Paroxetine for prevention of depressive symptoms induced by interferon-alpha and ribavirin for hepatitis C.

BACKGROUND: Whether antidepressants prevent depression during interferon-alpha/ribavirin treatment for hepatitis C virus infection has yet to be established. AIM: To investigate the use of paroxetine in a prospective, double-blind, placebo-controlled study for this indication. METHODS: Sixty-one hepatitis C virus-infected patients were randomly assigned to the antidepressant, paroxetine (n = 28), or placebo (n = 33), begun 2 weeks before and continued for 24 weeks during interferon-alpha/ribavirin treatment. Primary endpoints included development of major depression and severity of depressive symptoms measured by the Montgomery Asberg Depression Rating Scale (MADRS). RESULTS: Rates of major depression during the study were low (17%) and did not differ between groups. Nevertheless, using published MADRS cut-off scores, the percent of subjects who met criteria for mild, moderate or severe depression during interferon-alpha/ribavirin therapy was significantly lower in paroxetine- vs. placebo-treated subjects (P = 0.02, Fisher's exact test). Assignment to paroxetine was also associated with significantly reduced depressive symptom severity. This effect was largely accounted for by participants with depression scores above the median (MADRS > 3) at baseline in whom paroxetine was associated with a maximal reduction in MADRS scores of 10.3 (95% CI: 2.1-18.5) compared with placebo at 20 weeks (P < 0.01). Study limitations included a small sample size and high drop-out rate. CONCLUSION: This double-blind, placebo-controlled trial provides preliminary data in support of antidepressant pre-treatment in hepatitis C virus patients with elevated depressive symptoms at baseline.

New onset of body dysmorphic disorder following frontotemporal lesion.

The etiology and pathophysiology of body dysmorphic disorder (BDD) have not been delineated. The authors report a 24-year-old man who developed BDD at age 21 after an inflammatory brain process. Neuroimaging studies showed new atrophy in the frontotemporal region. The authors review cases from the literature with similar clinical features and neuroimaging findings as well as discuss the possible correlation between the neuroanatomic lesion and the clinical presentation of BDD in the patient.

Fluvoxamine in the treatment of panic disorder: a multi-center, double-blind, placebo-controlled study in outpatients.

Serotonergic mechanisms have been implicated in panic disorder, and several preliminary studies suggest that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is helpful in its treatment. This 8-week double-blind parallel-group study compared fluvoxamine with a placebo in 188 patients with DSM-III-R defined panic disorder with or without agoraphobia. Efficacy assessments included a Daily Panic Attack Inventory, the Sheehan Disability Scale, the Clinical Anxiety Scale and the Clinical Global Impression Scale. When compared with the placebo, fluvoxamine produced highly significant improvements in most measures of the frequency and severity of panic disorder and in the more global aspects of disability and distress. Significant improvement was evident as early as week 1 for some panic variables. Fluvoxamine is a potent anti-panic agent with a relatively rapid onset of action.

Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial.

