The effect of selective serotonin reuptake inhibitor treatment of panic disorder on emergency room and laboratory resource utilization.

BACKGROUND: While it has been well documented that patients with untreated panic disorder frequently utilize emergency room (ER) and laboratory services, no published data evaluate whether selective serotonin reuptake inhibitor (SSRI) treatment of patients with panic disorder is associated with decreased use of these services in the managed care organization setting. METHOD: A medical and pharmacy claims database representing individuals from several managed care organizations was used to analyze ER and laboratory resource utilization and cost for 120 patients with panic disorder (ICD-9-CM criteria) who received SSRI treatment. RESULTS: SSRI treatment was associated with a reduction in the mean number of ER and laboratory visits and costs in the 6-month period following therapy initiation compared with the 6-month period prior to therapy initiation (sertraline: visits, -79.5%; costs, -85.2%; p < .05; fluoxetine: visits, -25.0%; costs, -69.5%; p = NS; and paroxetine: visits, -8.6%; costs, -30.8%; p = NS). CONCLUSION: The results of the current study suggest that appropriate treatment of panic disorder may decrease unnecessary resource utilization for the medical symptoms associated with panic disorder.

A randomized effectiveness trial of collaborative care for patients with panic disorder in primary care.

BACKGROUND: Effectiveness studies have tested interventions to improve quality of care for depression in primary care, but none, to our knowledge, have been completed for panic disorder (PD) in this setting. This study sought to test the clinical effectiveness of PD pharmacotherapy embedded in a disease management framework of "collaborative care" (CC). METHODS: One hundred fifteen patients with PD from 3 primary care clinics were randomized to CC or "usual care" (UC). Patients in CC (n = 57) received educational videotapes and pamphlets; pharmacotherapy with the selective serotonin reuptake inhibitor paroxetine; 2 psychiatrist visits and 2 telephone calls in the first 8 weeks; and up to 5 telephone calls between 3 and 12 months' follow-up. Usual care patients (n = 58) were treated by their primary care physician. Telephone assessments of panic, anxiety sensitivity, depression, and disability variables were performed at 3, 6, 9, and 12 months' follow-up. Adequacy of pharmacotherapy was assessed with an algorithm based on a review of efficacy studies. RESULTS: Patients in CC were more likely to receive adequate (type, dose, duration) medication and more likely to adhere to this medication at 3 and 6 months. Random regression analyses showed that CC patients improved significantly more over time compared with UC patients on anxiety, depression, and disability measures, with the greatest effects at 3 and 6 months. CONCLUSIONS: Compared with UC, CC interventions significantly improved both quality of care and clinical and functional outcomes in primary care PD patients. Clinical differences were greatest in the first 6 months, corresponding to the greater quality of care and the greater intensity of intervention.

Reliability and clinical utility of DSM-IV substance-induced psychiatric disorders in acute psychiatric inpatients.

The goal of his study was to evaluate in 1,951 acute psychiatric inpatients the reliability, construct, convergent, and predictive validity of substance-induced psychiatric syndrome ratings made by clinical attending pschiatrists. The primary admitting condition for each subject was categorically rated by clinical attendings as not, mildly, moderately, or mostly substance-induced at both admission and discharge. Individual substance categories were associated with characteristic demographic, clinical treatment response, and length of stay, findings indicating good construct, predictive validity, and clinical utility. A linear dimensional approach to rating substance-induced syndromes in acute clinical populations may be preferable to the simple dichotomous approach used in DSM-IV.

Panic disorder in primary care: biopsychosocial differences between recognized and unrecognized patients.

