%) had definite mitral valve prolapse on the basis of clinical findings of an apical mid- or late systolic click and a murmur and/or a two-dimensional echocardiogram showing prolapse of one leaflet in two views or of two leaflets in a single view. Seven other patients (5%) had a probable diagnosis of mitral prolapse on the basis of a typical murmur alone or an intermittent apical mid- or late systolic click and a prolapsing leaflet in a single echocardiographic view. This finding confirms previous reports of the association between panic disorder and mitral valve prolapse.

Panic disorder in genotypic HLA identical sibling pairs.

The authors describe two HLA identical sibling pairs with panic disorder. To their knowledge, this is the first report of histocompatibility testing in patients with anxiety disorders.

Cocaine use by senior medical students.

The authors studied 589 senior medical students' attitudes about and use of cocaine. Reported use was 36% in the students' lifetimes, 17% in the past year, and 6% in the past month. Overall, these rates were lower than those of an age-matched cohort.

Resident physician substance use, by specialty.

OBJECTIVE: This study compares substance use by medical specialty among resident physicians. METHOD: The authors estimated the prevalence of substance use of 11 medical specialties from a national sample of 1,754 U.S. resident physicians. RESULTS: Emergency medicine and psychiatry residents showed higher rates of substance use than residents in other specialties. Emergency medicine residents reported more current use of cocaine and marijuana, and psychiatry residents reported more current use of benzodiazepines and marijuana. Contrary to recent concerns, anesthesiology residents did not have high rates of substance use. Family/general practice, internal medicine, and obstetrics/gynecology were not among the higher or lower use groups for most substances. Surgeons had lower rates of substance use except for alcohol. Pediatric and pathology residents were least likely to be substance users. CONCLUSIONS: The authors' previous research indicates that residents overall have lower rates of substance use than their age peers in society. Yet resident substance use patterns do differ by specialty. Residents in some specialties are more likely to use specific classes of drugs, to use a greater number of drug classes, and to be daily users of alcohol or cigarettes.

Panic attacks and the dexamethasone suppression test.

Of 51 patients with panic attacks, 11.8% (7.8% with a correction factor) had a positive dexamethasone suppression test. This is significantly lower than the rate for melancholia. This difference suggests that panic attacks and major depression may be associated with different biological mechanisms.

False positive results: a challenge for psychiatric screening in primary care.

OBJECTIVE: The goal of this study was to characterize primary care patients with false positive results on screens for mental disorders. METHOD: A sample of 1,001 primary care patients completed self-administered screens and structured interviews for DSM-IV diagnoses. RESULTS: A substantial proportion of the patients with false positive screen results for at least one diagnosis met the diagnostic criteria for other psychiatric disorders. They also had significantly greater functional impairment and higher rates of recent use of mental health services than the subjects with true negative results on the screens. CONCLUSIONS: Although the positive predictive values of screens for specific mental disorders are in line with those of other medical screens, false positive results are not uncommon. This may be due in part to the sensitivity of brief screening instruments to nonspecific symptoms. The results suggest that as with other screens used in primary care, patients with false positive results on screens for mental disorders should receive clinical attention.

Mental disorders and disability among patients in a primary care group practice.

OBJECTIVE: This article examines social and occupational disability associated with several DSM-IV mental disorders in a group of adult primary care outpatients. METHOD: The subjects were 1,001 primary care patients (aged 18-70 years) in a large health maintenance organization. Data on each patient's sociodemographic characteristics and functional disability, including scores on the Sheehan Disability Scale, were collected at the time of a medical visit. A structured diagnostic interview for current DSM-IV disorders was then completed by a mental health professional over the telephone within 4 days of the visit. RESULTS: The most prevalent disorders were phobias (7.7%), major depressive disorder (7.3%), alcohol use disorders (5.2%), generalized anxiety disorder (3.7%), and panic disorder (3.0%). A total of 8.3% of the patients met the criteria for more than one mental disorder. The proportion of patients with co-occurring mental disorders varied by index disorder from 50.0% (alcohol use disorder) to 89.2% (generalized anxiety disorder). Compared with patients who had a single mental disorder, patients with co-occurring disorders reported significantly more disability in social and occupational functioning. After adjustment for other mental disorders and demographic and general health factors, compared with patients with no mental disorder, only patients with major depressive disorder, bipolar disorder, phobias, and substance use disorders had significantly increased disability, as measured by the Sheehan Disability Scale. CONCLUSIONS: Primary care patients with more than one mental disorder are common and highly disabled. Individual mental disorders have distinct patterns of psychiatric comorbidity and disability.