CONTEXT: Despite the high prevalence, chronicity, and associated comorbidity of posttraumatic stress disorder (PTSD) in the community, few placebo-controlled studies have evaluated the efficacy of pharmacotherapy for this disorder. OBJECTIVE: To determine if treatment with sertraline hydrochloride effectively diminishes symptoms of PTSD of moderate to marked severity. DESIGN: Twelve-week, double-blind, placebo-controlled trial preceded by a 2-week, single-blind placebo lead-in period, conducted between May 1996 and June 1997. SETTING: Outpatient psychiatric clinics in 8 academic medical centers and 6 clinical research centers. PATIENTS: A total of 187 outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition diagnosis of PTSD and a Clinician Administered PTSD Scale Part 2 (CAPS-2) minimum total severity score of at least 50 at baseline (mean age, 40 years; mean duration of illness, 12 years; 73% were women; and 61.5% experienced physical or sexual assault). INTERVENTION: Patients were randomized to acute treatment with sertraline hydrochloride in flexible daily dosages of 50 to 200 mg/d, following 1 week at 25 mg/d (n=94); or placebo (n=93). MAIN OUTCOME MEASURES: Baseline-to-end-point changes in CAPS-2 total severity score, Impact of Event Scale total score (IES), and Clinical Global Impression-Severity (CGI-S), and CGI-Improvement (CGI-I) ratings, compared by treatment vs placebo groups. Results Sertraline treatment yielded significantly greater improvement than placebo on 3 of the 4 primary outcome measures (mean change from baseline to end point for CAPS-2 total score, -33.0 vs -23.2 [P =.02], and for CGI-S, -1.2 vs -0.8 [P=.01]; mean CGI-I score at end point, 2.5 vs 3.0 [P=.02]), with the fourth measure, the IES total score, showing a trend toward significance (mean change from baseline to end point, -16.2 vs -12.1; P=.07). Using a conservative last-observation-carried-forward analysis, treatment with sertraline resulted in a responder rate of 53% at study end point compared with 32% for placebo (P=.008, with responder defined as >30% reduction from baseline in CAPS-2 total severity score and a CGI-I score of 1 [very much improved], or 2 [much improved]). Significant (P<.05) efficacy was evident for sertraline from week 2 on the CAPS-2 total severity score. Sertraline had significant efficacy vs placebo on the CAPS-2 PTSD symptom clusters of avoidance/numbing (P=.02) and increased arousal (P=.03) but not on reexperiencing/intrusion (P=.14). Sertraline was well tolerated, with insomnia the only adverse effect reported significantly more often than placebo (16.0% vs 4.3%; P=.01). CONCLUSIONS: Our data suggest that sertraline is a safe, well-tolerated, and effective treatment for PTSD.

Zolpidem for persistent insomnia in SSRI-treated depressed patients.

BACKGROUND: Depressed individuals effectively treated with selective serotonin reuptake inhibitors (SSRIs) often report persistent insomnia and require adjunctive sleep-promoting therapy. METHOD: Men (N = 40) and women (N = 150) with a mean age of 41.6 years who had persistent insomnia in the presence of effective and stable treatment (at least 2 weeks) with fluoxetine (< or =40 mg/day), sertraline (< or =100 mg/day), or paroxetine (< or =40 mg/day) for DSM-IV major depressive disorder, dysthymic disorder, or minor depressive disorder of mild-to-moderate severity (and score of < or =2 on item 3 of the Hamilton Rating Scale for Depression [HAM-D]) participated in this randomized, double-blind, parallel-group study. At study entry, patients were required to score < or =12 on the HAM-D. During a 1-week single-blind placebo period, patients had to report on at least 3 nights a latency of > or =30 minutes or a sleep time of <6.5 hours and clinically significant daytime impairment. Patients received either placebo (N = 96) or zolpidem, 10 mg (N = 94) nightly, for 4 weeks and single-blind placebo for 1 week thereafter. Sleep was measured with daily questionnaires and during weekly physician visits. RESULTS: Compared with placebo, zolpidem was associated with improved sleep: longer sleep times (weeks 1 through 4, p<.05), greater sleep quality (weeks 1 through 4, p<.01), and reduced number of awakenings (weeks 1, 2, and 4; p<.05), together with feeling significantly more refreshed, less sleepy, and more able to concentrate. After placebo substitution, the zolpidem group showed significant worsening relative to pretreatment sleep on the first posttreatment night in total sleep time and sleep quality, reverted to pretreatment insomnia levels on the other hypnotic efficacy measures, or maintained improvement (fewer number of awakenings). There was no evidence of dependence or withdrawal from zolpidem (DSM-IV criteria). Incidence rates of adverse events were similar in both treatment groups (74% and 83% for placebo and zolpidem, respectively), but 7 zolpidem patients discontinued compared with 2 placebo patients. CONCLUSION: In this defined patient population, zolpidem, 10 mg, was effectively and safely co-administered with an SSRI, resulting in improved self-rated sleep, daytime functioning, and well-being.

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.

Dissociative symptomatology and aggressive behavior.

The present study examined the relationship between dissociative symptomatology and a range of aggressive behavior in a general psychiatric outpatient population. Of the total sample (n = 122), 29% scored above 25 on the Dissociative Experiences Scale (DES). Patients with high DES scores (> 25) were significantly more likely than patients with lower DES scores (< 25) to report a history of childhood sexual abuse, to have attempted suicide, and to report more assaultive behavior, irritability, and negativism. There were no differences between the patients with high versus low DES scores on homicidal behavior. To better manage and treat outpatients with dissociative symptomatology, it is important to clarify the association between outwardly aggressive behavior and dissociative experiences.