Studies suggest that the recognition of depression by primary care physicians (PCPs) is most likely in more symptomatic and impaired patients. As part of a randomized effectiveness study in primary care patients with panic disorder, we examined the baseline characteristics of study patients who were recruited by waiting room screen procedure (n=69) versus patients who were referred to the study by their PCP (n=41). Patients referred by their physicians had a significantly higher frequency of panic attacks, more intense attacks, and more anticipatory anxiety on the Panic Disorder Severity Scale, while screen-identified patients were more medically ill and had worse physical functioning on the SP36. There were no differences in anxiety sensitivity, phobic avoidance, depression, other SF36 measures, disability, or medical service utilization. In conclusion, differences in referred versus screened patients are mostly specific for panic attack-related symptoms, consistent with the notion that patients with more prominent physical symptoms (i.e., panic attacks) are more often recognized and referred in busy clinical settings. The better medical status and physical functioning of referred patients may indicate greater physician recognition of panic in patients who appear less medically ill. However, the many clinical and functional similarities between these two patient samples suggests that symptomatic primary care patients with panic may not always be identified by their PCPs and argues for the value of population-based screening for panic in primary care.

Psychiatric diagnoses among self-referred dental injection phobics.

In order to determine the psychiatric characteristics of people with dental injection phobia. 118 dental injection phobics were systematically assessed using a structured clinical interview and a written questionnaire. Fifty-four percent of subjects had a current Axis I diagnosis other than dental injection phobia, mainly anxiety, mood or adjustment disorder, and 68.6% of subjects had an additional lifetime Axis I diagnosis. Subjects with additional current Axis I diagnoses reported higher dental anxiety, greater severity of injection fear cognitions, and poorer relationships with dental professionals, than did subjects without any or with past Axis I diagnoses. Further investigation is needed to explore the treatment possibilities for patients with and without additional current diagnoses.

Nefazodone treatment of major depression in alcohol-dependent patients: a double-blind, placebo-controlled trial.

Depression is the most common comorbid psychiatric illness in patients with alcohol dependence. This double-blind study tested the efficacy of nefazodone versus placebo for the treatment of depression in actively drinking alcohol-dependent patients who were also participating in weekly group treatment for alcoholism. Sixty-four subjects with major depression disorder and alcohol dependence with a history of at least one prior episode of depression when not drinking were randomly assigned to receive 12 weeks of either nefazodone or placebo and participated in a weekly psychoeducational group on alcoholism. Subjects were assessed every 2 weeks for depression, anxiety, side effects, and drinking frequency. Subjects taking nefazodone were significantly more likely to complete the study (62%) than those taking placebo (34%). Analyses of covariance using drinks per week as a time-dependent covariate showed lower Hamilton Rating Scale for Depression scores at week 8 for end-point analysis and at weeks 8 and 12 for completers. The endpoint analysis demonstrated a significantly greater response in the nefazodone group (48%) than in the placebo group (16%). Both groups showed a similarly significant decrease in the average number of alcoholic drinks consumed per day over the course of the study. Although the number of adverse effects was significantly greater for the nefazodone group, there were no severe adverse events, and nefazodone was well tolerated. Nefazodone is a safe and effective antidepressant to use in a population of alcohol-dependent patients with depression who have a high degree of comorbidity. Nefazodone treatment was superior to placebo in alleviating depression in these patients but did not add any advantage over the psychoeducational group in terms of drinking outcomes.

Lifetime panic-depression comorbidity in the National Comorbidity Survey. Association with symptoms, impairment, course and help-seeking.

BACKGROUND: Most prior studies of panic-depression comorbidity have been limited methodologically by use of small clinical samples and incomplete analyses. AIMS: General population data were used to study the association of lifetime and recent (12 months) panic-depression comorbidity with symptom severity, impairment, course and help-seeking in the National Comorbidity Survey (NCS). METHOD: The NCS is a nationally representative survey of the prevalences and correlates of major DSM-III-R disorders in the US household population. RESULTS: Strong lifetime and current comorbidity were found between panic and depression. Comorbidity was associated with greater symptom severity, persistence, role impairment, suicidality and help-seeking, with many findings persisting after controlling for additional comorbid diagnoses. Findings did not differ according to which disorder was chronologically primary. CONCLUSIONS: Both lifetime and current panic-depression comorbidity are markers for more severe, persistent and disabling illness. Neither additional comorbid diagnoses nor the primary-secondary distinction were important moderators of these associations.

