Characteristics of responders and non-responders to risperidone monotherapy or placebo in co-occurring bipolar disorder and anxiety disorder.

Clinical characteristics predicting response and remission to psychopharmacological treatment of bipolar disorder (BD) and co-occurring anxiety disorders have been understudied. We hypothesized that non-response to risperidone or placebo in individuals with co-occurring BD and anxiety symptoms would be associated with a more severe clinical course of BD, and certain demographic variables. This study was a secondary analysis of a randomized, double-blind, parallel, 8-week study comparing risperidone monotherapy and placebo in individuals with BD plus current panic disorder, current generalized anxiety disorder (GAD), or lifetime panic disorder (n=111) [31]. We compared clinical characteristics of responders (50% improvement on the Hamilton Anxiety Scale [HAM-A]) and non-responders as well as remitters (HAM-A<7) and non-remitters in risperidone treatment (n=54) and placebo (n=57) groups. For non-responders in the risperidone group, co-occurring lifetime panic disorder was significantly more common than for non-responders in the placebo group. Apart from this, no significant differences in course of illness or demographics were found either between or across groups for patients with BD and co-occurring anxiety symptoms receiving risperidone or placebo in this acute phase study.

Assessment of Anxiety in Clinical Trials with Depressed Patients Using the Hamilton Depression Rating Scale.

BACKGROUND: The Hamilton Depression Rating Scale (HAMD17) is an outcome measure widely used in major depressive disorder (MDD) clinical trials. The objective of this analysis was to assess the validity of the anxiety/somatisation factor of the HAMD17 as a measure of anxiety in patients with MDD. METHODS: We pooled data from 1466 outpatients with MDD from four 8-week controlled studies of duloxetine. We performed a factor analysis of the HAMD17 to investigate the anxiety/somatisation factor. RESULTS: The HAMD17 factor analysis yielded 6 factors, but did not yield the pre-specified anxiety/somatisation factor. This latter factor showed weak correlation with the Hamilton Anxiety Scale total and subscale scores at baseline (0.46), but higher correlation coefficients over the trials up to 0.81. We identified another anxiety factor that included the hypochondriasis item in this sample. CONCLUSION: Findings from this large sample suggest that the factor structure of the HAMD17 is unstable in MDD and that the anxiety/somatisation subscale should not be routinely used for anxiety assessment in depressed patients.

Nicotinic acetylcholine receptors as targets for antidepressants.

While the monoamine deficiency hypothesis of depression is still most commonly used to explain the actions of antidepressant drugs, a growing body of evidence has accumulated that is not adequately explained by the hypothesis. This article draws attention to contributions from another apparently common pharmacological property of antidepressant medications--the inhibition of nicotinic acetylcholine receptors (nAChR). Evidence is presented suggesting the hypercholinergic neurotransmission, which is associated with depressed mood states, may be mediated through excessive neuronal nicotinic receptor activation and that the therapeutic actions of many antidepressants may be, in part, mediated through inhibition of these receptors. In support of this hypothesis, preliminary evidence is presented suggesting that the potent, centrally acting nAChR antagonist, mecamylamine, which is devoid of monoamine reuptake inhibition, may reduce symptoms of depression and mood instability in patients with comorbid depression and bipolar disorder. If this hypothesis is supported by further preclinical and clinical research, nicotinic acetylcholine receptor antagonists may represent a novel class of therapeutic agents for treating mood disorders.

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.

Multicenter, double-blind, placebo-controlled study of mecamylamine monotherapy for Tourette's disorder.

OBJECTIVE: The safety and efficacy of mecamylamine as a monotherapy in children and adolescents with Tourette's disorder (TD) was investigated in an 8-week multicenter, double-blind, placebo-controlled study. METHOD: Eligible subjects included subjects with TD (DSM-IV), with a naturalistic mix of comorbid diagnoses, nonsmokers, aged 8 to 17 years, whose behavioral and emotional symptoms (according to parents) were more disturbing than tics. After a washout period of all psychotropic medication, subjects were randomly assigned to either mecamylamine (n = 29) or placebo (n = 32). Mecamylamine doses ranged from 2.5 to 7.5 mg/day. Primary efficacy measures included the Tourette's Disorder Scale-Clinician Rated (TODS-CR) and 21-point Clinical Global Improvement scale; secondary efficacy measures included the Yale Global Tic Severity Scale and a rage-attack scale (RAScal). RESULTS: Of the 61 subjects who were randomized, 50 (82%) completed at least 3 weeks on medication and 38 (62%) completed the full 8-week trial. Study withdrawals included 12/29 on mecamylamine and 11/32 on placebo. For the total sample, mecamylamine was no more effective than placebo on any of the outcome measures. However, an item analysis of the TODS-CR suggested that mecamylamine may have reduced sudden mood changes and depression in moderately to severely affected subjects. Except for a slight increase in heart rate during the 1st week in both the mecamylamine and the placebo groups, there where no significant mecamylamine-related changes in vital signs, electrocardiogram, complete blood cell count, or blood chemistry values. CONCLUSIONS: Mecamylamine, in doses up to 7.5 mg/day, is well tolerated in children and adolescents, but as a monotherapy it does not appear to be an effective treatment for tics or for the total spectrum of symptoms associated with TD. However, further studies should be conducted to investigate its possible therapeutic effects in subjects with comorbid mood disorders and as an adjunct to neuroleptic medication.