Asking adolescents to explain discrepancies in self-reported suicidality.

We present a typology of adolescents' most common explanations for discrepant reporting of suicidal behavior. Forty-eight adolescents provided attempt histories by completing a self-report measure of suicidality. A select number of items were subsequently readministered (average interval = 5 days) using a semistructured interview format. Discrepancies in reporting were found among 50% of the sample. Adolescents were also asked to clarify, using an open-ended format, what might have accounted for a particular discrepancy. Based on these responses, seven mutually exclusive and exhaustive categories were derived. High rates of interrater agreement indicated that these categories were reliable.

Violence and homicidal behaviors in psychiatric disorders.

Our review evaluating the relationship between violent/homicidal behaviors and mental illness/psychiatric disorders used many different data including that assessing the prevalence of violent/homicidal behaviors in former psychiatric inpatients (just before hospitalization, during hospitalization, and after discharge) as outpatients and in community samples as well as evaluating the prevalence rate of psychiatric disorders in people who actually engaged in violent/homicidal disorders (jail detainees, prison inmates, and community samples). Irrespective of which line of investigation, there was convincing evidence that violent/ homicidal behavior was associated significantly with mental illness. Although earlier investigations failed to control for important variables, such as age and sociodemographics, most studies reviewed in this article did control for these items, further underlining the association of violence and mental illness. The question of whether specific psychiatric diagnostic categories are associated with violent/homicidal behavior is less definite across the various studies reviewed. The presence of substance abuse and dependence and alcohol abuse and dependence as well as antisocial personality disorder are particularly associated with an increased risk of violent/homicidal behaviors. The risk for these latter behaviors in schizophrenia, mood disorders, and anxiety disorders may appear somewhat greater than that for a general population but are not of the same magnitude of that for substance abuse or antisocial personality disorder. Interestingly, our outpatient study found that homicidal behaviors were not associated with any specific psychiatric diagnosis. Although understanding whether specific psychiatric diagnostic categories are more prone to violent behaviors may be of importance, most studies have been shortsighted regarding this evaluation. All the studies presented in this article except the ECA project, presented diagnostic data where either the presence of one psychiatric disorder did not preclude the diagnosis of another or assigned subjects/patients into the severest disorder of a predetermined hierarchy of diagnoses or only selected their principal/primary diagnosis. Thus, the effect of having a solitary psychiatric disorder (only one disorder present) as well as the effect of comorbidity per se on the relationship of psychiatric disorders and violent/homicidal behaviors were unexplored. Only the ECA study by Swanson and colleagues reported on the effect of comorbidity. As reviewed earlier in the article, Swanson et al found that comorbidity of psychiatric diagnostic categories further increased the risk of violent/ homicidal behaviors. In most cases, it was many more times than simply adding the rates of either diagnosis alone. Because more than 54% of respondents of the National Comorbidity Survey study who had one DSM-III-R diagnosis also had at least a second Axis I diagnosis, the association of violent/homicidal behaviors to mental illness may even be stronger than originally believed. Within the relationship of violent/homicidal behaviors and mental illness, this article suggests a number of particular risk factors. As just reviewed, substance/alcohol abuse and antisocial personality disorder as well as the presence of comorbid psychiatric disorders are significant risk factors. Which particular comorbid illness increases the risk still needs further elaboration. Studies must continue to try to define and understand the relationship of violent/homicidal behaviors in mental illness. Although mental disorders per se are significantly associated with violent/homicidal behaviors, it is reasonable to believe that targeting certain subgroups of patients should be helpful. Probably the presence of psychotic symptoms is a significant risk factor in violent/ homicidal behaviors in the mentally ill. Only one of the studies reviewed in this article evaluated this issue. (ABSTRACT TRUNCATED)

Serotonin function in panic disorder: intravenous administration of meta-chlorophenylpiperazine.

A placebo-controlled study of the direct serotonin receptor agonist meta-chlorophenylpiperazine (MCPP), intravenously infused over 90 s in a 0.06 mg/kg dose, was conducted in 10 patients with panic disorder and 9 normal control subjects. Cortisol, MCPP serum levels, and behavioral responses in both groups. Differences between intravenous and oral administration of MCPP are discussed, and the present findings are related to the serotonergic hypothesis of panic disorder.