Relationship between borderline personality disorder and Axis I diagnosis in severity of depression and anxiety.

BACKGROUND: This study tested the hypothesis that subjects with borderline personality disorder irrespective of the presence or absence of an Axis I mood or anxiety disorder would exhibit greater severity of depression and anxiety than subjects with either a personality disorder other than borderline personality disorder or no personality disorder. METHOD: Two hundred eighty-three subjects from an outpatient psychiatry clinic were administered the following assessments: the Structured Clinical Interview for DSM-III-R (SCID) for Axes I and II, the Hamilton Rating Scales for Depression and Anxiety, the Beck Depression Inventory, and the Spielberger State-Trait Anxiety Inventory. Subjects were categorized into borderline personality disorder, other personality disorder, and no personality disorder categories and into present versus absent categories on Axis I diagnosis of depression and of anxiety. A 2-factor multiple analysis of variance compared personality disorder status and Axis I diagnosis on severity of depression by observer rating and self-report. The analysis was repeated for anxiety. RESULTS: As hypothesized, significant main effects were found for borderline personality disorder and for both depression and anxiety. Subjects with borderline personality disorder showed greater severity on both depression and anxiety rating scales than did patients with another personality disorder, who showed greater severity than did patients with no personality disorder. Axis I diagnosis was also associated with greater severity on depression or anxiety rating scales. These differences were found for both observer ratings and self-report. An interaction was also found for depression: Subjects with borderline personality disorder but without an Axis I diagnosis of depression rated themselves as more severely depressed on the Beck Depression Inventory than did subjects with another or no personality disorder who also had an Axis I diagnosis of depression. CONCLUSION: Implications from the study are discussed including the need to assess for borderline personality disorder in research studies of depression and anxiety and to integrate treatments for borderline personality disorder into depression and anxiety treatment to maximize clinical outcomes.

Relationship between a GABAA alpha 6 Pro385Ser substitution and benzodiazepine sensitivity.

OBJECTIVE: In humans, interindividual variation in sensitivity to benzodiazepine drugs may correlate with behavioral variation, including vulnerability to disease states such as alcoholism. In the rat, variation in alcohol and benzodiazepine sensitivity has been correlated with an inherited variant of the GABAA alpha 6 receptor. The authors detected a Pro385Ser [1236C > T] amino acid substitution in the human GABAA alpha 6 that may influence alcohol sensitivity. In this pilot study, they evaluated the contribution of this polymorphism to benzodiazepine sensitivity. METHOD: Sensitivity to diazepam was assessed in 51 children of alcoholics by using two eye movement measures: peak saccadic velocity and average smooth pursuit gain. Association analysis was performed with saccadic velocity and smooth pursuit gain as dependent variables and comparing Pro385/Ser385 heterozygotes and Pro385/Pro385 homozygotes. RESULTS: The Pro385Ser genotype was associated with less diazepam-induced impairment of saccadic velocity but not with smooth pursuit gain. CONCLUSIONS: The Pro385Ser genotype may play a role in benzodiazepine sensitivity and conditions, such as alcoholism, that may be correlated with this trait.

Panic disorder in the primary care setting: comorbidity, disability, service utilization, and treatment.

