Placebo-controlled, multicenter study of sertraline treatment for obsessive-compulsive disorder.

The safety and efficacy of sertraline versus placebo were examined in a group of nondepressed outpatients with obsessive-compulsive disorder (OCD). Patients with moderate-to-severe OCD were recruited at 10 sites. After a 1-week placebo lead-in, patients were treated in a double-blind fashion for 12 weeks with sertraline or placebo. Sertraline was administered at a starting dose of 50 mg/day, with flexible titration up to 200 mg/day. The efficacy measures were the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH), and the Clinical Global Impression Scale (CGI) Severity of Illness and Improvement subscales. One hundred sixty-seven patients were randomly assigned and received at least one dose of double-blind medication: 86 received sertraline and 81 received placebo. All efficacy measures showed significantly greater improvement in the sertraline group from the end of week 8 until the end of week 12. Significantly greater improvement (p < 0.05) in the sertraline group first became apparent by the end of week 3 on the Y-BOCS and the CGI Improvement scale, and by the end of weeks 6 and 8, respectively, on the NIMH and CGI Severity scale. Sertraline was well tolerated, without serious adverse effects. In conclusion, sertraline was safe and effective in the treatment of patients with OCD.

A double-blind, placebo-controlled, multicenter study with alprazolam and extended-release alprazolam in the treatment of panic disorder.

This is a double-blind, placebo-controlled, flexible-dose, multicenter, 6-week study comparing regular alprazolam (compressed tablet, CT), given four times per day, and extended release alprazolam (XR), given once in the morning. The aim of the XR preparation is to offer less frequent dosing and to reduce interdose anxiety. Of the intent-to-treat group of 209 patients, 184 completed 3 weeks of medication and were evaluated according to protocol. There was a completer rate for the 6 weeks of 94% (CT), 97% (XR), and 87% (placebo). On global measures, Hamilton Rating Scale for Anxiety, phobia rating, and work disability measures, both active treatment groups were equally effective and significantly more efficacious than the placebo cell on endpoint MANOVA analysis. On analysis of the panic factor with endpoint data, both active treatment groups were equally effective throughout the 6-week trial and significantly more efficacious than the placebo group. Drowsiness occurred more frequently with CT alprazolam (86% of patients) than with the XR preparation (79%) or placebo (49%).

Autorotation test abnormalities of the horizontal and vertical vestibulo-ocular reflexes in panic disorder.

Patients with panic disorder often describe dizziness as a disturbing symptom, with more severe episodes reported than in other psychiatric populations. Nineteen patients diagnosed as having a panic disorder were tested for vestibulo-ocular (VOR) abnormalities with the Vestibular Autorotation Test (VAT), a computerized test of the high-frequency (2 to 6 Hz) VOR. The patients were unselected for the presence or absence of balance disorders. Results showed VOR abnormalities, relative to a normal population, in the horizontal and/or vertical VORs of all 19 patients. Vestibulo-ocular reflex asymmetries were commonly present. Because the VAT tested the VOR over a frequency range encountered during common daily activities, the observed abnormalities could result in a perceptually moving visual field (oscillopsia). We hypothesize that the resulting experience of a visual-vestibular disturbance--perhaps in a biologically or psychologically predisposed individual--is catastrophically misinterpreted, leading to more bodily symptoms and anxiety. These could then contribute to more misinterpretation in a positive feedback sense, ultimately leading to a panic attack.

Sertraline in social phobia.

Eleven consecutive SCID-diagnosed generalized social phobias without major depression, other prominent anxiety disorders, substance abuse, alcoholism or organic mental disorder, were treated, open label, with sertraline up to 200 mg daily for 12 weeks. There were seven completers. Of these, five showed substantial improvement, after being on sertraline 100 mg daily for two weeks (following no response to sertraline 50 mg daily for four weeks). There were few side effects among the completers. The four dropouts complained of side effects and loss of interest in continuing treatment. Final average dose for completers who responded was 170 mg daily.

Alprazolam levels and response in panic disorder: preliminary results.

Fifty-five young adult patients completed a study comparing alprazolam, propranolol, and placebo in the treatment of panic disorder and agoraphobia with panic attacks. Twenty completed 5 weeks of treatment with alprazolam. No concomitant psychological treatment was administered. Plasma alprazolam levels were determined at baseline and at the end of the trial by means of automated gas chromatography. These levels were significantly correlated with dose (p = 0.001). Dividing the data into quartiles based on alprazolam concentration, no direct, linear relationship was found between alprazolam levels and response (as defined by a criterion of zero panic attacks). However, analysis of the combined middle two quartiles versus the combined upper and lower quartiles showed a positive trend toward a curvilinear relationship; i.e., there was a greater response rate within the 18-62 ng/ml concentration range than in the combined 0-17 plus 63-107 ng/ml range, (chi 2 = 2.4; p = 0.12). The findings are very preliminary in nature. It remains to be seen if the results will reach significance with a large sample size and a more tightly controlled study design.

Clonazepam in the treatment of social phobia: a pilot study.