Childhood abuse, adult assault, and dissociation.

Recent studies have suggested an association between childhood physical and sexual abuse and adult dissociative experiences. The purpose of this study was to determine the relationship of both childhood and adult-onset abuse and their characteristics for adult dissociative symptoms. One hundred forty-four psychiatric outpatients completed self-report questionnaires on measures of dissociation (Dissociative Experience Scale [DES]) and histories of both past and current sexual and physical abuse (Traumatic Events Questionnaire [TEQ]). Of 114 subjects (30 men and 84 women) who completed both forms, 35% and 43% reported childhood physical and sexual abuse, respectively. Dissociative symptoms were significantly related to ethnicity and multiple episodes or combined types of abuse in childhood and adulthood. In terms of the characteristics of childhood abuse, numerous episodes of physical abuse (P = .01) and father-perpetrated sexual abuse (P = .02) were significantly related to the degree of dissociation. These findings emphasize the role of repeated childhood trauma and the combination of both childhood and adult traumatic experiences in the development of dissociative phenomena.

Atypical depression among psychiatric inpatients: clinical features and personality traits.

OBJECTIVE: This study investigates the frequency and characteristics of Atypical Depression (AD) among depressed inpatients. METHOD: Twenty-one depressed inpatients received DSM-IV diagnoses, were rated on the Hamilton Depression Rating Scale (HAMD), and assessed for AD using the Atypical Depressive Disorder Scale. AD was defined as the presence of mood reactivity and two of four associated features: hyperphagia, hypersomnia, leaden paralysis, rejection sensitivity. Mood reactivity was defined as the ability to reach 50% of a non-depressed mood. All subjects completed the SCL-90, MCMI-II, and a suicide survey. RESULTS: Seven patients (33%) met criteria for AD. AD and non-AD patients did not differ in terms of severity of depression, history of suicide attempts, levels of clinical symptomatology, age of onset of depression, prior hospitalizations, and most personality characteristics. However, AD patients scored significantly higher than non-AD patients on the SCL-90 Interpersonal Sensitivity and MCMI-II Avoidant scales, and were more likely to be single. CONCLUSION: AD is fairly prevalent on an inpatient service, comparable to the frequency found in outpatient settings. AD is not a milder form of depression. The only differences between AD and non-AD patients reflect the personality trait of rejection sensitivity which is a defining feature of AD.

Characteristics of suicidality among adolescents.

The identification of high-risk adolescent suicide attempters in a population of depressed and suicidal adolescents is of crucial importance. This retrospective study examined characteristics of suicidality (recent and lifetime, active and passive) and psychopathology (depression, aggression, impulsivity, stressful life events, SCL-90 dimensions) among four groups of depressed adolescent outpatients: (1) suicide attempters who required medical treatment (n = 84), (2) suicide attempters who did not require medical treatment (n = 57), (3) suicidal ideators who had never made a suicide attempt (n = 40), and (4) nonsuicidal patients (n = 44). Results indicate that the nonsuicidal group could be differentiated from the three suicidal groups on the basis of suicidality and psychopathology, and that the three suicidal groups could be differentiated from one another on the basis of suicidality but not psychopathology. These findings are discussed in terms of the usefulness of certain self-report measures of suicidality for identifying suicidal adolescents and for differentiating among them. Furthermore, the findings suggest that psychopathological factors do not determine which suicidal adolescents make a medically dangerous suicide attempt and which do not.

Biological and clinical validation of atypical depression.

Depressed patients with (a) mood reactivity alone (MR group), (b) mood reactivity plus one or more associated features (atypical depression, AD group), and (c) patients with neither mood reactivity nor atypical depression (non-MR/AD group) were compared on their cortisol response to 75 mg of desipramine (DMI), a relatively selective norepinephrine reuptake inhibitor. AD patients exhibited a significantly higher cortisol response to DMI compared with MR and non-MR/AD patients, suggesting that atypical depression may be associated with a less impaired norepinephrine system. MR and non-MR/AD patients did not differ, suggesting that mood reactivity alone is not associated with the biological profile observed in atypical depression. Results indicate that while mood reactivity may be necessary for the diagnosis of atypical depression, the additional presence of at least one associated symptom is required for a distinct biological profile. Our findings provide further biological validation of the concept of atypical depression.