BACKGROUND: Increased medical service utilization in patients with panic disorder has been described in epidemiologic studies, although service use in primary care panic patients relative to other primary care patients is less well characterized. Inadequate recognition of panic has been shown in several primary care studies, although the nature of usual care for panic in this setting has not been well documented. This study aimed to document increased service use in panic patients relative to other primary care patients and to characterize the nature of their usual care for panic and their outcome. METHOD: Using a waiting room screening questionnaire and follow-up telephone interview with the Composite International Diagnostic Interview, we identified a convenience sample of 81 patients with panic disorder (DSM-IV) and a control group of 183 psychiatrically healthy patients in 3 primary care settings on the West Coast and determined psychiatric diagnostic comorbidity, panic characteristics, disability, and medical and mental health service use, including medications. A subsample (N = 41) of panic patients was reinterviewed 4-10 months later to determine the persistence of panic and the adequacy of intervening treatment received using the Harvard/Brown Anxiety Disorders Research Program study criteria for cognitive-behavioral therapy (CBT) and an algorithm developed by the authors for medications. RESULTS: Seventy percent of panic patients had a comorbid psychiatric diagnosis. Patients had more disability in the last month (days missed or cut down activities) (p < .01), more utilization of emergency room and medical provider visits (p < .01), and more mental health visits (p < .05). Despite the latter, only 42% received psychotropic medication, 36% psychotherapy, and 64% any treatment. On follow-up, 85% still met diagnostic criteria for panic, and only 22% had received adequate medication (type and/or dose) and 12% adequate (i.e., CBT) psychotherapy. CONCLUSION: These findings suggest a need for improved treatment interventions for panic disorder in the primary care setting to decrease disability and potentially inappropriate medical service utilization.

Development of a brief diagnostic screen for panic disorder in primary care.

OBJECTIVE: The purpose of this study was to determine the utility of a brief screening tool for panic disorder in the primary care setting. METHODS: A total of 1476 primary care outpatients in three primary care medical clinics on the West Coast of the United States were studied. Patients completed a brief self-report measure, the five-item Autonomic Nervous System Questionnaire (ANS), while in the waiting room. The presence of DSM-IV panic disorder was subsequently determined in groups of "screen-positive" and "screen-negative" subjects using the Composite International Diagnostic Interview. A subset of patients (N = 511) also completed the 21-item Beck Anxiety Inventory. Indices of diagnostic utility were calculated using receiving operating characteristic analyses to guide the selection of optimal cutoff levels. RESULTS: The two-question version of the ANS had excellent sensitivity (range = 0.94-1.00 across the three clinic sites) and negative predictive value (0.94-1.00) but low specificity (0.25-0.59) and positive predictive value (range 0.18-0.40). The three- and five-question versions of the ANS had only modestly improved specificity, and this was achieved at the cost of reduced sensitivity and increased respondent burden to complete the questionnaire. The 21-item Beck Anxiety Inventory had maximal clinical utility at a cutoff level of > or =20, but sensitivity was lower than desirable for a screening instrument (0.67). CONCLUSIONS: The two-question version of the ANS shows promise as a screening instrument for panic disorder in the primary care setting.

Antidepressant efficacy in HIV-seropositive outpatients with major depressive disorder: an open trial of nefazodone.

BACKGROUND: Treatment studies of major depression in patients who are seropositive for the human immunodeficiency virus (HIV) have shown comparable efficacy for both tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). Nefazodone appears to be more tolerable than TCAs and similar to SSRIs. This study examined the efficacy and tolerability of nefazodone in an open 12-week trial of HIV-seropositive outpatients with major depressive disorder. METHOD: Fifteen HIV-seropositive patients with DSM-IV major depressive disorder and a 21-item Hamilton Rating Scale for Depression (HAM-D) score of > or =18 were treated with open-label nefazodone for 12 weeks. Hamilton Rating Scale for Anxiety, HAM-D, Clinical Global Impressions scale, and Systematic Assessment for Treatment Emergent Events general inquiry (for safety and tolerability) scores were obtained at weeks 2, 4, 6, 8, and 12. RESULTS: Of 15 patients receiving nefazodone, 4 discontinued treatment (1 for adverse effects). Of 11 patients who completed the trial, 8 (73%) were classified as full responders with a 50% reduction in HAM-D scores and final CGI score of 1 or 2, and 10 (91%) were classified as partial responders (only 50% reduction in HAM-D scores). Nefazodone-treated subjects experienced few total adverse effects (mean = 1.5), no sexual side effects, and low rates of adverse-effect-related dropout (1 subject, 7%). CONCLUSION: Depressed HIV-seropositive outpatients respond to nefazodone comparably to other outpatient populations and have few adverse effects, suggesting that nefazodone may have a role in the treatment of depression in HIV-seropositive patients. Potential drug interactions with protease inhibitors indicate that it is essential to evaluate for appropriate dosing to avoid adverse effects and increase overall antidepressant efficacy.