Social anxiety disorder.

In 1990s, it was found that GSAD is more common, more disabling, and more chronic than previously realized. For the first time, there are good data about a range of effective treatment options that can offer these patients substantial relief and protection from their disability.

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.

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.

Diagnostic errors of primary care screens for depression and panic disorder.

OBJECTIVE: As the health care reimbursement system has changed, brief screens for detecting mental disorders in primary care have been developed. These efforts have faced the formidable task of identifying patients with mental disorders, while at the same time minimizing the number of misclassified cases. Here we consider the balance between sensitivity and positive predictive value. Primary care patients with false positive and false negative results on screens for depression and panic disorder are compared with regard to comorbidity and functional impairment. METHODS: This was a cross-sectional psychometric study. The study sample included 1001 primary care patients from the Department of Internal Medicine at Kaiser Permanente in Oakland, California. The Symptom-Driven Diagnostic System for Primary Care (SDDS-PC) screens and Sheehan Disability Scale were completed by the subjects. The SDDS-PC diagnostic interviews were administered to all subjects. RESULTS: Patients with false positive results on the panic disorder screen did not differ from patients with false negatives results with regard to rates of other psychiatric disorders, functional impairment, or mental health service utilization. In contrast, patients with false negative depression screen results had significantly more psychiatric disorders and functional impairment than those with false positive depression results. CONCLUSIONS: A substantial number of patients with either false positive or false negative screen results met diagnostic criteria for other mental disorders. Given the nominal burden of follow-up assessments for patients with positive screens, these data suggest that erring on the side of sensitivity may have been preferable when algorithms for these screens were selected.

Physician substance use by medical specialty.

Self-reported past year use of alcohol, tobacco, marijuana, cocaine, and two controlled prescription substances (opiates, benzodiazepines); and self-reported lifetime substance abuse or dependence was estimated and compared for 12 specialties among 5,426 physicians participating in an anonymous mailed survey. Logistic regression models controlled for demographic and other characteristics that might explain observed specialty differences. Emergency medicine physicians used more illicit drugs. Psychiatrists used more benzodiazepines. Comparatively, pediatricians had overall low rates of use, as did surgeons, except for tobacco smoking. Anesthesiologists had higher use only for major opiates. Self-reported substance abuse and dependence were at highest levels among psychiatrists and emergency physicians, and lowest among surgeons. With evidence from studies such as this one, a specialty can organize prevention programs to address patterns of substance use specific to that specialty, the specialty characteristics of its members, and their unique practice environments that may contribute risk of substance abuse and dependence.

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.

A diagnostic aid for detecting (DSM-IV) mental disorders in primary care.

This study was designed to develop and validate a new computerized version of the Symptom Driven Diagnostic System for Primary Care (SDDS-PC) and examine its feasibility in primary care practice. One thousand and one patients (ages 18-70) coming for routine care to Kaiser-Permanente were screened on a self-administered symptom scale for major depression, alcohol and drug dependence, generalized anxiety, panic and obsessive compulsive disorders, and suicidal behavior. The screen was followed up by a brief diagnostic interview, administered by a nurse, which yielded a one-page summary of positive symptoms and a provisional computer-generated diagnosis for the physician. The physician reviewed the summary results and made a diagnosis. The nurse and physician were blind to the screen results. Patients were reinterviewed within 96 hours by a mental health professional (MHP) blind to previous results. The nurses' interviews ranged between 1.5 and 3.5 minutes for a screened positive diagnosis. Agreement between the nurse and physician diagnoses was excellent to moderate. Disagreement was usually in the direction of the physician ruling out major mental disorders in favor of subsyndromal or medical explanations. Only rarely did physicians diagnose disorders not detected by the nurse interview. Agreement between physician and MHP was moderate. Physicians using the SDDS-PC seldom made diagnoses that were not confirmed by the independent assessment of the MHP. The SDDS-PC may facilitate recognition of psychiatric disorders and minimize the physician's time in information gathering.

The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.

The Mini-International Neuropsychiatric Interview (M.I.N.I.) is a short structured diagnostic interview, developed jointly by psychiatrists and clinicians in the United States and Europe, for DSM-IV and ICD-10 psychiatric disorders. With an administration time of approximately 15 minutes, it was designed to meet the need for a short but accurate structured psychiatric interview for multicenter clinical trials and epidemiology studies and to be used as a first step in outcome tracking in nonresearch clinical settings. The authors describe the development of the M.I.N.I. and its family of interviews: the M.I.N.I.-Screen, the M.I.N.I.-Plus, and the M.I.N.I.-Kid. They report on validation of the M.I.N.I. in relation to the Structured Clinical Interview for DSM-III-R, Patient Version, the Composite International Diagnostic Interview, and expert professional opinion, and they comment on potential applications for this interview.