Prevalence and characteristics of physical and sexual abuse among psychiatric outpatients.

Eighty-six female and 34 male psychiatric outpatients completed a self-report questionnaire that retrospectively assessed their history of physical and sexual abuse and assault. Seventy percent reported an abusive experience in childhood or adulthood. Female subjects were more likely than male subjects to report childhood sexual abuse and adult physical and sexual assaults. For all subjects, childhood sexual abuse was associated with adult sexual and physical assault. The charts of several patients who reported abuse histories did not include any record of abuse.

Suicidal behavior and abuse in psychiatric outpatients.

The present study examines the relationship between suicidal behaviors and histories of abuse in psychiatric outpatients. Two hundred fifty-one psychiatric outpatients were evaluated for history of abuse, suicidal behavior, demographics, and clinical characteristics using self-report instruments and a face-to-face interview. Logistic regression analysis indicated that physical abuse (battering) in adulthood and histories of a combination of childhood and adulthood abuse were significant predictors of past suicide attempts and current suicidal ideation. Victims of abuse were more likely than nonvictim controls to have been suicidal at a younger age and to have made multiple suicide attempts. Among patients with a history of abuse, suicide attempters could be distinguished from nonattempters on the basis of higher levels of dissociation, depression, and somatization. Abusive experiences in adulthood appear to play an important role in suicidal behavior among psychiatric outpatients. High levels of specific symptoms (i.e., depression, somatization, and dissociation) among patients with a history of abuse can help to identify outpatients at risk for suicidal behavior.

Atypical depression: clinical aspects and noradrenergic function.

OBJECTIVE: The authors assessed the frequency of atypical depression in depressed outpatients and compared clinical and biological features of patients with atypical and nonatypical depression. METHOD: Depressed outpatients (N = 114) were diagnosed with the Schedule for Affective Disorders and Schizophrenia (SADS) according to Research Diagnostic Criteria. Patients were assessed for presence or absence of atypical depression with the Atypical Depressive Disorder Scale. Atypical depression was defined as the presence of mood reactivity during the depressive episode, along with at least one of four associated features: hypersomnia, hyperphagia, leaden paralysis, and rejection sensitivity. All patients completed the SCL-90 and were rated with the Hamilton Depression Rating Scale, extracted from the SADS. To assess biological functioning, the authors examined cortisol response to 75 mg of desipramine, a relatively selective norepinephrine reuptake inhibitor. RESULTS: Twenty-nine percent of patients met criteria for atypical depression. Patients with atypical depression were significantly more likely to be female. Patients with atypical and nonatypical depression did not differ on SCL-90 subscale scores. Although extracted Hamilton depression scale scores were significantly higher for patients with nonatypical depression, the difference was not clinically significant. Patients with atypical depression exhibited a significantly different cortisol response to desipramine injection than patients with nonatypical depression, which suggested that nonatypical depression may be associated with a more impaired norepinephrine system. CONCLUSIONS: In view of data in this study, as well as earlier studies, atypical depression has a unique symptom profile, may be widely prevalent, has a distinct treatment response, and may indicate a less impaired biological system than nonatypical depression. Since this is the first report to evaluate the frequency of atypical depression as well as the norepinephrine system in atypical depression, this study needs to be replicated. Nonetheless, the data support the inclusion of atypical depression as a subtype of the depressive disorders in DSM-IV.

Alprazolam blockade of CO2-provoked panic in patients with panic disorder.

The primary aim of this study was to determine if pretreatment with a single dose of alprazolam reduces anxiety and panic provoked by the inhalation of 35% carbon dioxide (CO2) in patients with panic disorder. Ten panic disorder patients participated in a CO2 challenge test after pretreatment with a single dose of alprazolam (1 mg p.o.) or placebo in a randomized, double-blind, within-subjects design. Seventy percent of the subjects had a panic attack with placebo, compared to only 10% with alprazolam. Alprazolam reduced the number and severity of panic symptoms and baseline anxiety significantly more than placebo. This study demonstrates the efficacy of the acute administration of alprazolam to block panic attacks and supports the usefulness of the CO2 challenge as an analogue method to study panic disorder.