Does ketamine-mediated N-methyl-D-aspartate receptor antagonism cause schizophrenia-like oculomotor abnormalities?

Evidence from histological and pharmacological challenge studies indicates that N-methyl-D-aspartate (NMDA) receptor hypofunction may play an important role in the pathophysiology of schizophrenia. Our goal was to characterize effects of NMDA hypofunction further, as related to schizophrenia-associated neuropsychological impairment. We administered progressively higher doses of ketamine (target plasma concentrations of 50, 100, 150, and 200 ng/ml) to 10 psychiatrically healthy young men in a randomized, single-blind, placebo-controlled design and assessed oculomotor, cognitive, and symptomatic changes. Mean ketamine plasma concentrations approximated target plasma concentrations at each infusion step. Verbal recall, recognition memory, verbal fluency, pursuit tracking, visually guided saccades, and fixation all deteriorated significantly during ketamine infusion; lateral gaze nystagmus explained some, but not all, of the smooth pursuit abnormalities. We concluded that ketamine induces changes in recall and recognition memory and verbal fluency reminiscent of schizophreniform psychosis. During smooth pursuit eye tracking, ketamine induces nystagmus as well as abnormalities characteristic of schizophrenia. These findings help delineate the similarities and differences between schizophreniform and NMDA-blockade-induced cognitive and oculomotor abnormalities.

Predictors and outcome of discharge against medical advice from the psychiatric units of a general hospital.

OBJECTIVE: The study examined predictors of discharge against medical advice (AMA) and outcomes of psychiatric patients with AMA discharges, as measured by poorer symptom ratings at discharge and higher rates of rehospitalization. METHODS: A total of 195 patients discharged AMA from general hospital psychiatric units were compared retrospectively with 2,230 regularly discharged patients. AMA status was defined as signing out against medical advice, being absent without leave, or being administratively discharged. All patients received standardized assessments within 24 hours of admission and at discharge. Demographic characteristics, psychiatric history, DSA-IV psychiatric and substance use diagnoses, and scores on an expanded 32-item version of the Psychiatric Symptom Assessment Scale were compared. RESULTS: The groups did not differ in primary psychiatric diagnoses. Patients discharged AMA were significantly less likely to be Caucasian or to be functionally impaired due to physical illness. They were more likely to live alone, have a substance use diagnosis, use more psychoactive substances, and have more previous hospitalizations. Patients discharged AMA had significantly shorter lengths of stay, higher rehospitalization rates, and more severe symptoms at discharge, even when length of stay was taken into account. The differences between the groups in male gender and young age were better accounted for by a greater likelihood of substance abuse in these groups. CONCLUSIONS: The results suggest a profile of patients who may be discharged AMA. Such patients have worse outcomes and are more likely to be high utilizers of inpatient resources. Aggressive identification of patients likely to be discharged AMA and early discharge planning for appropriate outpatient treatment are recommended.

Randomized, placebo-controlled trial of paroxetine versus imipramine in depressed HIV-positive outpatients.

