Sertraline treatment of generalized social phobia: a 20-week, double-blind, placebo-controlled study.

OBJECTIVE: The authors evaluated the efficacy, safety, and tolerability of sertraline, a selective serotonin reuptake inhibitor, in the treatment of generalized social phobia. METHOD: Adult outpatients with generalized social phobia (N=204) from 10 Canadian centers were randomly assigned to receive sertraline or placebo in a 2:1 ratio for a 20-week double-blind study following a 1-week, single-blind, placebo run-in. The initial dose of sertraline was 50 mg/day with increases of 50 mg/day every 3 weeks permitted after the fourth week of treatment (dosing was flexible up to a maximum of 200 mg/day). Primary efficacy assessments were the percentage of patients rated much or very much improved on the Clinical Global Impression (CGI) improvement item and the mean changes from baseline to study endpoint in total score on the social phobia subscale of the Marks Fear Questionnaire and total score on the Brief Social Phobia Scale. RESULTS: In intent-to-treat endpoint analyses of 203 of the patients, significantly more of the 134 patients given sertraline (N=71 [53%]) than of the 69 patients receiving placebo (N=20 [29%]) were considered responders according to their CGI improvement scores at the end of treatment. The mean reductions in the social phobia subscale of the Marks Fear Questionnaire and in the total score on the Brief Social Phobia Scale were 32.6% and 34.3% in the sertraline group and 10.8% and 18.6% in the placebo group, respectively. Analysis of covariance showed superiority of sertraline over placebo on all primary and secondary efficacy measures. Sertraline was well tolerated: 103 (76%) of the 135 sertraline-treated patients and 54 (78%) of the 69 placebo-treated patients completed the study. CONCLUSIONS: Sertraline is an effective treatment for patients with generalized social phobia.

The treatment of negative symptoms: a clinical and methodological study.

The primary objective of this study was to evaluate the efficacy, safety and tolerability of remoxipride (controlled release) versus haloperidol in patients with negative symptoms. The study comprised a multicentre, randomised, double-blind, parallel-group clinical trial. Two hundred and five patients were randomised to either remoxipride or haloperidol. Patients eligible for this study were aged 18-65 years, met the DSM-III-R diagnosis for chronic schizophrenia and the Positive and Negative Symptoms Scale (PANSS) criteria for predominant negative symptoms. There was a statistically significant reduction in the PANSS scores of at least 20% from baseline to last rating for 39 remoxipride (49.4%) and 45 haloperidol (47.6%) treated patients. There were no statistical differences found between the two treatment groups with respect to improvement of negative symptoms and adverse events. The PANSS data suggest that both remoxipride and haloperidol improve the cluster of negative symptoms concerned with social functioning. In addition, the design of the study provides a methodology that is appropriate to the study of primary negative symptoms in schizophrenia.

CCK4-induced panic in healthy subjects I: psychological and cardiovascular effects.

Sixteen healthy subjects participated in a crossover, double blind, and placebo-controlled study, designed to assess simultaneously the psychological and cardiovascular effects of cholecystokinin tetrapeptide (CCK4). Following an i.v. injection of 25 microg of CCK4, 44 percent of subjects experienced symptoms that fulfilled the DSM-IV criteria for a panic attack while no one panicked with placebo. CCK4 induced a significantly greater number and higher intensity of panic-like symptoms than placebo. A significant increase in state anxiety was observed in the period after CCK4 injection; this increase was significantly larger than the non-specific anxious reaction to placebo. CCK4 also affected cardiovascular signs. Both heart rate and mean blood pressure significantly increased after administration of CCK4. Again, these increases were significantly higher than those seen after placebo injection. We conclude that, in healthy subjects, CCK4 induces panic-like reaction characterized by a number of somatic, cognitive and emotional symptoms, which are accompanied by increases in heart rate and blood pressure.

CCK4-induced panic in healthy subjects II: neurochemical correlates.

Cholecystokinin tetrapeptide (CCK4) induces symptoms similar to those of panic attack. The present study investigated the effects of CCK4 administration on catecholaminergic system. In this double blind, randomised, crossover experiment, 16 healthy subjects received injections of either 25 microg of CCK4 or placebo on two separate occasions. Platelet and plasma catecholamine concentrations were assessed before the administration and compared to post-injection values. The results clearly show that both plasma and platelet concentrations of catecholamines are significantly affected by CCK4. Plasma norepinephrine (NE) and epinephrine (EPI) raised significantly above baseline in the immediate post-CCK4 period, while in plasma dopamine (DA), the significant increases were delayed. In the platelets, significant post-CCK4 increases of NE and EPI concentrations were observed with a delay of several minutes. In summary, we have demonstrated that, in healthy subjects, CCK4 increases peripheral concentrations of catecholamines in both plasma and platelets, with the most consistent changes occurring in platelet NE and plasma EPI concentrations.