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.

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.

Assessing psychiatric impairment in primary care with the Sheehan Disability Scale.

OBJECTIVE: Several recent studies have documented that substantial functional impairment is associated with many of the mental disorders seen in primary care. However, brief measures of mental health-related functional impairment are not commonly applied in primary care settings. The Sheehan Disability Scale (SDS), a three-item instrument for assessing such impairment, is evaluated in this study. METHOD: A psychometric analysis of the SDS was conducted with a sample of 1001 primary care patients at Kaiser Permanente In Oakland, California. The SDS and the Symptom Driven Diagnostic System for Primary Care assessments were completed. RESULTS: The internal consistency reliability of the SDS is high, with coefficient alpha of 0.89. The construct validity was substantiated in two ways. A one-factor model fit the data quite well. Furthermore, patients with each of six psychiatric disorders had significantly higher impairment scores than those who did not. Finally, over 80 percent of the patients with mental disorder diagnoses had an elevated SDS score and nearly 50 percent of those with elevated SDS scores had at least one disorder. CONCLUSIONS: The psychometric properties of the SDS were evaluated in primary care. The internal consistency reliability was high. The analyses also lend empirical support for the construct validity. The scale is a sensitive tool for identifying primary care patients with mental health-related functional impairment, who would warrant a diagnostically-oriented mental health assessment.

Psychotic symptoms in primary care.

BACKGROUND: Psychotic symptoms include a variety of disturbances in perception, reality testing, speech, and behavior. We examine the prevalence, distribution, treatment, and functional impairment associated with psychotic symptoms in primary care patients. METHODS: Data are drawn from a recent study of adult primary care patients (N = 1001) in a large, urban, prepaid group practice. At the medical visit, patients completed a questionnaire that probed demographic characteristics, health status, and mental health care utilization. Following the visit, patients received a telephone-administered, structured psychiatric interview that included 11 psychotic symptoms. Medication prescription data were also available. Comparisons are presented of patients with and without psychotic symptoms. RESULTS: Thirty-seven (3.7%) patients reported one or more psychotic symptoms, most commonly a belief that others were spying on or following them (n = 16). As compared with patients without psychotic symptoms, a larger proportion of the patients with psychotic symptoms reported mental health-related work loss (54.1% vs 17.9%, P < .0001), suicidal ideation (21.6% vs 2.6%, P < .0001), major depressive disorder (32.4% vs 6.3%, P < .0001), bipolar disorder (29.7% vs 1.2%, P < .0001), and several other mental disorders. An antipsychotic medication had been prescribed during the previous 17 to 20 months for only two (5.4%) of the patients with psychotic symptoms. CONCLUSIONS: Psychotic symptoms were relatively common (3.7%) in this practice and were strongly associated with functional impairment and affective, anxiety, or substance use disorders. Primary care physicians are encouraged to examine patients with these mental disorders for the presence of psychotic symptoms.

Suicidal ideation in primary care.

OBJECTIVE: To describe the prevalence and clinical characteristics of primary care patients who report suicidal ideation during the month before their medical visit. DESIGN: Analysis of a self-administered suicidal ideation screening item using sociodemographic data, treatment history, and clinical data from structured interviews. SETTING: Three Rhode Island private family practices, a South Carolina family medicine residency, and a California prepaid internal medicine group practice. PATIENTS: Adult primary care patients (N = 2,749), 18 to 70 years old, who are able to read and write English, able to complete study forms, and willing to provide informed consent. RESULTS: Sixty-seven (2.44%) of the patients reported suicidal ideation ("feeling suicidal") during the past month, and most of those patients (58.2%) received no mental health care during that time. The adjusted risk of suicidal ideation was significantly elevated for patients with self-reported fair or poor physical health (odds ratio [OR] 2.5; 95% confidence interval [CI] 1.5, 4.1), fair to poor emotional health (OR 18.0; 95% CI 8.8, 37.0), marital distress (OR 4.4; 95% CI 2.2, 8.8), and recent mental health-related work loss (OR 6.3; 95% CI 3.7, 10.5). In the California sample, patients with major depression (R 31.2; 95% CI 12.8, 76.1). generalized anxiety disorder (OR 23.4; 95% CI 8.1, 67.1), and drug abuse or dependence (OR 9.6; 95% CI 2.9, 31.6) were at increased risk of suicidal ideation. The "feeling suicidal" item identified 10 of 12 patients who acknowledged a recent plan to kill themselves. CONCLUSIONS: In these primary care patients, suicidal ideation is strongly associated with mental disorder and mental health-related functional impairment, and can be detected with a single self-report "feeling suicidal" item.