Twenty-three patients who met DSM-III-R criteria for social phobia were randomly assigned either to a clonazepam treatment group or to a nontreatment control group in an 8-week pilot study. Clonazepam was found to have a significant effect on the treated patients, as demonstrated by scores on a variety of instruments measuring overall anxiety and phobic avoidance, and social phobic symptoms. Initial sedation, which was experienced by 70% of the treated subjects, was the most common side effect of clonazepam treatment and usually resolved spontaneously or with dose reduction. The preliminary findings of this pilot study are sufficiently promising to warrant further study of the efficacy of clonazepam in this condition.

Generalized anxiety disorder: some biochemical aspects.

Fifty-one patients who met DSM-III criteria for generalized anxiety disorder, and who were recruited to participate in a drug outcome study, filled out a variety of rating scales and had blood samples drawn for plasma norepinephrine, epinephrine, and free 3-methoxy-4-hydroxyphenylglycol (MHPG) after a 20-min rest period. This group was compared to 15 normal controls who also had their blood drawn after a 20-min rest period. While the two groups were initially found to have significantly different levels of plasma free MHPG through the use of t tests, this finding was not confirmed by subsequent discriminant analysis.

Agoraphobia with and without current panic attacks.

MMPI and SCL-90-R profiles of agoraphobics with and without current panic attacks are presented. Agoraphobics with current panic attacks were more elevated on Psychopathic Deviate (4), Psychasthenia (7), and Social Introversion (0) scales of the MMPI. On the SCL-90-R agoraphobics with current panic attacks had higher scores on Interpersonal Sensitivity, Anxiety, Phobic Anxiety, and Total/90.

Alprazolam, propranolol, and placebo in the treatment of panic disorder and agoraphobia with panic attacks.

Fifty-five patients completed a 5-week double-blind study comparing alprazolam, propranolol, and placebo in the treatment of panic disorder and agoraphobia with panic attacks. There was no concomitant behavioral treatment. Patient and therapist rating scales included Sheehan's Panic and Anxiety Attack Scales, the Marks-Sheehan Phobia Scale, the Hamilton Anxiety Scale, the Hamilton Depression Scale, and the Side Effects Checklist. The results generally support the efficacy of alprazolam, but not propranolol, in the treatment of panic disorder and agoraphobia with panic attacks. The significance of the results are discussed, as well as a number of the unique aspects of our procedures and patient population.

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.

Nortriptyline in the treatment of panic disorder and agoraphobia with panic attacks.

Thirty-four consecutive patients with panic disorder or agoraphobia with panic attacks were treated with nortriptyline at the LAC-USC Medical Center's Anxiety Disorders Clinic. Fourteen (67%) of the 21 completers totally lost their panic attacks, five (24%) showed partial improvement, and two (10%) showed no improvement. The relationship of treatment outcome to pretreatment and posttreatment measures of depression is discussed, in addition to the potential role of nortriptyline in treating panic attacks in clinical practice.

Platelet [3H]imipramine binding in generalized anxiety disorder, panic disorder, and agoraphobia with panic attacks.

The density of platelet [3H]imipramine binding sites is reported to be decreased in unipolar depression and, hence, is a putative biological marker. There is considerable evidence for a phenomenological and biological relationship of panic disorder with affective disorder. We studied platelet [3H]imipramine binding site density in unmedicated subjects with generalized anxiety disorder (GAD; n = 55), panic disorder (PD) with and without agoraphobia (n = 52), and normal controls (n = 26) in order to determine whether or not patients with panic disorder differed from controls in this biological assay. We found no differences in binding site density (Bmax) or affinity (Kd) among the PD, PD with agoraphobia, GAD, and control groups. Nor did we find a relationship between Bmax or Kd and the severity of depressive symptoms or the presence of a family history of affective disorder. In view of two conflicting prior studies, the use of [3H]imipramine binding in panic disorder remains problematic.

Comparison of social anxiety in patients with social phobia and panic disorder.

Differential response patterns to the SCL-90R in patients with social phobia and panic disorder are presented. The differences are discussed in light of Liebowitz's distinction between primary social phobia and the secondary social fears of panic disorder patients. Treatment implications are also discussed.

The onset of driving phobias.

Thirty driving phobics who called the Psychiatry Outpatient Phobia Clinic (25 females and five males) were given a 20-min semi-standardized telephone interview during which they were asked about the circumstances of the onset of their driving fears. Twelve (40%) reported that their fears were precipitated by a panic attack on the freeway; six (20%) by a collision; and three (10%) by other frightening experiences in automobiles. Four (13.3%) related the onset to family stress or upheaval. Other modes of onset also occurred. The implications of these findings are discussed in terms of existing theories of fear acquisition and treatment approaches.

The treatment of phenelzine-induced hypotension with salt tablets: case report.

A 24-year-old woman who met DSM-III criteria for agoraphobia with panic attacks, and who could not tolerate other medications (imipramine and propranolol), was successfully treated with phenelzine sulfate and salt tablets for the accompanying hypotension.