Mixed anxiety and depression: from theory to practice.

The 10th International Classification of Disease (ICD-10) introduced the concept of mixed anxiety-depression to define patients presenting both anxiety and depressive symptoms of limited number and/or intensity, not sufficiently severe to fulfill criteria for a specific diagnosis of depressive or anxiety disorder. Epidemiologic surveys have shown that these patients may display significant levels of functional impairment, have unexplained somatic symptoms and a high use of nonpsychiatric medical care, have long-lasting symptoms, and are at risk for more severe psychiatric disorders. A DSM-IV field trial concluded that patients with affective-symptoms not meeting thresholds for DSM-III-R disorders were at least as common as patients with anxiety or mood disorders, and that their symptoms were associated with significant distress or impairment. Although some of these patients present residual symptoms from previous psychiatric episodes and may request treatment specific to these conditions, it is not known if those without a psychiatric history could benefit from pharmacologic or psychological treatments usually used in mild outpatient cases.

Elevated plasma levels of neuropeptide Y in patients with panic disorder.

OBJECTIVE: Neuropeptide Y is a pancreatic polypeptide closely associated with noradrenergic activity both in the central and peripheral nervous systems. The objective of this study was to assess plasma neuropeptide Y-like immunoreactivity in panic disorder. METHOD: Radioimmunoassays were performed in 12 patients with DSM-III-R panic disorder and two groups of normal comparison subjects (N = 22 and N = 16). RESULTS: Markedly higher plasma neuropeptide Y-like immunoreactivity was found in patients with panic disorder. CONCLUSIONS: Higher plasma neuropeptide Y-like immunoreactivity suggests that this peptide may be implicated in the etiology or expression of symptoms of panic disorder.

The treatment of avoidant personality disorder by social skills training in the clinic or in real-life settings.

Twenty-eight outpatients who met DSM-III diagnostic criteria for avoidant personality disorder completed 14 one and a half hour sessions of social skills training in the clinic only or a combination of four sessions in the clinic, four sessions in real-life and six follow-up sessions in the clinic. Subjects were assessed before treatment began, after four sessions, at the end of treatment and at three month follow-up points. Training in real-life did not enhance social skills training; no significant difference between the groups at any assessment points was found. In both groups improvement in time was significant and clinically worthwhile. The treatment effects were maintained up to the three month follow-up, where available. Social skills training appears to be a useful and promising intervention for avoidant personality disorder but its long term impact remains to be investigated.

Mixed anxiety and depression: diagnostic issues.

Mixed anxiety and depression (MAD) is a new diagnostic category introduced in the ICD-10 classification for patients seen mainly in primary care settings. These patients are defined as those suffering from symptoms of anxiety and depression of limited and equal intensity accompanied by at least some autonomic features, who do not qualify for specific diagnosis of anxiety or depressive disorders and are independent of stressful life events. The validity of this clinical entity is presently under investigation in the DSM-IV-MAD field trial. Cases of mixed anxiety and depression, however, are not limited to those meeting the criteria of this new "subsyndromal" category. Many patients fulfilling criteria for either depressive or anxiety disorders may also respectively present symptoms, syndromes, or a diagnosis of anxiety or depression. It is still not known whether anxious and depressive symptoms are two different expressions of the same psychopathologic underlying process. Tyrer's recent description of a "general neurotic syndrome" is an attempt to reunify syndromes separated in our present classifications. In this comprehensive approach, anxiety, depression, or MAD states are associated at different times with specific personality features and considered as expressing different levels of overreactivity to various stressful situations. This hypothesis would explain the close relationship existing between these two categories of symptoms and the common efficacy of some psychopharmacologic agents for both anxiety and depressive disorders.

Severe obsessive-compulsive syndrome in a 10 year old: a 3 year follow-up.

Obsessive-Compulsive Disorder is rare in children but when present, its very nature is so pervasive and so complex that the therapy must be specially tailored to fit the distinct character of the young patient. We report the course and treatment of one case; then we discuss the interplay of implicit as well as explicit factors in the active process of alleviating dysfunctional behavior.

Clinical phobias and avoidant personality disorder among alcoholics admitted to an alcoholism rehabilitation setting.

One hundred seventy-three abstinent patients were screened for phobias and avoidant personality disorder. Ninety-six patients were interviewed and diagnosed by two independent assessors who were in agreement on 74% of the diagnoses. In DSM-III terms, over half of the sample (51.4%) met criteria for agoraphobia (8.5%), social phobia (7.8%) and avoidant personality disorder (35.1%). More than 70% of the patients in each diagnostic category were men. For the vast majority of the patients in the sample the disorder preceded the abuse of alcohol which was used by at least 40% of them to relieve their distress in the past. For many it had still a moderating effect on distress at the present but appeared to be mainly used out of "psychological dependence".