OBJECTIVE: This study examined whether a selective serotonin reuptake inhibitor (paroxetine) had comparable efficacy but greater tolerability than a tricyclic antidepressant (imipramine) in depressed patients with HIV infection. METHOD: Seventy-five HIV-positive patients (45% of whom had AIDS) were blindly and randomly assigned to receive paroxetine (N = 25), imipramine (N = 25), or placebo (N = 25) in a 12-week trial. The Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, the Clinical Global Impression scale, and the SAFETEE general inquiry (for safety and tolerability) were administered at weeks 2, 4, 6, 8, and 12. RESULTS: Fifty-six (75%) of the 75 patients completed 6 weeks and 34 (45%) completed 12 weeks of the trial. The mean daily doses of both paroxetine (33.9 mg) and imipramine (162.5 mg) were significantly more effective than placebo; they were comparably effective at weeks 6, 8, and 12 according to the intent-to-treat analysis and at week 8 according to the analysis for the subjects who completed the trial (for them, only imipramine was superior to placebo at week 12). There were significantly more dropouts due to side effects from imipramine (48%) than from both paroxetine (20%) and placebo (24%). CONCLUSIONS: Depressed patients with HIV infection responded to imipramine or paroxetine at a higher rate than to placebo irrespective of severity of immunosuppression. Because paroxetine was much better tolerated than imipramine, its overall effectiveness may be greater. However, because of the small study group and the high attrition rate, these findings cannot be generalized and may need replication in a larger study group.

Psychedelic effects of ketamine in healthy volunteers: relationship to steady-state plasma concentrations.

BACKGROUND: Ketamine has been associated with a unique spectrum of subjective "psychedelic" effects in patients emerging from anesthesia. This study quantified these effects of ketamine and related them to steady-state plasma concentrations. METHODS: Ketamine or saline was administered in a single-blinded crossover protocol to 10 psychiatrically healthy volunteers using computer-assisted continuous infusion. A stepwise series of target plasma concentrations, 0, 50, 100, 150, and 200 ng/ml were maintained for 30 min each. After 20 min at each step, the volunteers completed a visual analog (VAS) rating of 13 symptom scales. Peripheral venous plasma ketamine concentrations were determined after 28 min at each step. One hour after discontinuation of the infusion, a psychological inventory, the hallucinogen rating scale, was completed. RESULTS: The relation of mean ketamine plasma concentrations to the target concentrations was highly linear, with a correlation coefficient of R = 0.997 (P = 0.0027). Ketamine produced dose-related psychedelic effects. The relation between steady-state ketamine plasma concentration and VAS scores was highly linear for all VAS items, with linear regression coefficients ranging from R = 0.93 to 0.99 (P < 0.024 to P < 0.0005). Hallucinogen rating scale scores were similar to those found in a previous study with psychedelic doses of N,N-dimethyltryptamine, an illicit LSD-25-like drug. CONCLUSIONS: Subanesthetic doses of ketamine produce psychedelic effects in healthy volunteers. The relation between steady-state venous plasma ketamine concentrations and effects is highly linear between 50 and 200 ng/ml.

Cognitive functions and complaints in HIV-1 individuals treated for depression.

Progressive neuropsychological dysfunction and complaints of cognitive difficulty frequently accompany HIV-1 infection. Providing appropriate treatment to HIV-1 patients requires determination of the extent to which the presentation of cognitive complaints reflects HIV-1-associated neuropsychological abnormalities or represents expression of depressive symptomatology. We prospectively treated 75 HIV-1 patients who were not demented but met criteria for major mood disorder with antidepressants for 12 weeks and compared pretreatment and posttreatment measures of depression, cognitive complaints, and neuropsychological performance. Complaints of difficulty with memory and attention were found to be independent of neuropsychological impairment, whereas memory complaints were highly correlated with severity of depression. Cognitive complaints declined significantly across the course of treatment for those patients who responded to antidepressant treatment. All patients, regardless of antidepressant treatment response, exhibited parallel improvement on 12-week follow- up neuropsychological examination. These findings suggest that treatment of depression affects cognitive complaints in HIV-1 individuals and that cognitive complaints of patients in asymptomatic or early symptomatic stages of HIV-1 infection may signal the need for evaluation of depression. In patients with more advanced HIV-1 infection, investigation into the basis of cognitive complaints may require a dual assessment of mood disturbance and neuropsychological status.