Neuroendocrine correlates of lactate-induced anxiety and their response to chronic alprazolam therapy.

Lactate infusions are anxiogenic in patients with panic disorder or agoraphobia with panic attacks, but few neuroendocrine profiles of this effect have appeared. The authors measured the number and intensity of panic symptoms and blood hormone levels during double-blind lactate infusions in 25 patients and 10 normal subjects and during placebo infusions in another five patients. Each patient was rechallenged with an identical infusate after chronic double-blind outpatient treatment with alprazolam or placebo. The results confirm the effectiveness of lactate infusions in evoking anxiety, extend previous hormone profiles of this maneuver, and indicate that chronic alprazolam treatment minimizes the neuroendocrine response to lactate challenges in patients with panic disorder or agoraphobia with panic attacks.

Current concepts in the treatment of panic disorder.

Panic disorder is a prevalent psychiatric condition that often is chronic and rarely resolves without medical intervention. Many patients with panic disorder initially present with a variety of somatic symptoms, including chest pain, nausea, or dizziness, and patients frequently seek care in ambulatory care settings. Although panic disorder is classified as a single entity, it can have many dimensions and may be associated with significant morbidity. During the past 2 decades, there have been significant advances in the treatment of panic disorder, and a range of therapeutic choices is now available. Four classes of medications, including the selective serotonin reuptake inhibitors (SSRIs), high-potency benzodiazepines, tricyclic antidepressants, and monoamine oxidase inhibitors, may be considered for the management of patients with panic disorder. Emerging clinical data favor the SSRIs as first-line treatment for patients with panic disorder, and paroxetine and sertraline have been approved by the U.S. Food and Drug Administration for use in panic disorder. This article reviews the efficacy and safety of these treatments, as well as their relative merits and disadvantages, and assists the practicing clinician in choosing among the various pharmacotherapies to tailor therapy to each patient's individual needs.

Attaining remission in generalized anxiety disorder: venlafaxine extended release comparative data.

Generalized anxiety disorder (GAD) is a chronic mental disorder that is characterized by excessive anxiety or worry. Traditionally, the treatment goal for GAD has been the attainment of a treatment response, clinically defined as a 40% to 50% symptomatic improvement relative to baseline. However, there is growing consensus among clinical psychiatrists that the treatment goal should be remission, a virtually asymptomatic state that corresponds to a score of < or = 7 on the Hamilton Rating Scale for Anxiety (HAM-A) or a > or = 70% symptomatic improvement from baseline. Venlafaxine extended release (XR), a serotonin-norepinephrine reuptake inhibitor, is the first pharmacotherapeutic agent to be indicated for both depression and GAD. This article reviews the efficacy data from several short- and long-term placebo-controlled studies of venlafaxine conducted to evaluate the potential of this agent to facilitate remission. Total scores on the HAM-A and the Clinical Global Impressions scale were used as the primary variables; scores for the HAM-A psychic and somatic anxiety factors and for the Hospital Anxiety and Depression scale were used as secondary variables. Venlafaxine XR showed a substantial effect size in the individual HAM-A items of worry, anxiety, and behavior at interview. The pooled analysis of 2 long-term studies indicated that the scores of venlafaxine remitters separated from those of responders by the second month, resulting in an overall increase in remitters. The results of these studies demonstrate the strong potential of venlafaxine XR in facilitating remission in GAD.

Venlafaxine extended release (XR) in the treatment of generalized anxiety disorder.

This article reviews results of reports suggesting that venlafaxine extended release (XR) may play an important role in the treatment of anxiety disorders, particularly generalized anxiety disorder (GAD). Statistically significant improvements in GAD for venlafaxine XR compared with placebo on the basis of the Hamilton Rating Scale for Anxiety were seen in the acute treatment studies up to 8 weeks and were maintained for 6 months. One comparative study found venlafaxine XR to be as effective as, or on some measures more effective than, buspirone at relieving GAD. Venlafaxine XR was safe and well tolerated in the GAD studies, with discontinuation rates due to adverse effects similar to the rates seen with placebo or buspirone.

Delineation of anxiety and phobic disorders responsive to monoamine oxidase inhibitors: implications for classification.

Studies of the treatment of panic anxiety and various other states with monoamine oxidase (MAO) inhibitors are critically reviewed. It is concluded that MAOIs have differential effects on several dimensions of pathologic anxiety. The association between depression and anxiety states is also reviewed; it is observed that MAOIs effectively treat severe anxiety and phobic disorders without operating strictly via their antidepressant mechanism. In addition, it is proposed that biologic depression and biologic anxiety should be considered to have some independence from one another. Guidelines for the clinical delineation of anxiety disorders are provided, and the clinical and research implications of the proposal for revision of DSM-III anxiety and phobic disorders section, are outlined in detail. It is suggested that anxiety and phobic disorders be classified into endogenous (disease) and exogenous (nondisease) types.

The role of SSRIs in panic disorder.

This article reviews all available studies reported in the literature or presented at national or international meetings on the efficacy of serotonin selective reuptake inhibitors and less selective serotonin uptake inhibitors in panic disorder. The research data lags behind-rather than leads-experience in everyday clinical practice. The emerging data suggest that serotonin uptake inhibitors are superior to placebo and better tolerated than most of the older alternatives. As a result they are now becoming first-choice treatments in panic disorder.

Medical evaluation of panic attacks.

Panic disorder with or without agoraphobia is dominated by the occurrence of panic attacks. However, panic attacks are also reported to occur as part of the clinical picture in several medical conditions, notably thyroid disease, hypoglycemia, and pheochromocytoma. The authors examine these conditions, review the relevant literature, and offer an evaluation strategy. Routine screening is not recommended. Panic disorder is also associated with mitral-valve prolapse and temporal lobe seizures. The authors explore the possible consequences of this association and outline an evaluation strategy. Again, routine screening is not recommended.

Panic anxiety: a new biological model.

Previously unrecognized similarities among metabolic responses to various maneuvers used to evoke anxiety in patients with panic disorder are described. On the basis of these observations, a new biological model is proposed for panic disorder, in which the primary defect--which is neuroendocrine rather than psychiatric--is operationally placed within the redox-regulating apparatus of the brain stem. This model is consistent with many clinical features of panic disorder and also provides a theoretical framework for further studies of the pathophysiology of this and related conditions (e.g., hyperventilation syndrome).

Thyroid indices in panic disorder.

Eighty-two patients suffering from panic attacks with or without phobias were examined for evidence of thyroid disease. None of the patients had abnormal total T4 or T3 resin uptake measurements, regardless of whether they were nonmedicated or treated with one of three antipanic drugs: alprazolam, phenelzine, or imipramine. A higher than expected incidence of undetectable TSH levels (22% overall) appeared in all groups. The clinical relevance of this finding is currently uncertain.

Lactate infusion in anxiety research: its evolution and practice.

The unpredictability of spontaneous unexpected panic attacks has inhibited the controlled study of this phenomenon. Previous studies demonstrated that an increase in blood lactic acid occurred concomitant with symptoms of anxiety in anxiety-prone patients who underwent standard physical exercise. The question of whether these patients had an excessive sensitivity to lactate led to the development of the lactate infusion model, in which anxiety is induced in a controlled environment. The history and current application of the lactate infusion model in the study of neurochemical correlates of panic are described, and a methodology for lactate infusion procedures is outlined.